DNA Damage/DNA Repair

[Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities]

15 | Feb 16 2024

Your research illuminates the unique mutational signatures in micropapillary components of early-stage invasive lung adenocarcinomas, unveiling the potential of ZNF469 as a diagnostic and prognostic biomarker while hinting at tailored therapeutic approaches for improved patient outcomes. [Read the Full Post]

Enhanced osteoblastic differentiation of parietal bone in a novel murine model of mucopolysaccharidosis type II

35 | Feb 14 2024

The study's identification of a genomic modification in Ids-deficient mice underscores a possible connection between IDS deficiency and the augmented differentiation of calvarial bone, shedding light on the enlarged head circumference observed in individuals affected by MPS II. [Read the Full Post]

Reduction of excessive unfolded protein response by 4-phenylbutyric acid may mitigate procymidone-induced testicular damage in mice by changing the levels of circRNA Scar and circZc3h4

61 | Feb 08 2024

4-PBA demonstrates promising protective effects against PCM-induced testicular injury in mice, mitigating damage by regulating specific circRNAs, such as Scar and Zc3h4, and suppressing the unfolded protein response pathway. [Read the Full Post]

Enhancing or Quenching of a Mitochondria-Targeted AIEgens-Floxuridine Sensor by the Regulation of pH-Dependent Self-assembly, Efficient Recognition of Hg2+, and Stimulated Response of GSH

50 | Feb 03 2024

The versatile TPE-FdU fluorescent probe, exhibiting pH-responsive behavior, selective Hg2+ ion detection, and intracellular mitochondrial visualization, represents a promising advancement with diverse applications in cell imaging, environmental monitoring, and biomedical research. [Read the Full Post]

Y box binding protein 1 inhibition as a targeted therapy for ovarian cancer

33 | Jan 30 2024

The discovery of SU056, a potent YB-1 inhibitor exhibiting multifaceted impacts on ovarian cancer progression, apoptosis promotion, and synergy with paclitaxel while reducing treatment-associated toxicities, suggests a promising strategy for combating tumor growth and treatment resistance. [Read the Full Post]

Covid-19 co-infection with Crimean Congo haemorrhagic fever (CCHF) in a CCHF endemic country: a case report

47 | Jan 22 2024

In regions where both Crimean-Congo hemorrhagic fever and severe COVID-19 coexist, differentiating between the two diseases is vital due to their overlapping clinical presentations, emphasizing the importance of accurate diagnostic testing to guide appropriate treatment strategies. [Read the Full Post]

PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy

33 | Jan 20 2024

The study highlights protocadherin 1 (PCDH1) as a pivotal prognostic biomarker and metastasis promoter in pancreatic adenocarcinoma (PAAD), suggesting flutamide's potential as a therapeutic avenue by down-regulating PCDH1 expression to impede PAAD progression. [Read the Full Post]

Drug Repositioning Identifies Six Drug Candidates for Systemic Autoimmune Diseases by Integrative Analyses of Transcriptomes from Scleroderma, Systemic Lupus Erythematosus, and Sjogren's Syndrome

0 | Jan 18 2024

This study utilizing transcriptome data and bioinformatic analysis identified common gene signatures across systemic autoimmune diseases, leading to the discovery of six potential small molecule drug candidates through drug repositioning, shedding light on novel therapeutic avenues for these conditions. [Read the Full Post]

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model

35 | Jan 14 2024

PP121, a dual tyrosine and phosphoinositide kinase inhibitor, demonstrates promising anti-contractile and anti-inflammatory effects in asthma treatment, suggesting its potential as a novel therapeutic compound for managing the condition. [Read the Full Post]

Immunotherapies against HER2-Positive Breast Cancer

21 | Jan 14 2024

Immunotherapy offers a promising array of strategies, from cancer vaccines to immune checkpoint blockade and adoptive cell therapy, holding the potential to transform the treatment landscape for HER2-positive breast cancer by enhancing immune responses and potentially preventing disease progression. [Read the Full Post]

GW0742 reduces mast cells degranulation and attenuates neurological impairments via PPARβ/δ/CD300a/SHP1 pathway after GMH in neonatal rats

31 | Jan 13 2024

The study presents compelling evidence that GW0742, a PPARβ/δ agonist, attenuates mast cell-induced inflammation post-germinal matrix hemorrhage (GMH) by activating the CD300a/SHP1 pathway, offering a promising avenue for mitigating brain injury in GMH patients. [Read the Full Post]

A Novel Polyamino Acid Sulfur Dioxide Prodrug Synergistically Elevates ROS with β-lapachone in Cancer Treatment

28 | Jan 12 2024

This groundbreaking study combines sulfur dioxide gas therapy and a specific ROS-inducing agent, β-lapachone, encapsulated in nanoparticles, demonstrating potent anticancer effects through oxidative stress induction in both in vitro and in vivo models. [Read the Full Post]

Epigenetic Activation of TUSC3 Sensitizes Glioblastoma to Temozolomide Independent of MGMT Promoter Methylation Status

27 | Jan 10 2024

This study presents compelling evidence that epigenetic reactivation of Tumor Suppressor Candidate 3 (TUSC3) can significantly enhance Temozolomide (TMZ) sensitivity in both MGMT-promoter-hypermethylated (MGMT-M) and MGMT-promoter-hypomethylated (MGMT-UM) glioblastoma stem cells, offering a potential breakthrough in addressing TMZ resistance and improving outcomes in glioblastoma patients. [Read the Full Post]

Utilization of AlphaFold models for drug discovery: Feasibility and challenges. Histone deacetylase 11 as a case study

60 | Jan 04 2024

Your study on optimizing the HDAC11 AlphaFold model, validating it through molecular dynamics simulations and successful docking of known inhibitors, provides a promising foundation for structure-based drug design targeting HDAC11. [Read the Full Post]

Epigenetic Compound Screening Uncovers Small Molecules for Reactivation of Latent HIV-1

64 | Jan 02 2024

The study utilized a cell-based reporter system under BSL-1 conditions to screen an epigenetic compound library, identifying two promising compounds, HPOB and SR-4370, with high reactivation efficiencies and low toxicity, offering potential as effective treatments for reversing HIV-1 latency. [Read the Full Post]

Role of parthenolide in paclitaxel-induced oxidative stress injury and impaired reproductive function in rat testicular tissue

111 | Dec 28 2023

Parthenolide treatment in rats demonstrated a dose-dependent mitigation of oxidative stress-induced testicular damage caused by paclitaxel, showing promise as a potential therapeutic avenue for addressing testicular toxicity and supporting reproductive function. [Read the Full Post]

Epigenetic upregulation of Schlafen11 renders WNT- and SHH-activated medulloblastomas sensitive to cisplatin

65 | Dec 22 2023

High SLFN11 expression, identified as a top prognostic marker, is associated with longer survival in WNT-activated and a subset of SHH-activated medulloblastomas, possibly through enhanced sensitivity to DNA damaging agents such as cisplatin, with pharmacological upregulation by RG2833 showing promise for therapeutic intervention. [Read the Full Post]

AZ32 Reverses ABCG2-Mediated Multidrug Resistance in Colorectal Cancer

43 | Dec 22 2023

The study established that the ATM kinase inhibitor AZ32 effectively sensitizes ABCG2-overexpressing colorectal cancer cells to chemotherapeutic drugs, such as mitoxantrone and doxorubicin, by retaining them inside cells, thus demonstrating its potential to reverse ABCG2-mediated multidrug resistance. [Read the Full Post]

Improving Speed and Affordability without Compromising Accuracy: Standard Binding Free-Energy Calculations Using an Enhanced Sampling Algorithm, Multiple-Time Stepping, and Hydrogen Mass Repartitioning

48 | Dec 21 2023

The study proposes an accelerated computational strategy, combining longer time steps with hydrogen-mass repartitioning and multiple time-stepping, to efficiently calculate protein-ligand binding free energies using well-tempered metadynamics, significantly reducing computational time without compromising accuracy. [Read the Full Post]

Predictive model for treatment outcomes of peripheral T-cell lymphoma, not otherwise specified, in Taiwanese patients

86 | Dec 20 2023

In this retrospective study of 104 peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) patients in Taiwan, the investigation revealed a poor prognosis, highlighted the potential efficacy of pralatrexate as salvage chemotherapy for eligible patients, identified adverse prognostic factors, and proposed a novel predictive index with distinct risk groups, emphasizing the need for further validation and exploration of improved treatment strategies. [Read the Full Post]

Prospects of Topoisomerase Inhibitors as Promising Anti-Cancer Agents

50 | Dec 16 2023

The review underscores the significance of topoisomerase inhibitors, such as irinotecan and etoposide, in cancer treatment by disrupting DNA replication and inducing cell death, emphasizing their potential as crucial anti-cancer medications. [Read the Full Post]

Therapeutical interference with the epigenetic landscape of germ cell tumors: a comparative drug study and new mechanistical insights

42 | Dec 15 2023

The study identified seven epigenetic inhibitors that efficiently decreased cell viability in cisplatin-resistant Type II germ cell tumors, highlighting their potential as alternative therapeutic options, and provided comprehensive insights into their off-target effects and modes of action. [Read the Full Post]

Exosomal EIF5A derived from Lewis lung carcinoma induced adipocyte wasting in cancer cachexia

62 | Dec 11 2023

The study reveals that exosomal EIF5A derived from Lewis lung carcinoma cells induces adipocyte lipolysis in cancer cachexia by binding with GPBAR1 mRNA, activating the CREB signaling pathway, implicating EIF5A as a potential therapeutic target. [Read the Full Post]

Increased recombinant adeno-associated virus production by HEK293 cells using small molecule chemical additives

24 | Dec 09 2023

The study demonstrates that the addition of small molecule bioactive chemical additives, nocodazole and M344, significantly enhances rAAV vector production in HEK cells, increasing genome titre up to three-fold and indicating a promising approach for improving the cost-effectiveness of gene therapy production processes. [Read the Full Post]

Targeted Regulation of Osteoblasts and Osteoclasts in Osteosarcoma Patients by CSF3R Receptor Inhibition of Osteolysis Caused by Tumor Inflammation Based on Transcriptional Spectrum Analysis and Drug Library Screening

33 | Dec 08 2023

**In summary, the study identifies CSF3R as a key regulator in osteosarcoma progression, influencing bone destruction and patient prognosis by modulating the inflammatory response of osteoblasts and osteoclasts, with Leucovorin and Methotrexate identified as potential therapeutic compounds.** [Read the Full Post]

The Crystal Structure of Engineered Nitroreductase NTR 2.0 and Impact of F70A and F108Y Substitutions on Substrate Specificity

25 | Dec 07 2023

A newly engineered nitroreductase enzyme, NTR 2.0, with enhanced reduction capabilities for the prodrug metronidazole, has been characterized through X-ray crystallography and substrate analysis, enabling faster cell ablation kinetics, cleaner interrogations of cell function, ablation of previously recalcitrant cell types, and extended ablation paradigms valuable for modeling chronic diseases and exploring applications such as alternative ablation prodrugs and environmental remediation. [Read the Full Post]

Hepatic arterial infusion chemotherapy with or without lenvatinib for unresectable cholangiocarcinoma: a single-center retrospective study

43 | Dec 05 2023

**Combining FOLFOX hepatic arterial infusion chemotherapy with lenvatinib significantly prolongs overall and progression-free survival, making it a promising and safe treatment option for patients with unresectable cholangiocarcinoma.** [Read the Full Post]

Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells

35 | Dec 01 2023

The study elucidates the role of NUDT5 in ADP-ribose metabolism and hormone-dependent gene regulation in breast cancer cells, presenting TH5427 as a potent inhibitor that blocks nuclear ATP synthesis, chromatin remodeling, and proliferation, highlighting its potential for targeted therapy and further research. [Read the Full Post]

HDAC3 inhibitor (BRD3308) modulates microglial pyroptosis and neuroinflammation through PPARγ/NLRP3/GSDMD to improve neurological function after intraventricular hemorrhage in mice

48 | Dec 01 2023

BRD3308 (BRD), an inhibitor of histone deacetylase 3 (HDAC3), reduces neuroinflammation, inhibits pyroptosis, and improves neurobehavioral outcomes in a mouse model of intraventricular hemorrhage by activating the PPARγ/NLRP3/GSDMD signaling pathway. [Read the Full Post]

Lauric Acid, a Dietary Saturated Medium-Chain Fatty Acid, Elicits Calcium-Dependent Eryptosis

35 | Nov 29 2023

The study demonstrates that lauric acid induces eryptosis, a programmed cell death in red blood cells, and disrupts leukocyte distribution, providing key insights into its role in cardiovascular diseases and informing dietary interventions for prevention and management. [Read the Full Post]

Carnosic acid and rosemary extract reversed the lipid accumulation induced by bisphenol A in the 3T3-L1 preadipocytes and C57BL/6J mice via SIRT1/FoxO1 pathway

33 | Nov 23 2023

Carnosic acid (CA) and rosemary extract counteracted Bisphenol A (BPA)-induced adipogenesis and lipid accumulation by downregulating adipogenic proteins, upregulating lipolytic proteins, and activating the SIRT1/FoxO1 pathway in both 3T3-L1 preadipocytes and C57BL/6 J mice. [Read the Full Post]

Viability of selected microorganisms in parenteral preparations for novel systemic anti-cancer therapy

38 | Nov 18 2023

**"This study reveals the persistence of viable pathogenic microorganisms in most aseptically prepared parenteral cancer therapy solutions, emphasizing the importance of strict aseptic conditions and careful consideration of antimicrobial activity when determining their shelf life."** [Read the Full Post]

Non-oncology drug (meticrane) shows anti-cancer ability in synergy with epigenetic inhibitors and appears to be involved passively in targeting cancer cells

98 | Nov 17 2023

Meticrane, a non-oncology drug originally used to treat hypertension, exhibits promising anti-cancer effects on leukemia and liver cancer cells, including synergistic interactions with epigenetic inhibitors, alterations in gene expression associated with non-cancer pathways, and considerable binding affinity to key cancer-related proteins, although it does not enhance the cytotoxicity of cytokine-induced killer cells, suggesting its potential as a novel cancer therapy warrants further investigation. [Read the Full Post]

Pin1 inhibitor API-1 sensitizes BRAF-mutant thyroid cancers to BRAF inhibitors by attenuating HER3-mediated feedback activation of MAPK/ERK and PI3K/AKT pathways

44 | Nov 15 2023

The study demonstrates that the Pin1 inhibitor API-1 enhances the sensitivity of BRAF-mutant thyroid cancer cells to the BRAF inhibitor PLX4032 by blocking the reactivation of MAPK/ERK and PI3K/AKT pathways via downregulation of HER3, offering a promising combination therapy for this cancer type. [Read the Full Post]

Multi-omics analysis reveals the association between elevated KIF18B expression and unfavorable prognosis, immune evasion, and regulatory T cell activation in nasopharyngeal carcinoma

43 | Nov 15 2023

Kinesin Family Member 18B (KIF18B) overexpression in Nasopharyngeal Carcinoma (NPC) is associated with poor prognosis, immune suppression, epithelial-mesenchymal transition (EMT), N6-methyladenosine (m6A) modification, and resistance to both immunotherapy and chemotherapy, making it a significant prognostic marker with potential therapeutic implications. [Read the Full Post]

Inaugural Results of the Individualized Screening Trial of Innovative Glioblastoma Therapy: A Phase II Platform Trial for Newly Diagnosed Glioblastoma Using Bayesian Adaptive Randomization

40 | Nov 13 2023

The Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) is a phase II platform trial that employs genomic profiling and adaptive randomization to evaluate novel therapies for glioblastoma, with abemaciclib and neratinib showing improved progression-free survival compared to the control arm, although none of the experimental therapies demonstrated a significant overall survival benefit. [Read the Full Post]

Deciphering the Allosteric Activation Mechanism of SIRT6 Using Molecular Dynamics Simulations

53 | Nov 13 2023

This study proposes a mechanism where myristic acid and synthetic SIRT6 activators stabilize NAD+ binding and substrate interactions, shedding light on SIRT6 activation and offering insights for the design of potential therapeutic agents. [Read the Full Post]

Rituximab at lower dose for neuromyelitis optica spectrum disorder: a multicenter, open-label, self-controlled, prospective follow-up study

66 | Nov 12 2023

The study provided evidence that a lower-dose rituximab (RTX) therapy strategy is effective and safe in treating neuromyelitis optica spectrum disorder (NMOSD), potentially changing the approach to NMOSD treatment by addressing optimal dosage and therapy initiation timing. [Read the Full Post]

Segmental Zoster Paresis Accompanied by Horner's Syndrome

143 | Nov 11 2023

In this case, a 90-year-old immunocompromised woman developed right upper limb weakness and Horner's syndrome following oral therapy for zoster on the right T2 dermatome, with aggressive intravenous treatment leading to improvement in the former but persistence of the latter. [Read the Full Post]

Senolytic Combination Treatment Is More Potent Than Single Drugs in Reducing Inflammatory and Senescence Burden in Cells from Painful Degenerating IVDs

46 | Nov 09 2023

Combining the senolytic drugs o-Vanillin and RG-7112 effectively removes senescent cells, reduces inflammation and pain mediators, and inhibits neuronal sprouting, offering promise as a potential treatment for low back pain associated with intervertebral disc degeneration. [Read the Full Post]

Efficacy and safety of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of esophageal squamous cell cancer: A prospective, open label, randomized phase II study

38 | Nov 08 2023

The combination of irinotecan and raltitrexed may lead to better progression-free survival and overall survival compared to irinotecan monotherapy, especially in the second-line treatment of metastatic esophageal squamous cell cancer. [Read the Full Post]

Epigenetic regulator BMI1 promotes alveolar rhabdomyosarcoma proliferation and constitutes a novel therapeutic target

35 | Nov 05 2023

This study suggests that targeting BMI1, an epigenetic regulator, may offer a potential therapeutic strategy for alveolar rhabdomyosarcoma (ARMS) by inhibiting cell growth, promoting apoptosis, and activating the Hippo pathway. [Read the Full Post]

Inhibition of histone deacetylases attenuates tumor progression and improves immunotherapy in breast cancer

60 | Oct 29 2023

HDAC inhibitors in breast cancer have demonstrated potent anti-tumor activity and the potential to improve immunotherapy outcomes, highlighting their potential as potent agents to enhance breast cancer treatment. [Read the Full Post]

Synthesis and biological evaluation of novel N-benzyltriazolyl-hydroxamate derivatives as selective histone deacetylase 6 inhibitors

54 | Oct 27 2023

The study designed and evaluated a novel N-benzyltriazolyl-hydroxamate scaffold, resulting in the identification of compound 4u as a highly potent and selective HDAC6 inhibitor, providing insights for the development of targeted therapies for neurodegenerative diseases, inflammation, and cancer. [Read the Full Post]

Ribonucleotide reductase regulatory subunit M2 drives glioblastoma TMZ resistance through modulation of dNTP production

86 | Oct 26 2023

In this study, the increased expression of ribonucleotide reductase regulatory subunit M2 (RRM2) and its regulation of dGTP and dCTP production during temozolomide (TMZ) therapy were identified as key factors in driving chemoresistance in glioblastoma (GBM), and treatment with the RRM2 inhibitor 3-AP (Triapine) improved the efficacy of TMZ therapy in patient-derived xenograft (PDX) models. [Read the Full Post]

The effect of iodine-131 beta-particles in combination with A-966492 and Topotecan on radio-sensitization of glioblastoma: An in-vitro study

34 | Oct 25 2023

The combination of iodine-131 with topoisomerase I and PARP inhibitors demonstrated marked effects in sensitizing glioblastoma cells to radiotherapy, indicating its potential as a targeted radionuclide therapy to enhance treatment efficacy. [Read the Full Post]

Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants

88 | Oct 23 2023

Stenoparib (2X-121), a poly (ADP-ribose) polymerase (PARP) inhibitor, demonstrates effective inhibition of SARS-CoV-2 and its variant strains in vitro, with the potential for enhanced antiviral activity when combined with remdesivir. [Read the Full Post]

Inhibition of HDAC6 With CAY10603 Ameliorates Diabetic Kidney Disease by Suppressing NLRP3 Inflammasome

72 | Oct 22 2023

The study identified CAY10603, an HDAC6 inhibitor, as a potential therapeutic drug for diabetic nephropathy by suppressing NLRP3 inflammasome activation in tubular cells and macrophages. [Read the Full Post]

SIRT6 ameliorates LPS-induced apoptosis and tight junction injury in ARDS through the ERK1/2 pathway and autophagy

41 | Oct 21 2023

SIRT6, through its regulation of the ERK1/2 pathway and enhancement of autophagy, demonstrates a beneficial role in acute respiratory distress syndrome (ARDS) by ameliorating tight junction protein loss, inflammation, and apoptosis, suggesting its potential as a therapeutic target for ARDS. [Read the Full Post]

Purine Antimetabolites associated Pneumocystis Jiroveci Pneumonia

120 | Oct 20 2023

The retrospective disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database revealed a significant safety signal for pneumocystis jiroveci pneumonia (PJP) associated with purine antimetabolites, particularly fludarabine and thioguanine, among populations with autoimmune disorders and cancer. [Read the Full Post]

Targeting eIF4F translation initiation complex with SBI-756 sensitises B lymphoma cells to venetoclax

44 | Oct 20 2023

The study demonstrated that the combination of the cap-dependent mRNA translation inhibitor SBI-756 with venetoclax enhances apoptosis and efficacy in DLBCL and MCL cells, highlighting a potential novel treatment approach for aggressive lymphomas. [Read the Full Post]

Targeting lipid-sensing nuclear receptors PPAR (α, γ, β/δ): HTVS and molecular docking/dynamics analysis of pharmacological ligands as potential pan-PPAR agonists

54 | Oct 19 2023

The study identified eprosartan as a potential PPAR pan-agonist with strong binding affinity to all PPAR isoforms, demonstrated superior stability in protein-ligand complex formation, and showed promising therapeutic effects in an in vitro model of NAFLD. [Read the Full Post]

Porcine cardiac blood - Salvia miltiorrhiza root alleviates cerebral ischemia reperfusion injury by inhibiting oxidative stress induced apoptosis through PI3K/AKT/Bcl-2/Bax signaling pathway

47 | Oct 17 2023

PCB-DS, a combination of Salvia miltiorrhiza and porcine cardiac blood, alleviates cerebral ischemia/reperfusion injury (CIRI) by inhibiting oxidative stress-induced apoptosis through the PI3K/AKT/Bcl-2/Bax signaling pathway. [Read the Full Post]

Synthesis, Anticancer, Antimicrobial and Antioxidant Potential of Novel 4-(Substituted phenyl-1,3,4-oxadiazol/thiadiazol-2-yl)-4-(4-substituted phenyl) Azetidin-2-One Derivatives

22 | Oct 16 2023

The synthesized 4-substitutedphenyl-1,3,4-oxadiazol/Thiadiazol-2-yl)-4-(4-substitutedphenyl) azetidin-2-one derivatives demonstrated high efficacy against MCF-7 cancer cell lines, significant antimicrobial potential, and potent antioxidant activity, suggesting their potential for further research and development as therapeutic agents. [Read the Full Post]

Potential New Therapeutic Approaches for Cisplatin-Resistant Testicular Germ Cell Tumors

62 | Oct 14 2023

The proteasome inhibitor MG-132 shows promise as a potential new drug for treating cisplatin-resistant testicular germ cell tumors (TGCTs), enhancing sensitivity to cisplatin and inducing apoptosis in both parental and resistant cell lines. [Read the Full Post]

Atypical Anti-Glomerular Basement Membrane Nephritis After the First Dose of the Severe Acute Respiratory Syndrome Coronavirus 2 mRNA Vaccine

62 | Oct 13 2023

Atypical anti-GBM nephritis, which can occur after the administration of the SARS-CoV-2 mRNA vaccine, is characterized by linear IgG deposition in the glomerular basement membrane without circulating anti-GBM antibodies or lung involvement, and its response to immunosuppressive therapy is uncertain. [Read the Full Post]

Bolgiano-Obukhov spectrum and mixing efficiency in stably stratified turbulence

69 | Oct 12 2023

The paper presents simulations of highly turbulent stably stratified flow using a shell model, revealing dual scaling behavior in the energy spectra, mixing efficiency variation with Richardson number for different stratification strengths, and Kolmogorov scaling in the inertial range. [Read the Full Post]

SIRT5 IS A DRUGGABLE METABOLIC VULNERABILITY IN ACUTE MYELOID LEUKEMIA

64 | Oct 08 2023

The discovery that the survival and growth of AML cells, irrespective of their genetic characteristics, rely on SIRT5 highlights its potential as a therapeutic target for AML treatment. [Read the Full Post]

Tamoxifen resistance induction results in the upregulation of ABCG2 expression and mitoxantrone resistance in MCF-7 breast cancer cells

77 | Oct 07 2023

The study found that prolonged exposure of ER+ MCF-7 breast cancer cells to tamoxifen led to increased expression of the ABCG2 pump, associated with TAM resistance and potential cross-resistance to mitoxantrone. [Read the Full Post]

Translation-dependent skin hyperplasia is promoted by type 1/17 inflammation in psoriasis

64 | Oct 05 2023

This study reveals that the molecule eukaryotic initiation factor 4E (eIF4E) plays a crucial role in the abnormal differentiation of keratinocytes driven by type 1/17 inflammation in psoriasis, suggesting its potential as a therapeutic target. [Read the Full Post]

Targeting homologous recombination deficiency in uterine leiomyosarcoma

22 | Sep 25 2023

This report highlights the significance of identifying homologous recombination deficiency in uterine leiomyosarcoma (uLMS) for therapeutic targeting with poly (ADP-ribose) polymerase (PARP) inhibitors and platinum agents, demonstrating encouraging clinical responses and suggesting the potential for PARP1-specific PARP inhibitors in future trials. [Read the Full Post]

Synergism of PARP inhibitor fluzoparib (HS10160) and MET inhibitor HS10241 in breast and ovarian cancer cells

96 | Sep 21 2023

The study validated the synergistic effect of combining a selective MET inhibitor (HS10241) with a PARP inhibitor (HS10160) in eliminating triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC) cells, suggesting its potential benefit for patients resistant to single-agent PARP inhibitor treatment. [Read the Full Post]

The synthetic oleanane triterpenoid CDDO-2P-Im binds GRP78/BiP to induce unfolded protein response-mediated apoptosis in myeloma

64 | Sep 21 2023

The study demonstrates that the synthetic oleanane triterpenoid 2P-Im induces apoptosis in multiple myeloma cells through activation of the unfolded protein response (UPR) and direct binding to the endoplasmic reticulum chaperone BiP (GRP78/BiP). [Read the Full Post]

Guidance on the management of adverse reactions induced by poly(ADP-ribose) polymerase inhibitors

103 | Sep 20 2023

The common adverse reactions of PARP inhibitors, including hematological toxicity, gastrointestinal toxicity, and fatigue, can be managed through measures such as regular blood tests, referral to specialists, symptomatic treatment, and monitoring for potential complications. [Read the Full Post]

Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): Clinical candidate for cancer therapy

102 | Sep 17 2023

VX-970 (berzosertib or M6620) is a promising small-molecule ATR inhibitor that shows potential as an effective anticancer drug, both as monotherapy and in combination with chemotherapy or radiotherapy strategies, based on preclinical data and ongoing phase I/II clinical trials. [Read the Full Post]

Selective inhibition of ATM-dependent double-strand break repair and checkpoint control synergistically enhances the efficacy of ATR inhibitors

99 | Sep 17 2023

Inhibition of ATR kinase and simultaneous suppression of ATM kinase synergistically enhance cancer cell death and show promise as a novel combination approach for cancer therapy. [Read the Full Post]

Indirect treatment comparison of lurbinectedin versus other second-line treatments for small-cell lung cancer

35 | Sep 15 2023

Lurbinectedin showed superior survival benefit and a favorable safety profile compared to other second-line treatments for platinum-sensitive small-cell lung cancer (SCLC). [Read the Full Post]

Anti-Klebsiella pneumoniae activity of secondary metabolism of Achromobacter from the intestine of Periplaneta americana

77 | Sep 13 2023

This study identifies a strain of Achromobacter from the intestinal tract of Periplaneta americana that exhibits strong antibacterial activity against Klebsiella pneumoniae, highlighting the potential for the development of novel antimicrobial compounds from insect intestinal microorganisms. [Read the Full Post]

Ursolic acid-downregulated long noncoding RNA ASMTL-AS1 inhibits renal cell carcinoma growth via binding to HuR and reducing vascular endothelial growth factor expression

45 | Sep 12 2023

The study found that ursolic acid (UA) inhibits renal cell carcinoma (RCC) growth and tumorigenesis by downregulating ASMTL-AS1, which destabilizes VEGF mRNA and suppresses RCC cell migration, invasion, and angiogenesis. [Read the Full Post]

Norepinephrine as the Intrinsic Contributor to Contact Lens-Induced Pseudomonas aeruginosa Keratitis

75 | Sep 11 2023

This study reveals that norepinephrine, acting through the β2-adrenergic receptor, promotes Pseudomonas aeruginosa keratitis during contact lens wear, suggesting potential therapeutic targets for treating the condition. [Read the Full Post]

REV1 promotes lung tumorigenesis by activating the Rad18/SERTAD2 axis

77 | Sep 02 2023

The study suggests that REV1 is a potential diagnostic marker and therapeutic target for lung cancer, and the novel REV1 inhibitor, JH-RE-06, shows promise as a safe and efficient therapeutic agent for NSCLC. [Read the Full Post]

Chemical inhibition of DNA-PKcs impairs the activation and cytotoxicity of CD4+ helper and CD8+ effector T cells

97 | Aug 31 2023

Inhibition of DNA-PKcs using small-molecule inhibitors abrogates T cell activation, impairs metabolic pathways and proliferation, and reduces cytotoxicity, highlighting its potential as a therapeutic target for immune modulation in autoimmune diseases, immune-related disorders, and cancer. [Read the Full Post]

Identification of a Cryptic Binding Site in CRISPR-Cas9 for Targeted Inhibition

55 | Aug 31 2023

This study discovered a hidden ligand binding site within the carboxyl-terminal domain (CTD) of CRISPR-Cas9, revealing how the binding of small molecules induces structural changes that inhibit the function of Cas9. [Read the Full Post]

Therapeutic inhibition of Bmi-1 ablates chemoresistant cancer stem cells in adenoid cystic carcinoma

75 | Aug 29 2023

Targeting Adenoid Cystic Carcinoma (ACC) Cancer Stem Cells (CSCs) with Bmi-1 inhibitors, such as PTC596, demonstrates the potential to overcome chemoresistance and prevent tumor relapse in ACC. [Read the Full Post]

Preclinical validation of a novel therapeutic strategy for choroid plexus carcinoma

104 | Aug 19 2023

This study represents a pioneering effort in identifying promising combinatorial therapeutics and highlighting the potential of intra-arterial delivery for the treatment of choroid plexus carcinoma, a rare and aggressive brain tumor in children. [Read the Full Post]

Nuclear pCHK1 as a potential biomarker of increased sensitivity to ATR inhibition

54 | Aug 19 2023

The study suggests that the nuclear-specific enrichment of checkpoint kinase 1 (CHK1) and higher levels of nuclear phosphorylated CHK1 (pCHK1) staining may serve as potential predictive biomarkers for sensitivity to the ATR inhibitor elimusertib in cancer cells. [Read the Full Post]

Nicotinamide ameliorates mitochondria-related neuronal apoptosis and cognitive impairment via the NAD+/SIRT3 pathway

55 | Aug 16 2023

Nicotinamide (NAM) can alleviate neuronal apoptosis and microglial over-activation in a rat model of schizophrenia by modulating the NAD+-SIRT3-SOD2 signaling pathway, indicating its potential as a novel treatment approach for the disorder. [Read the Full Post]

In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part III

93 | Aug 14 2023

The study utilized PBPK/PD modeling and virtual clinical trial simulations to evaluate the potential efficacy of the siremadlin and trametinib combination as a therapy for melanoma, based on in vitro studies and in vivo extrapolation. [Read the Full Post]

Co-Targeting of MDM2 and CDK4/6 with Siremadlin and Ribociclib for the Treatment of Patients with Well-Differentiated or Dedifferentiated Liposarcoma: Results from a Proof-of-Concept, Phase Ib Study

82 | Aug 14 2023

The combination of siremadlin and ribociclib showed manageable toxicity and early signs of antitumor activity in patients with advanced well-differentiated or dedifferentiated liposarcoma. [Read the Full Post]

BRCAness, Homologous Recombination Deficiencies, and Synthetic Lethality

29 | Aug 13 2023

BRCAness refers to a tumor's homologous recombination repair defect, either through genetic inactivation of BRCA or HRD genes, and can be identified through genomic profiling, with implications for selecting targeted therapies such as PARP inhibitors, TOP1 inhibitors, and platinum derivatives. [Read the Full Post]

Advanced ovarian clear cell carcinoma with RAD50 mutation treated by PARP inhibitor pamiparib combined with anti-angiogenesis therapy: a case report

35 | Aug 13 2023

Targeted combination therapy with the PARP inhibitor pamiparib and bevacizumab showed promising results in achieving partial remission and improving the quality of life in a 45-year-old female patient with advanced ovarian clear cell carcinoma (OCCC) and a RAD50 mutation. [Read the Full Post]

HDAC inhibitor chidamide overcomes drug resistance in chronic myeloid leukemia with the T315i mutation through the Akt-autophagy pathway

114 | Aug 12 2023

Chidamide, a Histone Deacetylase Inhibitor (HDACi) drug, shows promising anti-leukemia effects and has the potential to overcome T315I mutation-related drug resistance in Chronic Myeloid Leukemia (CML) when used in combination with Tyrosine Kinase Inhibitors (TKIs). [Read the Full Post]

Second-line Endocrine Therapy of Hormone Receptor-Positive/HER2-negative Advanced Breast Cancer: A Systematic Review and Network Meta-analysis

59 | Aug 12 2023

The network meta-analysis found that cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) combined with fulvestrant (Ful500) demonstrated the best progression-free survival (PFS) and overall survival (OS) outcomes as second-line therapy for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced/metastatic breast cancer, with palbociclib ranking first in terms of PFS and CDK4/6i ranking first in terms of OS. [Read the Full Post]

Targeting DNA Repair with Combined Inhibition of NHEJ and MMEJ Induces Synthetic Lethality in TP53-Mutant Cancers

39 | Aug 12 2023

Combining the DNA-PK/NHEJ inhibitor peposertib with the POLθ/MMEJ inhibitor novobiocin provides a rational treatment strategy for TP53-mutant solid tumors, resulting in synthetic lethality and potential therapeutic efficacy. [Read the Full Post]

Synergistic Targeting of DNA-PK and KIT Signaling Pathways in KIT Mutant Acute Myeloid Leukemia

33 | Aug 12 2023

This study demonstrates that targeting DNA-PK in KIT mutant acute myeloid leukemia (AML) cells, in combination with inhibitors of KIT signaling, shows synergistic effects and holds promise as a therapeutic strategy for this aggressive form of AML. [Read the Full Post]

HDAC9-mediated epithelial cell cycle arrest in G2/M contributes to kidney fibrosis in male mice

46 | Aug 07 2023

The study reveals that HDAC9 induction in renal tubular epithelial cells mediates G2/M cell cycle arrest, leading to tubulointerstitial fibrosis, and suggests HDAC9 as a potential therapeutic target for treating kidney fibrosis. [Read the Full Post]

Coupling the immunomodulatory properties of the HDAC6 inhibitor ACY241 with Oxaliplatin promotes robust anti-tumor response in non-small cell lung cancer

0 | Aug 05 2023

The study demonstrates that the HDAC6 inhibitor ACY241 promotes favorable changes in the tumor immune microenvironment, enhancing T cell function and macrophage activation, and when combined with Oxaliplatin, it leads to significantly improved tumor-associated T cell effector functionality, suggesting its potential as a therapeutic intervention in non-small cell lung cancer (NSCLC). [Read the Full Post]

HDAC8-Selective Inhibition by PCI-34051 Enhances the Anticancer Effects of ACY-241 in Ovarian Cancer Cells

0 | Aug 05 2023

Co-inhibition of HDAC6 and HDAC8 with selective inhibitors synergistically suppresses cancer cell proliferation, enhances apoptosis, and inhibits metastasis in p53 wild-type ovarian cancer cells, indicating a potential novel therapeutic approach for ovarian cancer. [Read the Full Post]

Effects of Hypolipidemic Drugs on Psoriasis

85 | Aug 02 2023

The systematic review of 41 original articles assessed the effect of different hypolipidemic treatments on the course of psoriasis, highlighting the potential benefits of statins, fibrates, glitazones, and GLP-1 receptor agonists in improving lipid abnormalities associated with the disease. [Read the Full Post]

Increased CMV disease and "severe" BK viremia with belatacept vs. sirolimus three-drug maintenance immunosuppression

40 | Aug 02 2023

The study found that belatacept therapy in kidney transplant recipients was associated with a higher risk of CMV disease and "severe" CMV and BK viremia, but did not significantly increase overall infection incidence and showed comparable rates of acute rejection and graft loss at 12 months compared to sirolimus therapy. [Read the Full Post]

Bioinformatics screening of colorectal-cancer causing molecular signatures through gene expression profiles to discover therapeutic targets and candidate agents

71 | Aug 02 2023

This study utilized integrated statistics and bioinformatics approaches to identify key genes, transcriptional regulators, and candidate therapeutic agents for colorectal cancer (CRC), highlighting their potential diagnostic, prognostic, and therapeutic significance. [Read the Full Post]

The effect of the ATM inhibitor AZD0156 on the radiosensitivity of human breast cancer and lung fibroblast cells

58 | Jul 31 2023

The combination of irradiation and AZD0156 showed enhanced efficacy in inducing cell cycle arrest and reducing clonogenic survival in breast cancer cells, while having minimal effect on fibroblast cells. [Read the Full Post]

Anal Cancer Prevention Through the Topical Use of Single or Dual PI3K/mTOR Inhibitors

69 | Jul 28 2023

In this study, topical inhibition of the mTOR and/or PI3K pathways demonstrated promising results in increasing tumor-free survival and reducing squamous cell carcinoma in mice with anal dysplasia and anal cancer. [Read the Full Post]

Novel therapeutic approaches for pleural mesothelioma identified by functional ex vivo drug sensitivity testing

34 | Jul 28 2023

The study found that mTOR and Chk1 pathway inhibitors showed promising efficacy in established and patient-derived cell models of pleural mesothelioma, suggesting their potential as novel treatment strategies. [Read the Full Post]

MAPK-interacting kinases inhibition by eFT508 overcomes chemoresistance in preclinical model of osteosarcoma

130 | Jul 26 2023

The study highlights the therapeutic potential of eFT508, a selective inhibitor of MNK1/2, alone and in combination with paclitaxel, as a promising treatment for osteosarcoma by inhibiting tumor growth and demonstrating selectivity and synergistic effects. [Read the Full Post]

Treatment with eFT-508 increases chemosensitivity in breast cancer cells by modulating the tumor microenvironment

88 | Jul 26 2023

Tomivosertib (eFT-508) demonstrates promising efficacy both in vitro and in vivo, including synergistic effects with adriamycin, suggesting its potential as a more efficacious therapeutic option for patients with triple-negative breast cancer (TNBC). [Read the Full Post]

The mRNA-binding protein DDX3 mediates TGF-β1 upregulation of translation and promotes pulmonary fibrosis

56 | Jul 25 2023

Inhibiting the mRNA-binding protein DDX3, which mediates TGF-β1 upregulation of translation, shows promise in reducing pulmonary fibrosis and associated inflammation in experimental models. [Read the Full Post]

Thiomyristoyl ameliorates colitis by blocking the differentiation of Th17 cells and inhibiting SIRT2-induced metabolic reprogramming

29 | Jul 24 2023

The study suggests that treatment with TM, a compound that targets SIRT2, reduces the progression of ulcerative colitis by inhibiting Th17 cell differentiation, promoting LDHA acetylation, and modulating inflammatory cytokines. [Read the Full Post]

Treating colorectal peritoneal metastases with an injectable cytostatic loaded supramolecular hydrogel in a rodent animal model

72 | Jul 21 2023

The experimental study demonstrated that treatment of peritoneal metastases with a supramolecular hydrogel loaded with mitomycin C (MMC) significantly improved overall survival compared to treatment with free MMC alone, suggesting the potential of this drug delivery system for enhancing therapeutic efficacy. [Read the Full Post]

The tumor stroma influences immune cell distribution and recruitment in a PDAC-on-a-chip model

135 | Jul 20 2023

This study utilized a 3D PDAC model to investigate the interaction between tumor stroma and immune cells, revealing that stromal cells create a physical and biochemical barrier that hinders immune cell infiltration, and targeting the stroma can increase immune cell infiltration, offering potential therapeutic strategies for PDAC. [Read the Full Post]

Effects of the Combined Treatment with a G-Quadruplex-Stabilizing Ligand and Photon Beams on Glioblastoma Stem-like Cells: A Magnetic Resonance Study

66 | Jul 19 2023

The study found that while the GSC line #1 showed significant metabolic changes and sensitivity to the treatments, the GSC line #83 did not exhibit distinct metabolic responses, and there were no synergistic effects observed from the combination of ligand #190 and photon beam radiation in either GSC line. [Read the Full Post]

Dynamic of centromere associated RNAs and the centromere loading of DNA repair proteins in growing oocytes

52 | Jul 17 2023

This study demonstrates that centromere transcription in growing oocytes, associated with DNA repair proteins, plays a role in maintaining centromere stability and kinetochore assembly, providing insights into the accurate segregation of chromosomes during oocyte maturation. [Read the Full Post]

A comparative analysis to determine the optimum histone deacetylase inhibitors and administration route for improving survival and organ injury in rats after hemorrhagic shock

0 | Jul 15 2023

The study found that intravenous administration of histone deacetylase inhibitors (HDACIs) was more effective than intraperitoneal administration, and both nonselective and isoform-specific HDACIs showed similar effects in improving survival and reducing histopathological damage, apoptosis, and inflammation in rats with hemorrhagic shock. [Read the Full Post]

Simultaneous Inhibition of Histone Deacetylases and RNA Synthesis Enables Totipotency Reprogramming in Pig SCNT Embryos

37 | Jul 14 2023

In this study, the combined inhibition of histone deacetylases and RNA synthesis in swine SCNT embryos improved their developmental outcomes and increased the efficiency of the genome-editing + SCNT platform. [Read the Full Post]

THZ531 Induces a State of BRCAness in Multiple Myeloma Cells: Synthetic Lethality with Combination Treatment of THZ 531 with DNA Repair Inhibitors

29 | Jul 14 2023

Combining the CDK12 inhibitor THZ531 with DNA repair inhibitors such as Olaparib holds potential as an effective therapeutic approach for multiple myeloma by inducing synergistic cell death and reducing tumor burden. [Read the Full Post]

PPARβ/δ Ligands Regulate Oxidative Status and Inflammatory Response in Inflamed Corpus Luteum-An In Vitro Study

39 | Jul 12 2023

This study revealed that PPARβ/δ agonists at different concentrations regulate the inflammatory response in the pig corpus luteum, with the lower dose showing anti-inflammatory effects and the higher dose potentially supporting the immune response against pathogens. [Read the Full Post]

Efficacy of favipiravir against influenza virus resistant to both baloxavir and neuraminidase inhibitors

70 | Jul 09 2023

The study findings suggest that favipiravir should be used as a treatment option for patients suspected of having influenza virus infections resistant to NA inhibitors and baloxavir. [Read the Full Post]

A Facile Raman Spectroscopy Method for Online Monitoring of Crystal Plane Orientation of Favipiravir

132 | Jul 09 2023

This paper describes a facile method for online monitoring of the crystal plane orientation of favipiravir using Raman spectroscopy, providing a non-contact, fast, and sample preparation-free approach with potential applications in pharmaceutical processes. [Read the Full Post]

On-chip real-time impedance monitoring of hiPSC-derived and artificial basement membrane-supported endothelium

138 | Jul 05 2023

Electrochemical impedance spectroscopy was successfully applied to monitor the stability and integrity of a human induced pluripotent stem cell-derived endothelial barrier supported by an artificial basement membrane, revealing enhanced stability in a serum-free and bromodeoxyuridine-containing culture medium and sensitivity to stimuli such as thrombin. [Read the Full Post]

Generation of a Live Attenuated Influenza A Vaccine Using Chemical-Triggered Intein

69 | Jul 01 2023

A novel method using 4-hydroxytamoxifen (4-HT)-dependent intein insertion into the polymerase acidic (PA) protein of influenza A virus generates recombinant viruses that demonstrate excellent replication characteristics and induce robust immunity, offering potential for the development of a more effective live attenuated influenza vaccine and possibly vaccines against other pathogens as well. [Read the Full Post]

5-Oxoproline Enhances 4-Hydroxytamoxifen-induced Cytotoxicity by Increasing Oxidative Stress in MCF-7 Breast Cancer Cells

0 | Jul 01 2023

In conclusion, the study demonstrates that 5-oxoproline enhances the cytotoxic effects of 4-hydroxytamoxifen in estrogen receptor-positive breast cancer cells under normal glucose conditions, suggesting the potential utility of monocarboxylate transporter inhibitors as adjunctive therapeutic agents. [Read the Full Post]

Sirtuin 1 activator alleviated lethal inflammatory injury via promotion of autophagic degradation of pyruvate kinase M2

74 | Jun 29 2023

The present study demonstrated that activation of SIRT1 through treatment with SRT2104 promotes autophagic degradation of pyruvate kinase M2 (PKM2), leading to reduced inflammation, improved organ function, and increased survival in lethal endotoxemia [Read the Full Post]

Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts

21 | Jun 26 2023

Targeting telomeres through TERT inhibition shows promise as a potential therapeutic strategy for reducing tumor growth and improving outcomes in non-small cell lung cancer (NSCLC). [Read the Full Post]

Intensity of endogenous thrombocytopenia after autologous stem cell transplantation in patients prophylactically transfused with platelets

23 | Jun 26 2023

The study demonstrated that monitoring endogenous platelet counts using digital droplet PCR can accurately assess the impact of myelosuppressive chemotherapies on platelet regeneration, aiding in the development of tailored platelet transfusion regimens for patients undergoing high-dose chemotherapy with autologous stem cell transplantation. [Read the Full Post]

Bridging Gaps in HDR Improvement: The Role of MAD2L2, SCAI, and SCR7

91 | Jun 25 2023

This study demonstrated that MAD2L2 knockdown and SCR7 treatment significantly improved homology-directed repair (HDR) efficiency during CRISPR/Cas-mediated genome editing, offering valuable insights for enhancing precise correction in gene editing. [Read the Full Post]

Expression of RNA polymerase I catalytic core is influenced by RPA12

39 | Jun 24 2023

The study demonstrates that while RPA12 influences the basal expression and localization of the Pol I subunits RPA194 and RPA135, it does not affect their interaction or the transcriptional activity of Pol I, and the degradation of RPA194 induced by the small-molecule inhibitor BMH-21 is independent of RPA12. [Read the Full Post]

Combination ATR (ceralasertib) and PARP (olaparib) Inhibitor (CAPRI) trial in acquired PARP-inhibitor-resistant homologous recombination deficient ovarian cancer

97 | Jun 23 2023

The combination of olaparib and ceralasertib shows promising activity and tolerability in patients with acquired PARPi-resistant high-grade serous ovarian cancer, suggesting the potential of ATRi to overcome PARPi resistance in this population. [Read the Full Post]

TK216 targets microtubules in Ewing sarcoma cells

80 | Jun 22 2023

The study reveals that TK216, initially developed as an EWSR1-FLI1 inhibitor, acts as a microtubule destabilizing agent, explaining its cytotoxicity and supporting a reevaluation of its clinical trials in combination with vincristine. [Read the Full Post]

Three dimensional models of dedifferentiated liposarcoma cell lines: scaffold-based and scaffold-free approaches

122 | Jun 20 2023

This study aimed to establish 3D cell culture models of liposarcomas using different methods, observing distinct structural differences and demonstrating the potential of these models to provide new insights into efficacy and toxicity, serving as an important step in the pre-clinical phase prior to clinical trials. [Read the Full Post]

MI-773, a breaker of the MDM2/p53 axis, exhibits anticancer effects in neuroblastoma via downregulation of INSM1

62 | Jun 19 2023

MI-773, a specific antagonist of MDM2, disrupts the MDM2/p53 axis, leading to suppressed proliferation, induced apoptosis, and cell cycle arrest in neuroblastoma cells, suggesting its potential as a novel treatment strategy for this pediatric malignancy. [Read the Full Post]

HDAC4 mediated LHPP deacetylation enhances its destabilization and promotes the proliferation and metastasis of nasopharyngeal carcinoma

88 | Jun 18 2023

The study reveals that the HDAC4/LHPP signaling axis promotes the proliferation and metastasis of nasopharyngeal carcinoma through upregulation of TYK2-STAT1 phosphorylation activation, providing new insights and potential intervention targets for NPC metastasis. [Read the Full Post]

Astrocytic c-Jun N-terminal kinase-histone deacetylase-2 cascade contributes to glutamate transporter-1 decrease and mechanical allodynia following peripheral nerve injury in rats

26 | Jun 17 2023

The decrease of glutamate transporter-1 (GLT-1) and upregulation of histone deacetylase 2 (HDAC2) in spinal astrocytes, mediated by the JNK-HDAC2 cascade and neuroimmune activation, contribute to enhanced excitatory transmission and the development of persistent pain following peripheral nerve injury. [Read the Full Post]

Porcine Deltacoronavirus Infection Cleaves HDAC2 to Attenuate Its Antiviral Activity

55 | Jun 17 2023

The study revealed that porcine deltacoronavirus (PDCoV) infection inhibits cellular histone deacetylase 2 (HDAC2) activity through cleavage by the viral nonstructural protein 5 (nsp5), highlighting a common strategy employed by mammalian coronaviruses to counteract the antiviral role of HDAC2 and providing potential targets for the development of antiviral drugs. [Read the Full Post]

SIRT2 inhibition by AGK2 enhances mycobacteria-specific stem cell memory responses by modulating beta-catenin and glycolysis

51 | Jun 16 2023

This study demonstrates that inhibiting SIRT2 during BCG vaccination enhances the immune response, particularly the generation of stem cell memory T cells, and suggests SIRT2 inhibitors as potential immunoprophylaxis against tuberculosis. [Read the Full Post]

The HDAC inhibitor domatinostat induces type I interferon α in Merkel cell carcinoma by HES1 repression

108 | Jun 15 2023

The study revealed that the anti-tumor effect of the HDAC inhibitor domatinostat on Merkel cell carcinoma cells is mediated through the suppression of HES1, allowing for the induction of IFNα and subsequent apoptosis. [Read the Full Post]

A comparative analysis to determine the optimum histone deacetylase inhibitors and administration route for improving survival and organ injury in rats after hemorrhagic shock

55 | Jun 15 2023

The study found that intravenous administration of nonselective and isoform-specific HDACIs, including MS-275, LMK-235, tubastatin A, and TSA, was superior to intraperitoneal administration in improving survival rates and reducing histopathological scores, apoptosis cell numbers, and inflammatory cytokine levels in rats with hemorrhagic shock. [Read the Full Post]

Stabilization of the Quadruplex-Forming G-Rich Sequences in the Rhinovirus Genome Inhibits Uncoating-Role of Na+ and K

17 | Jun 10 2023

This research investigated the potential of G-quadruplex structures in inhibiting the replication cycle of rhinoviruses, with GQ-stabilizing compounds interfering with viral uncoating and promoting the formation and/or stabilization of GQs, impairing RNA unraveling and release from the virion. [Read the Full Post]

A unique 7p/12q chromosomal abnormality associated with recurrent abortion and hypofibrinogenemia

35 | Jun 10 2023

Recurrent first-trimester abortions in a 25-year-old woman with hypofibrinogenemia and a unique chromosomal abnormality (t(7;12)) suggest a potential relationship between the two conditions, while successful gestation following fibrinogen infusion indicates the critical role of fibrinogen concentration in securing implantation [Read the Full Post]

Characterization of Plasmodium falciparum prohibitins as novel targets to block infection in humans by impairing the growth and transmission of the parasite

92 | Jun 08 2023

The study characterizes Plasmodium falciparum prohibitins (PHBs), showing their expression in both asexual and sexual blood stages and localization in mitochondria, and demonstrating their involvement in stabilizing mitochondrial DNA and maintaining integrity, with potential druggability for blocking parasite growth using Rocaglamide (Roc-A). [Read the Full Post]

Alpha-tocopherol enhances spermatogonial stem cell proliferation and restores mouse spermatogenesis by up-regulating BMI1

63 | Jun 05 2023

This study investigates the role of BMI1 in spermatogonial stem cell proliferation and male reproduction, and demonstrates the potential modulatory effect of alpha-tocopherol on BMI1 both in vitro and in vivo. [Read the Full Post]

The Class IIA Histone Deacetylase (HDAC) Inhibitor TMP269 Downregulates Ribosomal Proteins and Has Anti-Proliferative and Pro-Apoptotic Effects on AML Cells

37 | Jun 04 2023

The study found that HDAC genes are overexpressed in AML patients and cell lines, and that TMP269, a class IIA HDAC inhibitor, has anti-leukemic activity when combined with venetoclax and may be a potential therapeutic drug for AML. [Read the Full Post]

PARP1 Activation Induces HMGB1 Secretion Promoting Intestinal Inflammation in Mice and Human Intestinal Organoids

26 | Jun 02 2023

PARP1 promotes HMGB1 secretion in intestinal inflammation, and inhibiting PARP1 could be a novel approach to manage inflammatory bowel diseases. [Read the Full Post]

Pharmacologic inhibition of PARP5, but not that of PARP1 or 2, promotes cytokine production and osteoclastogenesis through different pathways

64 | May 31 2023

The study shows that pharmacologic inhibition of PARP5 unexpectedly induces adverse autoinflammatory side effects through activation of innate immunity, unlike inhibition of other PARPs. [Read the Full Post]

Differential requirement of Hippo cascade during CTNNB1 or AXIN1 mutation-driven hepatocarcinogenesis

65 | May 31 2023

The study shows that targeting YAP/TAZ is an effective treatment against hepatocellular carcinoma (HCC) with loss-of-function mutations of AXIN1. [Read the Full Post]

Combining radiation and the ATR inhibitor berzosertib activates STING signaling and enhances immunotherapy via inhibiting SHP1 function in colorectal cancer

24 | May 22 2023

This study found that combining ATR inhibitors, irradiation, and anti-PD-L1 therapy improved the efficacy of immunotherapy in colorectal cancer mouse models by promoting STING signaling and reinvigorating the tumor microenvironment. [Read the Full Post]

Kv1.3 blockade by ShK186 modulates CD4+ effector memory T-cell activity of patients with Granulomatosis with polyangiitis

49 | May 19 2023

The study suggests that Kv1.3 blockade using ShK-186 may be a potential treatment strategy for GPA by modulating the activity of CD4+TEM cells and reducing the production of pro-inflammatory cytokines, with less harmful side effects than current immunosuppressive regimens. [Read the Full Post]

Efficient production of recombinant proteins in suspension CHO cells culture using the Tol2 transposon system coupled with cycloheximide resistance selection

31 | May 16 2023

The study demonstrates an efficient method for producing therapeutic proteins using DNA recombination techniques in mammalian cells, combining the Tol2 transposon system and cell selection by cycloheximide resistance to produce stable cell lines with constant productivity and cell growth suitable for commercial production. [Read the Full Post]

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: Predictors of Clinical and Radiographic Failure from 636 Embolizations

91 | May 06 2023

The study identified multiple independent predictors of failure of middle meningeal artery embolization treatment for chronic subdural hematoma, with small diameter being the only factor independently associated with both clinical and radiographic failures. [Read the Full Post]

A Systematic Review of Second-Line Treatments in Antiviral Resistant Strains of HSV-1, HSV-2, and VZV

45 | May 04 2023

This study conducted a systematic review of the literature on second-line treatments for drug-resistant strains of herpes simplex viruses, and found that there are potential options that could effectively manage these infections. [Read the Full Post]

Safety and immunogenicity of a TK/ gI/gE gene-deleted feline herpesvirus-1 mutant constructed via CRISPR/Cas9 in feline

28 | Apr 28 2023

The study describes the development of a novel FHV-1 vaccine using CRISPR/Cas9-mediated homologous recombination, which showed improved safety and efficacy compared to the commercial modified live vaccine. [Read the Full Post]

Phase I clinical and pharmacological study of thymidine (NSC 21548) and cis-diamminedichloroplatinum(II) in patients with advanced cancer

61 | Apr 28 2023

A Phase I trial found that the maximally tolerated dose of thymidine plus cisplatin in patients with advanced cancer was 60 g/m2/day, with hematological toxicity being the dose-limiting factor, and recommended this dose for Phase II trials. [Read the Full Post]

Zearalenone induces mitochondria-associated endoplasmic reticulum membranes dysfunction in piglet Sertoli cells based on endoplasmic reticulum stress

58 | Apr 22 2023

The study found that ZEA induces dysfunction of MAM in piglet SCs via the ERS pathway, and pretreatment with the ERS inhibitor 4-PBA can reduce ZEA-induced toxicity and regulate the expression of key proteins involved in MAM function. [Read the Full Post]

HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis

42 | Apr 22 2023

The study found that the oncoprotein HBXIP promotes breast cancer cell migration by blocking myosin-IIA assembly, and that the anti-hyperlipidemic drug bezafibrate (BZF) can inhibit PKCβII-mediated NMHC-IIA phosphorylation and suppress breast cancer metastasis both in vitro and in vivo. [Read the Full Post]

Adequacy of energy and macronutrients intake in differently active slovenian adolescents

135 | Apr 21 2023

The study found that a significant proportion of Slovenian adolescents are not meeting national recommendations for energy and macronutrient intake, and there were differences in energy/macronutrient intake between boys of different physical activity levels, highlighting the need for interventions to encourage healthy eating and physical activity behaviors. [Read the Full Post]

Perinatal Stressors as a Factor in Impairments to Nervous System Development and Functions: Review of In Vivo Models

86 | Apr 21 2023

This review evaluates different models of perinatal pathology and their relationship with psychoemotional stressors in understanding the impact of stress on the developing brain and behavior. [Read the Full Post]

PPAR agonists for the treatment of primary biliary cholangitis: Old and new tales

99 | Apr 20 2023

PPAR agonists are a promising new class of drugs for PBC treatment, especially for UDCA non-responders or intolerant patients, but further studies are needed to confirm their efficacy, safety, and long-term benefits. [Read the Full Post]

Insights into the mechanisms of triptolide nephrotoxicity through network pharmacology-based analysis and RNA-seq

110 | Apr 19 2023

The combination of network pharmacology and deep RNA-seq analysis provides valuable insights into the molecular mechanisms of TPL nephrotoxicity, identifying potential targets and signaling pathways for further investigation. [Read the Full Post]

Chlorogenic acid, rutin, and quercetin from Lysimachia christinae alleviate triptolide-induced multi-organ injury in vivo by modulating immunity and AKT/mTOR signal pathway to inhibit ferroptosis and apoptosis

149 | Apr 18 2023

The study showed that a combination of organ-protective ingredients from Lysimachia christinae could protect against triptolide-induced multi-organ injury in vivo by activating the AKT/mTOR pathway and reducing cell death including ferroptosis and apoptosis inhibition. [Read the Full Post]

Investigation of the impact of rosuvastatin and telmisartan in doxorubicin-induced acute cardiotoxicity

84 | Apr 15 2023

The study found that pre-treatment with rosuvastatin and telmisartan, alone or in combination, showed significant cardio-protective effects against the acute cardiotoxicity induced by doxorubicin. [Read the Full Post]

Romidepsin-induced durable remission for relapsed nodal peripheral T-cell lymphoma with T follicular helper phenotype after allogeneic hematopoietic cell transplantation

71 | Apr 14 2023

This case report suggests that romidepsin may be a safe and effective treatment option for patients with relapsed or refractory PTCL-TFH after allogeneic HCT. [Read the Full Post]

Modulation of the endoplasmic reticulum stress and unfolded protein response mitigates the behavioral effects of early-life stress

89 | Apr 13 2023

The study suggests that modulation of ER stress and UPR processes may underlie susceptibility or resilience to early-life stress (ELS) in rats. [Read the Full Post]

Nicotinamide riboside supplementation is not associated with altered methylation homeostasis in Parkinson's disease

48 | Apr 13 2023

The study found that short-term therapy with high-dose nicotinamide riboside (NR) for up to 30 days had no negative impact on DNA methylation homeostasis in individuals with Parkinson's disease. [Read the Full Post]

[A convenient and time-saving method for primary culture of mature white adipocytes from mice]

90 | Apr 12 2023

The study established a simple, low-cost, and time-saving method for primary culture of mature white adipocytes from mice, enabling further functional studies. [Read the Full Post]

A Cell System-Assisted Strategy for Evaluating the Natural Antioxidant-Induced Double-Stranded DNA Break (DSB) Style

103 | Apr 11 2023

Researchers evaluated whether natural antioxidants induce DNA damage using gene-knockout cell lines and found that sulforaphane induces single-strand breaks or DNA strand crosslinks, quercetin induces double-strand breaks, while resveratrol exerts cytotoxic effects other than DNA damage, and the mechanisms through which kaempferol and genistein induce DNA damage remain unknown. [Read the Full Post]

miR-223 Plays a Key Role in Obesogen-Enhanced Adipogenesis in Mesenchymal Stem Cells and in Transgenerational Obesity

71 | Apr 10 2023

The study found that exposure to the obesogen tributyltin (TBT) increased levels of the microRNA miR-223 in mesenchymal stem cells (MSCs), which may play a role in the development of obesity in male offspring of exposed pregnant mice through the PPARγ pathway. [Read the Full Post]

N-palmitoylethanolamide synergizes the antinociception of morphine and gabapentin in the formalin test in mice

51 | Apr 06 2023

The study investigated the synergistic antinociceptive effect of PEA in combination with MOR or GBP and found that PPARα and opioid receptors are involved in both interactions, suggesting potential use in treating inflammatory pain. [Read the Full Post]

The role of transforming growth factor-β2 in cigarette smoke-induced lung inflammation and injury

111 | Apr 06 2023

The study found that TGF-β2 attenuated CSE-induced IL-8 production in PBECs and alleviated lung inflammation/injury in CS-exposed mice through the Smad3 signaling pathway. [Read the Full Post]

Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus

177 | Apr 05 2023

This research demonstrates that mutations in the K-D-K-E methyltransferase motif restrict the cell-to-cell spread of Newcastle disease virus via tunnelling nanotubes. [Read the Full Post]

Monitoring paxillin in astrocytes reveals the significance of the adhesion GPCR VLGR1/ADGRV1 for focal adhesion assembly

97 | Apr 04 2023

VLGR1 is a vital component of focal adhesions and regulates cell migration by controlling focal adhesion turnover during their assembly, and its dysfunctions may contribute to the pathogenesis of Usher syndrome, epilepsy, and other related diseases. [Read the Full Post]

Differential roles of phosphatidylinositol 3-kinase/akt pathway in retinal ganglion cell survival in rats with or without acute ocular hypertension

54 | Apr 03 2023

The study demonstrated that the PI3K/akt pathway is involved in mediating RGC survival following IOP elevation but not under normal conditions, suggesting its potential as a therapeutic target for ocular ischemic injuries and glaucoma. [Read the Full Post]

CUDC907, a dual phosphoinositide-3 kinase/histone deacetylase inhibitor, promotes apoptosis of NF2 Schwannoma cells

55 | Apr 03 2023

CUDC907, a dual HDAC/PI3K inhibitor, selectively reduces the viability of human merlin deficient Schwann cells (MD-SCs), promotes cell cycle arrest and caspase-3/7 activation, decreases levels of pAKT and YAP, and shows potential as a therapeutic option for Neurofibromatosis Type 2 (NF2). [Read the Full Post]

Co-targeting of HDAC, PI3K, and Bcl-2 results in metabolic and transcriptional reprogramming and decreased mitochondrial function in acute myeloid leukemia

54 | Apr 03 2023

The study found that the combination of CUDC-907 and venetoclax induces metabolic and transcriptomic reprogramming and suppresses oxidative phosphorylation in AML cells, providing a promising therapeutic approach for AML. [Read the Full Post]

Transporter‑mediated drug‑drug interactions involving poly (ADP‑ribose) polymerase inhibitors (Review)

103 | Apr 01 2023

Transporter-mediated drug-drug interactions should be considered when co-administering PARP inhibitors with other therapeutic agents to avoid potential toxicity or suboptimal efficacy. [Read the Full Post]

A first-in-class clinical G-quadruplex-targeting drug. The bench-to-bedside translation of the fluoroquinolone QQ58 to CX-5461 (Pidnarulex)

18 | Mar 28 2023

The development and mechanism of action of CX-3543 and CX-5461, as well as their potential clinical application in cancer therapy, highlight the promising approach of synthetic lethality for identifying cancer patients who may benefit from G-quadruplex-targeting compounds. [Read the Full Post]

Cold acclimation and pioglitazone combined increase thermogenic capacity of BAT and WAT but this does not translate into higher energy expenditure

37 | Mar 25 2023

The study found that combining cold acclimation and pharmacological PPARγ activation leads to a synergistic increase in brown and beige adipocytes UCP1 content and thermogenic capacity, but does not innately lead to higher energy expenditure. [Read the Full Post]

Circulating follistatin concentrations in adolescent PCOS: Divergent effects of randomized treatments

44 | Mar 25 2023

This study found that oral contraceptives increase serum follistatin levels in non-obese adolescent girls with PCOS, which is associated with worsened markers of insulin resistance and changes in liver fat. [Read the Full Post]

Luteolin-7-O-rutinoside Protects RIN-5F Cells from High-Glucose-Induced Toxicity, Improves Glucose Homeostasis in L6 Myotubes, and Prevents Onset of Type 2 Diabetes

48 | Mar 24 2023

Lut-7-O-rutin has been found to have a protective effect on high-glucose-induced toxicity to RIN-5F cells and improve insulin secretion and glucose uptake through various molecular mechanisms. [Read the Full Post]

Interplay of Breast Cancer Resistance Protein (Bcrp/Abcg2), Sex, and Fed State in Oral Pharmacokinetic Variability of Furosemide in Rats

33 | Mar 23 2023

The study investigated the effect of Bcrp-mediated transport, sex, and fed state on the pharmacokinetics of FUR in rats and found that Bcrp inhibition increased FUR exposure and that sex differences in Bcrp and Oat abundance in the kidney could influence PK. [Read the Full Post]

Mechanistic insight into the protective effects of fisetin against arsenic-induced reproductive toxicity in male rats

39 | Mar 22 2023

The study found that fisetin treatment was effective in mitigating the reproductive damage caused by arsenic exposure in male albino rats, indicating its potential as a therapeutic candidate against arsenic-generated male reproductive toxicity. [Read the Full Post]

Dipotassium Glycyrrhizininate Improves Skin Wound Healing by Modulating Inflammatory Process

115 | Mar 22 2023

The study evaluated the anti-inflammatory effect of topical Dipotassium Glycyrrhizinate (DPG) on the healing of cutaneous wounds by secondary intention in an in vivo experimental model and found that DPG promotes skin wound healing through modulation of distinct mechanisms and signaling pathways, including anti-inflammatory ones. [Read the Full Post]

Neurotherapeutic Effects of Quercetin and Its Metabolite Compounds on Cognitive Impairment and Parkinson's Disease: An In Silico Study

141 | Mar 22 2023

This study identified the metabolomic profile and potential therapeutic effects of quercetin and its metabolites in cognitive impairment and Parkinson's disease, but further research is needed to confirm these findings in vivo and address potential adverse effects. [Read the Full Post]

Managing Vibration Training Safety by Using Knee Flexion Angle and Rating Perceived Exertion

120 | Mar 22 2023

This study found that a knee flexion angle of approximately 110 degrees is most effective in reducing vibration transmissibility during whole-body vibration exercise, while also observing a positive correlation between the rating of perceived exertion and the platform-to-head transmissibility. [Read the Full Post]

Development and Optimisation of Inhalable EGCG Nano-Liposomes as a Potential Treatment for Pulmonary Arterial Hypertension by Implementation of the Design of Experiments Approach

88 | Mar 21 2023

The research developed an inhalable EGCG nano-liposome formulation with desirable properties and demonstrated its potential effectiveness in treating PAH by inhibiting the TGFβ pathway. [Read the Full Post]

Selective inhibition of HDAC6 promotes bladder cancer radiosensitization and mitigates the radiation-induced CXCL1 signalling

67 | Mar 20 2023

This study found that selective inhibition of histone deacetylase 6 (HDAC6) can enhance the radiosensitivity of bladder cancer cells and suppress radiation-induced oncogenic signaling, suggesting its potential as a therapeutic strategy in combination with radiation therapy. [Read the Full Post]

Delayed aortic regurgitation after TEVAR procedure: a case report

75 | Mar 20 2023

This case report underscores the importance of careful attention and technique when performing catheter-related procedures around the aortic valve to prevent delayed aortic insufficiency. [Read the Full Post]

Biweekly cetuximab in combination with capecitabine and oxaliplatin (XELOX) or irinotecan (XELIRI) in the first-line and second-line treatment of patients with RAS wild-type metastatic colorectal cancer

76 | Mar 18 2023

The study found that biweekly cetuximab in combination with XELOX or XELIRI is well-tolerated and effective in patients with RAS wild-type metastatic colorectal cancer, with favorable outcomes observed. [Read the Full Post]

PARP-1 inhibitor-AG14361 suppresses acute allograft rejection via stabilizing CD4+FoxP3+ regulatory T cells

35 | Mar 16 2023

The PARP-1 inhibitor AG14361 may be a promising agent to attenuate acute allograft rejection by maintaining the number and function of Treg cells in allografts. [Read the Full Post]

Immunostimulatory effects of dairy probiotic strains Bifidobacterium animalis ssp. lactis HY8002 and Lactobacillus plantarum HY7717

74 | Mar 14 2023

The study found that the combination of LAB strains HY8002 and HY7717 improved immune function in mice and has potential as an immunostimulant probiotic supplement for use in dairy foods. [Read the Full Post]

Management of antineutrophil cytoplasmic antibody-associated vasculitis: a changing tide

28 | Mar 14 2023

Recent advances in the treatment of AAV have focused on reducing the toxicity of existing treatments and exploring newer treatments with better safety profiles, including targeted PLEX use, lower GC dosing, and increased rituximab use. [Read the Full Post]

HDAC8-Selective Inhibition by PCI-34051 Enhances the Anticancer Effects of ACY-241 in Ovarian Cancer Cells

84 | Mar 13 2023

The study suggests that co-inhibition of HDAC6 and HDAC8 through selective inhibitors could be a novel therapeutic approach for ovarian cancer patients with wild-type p53. [Read the Full Post]

Effects of supplementing organic- and inorganic-based selenium with vitamin E on intestinal histomorphology, caecal bacterial proliferation, and short-chain fatty acid profile in layer hens

107 | Mar 12 2023

Organic selenium supplementation, particularly bacterial organic selenium, enhances intestinal histomorphology, increases beneficial caecal bacterial proliferation, and increases butyric acid content in layer chickens. [Read the Full Post]

Effects of extended oral antibiotic prophylaxis on surgical site infections after instrumented spinal fusion: a cohort study of 901 patients with a minimum follow-up of 1 year

29 | Mar 11 2023

Extended antibiotic prophylaxis is associated with a lower incidence of superficial surgical site infection in instrumented spine surgery. [Read the Full Post]

Chitosan-Enclosed Menadione Sodium Bisulfite as an Environmentally Friendly Alternative to Enhance Biostimulant Properties against Drought

56 | Mar 11 2023

The use of nanoencapsulation to deliver menadione sodium bisulfite has been shown to improve its protective properties against water deficit stress and reduce the need for continuous retreatment, highlighting the potential of nanotechnology to enhance the performance of biostimulants in agriculture. [Read the Full Post]

Emerging drug targets for sickle cell disease: shedding light on new knowledge and advances at the molecular level

88 | Mar 10 2023

Understanding early events in sickle cell disease pathogenesis associated with the presence of hemoglobin S is crucial for identifying new targets for treatment, including reducing HbS levels, reducing the impact of HbS polymers, and targeting membrane events, and exploiting the unique permeability of sickle cells for developing targeted therapies. [Read the Full Post]

DTIC (nsc-45388) and combination therapy for melanoma. I. Studies with DTIC, BCNU (NSC-409962), CCNU (NSC-79037), vincristine (NSC-67574), and hydroxyurea (NSC-32065)

49 | Mar 10 2023

The study found that combination chemotherapy regimens can improve response rates and survival times in patients with metastatic malignant melanoma, but careful monitoring of toxicity is necessary and treatment decisions should be individualized based on the patient's clinical profile. [Read the Full Post]

Kaempferol inhibits airway inflammation induced by allergic asthma through NOX4-Mediated autophagy

54 | Mar 10 2023

Kaempferol binds to NOX4 and inhibits NOX4-mediated autophagy, providing an effective therapeutic strategy for treating asthma by decreasing NOX4 expression and improving airway inflammation and remodeling. [Read the Full Post]

Effect of hybrid compounds of stilbene and pentadienone on inhibition of tubulin polymerization

99 | Mar 09 2023

The study designed and synthesized hybrid compounds with excellent anticancer properties that inhibit tubulin polymerization and induce cell cycle arrest in MDA-MB-231 human breast cancer cells. [Read the Full Post]

Clinical Characteristics and Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm

72 | Mar 08 2023

Blastic plasmacytoid dendritic cell neoplasm is a rare and aggressive hematological malignancy with diverse clinical manifestations and poor prognosis that requires a combination of clinical, morphological and immunophenotypic features for diagnosis and individualized treatment. [Read the Full Post]

Results from a phase I/II trial of cusatuzumab combined with azacitidine in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy

95 | Mar 07 2023

The phase I/II trial showed that cusatuzumab plus azacitidine was generally well-tolerated and showed preliminary efficacy in newly diagnosed AML patients ineligible for intensive chemotherapy, with ongoing investigation into the combination with venetoclax and azacitidine. [Read the Full Post]

Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis

28 | Mar 04 2023

The study found that Fludarabine/busulfan is the optimal conditioning regimen for allogeneic hematopoietic cell transplantation in myelofibrosis based on lower mortality and graft versus host disease rates. [Read the Full Post]

Effect of maca (Lepidium meyenii) extract on non-obstructive azoospermia in male mice

44 | Mar 04 2023

The study found that maca can improve azoospermia by promoting testicular recovery and increasing testosterone levels, with the polysaccharide fraction identified as the active component. [Read the Full Post]

Evaluation of the knowledge of hematologists about the management of infectious complications in hematologic patients

61 | Mar 02 2023

The study results highlight the need for continuous education for hematologists in Brazil to improve their knowledge and understanding of infectious complications in patients with hematologic malignancies and hematopoietic cell transplant recipients. [Read the Full Post]

Effect of MXRA7 on the Biological Functions of Acute B Lymphoblastic Leukemia Cell Line REH

83 | Mar 02 2023

The study found a positive correlation between the expression of MXRA7 and acute B-ALL and suggests that knockdown of MXRA7 may be a potential target for the treatment of B-ALL by reducing cell proliferation and increasing sensitivity to cytarabine, but further research is needed to confirm its usefulness. [Read the Full Post]

Role of STAT3 in the initiation, progression, proliferation and metastasis of breast cancer and strategies to deliver JAK and STAT3 inhibitors

66 | Feb 23 2023

This review article focuses on the role of STAT3 in the development and progression of breast cancer, and the potential of phytochemicals, synthetic molecules, and biologicals to inhibit JAK-STAT and STAT3, as a promising approach in the development of better therapeutics against breast cancer. [Read the Full Post]

The novel histone deacetylase inhibitor pracinostat suppresses the malignant phenotype in human glioma

33 | Feb 23 2023

Pracinostat is a promising novel therapy for human glioma, as it inhibited proliferation, induced apoptosis, and reduced migration and invasion, while also affecting the PI3K/Akt and STAT3 pathways. [Read the Full Post]

Emergence of monkeypox: a worldwide public health crisis

29 | Feb 23 2023

Monkeypox, a zoonotic virus similar to smallpox that infects humans, has become a global health threat with growing incidence and geographic distribution, and currently lacks a specific therapy but can be treated with vaccines and FDA-approved antiviral medications such as brincidofovir, tecovirimat, and cidofovir. [Read the Full Post]

Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT

68 | Feb 22 2023

In this study, results showed that TBI/Cy conditioning was associated with reduced risk of relapse and increased risk of grade 2-4 acute GVHD, while a matched-pair analysis revealed a reduced rate of relapse and no significant effect on other transplantation outcomes when compared to TBI/Flu, leading to the conclusion that TBI/Cy should be considered a preferable regimen for allo-HCT in adult patients with ALL in complete remission. [Read the Full Post]

Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise

216 | Feb 19 2023

Liver cancer treatment options depend on the progression stage of the disease and may include surgery, ablation and radiotherapy, first-line drugs and immunotherapy, and second-line chemotherapeutic drugs, while natural compounds like resveratrol, curcumin and diallyl sulfide are emerging as promising anticancer agents to manage liver cancer. [Read the Full Post]

Alpha-kinase1 promotes tubular injury and interstitial inflammation in diabetic nephropathy by canonical pyroptosis pathway

48 | Feb 15 2023

The study shows that ALPK1 activation in diabetic nephropathy causes renal injury and fibrosis through the activation of the canonical caspase-1-GSDMD pyroptosis pathway, which is regulated by the ALPK1/NF-κB pathway. [Read the Full Post]

Synthesis and mechanical properties of highly structure-controlled Zr-based metallic glasses by thermal rejuvenation technique

85 | Feb 15 2023

A new thermal rejuvenation process was developed for Zr-based bulk metallic glass to improve ductility by re-introducing free volume through rapid heating and indirect liquid nitrogen quenching, which was confirmed to reduce STZ volume and enhance homogeneous deformation by molecular dynamics simulations. [Read the Full Post]

Camptothecin analogs in malignant gliomas: comparative analysis and characterization

51 | Feb 14 2023

The authors compared and characterized several new classes of camptothecin analogs and found that 10,11-methylenedioxy class consistently demonstrated the greatest cytotoxicity and hold promise for more effective local antitumor treatments against malignant intracranial brain tumors. [Read the Full Post]

Population pharmacokinetic analysis of TQ-B3203 following intravenous administration of TQ-B3203 liposome injection in Chinese patients with advanced solid tumors

176 | Feb 14 2023

A population pharmacokinetic model was successfully developed for TQ-B3203, a novel topoisomerase I inhibitor, in Chinese patients with advanced solid tumors and showed that body mass index, lean body weight, and direct bilirubin were significant covariates that affected TQ-B3203 pharmacokinetics. [Read the Full Post]

Survival in a consecutive series of 467 glioblastoma patients: Association with prognostic factors and treatment at recurrence at two independent institutions

38 | Feb 11 2023

A study of 467 recurrent glioblastoma patients in Norway found that age, promoter methylation of MGMT, tumour location, and extent of resection at primary diagnosis were independent prognostic factors, while 60 Gray radiotherapy with concomitant and adjuvant temozolomide at primary diagnosis, gamma knife/stereotactic radiosurgery at first recurrence, and combination chemotherapy with or without bevacizumab at second recurrence were treatments associated with superior survival. [Read the Full Post]

Does PARP Inhibition Sensitize Chondrosarcoma Cell Lines to Chemotherapy or Radiotherapy? Results From a Three-dimensional Spheroid Cell Model

100 | Feb 11 2023

This study shows that long-term talazoparib treatment, a PARP inhibitor, effectively reduced the viability of three representative chondrosarcoma cell lines grown as spheroids, and the combination of talazoparib and temozolomide had a higher chance of success than combination with radiotherapy. [Read the Full Post]

A Camptothetin Analog, Topotecan, Promotes HIV Latency via Interference with HIV Transcription and RNA Splicing

43 | Feb 10 2023

The camptothecin analog topotecan reduces residual activity of HIV in an in vitro primary T cell model of HIV latency, with a reduction in HIV transcriptional activity and downregulation of HIV RNA that cannot be reversed by latency reversing agents; other camptothecin analogs, less toxic than topotecan, should be investigated as potential "block and lock" agents to further silence the HIV provirus and suppress residual inflammation. [Read the Full Post]

Targeting RNA G-quadruplex with repurposed drugs blocks SARS-CoV-2 entry

29 | Feb 10 2023

Topotecan (TPT) and Berbamine (BBM), two clinical approved drugs, have been found to have potential as broad-spectrum antivirals against SARS-CoV-2 by stabilizing RNA G-quadruplexes in several host factors and reducing SARS-CoV-2 pseudovirus entry into target cells in vitro and murine tissues in vivo. [Read the Full Post]

Effect of Severe Renal Dysfunction on the Plasma Levels of DNA-Reactive Platinum after Oxaliplatin Administration

39 | Feb 09 2023

Severe renal dysfunction has a limited effect on the elimination rate of reactive DNA-binding platinum (fPt) in plasma after oxaliplatin administration, as shown by the results from studies in rats with bilateral nephrectomy and in a hemodialysis patient with advanced metastatic gastric cancer. [Read the Full Post]

A multi-center phase Ib study of oxaliplatin (NSC#266046) in combination with fluorouracil and leucovorin in pediatric patients with advanced solid tumors

76 | Feb 09 2023

The maximum planned dose of oxaliplatin in combination with 5-fluorouracil and leucovorin was safe and well tolerated in pediatric patients with refractory or relapsed solid tumors, with modest activity noted, warranting further study. [Read the Full Post]

Identifying CDC7 as a synergistic target of chemotherapy in resistant small-cell lung cancer via CRISPR/Cas9 screening

53 | Feb 09 2023

CRISPR/Cas9 screening in a chemo-resistant SCLC cell line identified serine/threonine kinase CDC7 as a target and the CDC7 inhibitor XL413 was found to synergize with chemotherapy, increasing apoptosis and inducing G1/S phase arrest and DNA damage in chemo-resistant SCLC cells and improving efficacy in vitro and in vivo with patient-derived xenografts. [Read the Full Post]

Long-Term Complete Remission of a Patient With Double-Hit Diffuse Large B-Cell Lymphoma Treated by Chemoimmunotherapy and Chinese Herbal Medicine

116 | Feb 09 2023

A 73-year-old male diagnosed with double-hit diffuse large B-cell lymphoma underwent a successful treatment combining R-CHOP-14 and dose-adjusted DA-EPOCH-R chemotherapy with Chinese herbal medicine (Sijunzi Decoction and Prunella vulgaris) with no adverse events, resulting in no evidence of recurrence and a good quality of life for over 8 years. [Read the Full Post]

Biased Clonal Evolution in Acute Promyelocytic Leukemia through Imbalances Affecting the der(17) but Not the der(15) Chromosome: Report of Two Cases

35 | Feb 09 2023

Two cases of acute promyelocytic leukemia with the secondary chromosomal change of ider(17)(q10) were treated with ATRA plus idarubicin and achieved long event-free survival according to the PETHEMA LPA 2012 protocol. [Read the Full Post]

Loss of tRNA methyltransferase 9 and DNA damage response genes in yeast confers sensitivity to aminoglycosides

114 | Feb 08 2023

The study showed that Trm9-catalyzed tRNA modifications enhance the DNA damage response and that cells with tRNA modification dysregulation and DNA repair gene defects can be selectively sensitized using a combination of translation inhibitors and DNA damaging agents. [Read the Full Post]

DNA radiosensitization by terpyridine-platinum: damage induced by 5 and 10 eV transient anions

34 | Feb 08 2023

Tpy-Pt enhances DNA damage induced by monoenergetic electrons in CRT, with the highest enhancement for base damage-related crosslinks, potentially causing roadblocks to replication and transcription in genomic DNA, particularly within telomeres where it binds preferentially to G-quadruplexes. [Read the Full Post]

Phase II Trials of Iniparib (BSI-201) in Combination with Gemcitabine and Carboplatin in Patients with Recurrent Ovarian Cancer

94 | Feb 08 2023

In two parallel phase II studies of iniparib (BSI-201) combined with gemcitabine and carboplatin in ovarian cancer patients, the overall response rate was 66% in platinum-sensitive disease and 26% in platinum-resistant disease, with higher response rates in patients with BRCA mutations and the combination was generally well tolerated with no new toxicities. [Read the Full Post]

Final analysis of the phase 3 randomized clinical trial comparing HD201 vs. referent trastuzumab in patients with ERBB2-positive breast cancer treated in the neoadjuvant setting

35 | Feb 08 2023

The final analysis of the TROIKA trial confirmed that HD201 and trastuzumab were equally effective in terms of event-free and overall survival, and both treatments were safe with no serious adverse events related to the study treatment. [Read the Full Post]

DROEG: a method for cancer drug response prediction based on omics and essential genes integration

112 | Feb 08 2023

The study developed a novel method called DROEG for predicting drug response in cancer patients by integrating genomic, transcriptomic, methylomic and CRISPR essential gene information and found it to be a more accurate approach compared to existing algorithms. [Read the Full Post]

Comparative study between two different morphological structures based on polylactic acid, nanocellulose and magnetite for co-delivery of flurouracil and curcumin

69 | Feb 07 2023

The magnetic copolymeric micelles M-PLA-co-NC/5-FU/CUR showed superior antibacterial and antitumor efficacy, slower release and higher loading % of CUR compared to the blended formulation PLA/M-NC/5-FU/CUR, making them a promising nanomedicine against bacteria and multiple cell lines. [Read the Full Post]

Extracellular vesicles derived from dental mesenchymal stem/stromal cells with gemcitabine as cargo have an inhibitory effect on the growth of pancreatic carcinoma cell lines in vitro

63 | Feb 07 2023

DP-MSC-EVs have therapeutic potential as a drug delivery tool for cancer therapy by absorbing and secreting gemcitabine and expressing a suicide gene to convert non-toxic prodrug 5-FC to cytotoxic drug 5-FU, resulting in significant inhibition of cancer cell growth. [Read the Full Post]

Gancao Nourishing-Yin decoction combined with methotrexate in treatment of aging CIA mice: a study based on DIA proteomic analysis

144 | Feb 07 2023

Gancao Nourishing-Yin decoction (GCNY) added to methotrexate (MTX) showed better effects in treating elderly rheumatoid arthritis (ERA) mice model compared to either treatment alone, as seen through improved joint damage, decreased inflammation, and regulation of metabolism-related pathways, and ELISAs confirmed improved folic acid levels and anti-folate resistance pathways. [Read the Full Post]

Five-year cardiovascular event risk in early rheumatoid arthritis patients who received treat-to-target management: a case-control study

77 | Feb 07 2023

The study found that ERA patients managed using a treat-to-target strategy had a similar incidence of cardiovascular events compared to a CV risk factor-matched non-RA population, while a historical RA cohort receiving routine care had a significantly higher incidence. [Read the Full Post]

CXCL9 links skin inflammation and fibrosis via CXCR3-dependent upregulation of collagen 1a1 in fibroblasts

67 | Feb 07 2023

The study provides evidence that CXCL9 and its receptor CXCR3 play a key role in the development of inflammation and fibrosis in morphea through the induction of collagen 1a1 expression. [Read the Full Post]

[Single-center study of different treatment for advanced or unresectable angiosarcoma patients]

125 | Feb 06 2023

This study found that doxorubicin-based and paclitaxel-based chemotherapy are the most common treatments for advanced angiosarcoma, and combined targeted therapy with anti-PD-1 immunotherapy showed potential efficacy in some patients with long duration of response and moderate adverse events. [Read the Full Post]

Novel carboxymethyl cellulose-halloysite-polyethylene glycol nanocomposite for improved 5-FU delivery

114 | Feb 06 2023

This study synthesized a pH-responsive nanocomposite based on halloysite nanotube (HNT) coated with carboxymethyl cellulose (CMC)/polyethylene glycol (PEG) hydrogel for controlled delivery of 5-Fluorouracil (5-FU), a hydrophobic chemotherapy drug, using the W/O/W technique, achieving high drug entrapment and loading and showing improved and sustained 5-FU delivery in acid environment and considerable cytotoxicity on MCF-7 breast cancer cells. [Read the Full Post]

The effect of cladribine on immunoglobulin levels compared to B cell targeting therapies in multiple sclerosis

77 | Feb 05 2023

Cladribine therapy for RRMS does not significantly reduce immunoglobulin subset levels, unlike ocrelizumab and natalizumab which showed a statistically significant reduction in IgG and IgM levels. [Read the Full Post]

Real-world experience of cladribine treatment in relapsing-remitting multiple sclerosis: A Danish nationwide study

67 | Feb 05 2023

A registry-based observational cohort study of all Danish patients starting cladribine tablets for relapsing multiple sclerosis showed the treatment was safe with a significant reduction in annualized relapse rate, but a longer follow-up period is needed to fully assess the long-term benefit and risk. [Read the Full Post]

Decitabine enhances the tumoricidal potential of TRAIL via the epigenetic regulation of death receptor 4 in gastric cancer

84 | Feb 05 2023

Decitabine enhances the anti-tumor effect of TRAIL by upregulating DR4 expression through epigenetic modification, acting as a sensitizing agent, and providing a novel idea for gastric cancer treatment when used in combination. [Read the Full Post]

Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease

103 | Feb 05 2023

The study of combining decitabine and ipilimumab for AML/MDS showed that the clinical response to the combination therapy is primarily driven by decitabine-induced cytoreduction, but evidence of immune activation was only observed after ipilimumab exposure, and long-lasting responses require elimination of leukemic progenitor cells. [Read the Full Post]

A combination of telomerase inhibition and NK cell therapy increased breast cancer cell line apoptosis

44 | Feb 03 2023

Inhibiting telomerase with BIBR1532 increased the cytotoxicity of natural killer cells against breast cancer and synergistically enhanced cell death by suppressing hTERT and upregulating apoptotic-related genes, making breast cancer cells more sensitive to NK cell therapy and potentially useful in the treatment of breast cancer. [Read the Full Post]

Evaluating the role of polysaccharide extracted from Pleurotus columbinus on cisplatin-induced oxidative renal injury

80 | Feb 02 2023

The polysaccharide PsPc-3 from Pleurotus columbinus showed antioxidant activity and reduced oxidative renal injury induced by cisplatin in rats, indicating it may be a potential treatment for cisplatin-induced nephrotoxicity. [Read the Full Post]

Microglial P2Y12 Signaling Contributes to Cisplatin-induced Pain Hypersensitivity via IL-18-mediated Central Sensitization in the Spinal Cord

101 | Feb 02 2023

Microglia P2Y12-Src family kinase-p38 signaling contributes to cisplatin-induced pain hypersensitivity via IL-18-mediated central sensitization in the spinal cord, with P2Y12 being a potential target for preventing chemotherapy-induced pain hypersensitivity. [Read the Full Post]

Efficacy and safety of treatments for advanced thymic carcinoma after failure of first-line platinum-based chemotherapy: A systematic literature review and meta-analysis

126 | Feb 01 2023

This study conducted a systematic literature review of 19 clinical trials to assess the clinical outcomes of various regimens in patients with thymic carcinoma (TC) who failed first-line chemotherapy, finding limited treatment options with response rates ranging from 9% to 38% and prolonged duration of response with pembrolizumab, but a need for further well-powered clinical trials to better inform on optimal treatments. [Read the Full Post]

Lower SLC7A2 expression is associated with enhanced multidrug resistance, less immune infiltrates and worse prognosis of NSCLC

27 | Jan 31 2023

Shanshan Jiang et al. thought that SLC7A2 might act as a tumor suppressor to modulate drug sensitivity, immune infiltration and survival in NSCLC. [Read the Full Post]

Does neoadjuvant treatment in resectable pancreatic cancer improve overall survival? A systematic review and meta-analysis of randomized controlled trials

67 | Jan 31 2023

P L S Uson Junior et al. found that randomized ongoing trials were eagerly awaited with more active combined regimens including modified FOLFIRINOX. [Read the Full Post]

Impact of Results of TTF-1 Immunostaining on Efficacy of Platinum-Doublet Chemotherapy in Japanese Patients with Nonsquamous Non-Small-Cell Lung Cancer

92 | Jan 26 2023

Akira Nakao et al. thought that the positivity of TTF-1 immunostaining in tumors could be a predominant prognostic marker for patients who had advanced nonsq NSCLC. [Read the Full Post]

Exonuclease 1 genetic variant is associated with clinical outcomes of pemetrexed chemotherapy in lung adenocarcinoma

144 | Jan 26 2023

Mi Jeong Hong et al. thought that two SNPs in miRNA binding sites, especially EXO1 rs1047840G>A, were associated with the chemotherapy response and survival outcome in lung adenocarcinoma patients treated with pemetrexed. [Read the Full Post]

Phenolipid JE improves metabolic profile and inhibits gluconeogenesis via modulating AKT-mediated insulin signaling in STZ-induced diabetic mice

53 | Jan 22 2023

Guihua Wang et al. suggested that JE might be a potent activator for AKT-mediated insulin signaling pathway. [Read the Full Post]

Upregulation of glutamate transporter 1 by mTOR/Akt pathway in astrocyte culture during oxygen-glucose deprivation and reoxygenation

29 | Jan 21 2023

Mi Li et al. suggested that astrocytes might adapt to short-term ischemic-reperfusion injury by regulating cell morphology, apoptosis and GLT-1 upregulation. [Read the Full Post]

Construction and validation of a cuproptosis-related lncRNA signature as a novel and robust prognostic model for colon adenocarcinoma

57 | Jan 14 2023

Miaorong Xu et al. thought that a ten-cuproptosis-related lncRNA signature was constructed that provided promising insights into personalized prognosis and drug selection among COAD patients. [Read the Full Post]

Increased HRD score in cisplatin resistant penile cancer cells

55 | Jan 14 2023

Ria Winkelmann et al. found that UKF-PEC-1rCDDP2500 did not display sensitivity to PARP inhibitors. [Read the Full Post]

ATM deficiency aggravates the progression of liver fibrosis induced by carbon tetrachloride in mice

30 | Jan 13 2023

Ming Li et al. found that ATM might be a critical regulator of liver fibrosis progression. [Read the Full Post]

Pharmacologic screen identifies active combinations with BET inhibitors and LRRK2 as a novel putative target in lymphoma

113 | Jan 13 2023

Filippo Spriano et al. identified combinations that could improve the response to BET inhibitors in lymphomas. [Read the Full Post]

Case report: olaparib use in metastatic lung adenocarcinoma with BRCA2 pathogenic variant

36 | Jan 10 2023

Jonathan Soon Jian Hao et al. highlighted the utility of next-generation sequencing in identifying gene mutations. [Read the Full Post]

Racial and Ethnic Differences in Internal Medicine Residency Assessments

105 | Jan 06 2023

Dowin Boatright et al. found that URiM and Asian internal medicine residents received lower ratings on performance assessments than their White peers during the first and second years of training. [Read the Full Post]

PIK-24 Inhibits RSV-Induced Syncytium Formation via Direct Interaction with the p85α Subunit of PI3K

44 | Jan 03 2023

Li-Feng Chen et al. showed that a novel PI3K inhibitor inhibited RSV-induced PI3K signaling activation and actin cytoskeleton reorganization by targeting the p85α protein. [Read the Full Post]

Preclinical Evaluation of an 18F-Labeled SW-100 Derivative for PET Imaging of Histone Deacetylase 6 in the Brain

27 | Dec 19 2022

Tetsuro Tago et al. suggested that [18F]2 was a potentially useful PET radioligand for brain HDAC6 imaging. [Read the Full Post]

Targeting integrated stress response with ISRIB combined with imatinib treatment attenuates RAS/RAF/MAPK and STAT5 signaling and eradicates chronic myeloid leukemia cells

41 | Dec 14 2022

Wioleta Dudka et al. proposed that personalized treatment based on the genetic selection of patients carrying mutations that caused overactivation of the targeted pathways. [Read the Full Post]

Drug Stability and Minimized Acid-/Drug-Catalyzed Phospholipid Degradation in Liposomal Irinotecan

79 | Dec 06 2022

Dmitri B Kirpotin et al. demonstrated that a narrow set of conditions related to the external pH, temperature, intraliposomal concentration, identity of the drug-trapping agent, physical form of the drug inside the liposomes. [Read the Full Post]

The inhibition of MDM2 slows cell proliferation and activates apoptosis in ADPKD cell lines

43 | Dec 05 2022

Simone Patergnani et al. found that the targeting of MDM2 by RG7112 might represent a new therapeutic option for the treatment of ADPKD. [Read the Full Post]

Ricolinostat suppresses proliferation, promotes apoptosis, and enhances the antiproliferative activity of topoisomerase inhibitors in cervical cancer cells

59 | Nov 14 2022

Sumeet Kaur et al. found that ricolinostat suppressed proliferation by inducing G2/M phase arrest and promoted apoptosis in cervical cancer cells, indicating that ricolinostat might be a promising antitumor agent in cervical cancer. [Read the Full Post]

HDAC inhibitor quisinostat prevents estrogen deficiency-induced bone loss by suppressing bone resorption and promoting bone formation in mice

52 | Nov 01 2022

Shengxuan Sun et al. provided the first preclinical evidence to support Qst as a potential therapeutic agent for PMOP prevention and treatment. [Read the Full Post]

Inhibition of HDAC and Signal Transduction Pathways Induces Tight Junctions and Promotes Differentiation in p63-Positive Salivary Duct Adenocarcinoma

43 | Nov 01 2022

Masaya Nakano et al. showed that p63 was not only a diagnostic marker of salivary gland neoplasia, but it also promoted the malignancy. [Read the Full Post]

ATM kinase inhibitor AZD0156 in combination with irinotecan and 5-fluorouracil in preclinical models of colorectal cancer

68 | Oct 31 2022

S Lindsey Davis et al. found that AZD0156 and irinotecan provided a rational and active combination in preclinical colorectal cancer models. [Read the Full Post]

Combined ataxia telangiectasia mutated and DNA-dependent protein kinase inhibition radiosensitizes Madin-Darby canine kidney cells

31 | Oct 30 2022

Manabu Koike et al. suggested that MDCK cells might be useful in clarifying the cytotoxicity in canine epithelial cells due to radiation and/or radiosensitizers, such as molecule-targeted drugs. [Read the Full Post]

Bioinformatics and network-based screening and discovery of potential molecular targets and small molecular drugs for breast cancer

105 | Oct 28 2022

Md Shahin Alam et al. validated that masitinib inhibited the mTOR signaling pathway and induced apoptotic cell death. [Read the Full Post]

Low expression of the metabolism-related gene SLC25A21 predicts unfavourable prognosis in patients with acute myeloid leukaemia

63 | Oct 27 2022

Wenjun Wang et al. thought that a low expression level of SLC25A21 predicted an unfavourable prognosis in patients with AML. [Read the Full Post]

Expression patterns and therapeutic implications of histone deacetylase-1 across carcinomas: a comprehensive molecular docking and MD simulation study

69 | Oct 24 2022

Bader Alshehri signified that targeting HDAC1 was a promising therapeutic strategy, and exploring novel therapeutic agents through basic, translational design might lead to their ultimate use in cancer prevention. [Read the Full Post]

Clinical and immune correlate results from a phase 1b study of the histone deacetylase inhibitor mocetinostat with ipilimumab and nivolumab in unresectable stage III/IV melanoma

64 | Oct 24 2022

Jeffrey S Weber et al. found that combining CPI and mocetinostat had favorable response rates but with high levels of toxicity. [Read the Full Post]

UC-MSCs promote frozen-thawed ovaries angiogenesis via activation of the Wnt/β-catenin pathway in vitro ovarian culture system

59 | Oct 16 2022

Wenjuan Xu et al. showed the beneficial effects of UC-MSCs on thawed ovaries and explored a potential mechanism inducing angiogenesis. [Read the Full Post]

Histone Deacetylase Inhibition Regulates Lipid Homeostasis in a Mouse Model of Amyotrophic Lateral Sclerosis

0 | Oct 14 2022

Thibaut Burg et al. suggested that HDAC inhibition was a potential new therapeutic strategy to modulate lipid metabolism defects in ALS and potentially other neurodegenerative diseases. [Read the Full Post]

Helicase-primase inhibitors from Medshine Discovery Inc. (WO2018/127207 and WO2020/007355) for the treatment of herpes simplex virus infections - structure proposal for Phaeno Therapeutics drug candidate HN0037

35 | Sep 19 2022

Christian Gege described the opportunities and limitations of the helicase-primase inhibitor patent portfolio from Phaeno Therapeutics. [Read the Full Post]

Comprehensive clinical and virological characterization of three cases of fulminant liver failure owing to HSV1 primary infection

20 | Sep 19 2022

Stephan Spahn et al. thought that ACV/HPI-combinations might offer new therapeutic options for HSV-induced ALF. [Read the Full Post]

Determining the Potential of DNA Damage Response (DDR) Inhibitors in Cervical Cancer Therapy

30 | Sep 18 2022

Santu Saha et al. found that while all inhibitors investigated might increase the efficacy of CRT, the greatest clinical potential of rucaparib might be in limiting kidney damage, which was dose-limiting. [Read the Full Post]

Dibutyl phthalate promotes angiogenesis in EA.hy926 cells through estrogen receptor-dependent activation of ERK1/2, PI3K-Akt, and NO signaling pathways

63 | Sep 15 2022

Dunja Kokai et al. found that DBP exerted a pro-angiogenic effect on human vascular ECs and described the molecular mechanism involving ER- and GPER-dependent activation of ERK1/2, PI3K-Akt, and NO signaling pathways. [Read the Full Post]

Co-inhibition of ATM and ROCK synergistically improves cell proliferation in replicative senescence by activating FOXM1 and E2F1

33 | Sep 14 2022

Eun Jae Yang et al. demonstrated a FOXM1- and E2F1-mediated molecular pathway enhancing cell cycle progression in cells with proliferative potential under replicative senescence conditions. [Read the Full Post]

First-in-Class Hydrazide-Based HDAC6 Selective Inhibitor with Potent Oral Anti-Inflammatory Activity by Attenuating NLRP3 Inflammasome Activation

66 | Sep 13 2022

Kairui Yue et al. indicated that 35m could be a potential orally active therapeutic agent for the treatment of NLRP3-related diseases. [Read the Full Post]

HDAC3 Inhibitor RGFP966 Ameliorated Neuroinflammation in the Cuprizone-Induced Demyelinating Mouse Model and LPS-Stimulated BV2 Cells by Downregulating the P2X7R/STAT3/NF-κB65/NLRP3 Activation

41 | Sep 10 2022

Wei Sun et al. demonstrated that RFFP966 alleviated the inflammatory response and exerted a neuroprotective effect possibly by modulating P2X7R/STAT3/NF-κB65/NLRP3 signaling pathways. [Read the Full Post]

Unraveling the therapeutic potential of GANT61/Dactolisib combination as a novel prostate cancer modality

110 | Sep 08 2022

Mohamed Youssef et al. discovered that Dactolisib/GANT61 combination was promising in PCa treatment. [Read the Full Post]

BEZ235 Prolongs Murine Cardiac Allograft Survival Through the Autophagy Pathway

76 | Sep 08 2022

Xiaolong Miao et al. proposed a theoretical foundation for the strong connection between mTOR-induced autophagy and heart transplant. [Read the Full Post]

The Histone Deacetylase Inhibitor ITF2357 (Givinostat) Targets Oncogenic BRAF in Melanoma Cells and Promotes a Switch from Pro-Survival Autophagy to Apoptosis

34 | Sep 04 2022

Adriana Celesia et al. found that ITF2357 targeted oncogenic BRAF in melanoma cells and induced a switch from autophagy to classic apoptosis, thus representing a possible candidate in melanoma targeted therapy. [Read the Full Post]

Analysis of Givinostat/ITF2357 Treatment in a Rat Model of Neonatal Hypoxic-Ischemic Brain Damage

67 | Sep 04 2022

Paulina Pawelec et al. showed that Givinostat/ITF2357 did not prevent an inflammatory reaction after HI. [Read the Full Post]

Drug Repurposing Based on Protozoan Proteome: In Vitro Evaluation of In Silico Screened Compounds against Toxoplasma gondii

60 | Aug 27 2022

Débora Chaves Cajazeiro et al. found that interactions with the Na+/K+ ATPase transporter for Homo sapiens and Mus musculus, indicating a possible mechanism of action of this compound. [Read the Full Post]

Radical S-Adenosyl Methionine Enzyme BlsE Catalyzes a Radical-Mediated 1,2-Diol Dehydration during the Biosynthesis of Blasticidin S

43 | Aug 26 2022

Yu-Hsuan Lee et al. suggested that BlsE catalysis likely proceeded via direct elimination of water from the CGA C4' α-hydroxyalkyl radical as opposed to 1,2-migration of the C3'-hydroxyl prior to dehydration. [Read the Full Post]

Activation of SIRT1 Alleviates Ferroptosis in the Early Brain Injury after Subarachnoid Hemorrhage

32 | Aug 18 2022

Bin Yuan et al. found that ferroptosis could be a potential therapeutic target for SAH, and SIRT1 activation was a promising method to inhibit ferroptosis. [Read the Full Post]

Salidroside Ameliorates Ultraviolet-Induced Keratinocyte Injury by Inducing SIRT1-Dependent Autophagy

43 | Aug 18 2022

Jin Ke et al. thought that SAL suppressed UVB-induced injury and autophagy by enhancing SIRT1 expression. [Read the Full Post]

Chloroquine-Induced DNA Damage Synergizes with Nonhomologous End Joining Inhibition to Cause Ovarian Cancer Cell Cytotoxicity

60 | Aug 11 2022

María Ovejero-Sánchez et al. found that NHEJ inhibition increased the persistence of γH2AX foci after CQ-induced DNA damage, revealing an essential role of this pathway in the repair of the lesions. [Read the Full Post]

Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell Nanoparticles

65 | Aug 10 2022

Roshni Iyer et al. found that E-DSNPs displayed very high uptake by lung cancer cells compared to healthy lung epithelial cells. [Read the Full Post]

Downregulation of miR-34c-5p alleviates chronic intermittent hypoxia-induced myocardial damage by targeting sirtuin 1

34 | Aug 07 2022

Jun Zhang found that antagomiR-34c-5p injection markedly elevated Sirt1 protein expression in CIH-stimulated mice. AntagomiR-34c-5p or Sirt1 activator SRT1720 administration exhibited the antioxidative activity and cardioprotective roles in CIH-stimulated mice. [Read the Full Post]

Chinese Medicine, Succinum, Ameliorates Cognitive Impairment of Carotid Artery Ligation Rats and Inhibits Apoptosis of HT22 Hippocampal Cells via Regulation of the GSK3β/β-Catenin Pathway

36 | Aug 06 2022

Chongqi Wei et al. revealed the neuronal function of succinum, which explained the traditional effects of succinum and provided more modern scientific basis for its clinical application. [Read the Full Post]

Berberine encapsulated in exosomes derived from platelet-rich plasma promotes chondrogenic differentiation of the Bone Marrow Mesenchymal Stem Cells via the Wnt/β-catenin pathway

83 | Aug 05 2022

Bingjiang Dong et al. found that exos-Ber facilitated the differentiation of chondrogenic BMSCs by modulating the Wnt/β-catenin axis. [Read the Full Post]

Casein Kinase 2 Signaling in White Matter Stroke

103 | Aug 04 2022

Hung Nguyen et al. thought that miRNA regulation might be one of the protective actions of CX-4945 against WM ischemic injury. [Read the Full Post]

Anti-adipogenic and Pro-lipolytic Effects on 3T3-L1 Preadipocytes by CX-4945, an Inhibitor of Casein Kinase 2

102 | Aug 04 2022

Anil Kumar Yadav et al. found that CX-4945 had strong anti-adipogenic and pro-lipolytic effects on differentiating and differentiated 3T3-L1 cells, mediated by control of the expression and phosphorylation levels of CK2, C/EBP-α, PPAR-γ, FAS, ACC, perilipin A, AMPK, LKB-1, ERK-1/2, and HSL. [Read the Full Post]

Murine Double Minute 2 Antagonist Nutlin-3 Enhanced Chemosensitivity in Esophageal Squamous Cell Carcinoma

69 | Jul 31 2022

Ken Ito et al. found that the combination of nutlin-3 with chemotherapeutic agents might become a novel therapeutic strategy in esophageal cancer over-expressing MDM2. [Read the Full Post]

Results of the phase I CCTG IND.231 trial of CX-5461 in patients with advanced solid tumors enriched for DNA-repair deficiencies

45 | Jul 29 2022

John Hilton et al. found toxicity was related to the CX-5461 chemotype, independent of G-quadruplex synthetic lethality. [Read the Full Post]

Amplification of CDK4 and MDM2: a detailed study of a high-risk neuroblastoma subgroup

72 | Jul 29 2022

Angela Martinez-Monleon et al. presented detailed biological data of an aggressive neuroblastoma subgroup hallmarked by 12q amplification and atypical clinical presentation for which in vitro studies indicated that CDK4 and/or MDM2 inhibition also could be beneficial. [Read the Full Post]

Role of H4K16 acetylation in 53BP1 recruitment to double-strand break sites in in vitro aged cells

81 | Jul 26 2022

Lourdes González-Bermúdez et al. found that variations in H4K16Ac following the activation of the DNA damage response and aging point at this histone mark as a key mediator between DNA repair and age-associated chromatin alterations. [Read the Full Post]

Method for detecting acetylated PD-L1 in cell lysates by immunoprecipitation and western blot analysis

75 | Jul 26 2022

Frances Middleton-Davis et al. demonstrated that acetylation levels increase to 0.11-0.17% of total PD-L1 after a 4h treatment with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA). [Read the Full Post]

Genome-wide CRISPR/Cas9 screening for therapeutic targets in NSCLC carrying wild-type TP53 and receptor tyrosine kinase genes

90 | Jul 22 2022

Qianqian Wang et al. identified MDM2 as an essential gene and a potential therapeutic target in wtTP53-RTK NSCLC via a genome-wide CRISPR/Cas9 screening. [Read the Full Post]

Simulating Colorectal Cancer Trials Using Real-World Data

134 | Jul 18 2022

Zhaoyi Chen et al. simulated five CRC trials, and tested two simulation scenarios with several different configurations demonstrated that our simulations couldrobustly generated effectiveness and safety outcomes comparable with the original trials using real-world data. [Read the Full Post]

Machine Learning Screens Potential Drugs Targeting a Prognostic Gene Signature Associated With Proliferation in Hepatocellular Carcinoma

93 | Jul 16 2022

Jun Liu et al. found that the five-gene signature associated with proliferation can be used for survival prediction and risk stratification for HCC patients. Potential drugs targeting this gene signature deserve further attention in the treatment of HCC. [Read the Full Post]

Parp Inhibition and Beyond in Brca- Associated Breast Cancer in Women: A State- Of- The- Art Summary of (Pre) - Clinical Research into Risk Reduction and Clinical Benefits

80 | Jul 15 2022

Ernest K J Pauwels et al. described the various causes of PARP inhibitor resistance as well as the research that indicated how to overcome phenomenon. [Read the Full Post]

Class Ⅰ histone deacetylase inhibitor regulate of Mycobacteria-Driven guanylate-binding protein 1 gene expression

164 | Jul 01 2022

Meili Wei et al. showed that the CpG site of the GBP1 promoter was hypermethylated, and the methylation status of the GBP1 promoter did not change significantly upon Mtb infection. [Read the Full Post]

Tumor-targeted interleukin-12 synergizes with entinostat to overcome PD-1/PD-L1 blockade-resistant tumors harboring MHC-I and APM deficiencies

178 | Jun 30 2022

Christine M Minnar et al. demonstrated that the combination of entinostat and NHS-IL12 therapy elicited potent antitumor activity. [Read the Full Post]

Repression of HIV-1 reactivation mediated by CRISPR/dCas9-KRAB in lymphoid and myeloid cell models

204 | Jun 26 2022

Lendel Correia da Costa et al. demonstrated that KRAB repressor protein was crucial to reactivation resistance phenotype. [Read the Full Post]

Histone Deacetylase Inhibitors Counteract CGRP Signaling and Pronociceptive Sensitization in a Rat Model of Medication Overuse Headache

174 | Jun 26 2022

Matteo Urru et al. provided evidence for a key role of HDACs and epigenetics in MOH pathogenesis, highlighting the therapeutic potential of HDAC inhibition in the prevention of migraine chronification. [Read the Full Post]

The Application of ATR Kinase Inhibitor AZD6738 in Combination with Radiotherapy for the Treatment of Melanoma

102 | Jun 24 2022

Maryam Talebpoor et al. provided insight into the impact of Ataxia Telangiectasia and Rad3-related kinase (ATR) inhibition on the potential role of this kinase in the suppression of melanoma cell proliferation. [Read the Full Post]

The PRC2 molecule EED is a target of epigenetic therapy for neuroblastoma

221 | Jun 23 2022

Dilibaerguli Shaliman et al. suggested that inhibitory cell cycle-regulated gene sets were markedly up-regulated. [Read the Full Post]

Real-world experience in treating pediatric relapsed/refractory or therapy-related myeloid malignancies with decitabine, vorinostat, and FLAG therapy based on a phase 1 study run by the TACL consortium

187 | Jun 22 2022

Eric S Schafer et al. found that therapy was well tolerated and effective in pediatric patients with R/R myeloid neoplasms, particularly those with epigenetic alterations, t-AML, and refractory disease. [Read the Full Post]

Reduction of Metastasis via Epigenetic Modulation in a Murine Model of Metastatic Triple Negative Breast Cancer (TNBC)

178 | Jun 16 2022

Jessica L S Zylla et al. found that 4SC-202 treatment of tumors from a highly metastatic murine model of TNBC reduced metastasis and warrants further preclinical studies. [Read the Full Post]

Exposure to escalating olaparib does not induce acquired resistance to PARPi and to other chemotherapeutic compounds in ovarian cancer cell lines

144 | Jun 10 2022

André Fedier et al. found that olaparib exposure was unlikely to produce an acquired resistance phenotype and that PARPi‑sensitive ovarian cancer cells were also cross‑sensitive to non‑platinum and even to compounds not directly interacting with the DNA. [Read the Full Post]

ARHGAP9 inhibits colorectal cancer cell proliferation, invasion and EMT via targeting PI3K/AKT/mTOR signaling pathway

381 | Jun 10 2022

Jufeng Sun et al. thought that ARHGAP9 inhibited the malignant phenotypes of CRC cells via interdicting PI3K/AKT/mTOR signaling pathway. [Read the Full Post]

Review of second-generation androgen receptor inhibitor therapies and their role in prostate cancer management

119 | May 27 2022

Seyed Behzad Jazayeri et al. thought that olaparib and rucaparib had shown clinical benefit in heavily pretreated patients with mCRPC and DNA repair mutation genes. [Read the Full Post]

Evaluation of mitochondrial oxidative toxicity in mammalian cardiomyocytes by determining the highly reproducible and reliable increase in mitochondrial superoxides after exposure to therapeutic drugs

291 | May 27 2022

Dohee Ahn et al. found that a screening system using MitoSOX™ had the potential to be applied as a reliable biomarker for determining mitochondrial oxidative toxicity in new drug development. [Read the Full Post]

Imaging PARP with [ 18 F]rucaparib in pancreatic cancer models

104 | May 26 2022

Chung Ying Chan et al. demonstrated the potential of [18F]rucaparib as a non-invasive PARP-targeting imaging agent for pancreatic cancers. [Read the Full Post]

Identification of biomarkers of response to preoperative talazoparib monotherapy in treatment naïve gBRCA+ breast cancers

132 | May 24 2022

Xuan Liu et al. indicated that the deep analysis of pre-treatment tumors could identify biomarkers that were predictive of response to talazoparib and potentially other PARP inhibitors. [Read the Full Post]

Talazoparib Dual-targeting on Poly (ADP-ribose) Polymerase-1 and -16 Enzymes Offers a Promising Therapeutic Strategy in Small Cell Lung Cancer Therapy: Insight from Biophysical Computations

115 | May 23 2022

Chwayita Mgoboza et al. found that binding residues with total binding energy greater than 1.00 kcal/mol contributed considerably to the Talazoparib's binding activities on PARP-1 and PARP-16. [Read the Full Post]

The antidepressant imipramine inhibits breast cancer growth by targeting estrogen receptor signaling and DNA repair events

139 | May 16 2022

Santosh Timilsina et al. designed an ongoing clinical trial, where they were testing the efficacy of imipramine for treating patients with triple-negative and estrogen receptor-positive breast cancer. [Read the Full Post]

COVID-19: Implications Regarding the Properties and Behaviors of the Coronavirus Disease

192 | May 14 2022

COVID-19 may be inaccurate due to errors in diagnosing and reporting, since other similar illnesses may exhibit similar symptoms. [Read the Full Post]

Inhibitory Effect of a Glutamine Antagonist on Proliferation and Migration of VSMCs via Simultaneous Attenuation of Glycolysis and Oxidative Phosphorylation

0 | May 11 2022

Hyeon Young Park et al. suggested that treatment with a glutamine antagonist was a promising approach to prevent progression of atherosclerosis and restenosis. [Read the Full Post]

The Mycotoxin Beauvericin Exhibits Immunostimulatory Effects on Dendritic Cells via Activating the TLR4 Signaling Pathway

295 | May 10 2022

Xiaoli Yang et al. identified TLR4 as a cellular BEA sensor and define BEA as a potent activator of BMDCs, implying that this compound could be exploited as a promising candidate structure for vaccine adjuvants or cancer immunotherapies. [Read the Full Post]

Inhibitors of the Ubiquitin Proteasome System block myofibril assembly in cardiomyocytes derived from chick embryos and human pluripotent stem cells

207 | May 05 2022

Jushuo Wang et al. suggested a possible explanation for the cardiac and skeletal muscle off-target effects reported in multiple myeloma patients treated with proteasome inhibitors. [Read the Full Post]

Longitudinal monitoring of STAT3 phosphorylation and histologic outcome of tofacitinib therapy in patients with ulcerative colitis

221 | May 01 2022

Bram Verstockt et al. showed that Longitudinal monitoring of nuclear pSTAT3 in mucosal tissue compartments reflected distinctive on-target effects, independently of long-term treatment outcomes. [Read the Full Post]

Utilizing Three-Dimensional Culture Methods to Improve High-Throughput Drug Screening in Anaplastic Thyroid Carcinoma

220 | Apr 29 2022

Kensey Bergdorf et al. utilized three-dimensional culture methods, as they had been shown to more accurately recapitulate tumor responses in vivo. [Read the Full Post]

Treatment of a Double Cancer Patient With Primary Inferior Vena Cava Sarcoma and Lung Adenocarcinoma: A Case Report and Literature Review

206 | Apr 26 2022

Xiaohu Guo et al. found that surgery was still an effective treatment for patients with a primary IVC leiomyosarcoma and lung adenocarcinoma at present. [Read the Full Post]

Proangiogenesis effects of compound danshen dripping pills in zebrafish

158 | Apr 24 2022

Yang-Xi Hu et al. found that CDDP had a proangiogenic effect, the mechanism of which involved the VEGF/VEGFR and PI3K/AKT signaling pathways. [Read the Full Post]

First-line therapy in non-small cell lung cancer patients with EGFR activating mutations: a consideration of the clinical position of osimertinib based on the subset of Japanese patients in the FLAURA study

228 | Apr 22 2022

Yoko Tsukita et al. reviewed data from the randomized clinical trials of first-line EGFR-TKIs including a subset of Japanese patients and discussed first-line therapies for patients with NSCLC harbouring EGFR mutations. [Read the Full Post]

Clinically relevant CHK1 inhibitors abrogate wild-type and Y537S mutant ERα expression and proliferation in luminal primary and metastatic breast cancer cells

450 | Apr 20 2022

Sara Pescatori et al. thought that CHK1 could be considered as an appealing novel pharmacological target for the treatment of luminal primary and MBCs. [Read the Full Post]

High expression level of ROR1 and ROR1-signaling associates with venetoclax resistance in chronic lymphocytic leukemia

312 | Apr 15 2022

Emanuela M Ghia et al. found that Wnt5a-induced ROR1-signaling can enhance resistance to venetoclax therapy. [Read the Full Post]

Factors Influencing the Intracellular Concentrations of the Sofosbuvir Metabolite GS-331007 (in PBMCs) at 30 Days of Therapy

309 | Apr 02 2022

Jessica Cusato et al. presented data on an IC evaluation in a cohort of patients treated with SOF, also considering pharmacogenetics. [Read the Full Post]

Drug repurposing through virtual screening and in vitro validation identifies tigecycline as a novel putative HCV polymerase inhibitor

277 | Apr 01 2022

Mahmoud ElHefnawi et al. found that tigecycline displayed synergistic activity with sofosbuvir and daclatasvir against HCV. [Read the Full Post]

DNA repair protein DNA-PK protects PC12 cells from oxidative stress-induced apoptosis involving AKT phosphorylation

247 | Mar 30 2022

Alessio Cardinale et al. found that DNA-PK could protect cells from oxidative stress induced-apoptosis independently from its function of DSB repair enzyme. [Read the Full Post]

Hdac8 Inhibitor Alleviates Transverse Aortic Constriction-Induced Heart Failure in Mice by Downregulating Ace1

316 | Mar 25 2022

Tingwei Zhao et al. suggested that HDAC8 was a potential novel therapeutic target for heart failure accompanied by pathological lung diseases. [Read the Full Post]

Selinexor improves the anti-cancer effect of tucidinostat on TP53 wild-type breast cancer

344 | Mar 20 2022

Yingfang Shi et al. thought that the molecular mechanism might be through enhancing the activity of p53 in the nucleus of BC cells to suppress proliferation and invasion and promote apoptosis. [Read the Full Post]

Defining Endocytic Pathways of Fucoidan-Coated PIBCA Nanoparticles from the Design of their Surface Architecture

635 | Mar 19 2022

M C B Lira-Nogueira et al. found that internalization pathways of PIBCA nanoparticles by J774A.1 macrophages could be determined by nanoparticle fucoidan surface composition and architecture. [Read the Full Post]

The beneficial effect of salubrinal on neuroinflammation and neuronal loss in intranigral LPS-induced hemi-Parkinson disease model in rats

402 | Mar 18 2022

Fatma Nihan Cankara et al. found that salubrinal was attenuating several inflammatory mediators and thereby decreased the inflammatory effects of LPS in the neurons of the SN. [Read the Full Post]

Tubastatin A suppresses the proliferation of fibroblasts in epidural fibrosis through phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway

355 | Mar 12 2022

Yang Liu et al.discovered that Tub A could prevent epidural fibrosis formation by inhibiting fibroblast proliferation through mediating PI3K/AKT/mTOR pathway. [Read the Full Post]

Dual Targeting of PI3K and HDAC by CUDC-907 Inhibits Pediatric Neuroblastoma Growth

425 | Mar 07 2022

Rameswari Chilamakuri et al. found that the dual inhibition of PI3K and HDAC by CUDC-907 was an effective therapeutic strategy for NB and other MYC-dependent cancers. [Read the Full Post]

Estimating Drug Efficacy with a Diet-Induced NASH Model in Chimeric Mice with Humanized Livers

272 | Mar 05 2022

Keishi Kisoh et al. showed that CDAHFD feeding induced similar histological changes to human NASH patients, including ballooning, inflammation, apoptosis, regeneration of human hepatocytes, and pericellular and perisinusoidal fibrosis. [Read the Full Post]

Deacetylation of ZKSCAN3 by SIRT1 induces autophagy and protects SN4741 cells against MPP +-induced oxidative stress

194 | Mar 01 2022

Xian Wu et al. identified a novel acetylation-dependent regulatory mechanism of nuclear translocation of ZKSCAN3. [Read the Full Post]

Hyperactivation of MAPK Induces Tamoxifen Resistance in SPRED2-Deficient ERα-Positive Breast Cancer

192 | Feb 27 2022

Vasiliki Vafeiadou et al. indicated that SPRED2 might also be a tumor suppressor for breast cancer and that it was a key regulator of cellular sensitivity to 4-OHT. [Read the Full Post]

Inhibition MNK-eIF4E-β-catenin preferentially sensitizes gastric cancer to chemotherapy

557 | Feb 25 2022

Xiaolin Yang et al. provided preclinical evidence to initialize clinical trials for gastric cancer using tomivosertib in combination with chemotherapy. [Read the Full Post]

Predictors of Treatment Response and Long-Term Outcomes in Young Children with Steroid-Dependent Nephrotic Syndrome Treated with High-Dose Mizoribine as First-Line Steroid-Sparing Agent

316 | Feb 23 2022

Shuichiro Fujinaga et al. discovered that high-dose mizoribine might be an attractive treatment option as initial SSA in young children with low steroid-dependent dose for improved long-term outcomes. [Read the Full Post]

Fin56-induced ferroptosis is supported by autophagy-mediated GPX4 degradation and functions synergistically with mTOR inhibition to kill bladder cancer cells

485 | Feb 21 2022

Yadong Sun et al. thought that the combined application of ferroptosis inducers and mTOR inhibitors was a promising approach to improve therapeutic options in the treatment of bladder cancer. [Read the Full Post]

ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization

386 | Feb 18 2022

Tingting Qin et al. found that ATRX-deficient high-grade gliomas (HGGs) displayed Chk1-mediated dysregulation of cell-cycle phase transitions. [Read the Full Post]

Functional impact and targetability of PI3KCA, GNAS, and PTEN mutations in a spindle cell rhabdomyosarcoma with MYOD1 L122R mutation

245 | Jan 20 2022

Florence Choo et al. suggested that molecularly targeted strategies might be effective in PI3K/AKT/mTOR-activated ssRMS. [Read the Full Post]

Regulation of the mammalian maternal-to-embryonic transition by eukaryotic translation initiation factor 4E

555 | Jan 18 2022

Yan Li et al. thought that eIF4E activity was regulated at key embryonic transitions in the mammalian embryo and was essential for the successful transition from maternal to embryonic control of development. [Read the Full Post]

Establishment of gastric signet ring cell carcinoma organoid for the therapeutic drug testing

287 | Jan 13 2022

Guoliang Li et al. thought that gastric organoid drug models, including SRCC, were highly similar to the original tumors in phenotypic and genotypic profiling and could be as living biomarkers for drug response testing. [Read the Full Post]

Combined Drug Targeting of p53-dependent and -independent Pathways Depletes Myelofibrosis Hematopoietic Stem/Progenitor Cells

218 | Jan 11 2022

Min Lu et al. thought that treatment with ONC201 combined with RG7112 could be a potentially effective strategy for treating MF patients. [Read the Full Post]

4-Acyl Pyrrole Capped HDAC Inhibitors: A New Scaffold for Hybrid Inhibitors of BET Proteins and Histone Deacetylases as Antileukemia Drug Leads

466 | Dec 22 2021

Linda Schäker-Hübner et al. suggested an advantage of dual HDAC/BET inhibitors over the combination of two single targeted compounds. [Read the Full Post]

Regulation of NADPH Oxidase-Mediated Superoxide Production by Acetylation and Deacetylation

498 | Dec 08 2021

Ning Xia et al. found that both SIRT1 and non-sirtuin deacetylases played a role in regulating NADPH oxidase activity. [Read the Full Post]

Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities

435 | Dec 07 2021

Ananda Chowdhury et al. thought that the proposed self-assembly process might present a simple alternative to more sophisticated delivery modalities. [Read the Full Post]

MAD2B-mediated cell cycle reentry of podocytes is involved in the pathogenesis of FSGS

439 | Dec 06 2021

Dian Bao et al. found that ATM kinase-MAD2B axis importantly contributed to the cell cycle reentry of podocytes. [Read the Full Post]

Targeting the ATM Kinase to Enhance the Efficacy of Radiotherapy and Outcomes for Cancer Patients

409 | Dec 06 2021

María E Guerra García et al. suggest that ATM inhibitors might be particularly effective in tumors with defects in other nodes of the DNA damage response. [Read the Full Post]

The histone deacetylase inhibitor belinostat ameliorates experimental autoimmune encephalomyelitis in mice by inhibiting TLR2/MyD88 and HDAC3/ NF-κB p65-mediated neuroinflammation

460 | Dec 03 2021

Yanjia Shen et al. found that belinostat ameliorated EAE in mice through inhibiting neuroinflammation via suppressing M1 microglial polarization. [Read the Full Post]

Intravitreal HDAC Inhibitor Belinostat Effectively Eradicates Vitreous Seeds Without Retinal Toxicity In Vivo in a Rabbit Retinoblastoma Model

499 | Dec 03 2021

Jessica V Kaczmarek et al. thought that Belinostat might therefore be an attractive agent to pursue clinically for intravitreal treatment of retinoblastoma. [Read the Full Post]

Comparing the Effect of Multiple Histone Deacetylase Inhibitors on SSTR2 Expression and [ 111 In]In-DOTATATE Uptake in NET Cells

577 | Nov 30 2021

Maria J Klomp rt al. suggested that proper timing of HDACi treatment was most likely essential for a beneficial outcome. [Read the Full Post]

Butyrate and Class I Histone Deacetylase Inhibitors Promote Differentiation of Neonatal Porcine Islet Cells into Beta Cells

650 | Nov 29 2021

Yichen Zhang et al. revealed that butyrate treatment had the capacity to increase the number of beta cells, which might be predominantly mediated through its HDAC inhibitory activity. [Read the Full Post]

Mutual regulation between chicken telomerase reverse transcriptase and the Wnt/β-catenin signalling pathway inhibits apoptosis and promotes the replication of ALV-J in LMH cells

564 | Nov 21 2021

Yong Xiang et al. found that chTERT not only shortened the cell cycle to promote proliferation but also inhibited apoptosis by downregulating the expression of Caspase 3, Caspase 9 and BAX. [Read the Full Post]

Discovering potential inhibitors against SARS-CoV-2 by targeting Nsp13 Helicase

377 | Oct 28 2021

Rajat Nandi et al. suggested that pritelivir might work as viable therapeutics for efficient drug advancement against SARS-CoV-2 Nsp13 helicase, potentially arresting the SARS-CoV-2 replication. [Read the Full Post]

Novel Cost-Efficient Graphene-Based Impedance Biosensor for the Analysis of Viral Cytopathogenicity and the Effect of Antiviral Drugs

306 | Oct 28 2021

Anke Schultz et al. found the suitability of the printed graphene biosensors for impedance-based monitoring of viral cytopathogenicity and its inhibition in the presence of antiviral drugs. [Read the Full Post]

Exploring the ATR-CHK1 pathway in the response of doxorubicin-induced DNA damages in acute lymphoblastic leukemia cells

338 | Oct 27 2021

Andrea Ghelli Luserna Di Rorà et al. found that the ATR-CHK1 pathway was involved in the response to Dox-induced DNA damage. [Read the Full Post]

Ceramide modulates electrophysiological characteristics and oxidative stress of pulmonary vein cardiomyocytes

767 | Oct 24 2021

Shih-Yu Huang et al. thought that C2 ceramide might exert the distinctive electrophysiological effect of modulating PV activities. [Read the Full Post]

Small-molecule compounds boost genome-editing efficiency of cytosine base editor

580 | Oct 23 2021

Tianyuan Zhao et al. provided a new strategy to improve the activity and specificity of CBE in human cells. Ricolinostat and Nexturastat A augment the effectiveness and applicability of CBE. [Read the Full Post]

HDAC3 inhibitor suppresses endothelial-to-mesenchymal transition via modulating inflammatory response in atherosclerosis

562 | Oct 19 2021

Lifang Chen et al. suggested that HDAC3 inhibitor suppressed EndMT via modulating inflammatory response in ApoE-/- mice and HUVECs. [Read the Full Post]

Dual PI3K/mTOR inhibitor NVP‑BEZ235 decreases the proliferation of doxorubicin‑resistant K562 cells

1469 | Oct 17 2021

Jie Li et al. suggested that BEZ235 might reverse Doxo resistance in leukemia cells. [Read the Full Post]

Targeting mTOR signaling overcomes acquired resistance to combined BRAF and MEK inhibition in BRAF-mutant melanoma

749 | Oct 17 2021

Beike Wang et al. revealed that mTOR activation was essential for drug resistance of melanoma to MAPK inhibitors, and provided insight into the rewiring of the signaling networks in CR melanoma. [Read the Full Post]

Targeting HDAC8 to ameliorate skeletal muscle differentiation in Duchenne muscular dystrophy

640 | Oct 13 2021

Marco Spreafico et al. provided evidence of HDAC8 overexpression in DMD patients and zebrafish and supported its specific inhibition as a new valuable therapeutic approach in the treatment of this pathology. [Read the Full Post]

Histone deacetylase inhibitor givinostat attenuates nonalcoholic steatohepatitis and liver fibrosis

571 | Oct 12 2021

He-Ming Huang et al. found that givinostat was efficacious in reversing diet-induced NASH, and might serve as a therapeutic agent for the treatment of human NASH. [Read the Full Post]

Successful treatment of hepatosplenic T-cell lymphoma with fludarabine, high-dose cytarabine and subsequent unrelated umbilical cord blood transplantation

679 | Oct 04 2021

Takaya Honda et al. found a heterozygous nonsense c.2961C>G (p.Tyr987Ter) variant of the KMT2C gene. [Read the Full Post]

A [3Fe-4S] cluster and tRNA-dependent aminoacyltransferase BlsK in the biosynthesis of Blasticidin S

636 | Oct 03 2021

Xiankun Wang et al. provided an example of an iron-sulfur protein that catalyzed an aminoacyl-tRNA (aa-tRNA)-dependent amide bond formation in a natural product biosynthetic pathway. [Read the Full Post]

Roflupram protects against rotenone-induced neurotoxicity and facilitates α-synuclein degradation in Parkinson's disease models

499 | Sep 23 2021

Wen-Li Dong et al. thought that the mechanisms underlying ROF neuroprotective effects appeared to be associated with NAD+/SIRT1-dependent activation of lysosomal function. [Read the Full Post]

Sodium tanshinone IIA sulfonate attenuates cigarette smoke extract-induced mitochondrial dysfunction, oxidative stress and apoptosis in alveolar epithelial cells by enhancing SIRT1 pathway

347 | Sep 23 2021

Ruijuan Guan et al. found that STS ameliorated CSE-induced AEC apoptosis by improving mitochondrial function and reducing oxidative stress via enhancing SIRT1 pathway. [Read the Full Post]

Improvement of the LbCas12a-crRNA System for Efficient Gene Targeting in Tomato

619 | Sep 16 2021

Tien Van Vu et al. demonstrated the significance of the selection of gene scissors, the appropriate design and number of LbCas12a crRNAs, the use of chemical treatments. [Read the Full Post]

SRT1720 inhibits the growth of bladder cancer in organoids and murine models through the SIRT1-HIF axis

590 | Sep 13 2021

Ping Tan et al. demonstrated the power of cancer organoid-based drug discovery and, in principle, identified SRT1720 as a new treatment for bladder cancer. [Read the Full Post]

Effect of High Cholesterol Regulation of LRP1 and RAGE on Aβ Transport Across the Blood-brain Barrier in Alzheimer's Disease

717 | Sep 11 2021

Rui Zhou et al. found that high cholesterol decreased LRP1 expression and increased RAGE expression in cerebral microvascular endothelial cells, which led to Aβ transport disorder in the blood-brain barrier. [Read the Full Post]

Small Molecule "Silmitasertib" Repurposed as Inhibitor of Transforming Growth Factor Beta 1 for the Development of Therapeutics for Oral Submucous Fibrosis

912 | Sep 10 2021

Nezar Boreak et al. suggested that the molecule could be validated and implemented for the treatment of OSMF. [Read the Full Post]

An Iron Shield to Protect Epigallocatehin-3-Gallate from Degradation: Multifunctional Self-Assembled Iron Oxide Nanocarrier Enhances Protein Kinase CK2 Intracellular Targeting and Inhibition

710 | Sep 10 2021

Luca Fasolato et al. found that the nanohybrid was able to successfully deliver EGCG into cancer cells, displaying impressive protein kinase CK2 inhibition comparable to that obtained with the most specific CK2 inhibitor, CX-4945 (5.5 vs. 3 µM). [Read the Full Post]

The balance between p53 isoforms modulates the efficiency of HIV-1 infection in macrophages

425 | Sep 06 2021

Yann Breton et al. demonstrated the involvement of p53 isoforms, which regulated p53 activity and defined the cellular environment influencing viral replication. [Read the Full Post]

P53 Is Involved in Sunitinib Resistance and Poor Progression-free Survival After Sunitinib Treatment of Renal Cell Carcinoma

417 | Sep 05 2021

Yohei Sekino et al. thought that p53 might be involved in sunitinib resistance and represent a valuable marker for sunitinib treatment in mRCC. [Read the Full Post]

G-quadruplex DNA: a novel target for drug design

425 | Sep 03 2021

Fang-Yuan Teng et al. summarized the G4 unfolding mechanisms emerged recently by multiple G4-specific DNA helicases, such as Pif1, RecQ family helicases, FANCJ, and DHX36. [Read the Full Post]

CHFR regulates chemoresistance in triple-negative breast cancer through destabilizing ZEB1

646 | Sep 01 2021

Hong Luo et al. found the therapeutic potential for targeting CHFR-ZEB1 signaling in resistant malignant breast cancers. [Read the Full Post]

Oncolytic Bovine Herpesvirus 1 Inhibits Human Lung Adenocarcinoma A549 Cell Proliferation and Tumor Growth by Inducing DNA Damage

582 | Sep 01 2021

Wencai Qiu et al. thought that BoHV-1 had oncolytic effects against human lung adenocarcinoma in vivo. [Read the Full Post]

Phase I study of daily and weekly regimens of the orally administered MDM2 antagonist idasanutlin in patients with advanced tumors

269 | Aug 29 2021

Antoine Italiano et al. demonstrated dose- and schedule-dependent p53 activation with durable disease stabilization in some patients. [Read the Full Post]

ARTEMIN Promotes Oncogenicity and Resistance to 5-Fluorouracil in Colorectal Carcinoma by p44/42 MAPK Dependent Expression of CDH2

811 | Aug 25 2021

Qiu-Shi Zhuang et al. thought that ARTN might be of prognostic and theranostic utility in CRC. [Read the Full Post]

Phase II trial of veliparib and temozolomide in metastatic breast cancer patients with and without BRCA1/2 mutations

645 | Aug 23 2021

Jing Xu et al. found that veliparib and temozolomide demonstrated clinical activity in platinum-naïve BRCA-associated metastatic breast cancer with manageable toxicity at doses of veliparib well below the single-agent active dose. [Read the Full Post]

Poly (ADP-Ribose) Polymerase Inhibitor, ABT888, Improved Cisplatin Effect in Human Oral Cell Carcinoma

629 | Aug 23 2021

Irene Paterniti et al. indicated PARP inhibitors as adjuvants for therapeutic strategy of oral cancer. [Read the Full Post]

HDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast cancer

782 | Aug 06 2021

Miranda E Clements et al. suggested HDACi as a potential therapeutic avenue to promote dormancy, prevent recurrence, and improve patient outcomes in breast cancer. [Read the Full Post]

Phase I Study and Pilot Efficacy Analysis of Entinostat, a Novel Histone Deacetylase Inhibitor, in Chinese Postmenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer

841 | Aug 06 2021

Jiani Wang et al. found that entinostat with exemestane showed reasonable safety, tolerability, and encouraging efficacy in Chinese patients with HR+/HER2- MBC. [Read the Full Post]

Local ablation of gastric cancer by reconstituted apolipoprotein B lipoparticles carrying epigenetic drugs

1000 | Aug 03 2021

Chia-Lung Yang et al. established rABL-based nanoparticles embedded epigenetic inhibitors for local treatment of gastric cancer, which had good therapeutic effects but do not cause severe side effects. [Read the Full Post]

High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas

1044 | Aug 02 2021

Philip D Tatman et al. suggested an important role of HDACs in meningioma biology and as a targetable mechanism. [Read the Full Post]

Ceralasertib (AZD6738), an oral ATR kinase inhibitor, in combination with carboplatin in patients with advanced solid tumors: a Phase I study

442 | Aug 01 2021

Timothy A Yap et al. reported the safety, tolerability, maximum tolerated dose (MTD), recommended Phase II dose (RP2D), pharmacokinetic/pharmacodynamic profile and preliminary antitumor activity of ceralasertib combined with carboplatin in patients with advanced solid tumors [Read the Full Post]

Effect of Decitabine (5-aza-2'-deoxycytidine, 5-aza-CdR) in Comparison with Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) on DNMT1, DNMT3a and DNMT3b, HDAC 1-3, SOCS 1, SOCS 3, JAK2, and STAT3 Gene Expression in Hepatocellular Carcinoma HLE and LCL-PI 11 Cell Lines

747 | Jul 31 2021

Masumeh Sanaei et al. found that 5-Aza-CdR and SAHA could induce cell growth inhibition and apoptosis induction through the JAK/STAT pathway. [Read the Full Post]

4sc-202 and Ink-128 cooperate to reverse the epithelial to mesenchymal transition in OSCC

570 | Jul 25 2021

Xi Yang et al. identified an effective combination therapy involving class I histone deacetylase and mammalian target of rapamycin complex 1/2 inhibition that effectively blocked the EMT of tumor cells by upregulating FoxO1 expression to inhibit Twist1 transcription. [Read the Full Post]

Cost-effectiveness analysis of olaparib and niraparib as maintenance therapy for women with recurrent platinum-sensitive ovarian cancer

526 | Jul 20 2021

John Hang Leung et al. showed that olaparib was considered to be a cost-effective maintenance therapy for patients with recurrent platinum-sensitive ovarian cancer from the Taiwan NHIA perspective. [Read the Full Post]

Peptide 11R‑VIVIT promotes fracture healing in osteoporotic rats

2642 | Jul 20 2021

Changju Hou et al. demonstrated that 11R‑VIVIT promoted fracture healing in osteoporotic rats and enhanced the osteogenic differentiation of osteoporotic BMSCs by dysregulating the AKT/NFATc1 signaling pathway. [Read the Full Post]

Evaluation of the management of PARP inhibitor toxicities in ovarian and endometrial cancer within a multi-institution health-system

409 | Jul 08 2021

Rachel V Hatch et al. suggested that PARPi therapy was associated with numerous toxicities that were best managed through a multi-modal approach. [Read the Full Post]

Successful Treatment of a Locally Recurrent and Metastatic Malignant Phyllodes Tumor with Accelerated Radiotherapy and Nab-Paclitaxel, Cisplatin, and Liposomal Doxorubicin Chemotherapy

1173 | Jul 08 2021

Ioannis M Koukourakis et al. found that the combination of cisplatin with nab-paclitaxel and liposomal doxorubicin chemotherapy had acceptable toxicity and was highly effective in eradicating metastatic lesions. [Read the Full Post]

Nuclear Export Inhibitor KPT-8602 Synergizes with PARP Inhibitors in Escalating Apoptosis in Castration Resistant Cancer Cells

604 | Jul 07 2021

Md Hafiz Uddin found that KPT-8602 with or without olaparib was shown to reduce homologous recombination-regulated DNA damage response targets including BRCA1, BRCA2, CHEK1, EXO1, BLM, RAD51, LIG1, XRCC3 and RMI2. [Read the Full Post]

Research progress of PARP inhibitor monotherapy and combination therapy for endometrial cancer

501 | Jul 05 2021

Ke Shen et al. found that PARP inhibitors played an important role in killing tumor cells with defects in homologous recombination repair. [Read the Full Post]

Safety, pharmacokinetics, and preliminary efficacy of the PARP inhibitor talazoparib in Japanese patients with advanced solid tumors: phase 1 study

442 | Jul 04 2021

Yoichi Naito et al. showed that single-agent talazoparib was well tolerated and had preliminary antitumor activity in Japanese patients with advanced solid tumors. [Read the Full Post]

PARP and CDK4/6 inhibitor combination therapy induces apoptosis and suppresses neuroendocrine differentiation in prostate cancer

501 | Jun 24 2021

Cheng Wu et al. provided a molecular rationale for PARPi and CDK4/6i combination therapy and revealed mechanism-based clinical trial opportunities for men with NEPC. [Read the Full Post]

Allosteric Activation of SARS-CoV-2 RNA-Dependent RNA Polymerase by Remdesivir Triphosphate and Other Phosphorylated Nucleotides

552 | Jun 23 2021

Bing Wang et al. demonstrated that RdRp was allosterically activated by nontemplating phosphorylated nucleotides, including naturally occurring alarmone ppGpp and synthetic remdesivir triphosphate. [Read the Full Post]

Inhibitory Effect of a Glutamine Antagonist on Proliferation and Migration of VSMCs via Simultaneous Attenuation of Glycolysis and Oxidative Phosphorylation

639 | Jun 19 2021

Hyeon Young Park et al. found that treatment with a glutamine antagonist is a promising approach to prevent progression of atherosclerosis and restenosis. [Read the Full Post]

HeLa TI cell-based assay as a new approach to screen for chemicals able to reactivate the expression of epigenetically silenced genes

708 | Jun 18 2021

Varvara Maksimova et al. showed that N-nitrosodiphenylamine and N-nitrosodimethylamine reactivated epigenetically silenced genes, probably by affecting DNA methylation. [Read the Full Post]

Tofacitinib Therapy in Children and Young Adults with Pediatric-Onset Medically-Refractory Inflammatory Bowel Disease

567 | Jun 07 2021

Hillary Moore et al. found that tofacitinib induced rapid clinical response with sustained efficacy in nearly half of subjects. [Read the Full Post]

Modeling clinical responses to targeted therapies by patient-derived organoids of advanced lung adenocarcinoma

579 | Jun 06 2021

Seok-Young Kim et al. demonstrated translational relevance of PDOs in advanced lung adenocarcinoma. [Read the Full Post]

Vismodegib in neoadjuvant treatment of locally advanced basal cell carcinoma: First results of a multicenter, open-label, phase 2 trial (VISMONEO study): Neoadjuvant Vismodegib in Locally Advanced Basal Cell Carcinoma

393 | Jun 03 2021

Nicolas Bertrand et al. found that Neoadjuvant vismodegib allowed for a downstaging of the surgical procedure for laBCCs in functionally sensitive locations. [Read the Full Post]

TIP30 overcomes gefitinib resistance by regulating cytoplasmic and nuclear EGFR signaling in non-small cell lung cancer

530 | Jun 01 2021

Shuai Shuai et al. revealed that TIP30 overexpression restored gefitinib sensitivity in NSCLC cells and attenuated the cytoplasmic and nuclear EGFR signaling pathways. [Read the Full Post]

High response rate and durability driven by HLA genetic diversity in kidney cancer patients treated with the immunotherapy combination lenvatinib and pembrolizumab

414 | May 28 2021

Chung-Han Lee et al. identified lenvatinib plus pembrolizumab as a highly active treatment strategy in RCC and reveal HLA-I diversity as a critical determinant of efficacy for this combination. [Read the Full Post]

Efficacy and Safety of Combination Treatment With Apatinib and Osimertinib After Osimertinib Resistance in Epidermal Growth Factor Receptor-Mutant Non-small Cell Lung Carcinoma-A Retrospective Analysis of a Multicenter Clinical Study

442 | May 26 2021

Xue Yang et al. found that the combination of apatinib and osimertinib improved the ORR and the DCR of patients with osimertinib-refractory EGFR-positive NSCLC, thus making it a reasonable treatment choice after the development of osimertinib resistance. [Read the Full Post]

Treatment of Luminal Metastatic Breast Cancer beyond CDK4/6 Inhibition: Is There a Standard of Care in Clinical Practice?

1219 | May 21 2021

Athanasios Mavratzas et al. thought that treatment of metastatic luminal breast cancer after progression on CDK4/6 inhibitors remained a challenge. [Read the Full Post]

Ibrutinib-induced acute kidney injury via interstitial nephritis

472 | May 12 2021

Csilla Markóth et al. concluded that despite the beneficial effect on cytokines response in Th1 direction, ibrutinib could cause acute interstitial nephritis. [Read the Full Post]

In vitro antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19

600 | Apr 22 2021

Carolina Q Sacramento et al. found that daclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, might be further fostered as an anti-COVID-19 therapy. [Read the Full Post]

Naturally Occurring Resistance Associated Substitutions in Non-Cirrhotic, Treatment Naive HCV-HIV Co-Infected Patients Does Not Affect the Treatment Response for Anti-HCV Antiviral Therapy

593 | Apr 22 2021

Ekta Gupta et al. showed that BL-RAS were common in HCV-HIV co-infected patients. [Read the Full Post]

Inhibiting Importin 4-mediated nuclear import of CEBPD enhances chemosensitivity by repression of PRKDC-driven DNA damage repair in cervical cancer

440 | Apr 19 2021

Yang Zhou et al. demonstrated that IPO4 and CEBPD knockdown improved CDDP-induced cytotoxicity in vitro and in vivo. [Read the Full Post]

HDAC6-selective inhibitors enhance anticancer effects of paclitaxel in ovarian cancer cells

500 | Apr 15 2021

Jung Yoo et al. found synergy between paclitaxel and HDAC6-selective inhibitors, providing further impetus for clinical trials of combination therapy using HDAC6-selective inhibitors, not only in ovarian cancer but also in other tumors. [Read the Full Post]

Overexpression of Human ABCB1 and ABCG2 Reduces the Susceptibility of Cancer Cells to the Histone Deacetylase 6-Specific Inhibitor Citarinostat

390 | Apr 14 2021

Chung-Pu Wu et al. suggested that the co-administration of citarinostat with a non-toxic modulator of ABCB1 and ABCG2 might optimize its therapeutic application in the clinic. [Read the Full Post]

The clinical significance of histone deacetylase-8 in human breast cancer

510 | Apr 13 2021

Golebagh Rahmani et al. highlighted the role and existing inhibitors of HDAC8 in BC pathogenesis and therapy. [Read the Full Post]

Clinical efficacy and molecular biomarkers in a phase II study of tucidinostat plus R-CHOP in elderly patients with newly diagnosed diffuse large B-cell lymphoma

488 | Apr 07 2021

Mu-Chen Zhang et al. found that CR-CHOP was effective and safe in elderly patients with newly diagnosed DLBCL. [Read the Full Post]

Melanin Distribution in Human Skin: Influence of Cytoskeletal, Polarity, and Centrosome-Related Machinery of Stratum basale Keratinocytes

1068 | Apr 06 2021

Irene Castellano-Pellicena et al. explored the role of actin, microtubules, and centrosome-associated machinery in distributing melanin within KCs. [Read the Full Post]

Protective effects of NAC and salubrinal on apoptosis of retinal pigment epithelial cells induced by all-trans retinoic acid

1035 | Apr 02 2021

Juan Wu et al. thought that ATRA might play an important role in the prevention, diagnosis and treatment of age-related macular degeneration. [Read the Full Post]

Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy

526 | Mar 24 2021

Zhonghai Shen et al. thought that HDAC6 inhibition prevented OA development, and HDAC6 could be applied as a potential therapeutic target for OA management. [Read the Full Post]

Targeting phosphoinositide 3-kinases and histone deacetylases in multiple myeloma

557 | Mar 19 2021

Seiichi Okabe et al. suggested that the administration of CUDC-907 might be a powerful strategy against myeloma cells, to enhance the cytotoxic effects of proteasome inhibitors. [Read the Full Post]

Beneficial effects of elafibranor on NASH in E3L.CETP mice and differences between mice and men

466 | Mar 17 2021

Anita M van den Hoek et al. concluded that elafibranor might be particularly useful to reduce hepatic inflammation and could be a pharmacologically useful agent for human NASH, but probably in combination with other agents. [Read the Full Post]

Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors

410 | Mar 12 2021

Nina Schmid et al. found that several SIRTs were expressed by GCTs, and SIRT1 and SIRT3 were involved in the growth regulation of KGN. [Read the Full Post]

4-hydroxytamoxifen does not deteriorate cardiac function in cardiomyocyte-specific MerCreMer transgenic mice

500 | Mar 09 2021

Andre Heinen et al. investigated potential adverse effects of DNA editing by the αMHC-MerCreMer/loxP system in combination with a low-dose treatment protocol with the tamoxifen metabolite 4-hydroxytamoxifen (OH-Txf). [Read the Full Post]

Mnk inhibitors: a patent review

1283 | Mar 07 2021

Ahmed M Abdelaziz et al. provided a succinct review of the current state of development of pyridone-aminal-derived Mnk inhibitors through the analysis of relevant patent applications filed in the last 5 years. [Read the Full Post]

Comparison of Treatment Effect and Tolerance of the Topical Application of Mizoribine and Cyclosporine A in a Mouse Dry Eye Model

715 | Mar 05 2021

Xiang Lin et al. found that MZR (0.05% in PBS) could be a good competitive product for Restasis because of the comparable treatment effect in dry eye diseases and better ocular tolerability in ocular itch and pain. [Read the Full Post]

Manipulating bovine granulosa cell energy metabolism limits inflammation

717 | Mar 03 2021

Anthony D Horlock et al. implied that energy stress compromised ovarian follicle immune defences. [Read the Full Post]

Inhibition of ATM induces hypersensitivity to proton irradiation by upregulating toxic end joining

446 | Feb 28 2021

Qin Zhou et al. found that inherent defects in HR or administration of an ATM inhibitor in HR proficient tumors selectively enhanced the relative biological effectiveness of proton Bragg peak irradiation. [Read the Full Post]

Selective Elimination of Osteosarcoma Cell Lines with Short Telomeres by Ataxia Telangiectasia and Rad3-Related Inhibitors

397 | Feb 18 2021

Tomas Goncalves et al. provided a resource to identify links between the mode of telomere maintenance and drug sensitivity in osteosarcoma and indicated that telomere length predictd ATR inhibitor sensitivity in cancer. [Read the Full Post]

Preclinical evaluation and Phase 1b study of prexasertib, a CHK1 inhibitor, and samotolisib (LY3023414), a dual PI3K/mTOR inhibitor

621 | Jan 27 2021

David S Hong et al found that Prexasertib+samotolisib showed antitumor activity in preclinical models and preliminary efficacy in heavily-pretreated patients. [Read the Full Post]

De novo protein synthesis is necessary for priming in preclinical models of migraine

905 | Jan 26 2021

Jacob Lackovic et al. suggested that targeting the regulation of protein synthesis might be a novel approach for new migraine treatment strategies. [Read the Full Post]

Downregulation of breast cancer resistance protein by long-term fractionated radiotherapy sensitizes lung adenocarcinoma to SN-38

511 | Jan 23 2021

Yuqing Wang et al. suggested that irinotecan (the prodrug of SN-38) might be a promising drug candidate for lung adenocarcinoma patients with acquired radioresistance. [Read the Full Post]

MDM2 inhibition: an important step forward in cancer therapy

466 | Jan 21 2021

Marina Konopleva et al. thought that targeting MDM2 was a promising treatment strategy. [Read the Full Post]

HDAC6 Degradation Inhibits the Growth of High-Grade Serous Ovarian Cancer Cells

542 | Jan 01 2021

Ahlam Ali et al. found that inhibition of HDAC6 catalytic activity with first generation HDAC6 inhibitors has limited efficacy as a monotherapy in HGSOC. [Read the Full Post]

A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1

476 | Dec 20 2020

Zhenghui Huang et al. found that PfHDAC1 was a potential drug target for overcoming multidrug resistance and that JX21108 treated malaria and blocked parasite transmission simultaneously. [Read the Full Post]

HDAC Inhibition Increases HLA Class I Expression in Uveal Melanoma

439 | Dec 19 2020

Zahra Souri et al. found that epigenetic drugs (in this case an HDAC inhibitor) may influence the expression of immunologically relevant cell surface molecules in UM, demonstrating that these drugs potentially influence immunotherapy. [Read the Full Post]

Decreased activation of ataxia telangiectasia mutated (ATM) in monocytes from patients with systemic sclerosis

508 | Dec 18 2020

Komei Sakata et al. found that decreased ATM activation in monocytes was associated with SSc-interstitial lung disease and that impaired ATM activation in monocytes may contribute to the disease process of SSc via uncontrolled reactive oxygen species production. [Read the Full Post]

Establishment of multiplex allele-specific blocker PCR for enrichment and detection of 4 common EGFR mutations in non-small cell lung cancer

480 | Dec 18 2020

Hongyuan Chen et al. provided a solution for minor allele detection from ctDNA. [Read the Full Post]

Histone Deacetylase Inhibitors and Papillary Thyroid Cancer

589 | Dec 16 2020

Eleftherios Spartalis et al. showed that HDACIs had no significant effect as monotherapy against PTC but further research needed to be conducted in order to investigate their potential effect when used as an additional modality. [Read the Full Post]

Inhibition of Human UDP-Glucuronosyltransferase Enzyme by Belinostat: Implications for Drug-Drug Interactions

519 | Dec 15 2020

Xiaoyu Wang et al. indicated that the intravenous infusion of belinostat at clinical available dose could contribute a significant increase to the AUC of co-administrated drugs primarily cleared by UGT1A3 or UGT1A1. [Read the Full Post]

Design, synthesis and evaluation of novel indirubin-based N-hydroxybenzamides, N-hydroxypropenamides and N-hydroxyheptanamides as histone deacetylase inhibitors and antitumor agents

554 | Dec 12 2020

Duong Tien Anh et.al found that the potential of the indirubin-hydroxamic acid hybrids and these compounds should be very promising for further development. [Read the Full Post]

Histone Deacetylase Inhibition Attenuates Aortic Remodeling in Rats under Pressure Overload

694 | Dec 12 2020

Hanna Jung et al. indicated that MGCD, an HDAC inhibitor, attenuated aortic remodeling in rats with TAC-induced pressure overload rats and might serve as a potential therapeutic target of antiaortic remodeling in pressure overload-induced hypertension-related diseases. [Read the Full Post]

LGR5 induces β activation and augments tumor progression by activating STAT3 in human intrahepatic cholangiocarcinoma

1019 | Dec 04 2020

Keishi Kawasaki et al. thought that LGR5 was an excellent prognostic predictor and a promising therapeutic target for ICC. [Read the Full Post]

HDAC6-selective inhibitors decrease nerve-injury and inflammation-associated mechanical hypersensitivity in mice

497 | Dec 02 2020

Farhana Sakloth et al. suggested that inhibition of HDAC6 provided a promising therapeutic avenue for the alleviation of mechanical allodynia associated with peripheral nerve injury and peripheral inflammation. [Read the Full Post]

Optimization and Evaluation of Propolis liposomes as a promising therapeutic approach for COVID-19

523 | Nov 11 2020

Hesham Refaat et al. identified the potential of propolis liposomes as a promising treatment approach against COVID-19. [Read the Full Post]

A Preclinical Model for Studying Herpes Simplex Virus Infection

0 | Nov 06 2020

Poojabahen Tajpara et al. discovered that both drugs had a comparable efficacy for inhibiting HSV-1 replication, suggesting that pritelivir could be an alternative therapeutic agent for patients infected with acyclovir-resistant strains. [Read the Full Post]

Characterisation of Ovarian Cancer Cell Line NIH-OVCAR3 and Implications of Genomic, Transcriptomic, Proteomic and Functional DNA Damage Response Biomarkers for Therapeutic Targeting

342 | Nov 05 2020

Alice Bradbury et al. thought that NIH-OVCAR3 cells highlighted the complexity of HGSOCs and that genomic or functional characterization alone might not be enough to predict/explain chemotherapy response. [Read the Full Post]

Identification of antiviral compounds against equid herpesvirus-1 using real-time cell assay screening: Efficacy of decitabine and valganciclovir alone or in combination

244 | Nov 05 2020

Côme Thieulent et al. showed that deoxycytidine reverts the antiviral effect of decitabine, thus supporting some competition at the level of nucleoside phosphorylation by deoxycytidine kinase and/or DNA synthesis. [Read the Full Post]

Small molecule 2,3-DCPE induces S phase arrest by activating the ATM/ATR-Chk1-Cdc25A signaling pathway in DLD-1 colon cancer cells

644 | Oct 29 2020

Bingjun Bai et al. suggested that 2,3-DCPE caused DNA damage in colon cancer cells and that 2,3-DCPE-induced S phase arrest was associated with the activation of the ATM/ATR-Chk1-Cdc25A pathway. [Read the Full Post]

Histone deacetylase 6 inhibition mitigates renal fibrosis by suppressing TGFß and EGFR signaling pathways in obstructive nephropathy

468 | Oct 28 2020

Xingying Chen et al. indicated that HDAC6 inhibition could attenuate development of renal fibrosis by suppression of TGFb1 and EGFR signaling, and suggested that HDAC6 would be a potential therapeutic target for the treatment of renal fibrosis. [Read the Full Post]

EBV encoded miRNA BART8-3p promotes radioresistance in nasopharyngeal carcinoma by regulating ATM/ATR signaling pathway

305 | Oct 28 2020

Xiaohan Zhou et al. indicated that EBV-miR-BART8-3p promoted radioresistance in NPC by modulating the activity of ATM/ATR signaling pathway. [Read the Full Post]

Histone deacetylase 3 aberration inhibits Klotho transcription and promotes renal fibrosis

460 | Oct 23 2020

Fang Chen et al.found that HDAC3 aberration and the subsequent Klotho suppression constituted an important regulatory loop that promotes MTD and renal fibrosis and uses of HDAC3-selective inhibitors were potentially effective in treating renal fibrotic disorders. [Read the Full Post]

A phase I study of a dual PI3-kinase/mTOR inhibitor BEZ235 in adult patients with relapsed or refractory acute leukemia

614 | Oct 22 2020

Fabian Lang et al.thought that combined inhibition of PI3K and mTOR inhibited a clinically meaningful driver pathway in a small subset of patients with ALL, with no benefit in patients with AML. [Read the Full Post]

HPV-induced Nurr1 promotes cancer aggressiveness, self-renewal, and radioresistance via ERK and AKT signaling in cervical cancer

578 | Oct 20 2020

Peter Kok-Ting Wan et al. provided that BEZ, but not GSK, could abolish Nurr1-enhanced radioresistance, suggesting its potential value for radiosensitizing CSLCs in the clinical setting. [Read the Full Post]

HDAC3 Regulates Gingival Fibroblast Inflammatory Responses in Periodontitis

465 | Oct 15 2020

K B Lagosz et al. identified HDAC3 as an important regulator of inflammatory gene expression in GFs and suggested that therapeutic targeting of HDAC activity, in particular HDAC3, may be clinically beneficial in suppressing inflammation in periodontal disease. [Read the Full Post]

Development of Artificial Plasma Membranes Derived Nanovesicles Suitable for Drugs Encapsulation

466 | Oct 14 2020

Carolina Martinelli et al.documented the possibility to easily generate scalable nanovesicles with specific therapeutic cargo modifications useful in different drug delivery contexts. [Read the Full Post]

A study of human leukocyte antigen-haploidentical hematopoietic stem cells transplantation combined with allogenic mesenchymal stem cell infusion for treatment of severe aplastic anemia in pediatric and adolescent patients

633 | Sep 29 2020

Li Ding et al. suggested that cotransplantation of HLA-haploidentical HSC and allogenic mesenchymal stem cell might provide an effective and safe treatment for children and adolescents with SAA who lacked matched donors. [Read the Full Post]

CTELS: A Cell-Free System for the Analysis of Translation Termination Rate

623 | Sep 28 2020

Kseniya A Lashkevich et al. revealed a transient stalling event at a "leaky" stop codon context, which likely defined the basis of nonsense suppression. [Read the Full Post]

Mst1 promotes mitochondrial dysfunction and apoptosis in oxidative stress-induced rheumatoid arthritis synoviocytes

446 | Sep 16 2020

Yingjie Wang et al. suggested the Mst1-AMPK-Sirt1 axis was a potential target for RA therapy. [Read the Full Post]

SIRT1 Mediates Neuropathic Pain Induced by Sciatic Nerve Chronic Constrictive Injury in the VTA-NAc Pathway

466 | Sep 16 2020

Yangyang Li et al. proposed that the discovery of the effect of SIRT1 on neuropathic pain in the VTA represented an important step forward in understanding the analgesic mechanisms of the VTA-NAc pathway. [Read the Full Post]

Combined PARP and ATR inhibition potentiates genome instability and cell death in ATM-deficient cancer cells

304 | Sep 11 2020

Rebecca L Lloyd et al. provided a mechanistic understanding of combined PARP and ATR inhibition in ATM-deficient models, and supported the clinical development of AZD6738 in combination with olaparib. [Read the Full Post]

Fluvastatin potentiates anticancer activity of vorinostat in renal cancer cells

779 | Sep 10 2020

Kazuki Okubo et al. found that there was a positive feedback cycle among AMPK activation, histone acetylation, and ER stress induction. [Read the Full Post]

Inhibition of DNA-PKcs activity re-sensitizes uveal melanoma cells to radio- and chemotherapy

566 | Sep 03 2020

Bingjie Zhang et al. demonstrated increased DNA double strand break repair as a mechanism of resistance to ionizing radiation and Selumetinib, and identified DNA-PKcs as a promising target for radio-and chemotherapy in UM patients. [Read the Full Post]

Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks

0 | Sep 03 2020

Tong Zhou et al. suggested a role for TDP1 in repair of 3'-PG double-strand breaks in vivo. [Read the Full Post]

Role of sirtuin-1 (SIRT1) in hypoxic injury in pancreatic β-cells

568 | Aug 30 2020

Ye-Jee Lee et al. suggested that SIRT1 was a potential target for the protection of pancreatic β-cells against hypoxic damage during ITx. [Read the Full Post]

Quercetin promotes human epidermal stem cell proliferation through the estrogen receptor/β-catenin/c-Myc/cyclin A2 signaling pathway

496 | Aug 28 2020

Zhaodong Wang et al.showed that EpSCs were used not only in clinic to treat skin wounds but also as seed cells in skin tissue engineering.Quercetin was a useful reagent to expand EpSCs for basic research, skin wound treatment, and skin tissue engineering. [Read the Full Post]

Protein Kinase CK2 in Cancer Energetics

911 | Aug 27 2020

Eduardo Silva-Pavez et al. proposed that the specific inhibition of CK2 might lead to a catastrophic death of cancer cells, which could become a feasible therapeutic strategy to beat this devastating disease. [Read the Full Post]

Casein kinase 2 inhibitor CX-4945 elicits an anti-Warburg effects through the downregulation of TAp73 and inhibits gastric tumorigenesis

810 | Aug 27 2020

Shengli Tang et al. suggested that CX-4945 elicited an anti-Warburg effects in gastric cancer overexpressing Tap73 and inhibited gastric tumorigenesis. [Read the Full Post]

Resurrecting a p53 peptide activator - An enabling nanoengineering strategy for peptide therapeutics

542 | Aug 20 2020

Wangxiao He et al. proposed that this clinically viable drug delivery strategy could be applied not only to peptide activators of p53 for cancer therapy, but also to peptide therapeutics in general aimed at targeting intracellular protein-protein interactions for disease intervention. [Read the Full Post]

F-box protein FBXO31 modulates apoptosis and epithelial-mesenchymal transition of cervical cancer via inactivation of the PI3K/AKT-mediated MDM2/p53 axis

472 | Aug 19 2020

Keying Liu et al. revealed that FBXO31 down-regulated CC progression by blocking the PI3K/AKT-mediated MDM2/p53 axis, suggesting that FBXO31 might serve as a promising therapeutic target for CC treatment. [Read the Full Post]

The rRNA synthesis inhibitor CX-5461 may induce autophagy that inhibits anticancer drug-induced cell damage to leukemia cells

367 | Aug 18 2020

Shuichiro Okamoto et al. showed the autophagy which might be induced by CX-5461 was the second type. [Read the Full Post]

The Antitumor Efficiency of Zinc Finger Nuclease combined with Cisplatin and Trichostatin A in Cervical Cancer Cells

517 | Aug 16 2020

Ci Ren et al. demonstrated that ZFNs combined with DDP or TSA functioned effectively in cervical cancer cells, and it provided novel ideas for the prevention and treatment of HPV-related cervical malignances. [Read the Full Post]

Trichostatin A modulates the macrophage phenotype by enhancing autophagy to reduce inflammation during polymicrobial sepsis

511 | Aug 13 2020

Shu-Nan Cui et al. showed that TSA promoted the macrophage M2 phenotype by enhancing autophagy to reduce systemic inflammation and ultimately improved the survival of mice with polymicrobial sepsis. [Read the Full Post]

Targeting p53 for the treatment of cancer

372 | Aug 11 2020

Michael J Duffy et al. indicated that it was likely to usher in a new era in cancer treatment, especially as p53 dysfunction is so prevalent in human cancers if any of the compounds currently being evaluated in clinical trials be shown to have efficacy [Read the Full Post]

Gemcitabine combined with cisplatin vs. taxane, cisplatin, and fluorouracil in the treatment of locally advanced nasopharyngeal carcinoma: a retrospective case-control study

628 | Aug 04 2020

Y-M Huang et al. showed that the clinical efficacy of the GP regimen combined with CCRT for the treatment of locoregionally advanced NPC might be better than that of the TPF regimen. [Read the Full Post]

In Vitro and In Vivo Efficacy of DNA Damage Repair Inhibitor Veliparib in Combination with Artesunate against Echinococcus granulosus

467 | Aug 02 2020

Y F Li et al. demonstrated that AS or AS in combination with Veliparib was effective for treating CE, especially the combination group. [Read the Full Post]

Evaluation of the Efficacy and Safety of PARP Inhibitors in Advanced-Stage Epithelial Ovarian Cancer

587 | Aug 02 2020

Yifan Jiang et al. found that PARP inhibitors were an effective and well-tolerated treatment for patients with advanced-stage epithelial ovarian cancer. [Read the Full Post]

4SC-202 induces apoptosis in myelodysplastic syndromes and the underlying mechanism

587 | Jul 18 2020

Weili Wang et al. provided a novel therapeutic strategy for MDS. [Read the Full Post]

Protein Acetylation Derepresses Serotonin Synthesis to Potentiate Pancreatic Beta-Cell Function Through HDAC1-PKA-Tph1 Signaling

719 | Jul 13 2020

Yuqing Zhang et al. highlighted a novel role of HDAC1-PKA-Tph1 signaling in governing β-cell functional compensation by derepressing serotonin synthesis. [Read the Full Post]

In Vitro Assessment of the Genotoxic Hazard of Novel Hydroxamic Acid- And Benzamide-Type Histone Deacetylase Inhibitors (HDACi)

782 | Jul 12 2020

Annabelle Friedrich et al. found that KSK64 revealed the highest genotoxic hazard and DDR stimulating potential, while TOK77 and MPK77 showed the lowest DNA damaging capacity. [Read the Full Post]

Histone Deacetylase Inhibition Prevents the Growth of Primary and Metastatic Osteosarcoma

1048 | Jul 07 2020

Jeremy J McGuire et al. provided rationale for clinical trials in osteosarcoma patients using the approved therapies panobinostat or romidepsin. [Read the Full Post]

Berzosertib Plus Gemcitabine Versus Gemcitabine Alone in Platinum-Resistant High-Grade Serous Ovarian Cancer: A Multicentre, Open-Label, Randomised, Phase 2 Trial

417 | Jul 06 2020

Panagiotis A Konstantinopoulos et al. showed a benefit of adding berzosertib to gemcitabine in platinum-resistant high-grade serous ovarian cancer. [Read the Full Post]

Combination BET Family Protein and HDAC Inhibition Synergistically Elicits Chondrosarcoma Cell Apoptosis Through RAD51-Related DNA Damage Repair

882 | Jul 06 2020

Songwei Huan et al. disclosed that BET and HDAC inhibition synergistically inhibited cell growth and induced cell apoptosis through a mechanism that involved the suppression of RAD51-related HR DNA repair in chondrosarcoma cells. [Read the Full Post]

Differential Therapeutic Effects of PARP and ATR Inhibition Combined With Radiotherapy in the Treatment of Subcutaneous Versus Orthotopic Lung Tumour Models

350 | Jul 02 2020

Vanessa Tran Chau et al. highlighted the importance of using more pathologically relevant models, such as syngeneic orthotopic models, to determine the most appropriate therapeutic approaches for translation to the clinic. [Read the Full Post]

18 F-Fluoroestradiol ( 18 F-FES)-PET Imaging in a Phase II Trial of Vorinostat to Restore Endocrine Sensitivity in ER+/HER2- Metastatic Breast Cancer

820 | Jul 01 2020

Lanell M Peterson et al. found that Simultaneous HDACi and AI dosing in patients with cancers resistant to AI alone showed clinical benefit (6+ months without progression) in 4 of 10 evaluable patients. [Read the Full Post]

Imaging Assisted Evaluation of Antitumor Efficacy of a New Histone Deacetylase Inhibitor in the Castration-Resistant Prostate Cancer

753 | Jul 01 2020

Zude Chen et al. provided not only a novel epigenetic approach for prostate cancer therapy but also offering a potential tool, [11C] Martinostat PET/CT imaging, to detect the early phase of prostate cancer and monitor therapeutic effect of CN133. [Read the Full Post]

Analysis of Dual Class I Histone Deacetylase and Lysine Demethylase Inhibitor Domatinostat (4SC-202) on Growth and Cellular and Genomic Landscape of Atypical Teratoid/Rhabdoid

484 | Jun 24 2020

Mariah M Hoffman et al. indicated that 4SC-202 had both cytotoxic and cytostatic effects on ATRT, targets specific cell sub-populations, including those with cancer stem-like features, and was an important potential cancer therapeutic to be investigated in vivo. [Read the Full Post]

Effects of the PI3K/Akt Signaling Pathway on the Apoptosis of Early Host Cells Infected With Eimeria Tenella

1253 | Jun 21 2020

Xuesong Zhang et al. investigated the role of PI3K/Akt signaling pathway on host cell apoptosis in the early infection of Eimeria tenella,the early development of E. tenella could inhibit host cell apoptosis by downregulating the Caspase-3 activity. [Read the Full Post]

Revealing the Selective Mechanisms of Inhibitors to PARP-1 and PARP-2 via Multiple Computational Methods

480 | Jun 17 2020

Hongye Hu et al. provided new insights about how inhibitors specifically bound to PARP-1 over PARP-2, which might help facilitate the design of highly selective PARP-1 inhibitors in the future. [Read the Full Post]

Mechanism and Current Progress of Poly ADP-ribose Polymerase (PARP) Inhibitors in the Treatment of Ovarian Cancer

0 | Jun 15 2020

Feiyue Zheng et al. highlighted the current research progress on PARP inhibitor resistance, which has become a challenge in clinics. [Read the Full Post]

Cell Cycle Arrest and Apoptosis Are Not Dependent on p53 Prior to p53-dependent Embryonic Stem Cell Differentiation

1260 | Jun 02 2020

Sushil K Jaiswal et al. found that the multiple roles of p53 in cell cycle regulation and apoptosis were first acquired during pluripotent stem cell differentiation. [Read the Full Post]

CDK12-Altered Prostate Cancer: Clinical Features and Therapeutic Outcomes to Standard Systemic Therapies, Poly (ADP-Ribose) Polymerase Inhibitors, and PD-1 Inhibitors

382 | Jun 01 2020

Emmanuel S Antonarakis et al. found that CDK12-altered prostate cancer was an aggressive subtype with poor outcomes to hormonal and taxane therapies as well as to PARP inhibitors. A proportion of these patients might respond favorably to PD-1 inhibitors, which implicated CDK12 deficiency in immunotherapy sensitivity. [Read the Full Post]

PARP and PARG Inhibitors in Cancer Treatment

483 | May 28 2020

Dea Slade highlighted clinical performance of four PARP inhibitors used in cancer therapy (olaparib, rucaparib, niraparib, and talazoparib) and discussed the predictive biomarkers of inhibitor sensitivity, mechanisms of resistance as well as the means of overcoming them through combination therapy. [Read the Full Post]

Talazoparib in Patients With a Germline BRCA-Mutated Advanced Breast Cancer: Detailed Safety Analyses From the Phase III EMBRACA Trial

525 | May 27 2020

Sara A Hurvitz et al. found that Talazoparib was associated with superior efficacy, favorable PROs, and lower HRU rate versus chemotherapy in gBRCA-mutated ABC. Toxicities were manageable with talazoparib dose modification and supportive care. [Read the Full Post]

Combination of PARP inhibitor olaparib, and PD-L1 inhibitor durvalumab, in recurrent ovarian cancer: a proof-of-concept phase 2 study.

417 | May 15 2020

Lampert EJ et al. found that he PARPi and anti-PD-L1 combination showed modest clinical activity in recurrent ovarian cancer. Their correlative study results suggested immunomodulatory effects by olaparib/durvalumab in patients and indicate that VEGF/VEGFR pathway blockade would be necessary for improved efficacy of the combination [Read the Full Post]

Functional evaluation of five BRCA2 unclassified variants identified in a Sri Lankan cohort with inherited cancer syndromes using a mouse embryonic stem cell-based assay

391 | May 13 2020

Sirisena N et al. highlighted the value of mouse embryonic stem cell-based assays for determining the functional significance of variants of unknown clinical significance and provide valuable information regarding risk estimation and genetic counseling of families carrying these BRCA2 variants. [Read the Full Post]

Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination With Bortezomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma

515 | Apr 27 2020

Dan T Vogl et al. showed that at the recommended phase II dose of ricolinostat of 160 mg daily, the combination with bortezomib and dexamethasone is safe, well-tolerated, and active, suggesting that selective inhibition of HDAC6 is a promising approach to multiple myeloma therapy. [Read the Full Post]

Targeting NAD+ biosynthesis overcomes panobinostat and bortezomib-induced malignant glioma resistance

692 | Apr 09 2020

Jane EP et al. provided new insights into mechanisms of treatment resistance in gliomas, hold promise for targeting recurrent disease, and provided a potential strategy for further exploration of next generation inhibitors. [Read the Full Post]

Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery

0 | Mar 30 2020

Colclough N et al. demonstrated how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders. [Read the Full Post]

JNJ-26481585 primes rhabdomyosarcoma cells for chemotherapeutics by engaging the mitochondrial pathway of apoptosis

678 | Mar 19 2020

Heinicke U et al. indicated the second-generation HDACI JNJ-26481585 cooperates with chemotherapeutics to engage mitochondrial apoptosis in RMS cells, demonstrating that JNJ-26481585 represents a promising strategy for chemosensitization of RMS. [Read the Full Post]

The HDAC Inhibitor Quisinostat (JNJ-26481585) Supresses Hepatocellular Carcinoma alone and Synergistically in Combination with Sorafenib by G0/G1 phase arrest and Apoptosis induction

585 | Mar 17 2020

He B et al. indicated that quisinostat, as a novel chemotherapy for HCC, exhibited excellent antitumor activity in vitro and vivo, which was even enhanced by the addition of sorafenib, implying combination of quisinostat with sorafenib a promising and alternative therapy for patients with advanced hepatocellular carcinoma. [Read the Full Post]

Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

467 | Mar 16 2020

Tian X et al.demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment. [Read the Full Post]

Structure of the intact ATM/Tel1 kinase

511 | Mar 16 2020

Wang X et al. provided a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents. [Read the Full Post]

ATM induces MacroD2 nuclear export upon DNA damage

555 | Mar 13 2020

Golia B et al. identified a novel feedback regulation between two crucial DNA damage-induced signaling pathways: ADP-ribosylation and ATM activation. [Read the Full Post]

PXD101 significantly improves nuclear reprogramming and the in vitro developmental competence of porcine SCNT embryos

664 | Mar 12 2020

Jin JX et al. demonstrated that PXD101 can significantly improve the in vitro and in vivo developmental competence of porcine SCNT embryos and can enhance their nuclear reprogramming. [Read the Full Post]

Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study

664 | Mar 11 2020

O'Connor OA et al. showed that monotherapy with belinostat produced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across the major subtypes, irrespective of number or type of prior therapies. These results have led to US Food and Drug Administration approval of belinostat for this indication. [Read the Full Post]

MGCD0103, a selective histone deacetylase inhibitor, coameliorates oligomeric Aβ25-35 -induced anxiety and cognitive deficits in a mouse model

1788 | Mar 08 2020

Huang HJ et al. revealed MGCD0103 could be a potential therapeutic agent against AD. [Read the Full Post]

The class I/IV HDAC inhibitor mocetinostat increases tumor antigen presentation, decreases immune suppressive cell types and augments checkpoint inhibitor therapy

607 | Mar 06 2020

Briere D et al. provided evidence that mocetinostat modulates immune-related genes in tumor cells as well as immune cell types in the tumor microenvironment and enhances checkpoint inhibitor therapy. [Read the Full Post]

Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery

0 | Feb 16 2020

Colclough N et al. demonstrated how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders. [Read the Full Post]

MiR-509-3 augments the synthetic lethality of PARPi by regulating HR repair in PDX model of HGSOC

446 | Feb 11 2020

Sun C found that MiR-509-3 can sensitize ovarian cancer cells to Olaparib by impeding HR, which makes it a potential target in PARPi synergistic treatment. [Read the Full Post]

Synergistic lethality between PARP-trapping and alantolactone-induced oxidative DNA damage in homologous recombination-proficient cancer cells

410 | Feb 10 2020

Wang H found that PARP trapping combined with specific pro-oxidative agents may provide safe and effective ways to broaden the therapeutic potential of PARP inhibitors. [Read the Full Post]

The histone deacetylase inhibitor romidepsin spares normal tissues while acting as an effective radiosensitiser in bladder tumours in vivo

608 | Feb 09 2020

Paillas S et al. demonstrated that romidepsin is an effective radiosensitiser in vitro and in vivo and does not increase the acute and late toxicity after ionising radiation. [Read the Full Post]

The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity

384 | Feb 08 2020

Timm KN et al. introduced different agents known to activate AMPK (metformin, statins, resveratrol, thiazolidinediones, AICAR, specific AMPK activators) as well as exercise and dietary restriction, and discussed the existing evidence for their potential role in cardioprotection from doxorubicin cardiotoxicity. [Read the Full Post]

Role of H3K18ac-regulated nucleotide excision repair-related genes in arsenic-induced DNA damage and repair of HaCaT cells

624 | Feb 07 2020

Zhang AL et al. provided new ideas for understanding the molecular mechanisms underlying arsenic-induced skin damage. [Read the Full Post]

PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells

514 | Jan 21 2020

Liu C et al. indicated that Olaparib may help individualize treatment and improve their outcomes of hypopharyngeal cancer patients treated with radiation. [Read the Full Post]

Mechanism and current progress of Poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer

803 | Jan 21 2020

Zheng F et al. highlighted the current research progress on PARP inhibitor resistance, which has become a challenge in clinics. [Read the Full Post]

Poly (ADP-ribose) Polymerase Inhibition in Patients with Breast Cancer and BRCA 1 and 2 Mutations

475 | Jan 20 2020

Jerez Y et al. discussed the future development of PARPi in BC, their potential combination with other strategies, including chemotherapy and immune-checkpoint inhibitors, and the impact of these treatments in current genetic counselling. [Read the Full Post]

Inhibition of PARP Sensitizes Chondrosarcoma Cell Lines to Chemo- and Radiotherapy Irrespective of the IDH1 or IDH2 Mutation Status

419 | Jan 20 2020

Venneker S et al. suggested that talazoparib combined with temozolomide or radiation are promising therapeutic strategies for chondrosarcoma, irrespective of IDH mutation status. A subset of chondrosarcomas may be deficient in nonclassical DNA repair pathways, suggesting that PARP inhibitor sensitivity is multifactorial in chondrosarcoma. [Read the Full Post]

Efficacy of pritelivir and acyclovir in the treatment of herpes simplex virus infections in a mouse model of herpes simplex encephalitis

409 | Jan 13 2020

Quenelle DC et al. concluded pritelivir has potent and resistance-breaking antiviral efficacy with potential for the treatment of potentially life-threatening HSV type 1 and 2 infections, including herpes simplex encephalitis. [Read the Full Post]

Sulfoximines as ATR inhibitors: Analogs of VE-821

0 | Jan 12 2020

Hendriks CMM et al. suggested that the sulfilimidoyl- and sulfoximidoyl-substituted analogs are efficient ATR inhibitors. [Read the Full Post]

PI3K inhibitor LY294002, as opposed to wortmannin, enhances AKT phosphorylation in gemcitabine-resistant pancreatic cancer cells

622 | Jan 06 2020

Wang Y et al. revealed that LY294002 displays the opposite effect on PI3K-dependent AKT phosphorylation, which maintains cell survival from the cytotoxicity introduced by LY294002 itself in GEM-resistant pancreatic cancer cells. We suggest that targeting the PI3K/AKT signaling pathway with inhibitors may be counterproductive for patients with PC who have acquired GEM-resistance. [Read the Full Post]

Predictability, efficacy and safety of radiosensitization of glioblastoma-initiating cells by the ATM inhibitor KU-60019

461 | Jan 05 2020

Vecchio D et al. suggested that GIC-driven tumors with low expression of TP53 and high expression of PI3K might be effectively and safely radiosensitized by KU-60019. [Read the Full Post]

Ricolinostat (ACY-1215) suppresses proliferation and promotes apoptosis in esophageal squamous cell carcinoma via miR-30d/PI3K/AKT/mTOR and ERK pathways

716 | Jan 03 2020

Cao J et al. showed that ACY-1215 suppressed proliferation and promoted apoptosis in ESCC via miR-30d/PI3K/AKT/mTOR and ERK pathways and that ACY-1215 may be a promising antitumor agent in ESCC. [Read the Full Post]

The SIRT1 inhibitor EX-527 suppresses mTOR activation and alleviates acute lung injury in mice with endotoxiemia

0 | Dec 28 2019

Huang J et al. suggested that selective inhibition of SIRT1 by EX-527 might alleviate endotoxemia-associated acute lung injury partially via suppression of mTOR, which implies that SIRT1 selective inhibitors might have potential value for the pharmacological intervention of inflammatory lung injury. [Read the Full Post]

Proteomic Analysis of HDAC3 Selective Inhibitor in the Regulation of Inflammatory Response of Primary Microglia

619 | Dec 26 2019

Xia M et al. provided a hint that RGFP966 may be a potential therapeutic medication combating microglia activation and inflammatory response in central nervous system, which was probably related to its repressive impacts on TLR signaling pathways and STAT3/STAT5 pathways. [Read the Full Post]

NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma

572 | Dec 24 2019

Huang JC et al. suggested NVP-BEZ235 could synergize cisplatin sensitivity in OS, combination of NVP-BEZ235 with cisplatin could represent a novel therapeutic strategy for treatment of OS. [Read the Full Post]

The PI3K/mTOR dual inhibitor BEZ235 suppresses proliferation and migration and reverses multidrug resistance in acute myeloid leukemia

488 | Dec 24 2019

Deng L et al. indicated that the PI3K/mTOR dual inhibitor BEZ235 effectively chemosensitizes AML cells via increasing miR-1-3p and subsequently down-regulating BAG4, EDN1 and ABCB1. [Read the Full Post]

Dactolisib (NVP-BEZ235) toxicity in murine brain tumour models

541 | Dec 23 2019

Netland IA et al. suggested that despite the anti-neoplastic efficacy of dactolisib in glioma treatment in vitro, its utility in vivo is questionable due to toxicity. [Read the Full Post]

Histone deacetylase inhibitor ITF2357 leads to apoptosis and enhances doxorubicin cytotoxicity in preclinical models of human sarcoma

580 | Dec 18 2019

Di Martile M et al. indicated their study highlights the therapeutic potential of ITF2357, alone or in rational combination therapies, for bone and soft tissue sarcomas management. [Read the Full Post]

Histological effects of givinostat in boys with Duchenne muscular dystrophy

646 | Dec 16 2019

Bettica P et al. showed that treatment with Givinostat for more than 1 year significantly counteracted histological disease progression in ambulant DMD boys aged 7 to 10 years. [Read the Full Post]

Fludarabine-PET in a murine model of multiple myeloma

926 | Dec 08 2019

Hovhannisyan N et al. suggested that [18F]fludarabine-PET might represent an alternative and perhaps more specific modality for MM imaging when compared to [18F]FDG. Nevertheless, more investigations are required to extend this conclusion to humans. [Read the Full Post]

Inhibitory Activities of Blasticidin S Derivatives on Aflatoxin Production by Aspergillus Flavus

0 | Dec 06 2019

Yoshinari T et al. indicated that the inhibitory activity of BcS against aflatoxin production was enhanced by esterification of its carboxyl group and that the carboxymethyl ester derivative might be more suitable for practical use than BcS because of the specificity of the carboxymethyl ester derivative, which inhibited aflatoxin production more than BcS. [Read the Full Post]

Salidroside attenuates dextran sulfate sodium-induced colitis in mice via SIRT1/FoxOs signaling pathway

638 | Nov 22 2019

Li H et al. manifested that Sal may protect colitis mice by activating the SIRT1/FoxOs pathway, which is related to oxidative stress and apoptosis in colon tissues. [Read the Full Post]

NU7441 Enhances the Radiosensitivity of Liver Cancer Cells

606 | Nov 15 2019

Yang C et al. showed that NU7441 inhibited the growth of liver cancer cells, enhanced the radiosensitization of these cancer cells by interfering with the DNA repair and cell cycle checkpoint. These data implicate NU7441 as a potential radiotherapy sensitizer for the treatment of liver cancer. [Read the Full Post]

Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks

0 | Nov 15 2019

Zhou T et al. indicated this chromosomal hypersensitivity, as well as a small but reproducible enhancement of calicheamicin cytotoxicity following siRNA-mediated TDP1 knockdown, suggests a role for TDP1 in repair of 3'-PG double-strand breaks in vivo. [Read the Full Post]

The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress

0 | Nov 11 2019

Ren Y et al. showed the Sirt1 activator may therefore be prove to be a potent therapeutic agent for the treatment of fibrotic kidney disease. [Read the Full Post]

CX-4945: the protein kinase CK2 inhibitor and anti-cancer drug shows anti-fungal activity

957 | Nov 07 2019

Masłyk M et al. indicated their data unveil the dual-activity of CX-4945; when used in anti-cancer therapy, it may simultaneously prevent cancer-associated candidiasis. [Read the Full Post]

Nutlin-3 enhances the bortezomib sensitivity of p53-defective cancer cells by inducing paraptosis

689 | Nov 01 2019

Lee DM et al. suggested that bortezomib/nutlin-3 perturbs proteostasis, triggering ER/mitochondria stress and irrecoverable impairments in their structure and function, ultimately leading to paraptotic cell death. [Read the Full Post]

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours

0 | Oct 29 2019

Xu H et al. indicated these data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. CX-5461 is now in advanced phase I clinical trial for patients with BRCA1/2 deficient tumours (Canadian trial, NCT02719977, opened May 2016). [Read the Full Post]

Nutlin-3a selects for cells harbouring TP53 mutations

0 | Oct 29 2019

Kucab JE et al. suggested that including a Nutlin-3a counter-screen significantly improves the specificity and efficiency of the HIMA, whereby TP53-mutated clones are selected prior to sequencing and TP53-WT clones can be discarded. [Read the Full Post]

RBBP8/CtIP suppresses P21 expression by interacting with CtBP and BRCA1 in gastric cancer

715 | Oct 24 2019

Yu Y et al. revealed the chromatin modification role of RBBP8, which could suppress the histone acetylation level of P21 promoter by recruiting CtBP co-repressor complex to BRCA1 binding site. [Read the Full Post]

Trichostatin A and 5-Aza-2'-Deoxycytidine influence the expression of cold-induced genes in Arabidopsis

764 | Oct 22 2019

Song Y et al. showed this result will advance our understanding of plant freezing responses and may provide a helpful strategy for cold tolerance improvement in crops. [Read the Full Post]

Prolonged Idasanutlin (RG7388) Treatment Leads to the Generation of p53-Mutated Cells

425 | Oct 20 2019

Skalniak L et al. showed that although idasanutlin presents much improved activities compared to its precursor, it displays the similar weaknesses, which are limited elimination of cancer cells and the generation of p53-mutated drug-resistant subpopulations. [Read the Full Post]

The Herb-Drug Pharmacokinetic Interaction of 5-Fluorouracil and Its Metabolite 5-Fluoro-5,6-Dihydrouracil with a Traditional Chinese Medicine in Rats

431 | Oct 17 2019

Liu JH et al. indicated the pharmacokinetic results confirm the safety of coadministering 5-FU with XSLJZT, and provide practical dosage information for clinical practice. [Read the Full Post]

ABT-888 restores sensitivity in temozolomide resistant glioma cells and xenografts

542 | Oct 14 2019

Yuan AL et al. indicated that in laboratory models, the addition of ABT-888 to TMZ overcame resistance to TMZ. [Read the Full Post]

Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer

611 | Oct 13 2019

Coleman RL et al. indicated that across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. [Read the Full Post]

Activity of BET-proteolysis targeting chimeric (PROTAC) compounds in triple negative breast cancer

561 | Oct 11 2019

Noblejas-López MDM et al. provided options for further clinical development of these agents in TNBC. [Read the Full Post]

Panobinostat for the Treatment of Multiple Myeloma

783 | Oct 11 2019

Laubach JP et al. indicated The review focuses on panobinostat and its mechanism of action, pharmacokinetics, and clinical data in the treatment of relapsed or relapsed and refractory multiple myeloma. [Read the Full Post]

FK228 augmented temozolomide sensitivity in human glioma cells by blocking PI3K/AKT/mTOR signal pathways

865 | Oct 05 2019

Wu Y et al. suggested that FK228 augmented temozolomide sensitivity in human glioma cells partially by blocking PI3K/AKT/mTOR signal pathways. It thus may provide a promising target for improving the therapeutic outcome of TMZ-resistant gliomas, although further studies will be needed. [Read the Full Post]

AZD6738, A Novel Oral Inhibitor of ATR, Induces Synthetic Lethality with ATM Deficiency in Gastric Cancer Cells

624 | Oct 04 2019

Min A et al. suggested synthetic lethality between ATR inhibition and ATM deficiency in gastric cancer cells. Further clinical studies on the interaction between AZD 6738 and ATM deficiency are warranted to develop novel treatment strategies for gastric cancer. [Read the Full Post]

Entinostat for the treatment of breast cancer

763 | Sep 20 2019

Trapani D et a. offered the rationale for combining HDAC inhibitors with immunotherapy, including therapeutic cancer vaccines. [Read the Full Post]

Acetazolamide potentiates the anti-tumor potential of HDACi, MS-275, in neuroblastoma

737 | Sep 20 2019

Bayat Mokhtari R et al. indicated the significant reduction in initial tumorigenicity and subsequent abrogation upon serial xenografting suggests potential elimination of the NB CSC fraction. The significant potentiation of MS-275 by AZ is a promising therapeutic approach and one amenable for administration to patients given their current clinical utility. [Read the Full Post]

LBH589 Inhibits Glioblastoma Growth and Angiogenesis Through Suppression of HIF-1α Expression

2081 | Sep 14 2019

Yao ZG et al. supports the role of HDAC inhibitors as a therapeutic strategy to target tumor angiogenesis. [Read the Full Post]

Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation

481 | Sep 12 2019

Fokas E et al. support ATR inhibition as a promising new approach to improve the therapeutic ration of radiochemotherapy for patients with PDAC. [Read the Full Post]

Kinetic Tuning of HDAC Inhibitors Affords Potent Inducers of Progranulin Expression

812 | Sep 09 2019

Moreno-Yruela C et al. demonstrated induction of PGRN expression by fast-on/fast-off, highly potent, macrocyclic HDAC inhibitors with ethyl ketone or ethyl ester Zn2+ binding groups. [Read the Full Post]

SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells

768 | Sep 09 2019

Sun QY et al. revealed an unappreciated role of SOX7 in regulation of cellular apoptosis through control of MAPK/ERK-BIM signaling. [Read the Full Post]

Activation of Wnt signaling promotes olaparib resistant ovarian cancer

581 | Sep 08 2019

Yamamoto TM et al. demonstrated that Wnt signaling can mediate PARPi resistance in HGSOC and provides a clinical rationale for combining PARP and Wnt inhibitors. [Read the Full Post]

Rucaparib: the past, present, and future of a newly approved PARP inhibitor for ovarian cancer

525 | Sep 08 2019

Dockery LE et al. indicated this article reviews the mechanisms of action, safety, approval, and indications for use of the PARP inhibitor rucaparib as well as future trials and use of rucaparib's companion diagnostic test. [Read the Full Post]

Quantifying Risk Pathway Crosstalk Mediated by miRNA to Screen Precision drugs for Breast Cancer Patients

888 | Sep 03 2019

Xu Y et al. offers an effective way to screen precision drugs for various breast cancer subtype treatments. We also dissected the mechanism of optimal therapeutic drugs, which may provide novel insight into the precise treatment of cancer and promote researches on the mechanisms of action of drugs. [Read the Full Post]

Vorinostat-eluting poly(DL-lactide-co-glycolide) nanofiber-coated stent for inhibition of cholangiocarcinoma cells

855 | Sep 02 2019

Kwak TW et al. suggested the vorinostat nanofiber-coated stent may be a promising candidate for CCA treatment. [Read the Full Post]

Oncogenic enhancer of zeste homolog 2 is an actionable target in patients with non-small cell lung cancer

820 | Sep 02 2019

Shi B et al. showed that overexpression of EZH2 is a negative prognostic indicator. Increased EZH2 expression predicts for response to HDAC inhibitors and thus could serve as a biomarker for selecting NSCLC patients for treatment with HDAC inhibitors. [Read the Full Post]

PARP Inhibition Suppresses GR-MYCN-CDK5-RB1-E2F1 Signaling and Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer

482 | Aug 30 2019

Liu B et al. demonstrated efficacy for OLA+DINA combination therapy in NEPC xenograft models. [Read the Full Post]

Metformin and 4SC-202 synergistically promote intrinsic cell apoptosis by accelerating ΔNp63 ubiquitination and degradation in oral squamous cell carcinoma

1944 | Aug 25 2019

He Y et al. revealed that ΔNp63 mediated anticancer effects of metformin and 4SC-202, as overexpression or suppression of ΔNp63 could attenuate or facilitate the apoptosis rate of OSCC under metformin or/and 4SC-202 treatment. Collectively, metformin and 4SC-202 synergistically promote intrinsic apoptosis through accelerating ubiquitin-mediated degradation of ΔNp63 in OSCC, and this co-treatment can serve as a potential therapeutic scheme for OSCC. [Read the Full Post]

PARP1 Inhibition Radiosensitizes Models of Inflammatory Breast Cancer to Ionizing Radiation

638 | Aug 17 2019

Michmerhuizen AR et al. demonstrated that PARPi improves the effectiveness of radiotherapy in IBC models and provides the preclinical rationale for the opening phase II randomized trial of RT +/- PARPi in women with IBC [Read the Full Post]

Combined Strategies with Poly (ADP-Ribose) Polymerase (PARP) Inhibitors for the Treatment of Ovarian Cancer: A Literature Review.

501 | Aug 17 2019

Boussios S et al. discussed multiple clinical trials that are underway examining the antitumor activity of such combination strategies. [Read the Full Post]

Irinotecan monotherapy as third-line or later treatment in advanced gastric cancer

503 | Aug 09 2019

Makiyama A et al. showed that Irinotecan monotherapy was relatively safely performed as salvage-line treatment for AGC in Japanese clinical practice. Careful patient selection and intensive modification of the dose of irinotecan might possibly be associated with favorable survival. [Read the Full Post]

Targeting autophagy potentiates the anti-tumor effect of PARP inhibitor in pediatric chronic myeloid leukemia

588 | Aug 07 2019

Liu Y et al. demonstrated that autophagy played a cyto-protective role in talazoparib-treated pediatric CML and co-treatment with talazoparib and autophagy inhibitor could induce synergetic anti-tumor effect, providing novel insights for pediatric CML treatment. [Read the Full Post]

The 5-hydrazino-3-methylisothiazole-4-carboxylic acid, its new 5-substituted derivatives and their antiproliferative activity

474 | Jul 29 2019

Jęśkowiak I et al. showed in the conducted studies, their activity against breast adenocarcinoma MCF-7 and normal non-tumorigenic epithelial cell line derived from mammary gland MCF-10A was substantially lower. The result of this work is claimed Polish patent application. [Read the Full Post]

Kinetic Tuning of HDAC Inhibitors Affords Potent Inducers of Progranulin Expression

0 | Jul 27 2019

Moreno-Yruela C et al. demonstrated induction of PGRN expression by fast-on/fast-off, highly potent, macrocyclic HDAC inhibitors with ethyl ketone or ethyl ester Zn2+ binding groups. [Read the Full Post]

Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer

523 | Jul 22 2019

Belz JE et al. demonstrated that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors. [Read the Full Post]

The PARP inhibitor AZD2281 (Olaparib) induces autophagy/mitophagy in BRCA1 and BRCA2 mutant breast cancer cells

508 | Jul 14 2019

Arun B et al. indicated that the patients with BRCA1 allelic loss may also benefit from PARP inhibitor therapy if BRCA is further inhibited. [Read the Full Post]

BRCA1, PARP1 and γH2AX in acute myeloid leukemia: Role as biomarkers of response to the PARP inhibitor olaparib

1573 | Jul 14 2019

Faraoni I et al. showed the high sensitivity of AML blasts and the identification of biomarkers potentially able to predict response and/or resistance may foster further investigation of olaparib monotherapy for AML patients unfit to conventional chemotherapy. [Read the Full Post]

Genomic testing, tumor microenvironment and targeted therapy of Hedgehog-related human cancers

773 | Jul 03 2019

Katoh M indicated that SMO inhibitors can remodel the immunosuppressive TME that is dominated by M2-like tumor-associated macrophages (M2-TAMs), myeloid-derived suppressor cells and regulatory T cells, and thus, a Phase I/II clinical trial of the immune checkpoint inhibitor pembrolizumab with or without vismodegib in BCC patients is ongoing. [Read the Full Post]

Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery

722 | Jun 27 2019

Colclough N et al. demonstrated how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders. [Read the Full Post]

Structural States of Hdm2 and HdmX: X-ray Elucidation of Adaptations and Binding Interactions for Different Chemical Compound Classes

423 | Jun 26 2019

Kallen J et al. used the same numbering for Hdm2 (as in Q00987) and HdmX (as in O15151, but minus 1). Taken together, these structural insights should prove useful for the design and optimization of further selective and/or dual Hdm2/HdmX inhibitors. [Read the Full Post]

Age-related macular degeneration (AMD) mitochondria modulate epigenetic mechanisms in retinal pigment epithelial cells

898 | Jun 23 2019

Nashine S et al. revealed that AMD mitochondria regulate epigenetic mechanisms i.e., methylation and acetylation status. Demethylation using 5-Aza-2'-deoxycytidine (DAC) caused differential expression of VEGF-A gene in AMD cells. Trichostatin A (TSA), an HDAC inhibitor, also influenced protein levels of VEGF-A, HIF1α, NFκB, and CFH in AMD cells. This study might advance the field of AMD research since in addition to highlighting the critical role of nuclear-mitochondrial interactions that influence epigenetic mechanisms in AMD patients, this work suggests epigenetic profiles as potential therapeutic targets for AMD. [Read the Full Post]

Non-Photoinduced Biological Properties of Verteporfin

929 | Jun 23 2019

Gibault F et al. showed that VP is a multi-target drug interacting with several proteins implicated in major cellular processes. Although this does not impact its clinical use, VP does not seem to be the ideal drug for pharmacological inhibitions of YAP/TEAD. [Read the Full Post]

BAY 87-2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK-3β activation

764 | Jun 22 2019

Li YL et al. found that BAY 87-2243 combined with HDAC inhibitors might be an attractive chemotherapy strategy for HCC therapy. [Read the Full Post]

Reciprocal Relationship Between HDAC2 and P-Glycoprotein/MRP-1 and Their Role in Steroid Resistance in Childhood Nephrotic Syndrome

741 | Jun 22 2019

Singh H et al. found that reduced HDAC2 and increased P-gp/MRP-1 activity may play a role in response to steroids in childhood NS. HDAC2 and P-gp/MRP-1 are in reciprocal relationship with each other. [Read the Full Post]

Histone deacetylase 6 inhibitor ACY-1215 protects against experimental acute liver failure by regulating the TLR4-MAPK/NF-κB pathway

2252 | Jun 19 2019

Zhang WB et al. showed that ACY-1215 has potential therapeutic value in mice with ALF by directly inhibiting inflammatory response via regulation of the TLR4-MAPK/NF-kB pathway. [Read the Full Post]

Safety evaluation of combination carboplatin and toceranib phosphate (Palladia) in tumour-bearing dogs: A phase I dose finding study

554 | Jun 09 2019

Wouda RM et al. indicated the dose-limiting toxicity was neutropenia. Two dogs experienced a partial response, and 6 maintained stable disease. Combination carboplatin and toceranib chemotherapy was well-tolerated. Clinical benefit was observed in most cases. This protocol warrants further investigation in phase II/III trials. [Read the Full Post]

CX-4945, a Selective Inhibitor of Casein Kinase 2, Synergizes with B Cell Receptor Signaling Inhibitors in Inducing Diffuse Large B Cell Lymphoma Cell Death

925 | Jun 08 2019

Mandato E et al. suggested a role for CK2 downstream of the BCR in controlling survival pathways crucial for cell growth of different DLBCL subtypes. Also, the use of CX-4945 in combination with BCR signaling blockers could represent a novel rational therapeutic approach in the DLBCL. [Read the Full Post]

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models

700 | Jun 08 2019

Lehmann C et al provided functional and molecular insight on the superior anti-tumor activity of combined idasanutlin and venetoclax treatment in AML and support its further exploration in clinical studies. [Read the Full Post]

Inhibitory Activities of Blasticidin S Derivatives on Aflatoxin Production by Aspergillus Flavus

502 | Jun 03 2019

Yoshinari T et al. indicated that the inhibitory activity of BcS against aflatoxin production was enhanced by esterification of its carboxyl group and that the carboxymethyl ester derivative might be more suitable for practical use than BcS because of the specificity of the carboxymethyl ester derivative, which inhibited aflatoxin production more than BcS. [Read the Full Post]

A Preclinical Model for Studying Herpes Simplex Virus Infection

0 | May 25 2019

Tajpara P et al. present a previously unreported ex vivo HSV-1 infection model with abdominal human skin to test antiviral drugs, thus bridging the gap between in vitro and in vivo drug screening and providing a valuable preclinical platform for HSV research. [Read the Full Post]

Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial

1063 | May 21 2019

Rummel M et al. indicated that in combination with rituximab, bendamustine was more effective than fludarabine, suggesting that bendamustine plus rituximab may be the preferred treatment option for patients with relapsed indolent and mantle-cell lymphomas. [Read the Full Post]

Targeted blockade of HSP90 impairs DNA-damage response proteins and increases the sensitivity of ovarian carcinoma cells to PARP inhibition

512 | May 19 2019

Gabbasov R et al. suggested that HSP90 inhibition has the potential to sensitize some HGSOC patients without HR pathway alterations to PARPi, and potentially other DNA-damage inducing agents. [Read the Full Post]

Hydroxysafflor yellow A inhibited lipopolysaccharide-induced non-small cell lung cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT/mTOR and ERK/MAPK signaling pathways

443 | May 18 2019

HYSA suppressed LPS-mediated proliferation, migration, invasion, and EMT in A549 and H1299 cells by inhibiting the PI3K/Akt/mTOR and ERK/MAPK signaling pathways, indicating that HYSA may be a potential candidate to treat inflammation-mediated NSCLC. [Read the Full Post]

A Preclinical Model for Studying Herpes Simplex Virus Infection

700 | Apr 29 2019

Tajpara P et al. discovered that both drugs had a comparable efficacy for inhibiting HSV-1 replication, suggesting that pritelivir could be an alternative therapeutic agent for patients infected with acyclovir-resistant strains. To our knowledge, we present a previously unreported ex vivo HSV-1 infection model with abdominal human skin to test antiviral drugs, thus bridging the gap between in vitro and in vivo drug screening and providing a valuable preclinical platform for HSV research. [Read the Full Post]

ITF2357 transactivates Id3 and regulate TGFβ/BMP7 signaling pathways to attenuate corneal fibrosis

2627 | Apr 21 2019

Lim RR et al. concludd that ITF2357 is a potential anti-fibrotic drug that exerts its action via activation of Id3, a downstream target of TGFβ/BMP7 signaling pathways. [Read the Full Post]

Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models

705 | Apr 17 2019

Kuk MU et al. indicated that the mitochondrial functional recovery by ATM inhibition might represent a promising strategy to ameliorate the accelerated aging phenotypes and to treat age-related disease. [Read the Full Post]

Prevention of Intraabdominal Adhesions: An Experimental Study Using Mitomycin-C and 4% Icodextrin

0 | Apr 16 2019

Urkan M et al. indicated that despite its potential for bone marrow toxicity, Mitomycin-C seems to effectively prevent adhesions. Further studies that prove an acceptable safety profile relating to this promising anti-adhesive agent are required before moving into clinical trials. [Read the Full Post]

The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL

883 | Apr 13 2019

Savino AM et al. indicated givinostat killed ruxolitinib-resistant cells and potentiated the effect of current chemotherapy. Thus, givinostat in combination with conventional chemotherapy may represent an effective therapeutic option for these difficult-to-treat subsets of ALL. Lastly, the selective killing of cancer cells by givinostat may allow the design of reduced intensity regimens in CRLF2-rearranged Down syndrome-associated BCP-ALL patients with an overall benefit in terms of both toxicity and related complications. [Read the Full Post]

CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells

919 | Apr 13 2019

Silva-Pavez E et al. suggested that an aberrantly elevated expression/activity of CK2 may play a key role in CRC, promoting cell viability and proliferation in untreated cells, however, its inhibition with silmitasertib promotes methuosis-like cell death associated to massive catastrophic vacuolization, accounting for decreased tumorigenicity at later times. These characteristics of silmitasertib support a potential therapeutic use in CRC patients and probably other CK2-dependent cancers. [Read the Full Post]

Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial

550 | Apr 09 2019

Moore KN et al. identified no new safety signals. Our data support expansion of the treatment indication for poly(ADP-ribose) polymerase inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutations. [Read the Full Post]

Slow release of etoposide from dextran conjugation shifts etoposide activity from cytotoxicity to differentiation: A promising tool for dosage control in anticancer metronomic therapy

576 | Apr 01 2019

De Nicola M et al. indicated slow release as a promising novel strategy for stabilizing low drug levels in metronomic regimens. [Read the Full Post]

MYC status as a determinant of synergistic response to Olaparib and Palbociclib in ovarian cancer

643 | Mar 29 2019

Yi J et al. show for the first time that combining PARP and CDK4/6 inhibition has synergistic effects against MYC overexpressing ovarian cancer cells both in vitro and in vivo. [Read the Full Post]

The SIRT1 inhibitor EX-527 suppresses mTOR activation and alleviates acute lung injury in mice with endotoxiemia

866 | Mar 28 2019

Huang J et al. suggested that selective inhibition of SIRT1 by EX-527 might alleviate endotoxemia-associated acute lung injury partially via suppression of mTOR, which implies that SIRT1 selective inhibitors might have potential value for the pharmacological intervention of inflammatory lung injury. [Read the Full Post]

The antinociceptive effect of resveratrol in bone cancer pain is inhibited by the Silent Information Regulator 1 inhibitor selisistat

692 | Mar 28 2019

Lux S et al. showed that acute and chronic resveratrol induces antinociceptive effect in the model of metastatic osseous oncological pain, an effect that would be mediated by SIRT1 molecular signalling. [Read the Full Post]

DNA-PK inhibition by NU7441 sensitizes breast cancer cells to ionizing radiation and doxorubicin

898 | Mar 26 2019

Ciszewski WM et al. indicated that DNA-PK might be an effective target for chemo- and radio-potentiation in breast cancer and suggest that further development of DNA-PK inhibitors for clinical use is warranted. [Read the Full Post]

Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks

1008 | Mar 26 2019

Zhou T et al. indicated This chromosomal hypersensitivity, as well as a small but reproducible enhancement of calicheamicin cytotoxicity following siRNA-mediated TDP1 knockdown, suggests a role for TDP1 in repair of 3'-PG double-strand breaks in vivo. [Read the Full Post]

The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress

781 | Mar 24 2019

Ren Y et al. indicated that the Sirt1 activator, SRT1720, exerts protective effects against UUO-induced tubulointerstitial fibrosis. The mechanisms of action of SRT1720 may include, at least in part, the suppression of renal oxidative stress and the TGF-β1/CTGF signalling pathway. The Sirt1 activator may therefore be prove to be a potent therapeutic agent for the treatment of fibrotic kidney disease. [Read the Full Post]

Ten-Year and Beyond Follow-up After Treatment With Highly Purified Liquid-Injectable Silicone for HIV-Associated Facial Lipoatrophy: A Report of 164 Patients

481 | Mar 22 2019

Jones DH et al. showed that liquid-injectable silicone is an effective long-term treatment option for HIV-FLA. When injected in small quantities with the microdroplet serial puncture technique at monthly or greater intervals, optimal correction appears durable for more than 10 years. Adverse events consisted mostly of excess fibroplasia and were treatable. [Read the Full Post]

5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer

628 | Mar 22 2019

Morawska K et al. showed at a cycle 1, the 5-FU dose was calculated using patient's Body Surface Area (BSA) method. A blood sample was drawn on Day 2 to measure 5-FUconcentration. At cycle 2, the 5-FU dose was adjusted using a PK-guided dosing strategy targeting a plasma AUC range of 18-28 mg·h/L, based on cycle 1 concentration. Assessments of toxicity was performed at the beginning of every cycle. [Read the Full Post]

[Evolving 5-Fluorouracil Therapy to Achieve Enhanced Efficacy-Past and Current Efforts of Researchers]

513 | Mar 20 2019

Maehara Y et al. indicated that in the current standard treatment for gastrointestinal cancers, anticancer 5-FU derivatives serve as a platform for combination regimens with other cytotoxic agents or molecular- targeted drugs. To provide further improvements in anticancer therapy outcomes, novel molecular-targeted agents, immune checkpoint inhibitors, and other drugs are being developed, but 5-FU remains an attractive target that shows further potential for increased efficacy. In the future, the evolution of anticancer therapy with 5-FU derivatives is expected to continue via a variety of approaches. [Read the Full Post]

Monitoring the Activation of the DNA Damage Response Pathway in a 3D Spheroid Model

654 | Mar 15 2019

Mondesert O et al. demonstrated that DDR activation and its pharmacological manipulation with inhibitory and activatory compounds can be efficiently monitored in live 3D spheroid model. [Read the Full Post]

Targeting HDAC3 Activity with RGFP966 Protects Against Retinal Ganglion Cell Nuclear Atrophy and Apoptosis After Optic Nerve Injury

818 | Mar 12 2019

Schmitt HM et al. showed the inhibition of HDAC3 activity with systemic dosing of RGFP966 prevents apoptosis-related histone deacetylation and attenuates RGC loss after acute optic nerve injury. [Read the Full Post]

Nutlin-3a selects for cells harbouring TP53 mutations

573 | Mar 04 2019

Kucab JE et al. suggested that including a Nutlin-3a counter-screen significantly improves the specificity and efficiency of the HIMA, whereby TP53-mutated clones are selected prior to sequencing and TP53-WT clones can be discarded. [Read the Full Post]

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours

789 | Feb 14 2019

Xu H et al. indicated these data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. [Read the Full Post]

In vivo activation of invariant natural killer T cells induces systemic and local alterations in T-cell subsets prior to preterm birth

675 | Feb 11 2019

Gomez-Lopez N et al. found that iNKT-cell activation altered the systemic and local T-cell subsets prior to preterm labour/birth; however, treatment with rosiglitazone partially reversed such effects. [Read the Full Post]

Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells

562 | Feb 09 2019

Vallo S et al. suggested that the overexpression of ABCB1 confers resistance to nab-paclitaxel in urothelial cancer cells. Additionally, small molecules may overcome resistance to anticancer drugs that are substrates of ABCB1. [Read the Full Post]

An Oncogenic ALK Fusion and an RRAS Mutation in KRAS Mutation-Negative Pancreatic Ductal Adenocarcinoma

0 | Feb 09 2019

Shimada Y et al. found that rare oncogenic aberrations, such as the ALK fusion and RRAS mutation, may drive pancreatic carcinogenesis independent of the KRAS mutation. [Read the Full Post]

MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic Implications and Prognostic Values

513 | Feb 08 2019

Lee GD et al. found that the prognosis of patients with METex14 skipping was similar to that of patients with major driver mutations. siRNA targeting the junction of METex14 skipping could inhibit MET-driven signaling pathways in cells with METex14 skipping. [Read the Full Post]

Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment

836 | Feb 05 2019

Yee-Lin V et al. Nutlin-3, a small molecule inhibitor that specifically targets p53-Mdm2 interaction offers new therapeutic opportunities by enhancing cancer cell growth arrest and apoptosis through the restoration of the p53-mediated tumor suppression pathway while producing minimal cytotoxicity and side effects. [Read the Full Post]

Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer

781 | Feb 03 2019

Valle J et al. showed that as compared with gemcitabine alone, cisplatin plus gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity. Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer. [Read the Full Post]

Sulfoximines as ATR inhibitors: Analogs of VE-821

843 | Feb 01 2019

Hendriks CMM et al. suggested that the sulfilimidoyl- and sulfoximidoyl-substituted analogs are efficient ATR inhibitors. [Read the Full Post]

MDM2 is implicated in high-glucose-induced podocyte mitotic catastrophe via Notch1 signalling

575 | Jan 29 2019

Tang H, et al. found that high glucose up-regulates MDM2 expression and leads to podocyte MC. Notch1 signalling is an essential downstream pathway of MDM2 in mediating HG-induced MC in podocytes. [Read the Full Post]

Expression and function of MutT homolog 1 in distinct subtypes of breast cancer

648 | Jan 29 2019

Treatment with the MTH1 inhibitor appears to be safe; however, further studies are required prior to the clinical use of MTH1 inhibitors. [Read the Full Post]

Synergistic antitumor effect of NVP-BEZ235 and CAPE on MDA-MB-231 breast cancer cells

715 | Jan 24 2019

Torki S et al. suggested that tumor metastasis and progression in TNBC cells can be effectively reduced through the concurrent use of NVP-BEZ235 and CAPE. This could be of particular interest in assessing the effects of this therapy in the reduction of tumor metastasis and progression in other tumor types. [Read the Full Post]

Phase Ib dose-finding study of abiraterone acetate plus buparlisib (BKM120) or dactolisib (BEZ235) in patients with castration-resistant prostate cancer

721 | Jan 24 2019

Massard C et al. indicated that based on the assessment of available pharmacokinetics, safety, and efficacy data, no further study is planned for either buparlisib or dactolisib in combination with AA in CRPC. [Read the Full Post]

A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening

997 | Jan 23 2019

Yan HHN et al. indicated this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy. [Read the Full Post]

Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor-Naïve Advanced Pancreatic Neuroendocrine Tumors

2478 | Jan 23 2019

Salazar R et al. showed thta BEZ235 treatment in mTOR inhibitor-naïve patients with advanced pNET did not demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile. [Read the Full Post]

Cisplatin is retained in the cochlea indefinitely following chemotherapy

562 | Jan 17 2019

Breglio AM et al. demonstrated long-term retention of cisplatin in the human cochlea, and they point to the stria vascularis as an important therapeutic target for preventing cisplatin ototoxicity. [Read the Full Post]

Efficacy of a bleomycin microneedle patch for the treatment of warts

621 | Jan 15 2019

Ryu HR et al. indicated the bleomycin microneedle patch can be an effective, convenient, and innovative treatment modality for warts. [Read the Full Post]

Wortmannin-induced vacuole fusion enhances amyloplast dynamics in Arabidopsis zigzag1 hypocotyls

923 | Jan 14 2019

Alvarez AA et al. suggested that vacuole membrane remodeling may be involved in regulating the association of vacuoles and amyloplasts during graviperception. [Read the Full Post]

Inhibition of Histone Deacetylases Permits Lipopolysaccharide-Mediated Secretion of Bioactive IL-1β via a Caspase-1-Independent Mechanism

2575 | Jan 11 2019

Stammler D et al. indicated that in addition to the conventional inflammasome-dependent IL-1β cleavage pathway, dendritic cells and macrophages are capable of generating, secreting, and processing bioactive IL-1β by a novel, caspase-8-dependent mechanism. [Read the Full Post]

Inhibition of Histone Deacetylase 3 (HDAC3) Mediates Ischemic Preconditioning and Protects Cortical Neurons against Ischemia in Rats

885 | Jan 09 2019

Yang X et al. demonstrated that the inhibition of HDAC3 preconditions the brain against ischemic insults, indicating a new approach to evoke endogenous protection against stroke. [Read the Full Post]

Differential effects of histone deacetylase inhibitors on cellular drug transporters and their implications for using epigenetic modifiers in combination chemotherapy

0 | Jan 07 2019

Valdez BC et al. further imply the possibility of antagonistic effects when HDAC inhibitors are combined with anthracyclines and other MDR1 drug ligands in chemotherapy. [Read the Full Post]

GM-CSF and IL-3 Modulate Human Monocyte TNF-α Production and Renewal in In Vitro Models of Trained Immunity

2078 | Jan 03 2019

Borriello F et al. provided insights to understand the biology of monocytes in health and disease conditions in which the hematopoietic cytokines GM-CSF and IL-3 play a role and also extend our knowledge of the cellular and molecular mechanisms of trained immunity. [Read the Full Post]

Dual inhibition of ATR and ATM potentiates the activity of trabectedin and lurbinectedin by perturbing the DNA damage response and homologous recombination repair

856 | Jan 01 2019

Lima M et al. identify ATR and ATM as central coordinators of the DDR to ecteinascidins and provide a mechanistic rationale for combining these compounds with ATR and ATM inhibitors. [Read the Full Post]

PPARβ/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats

1569 | Dec 27 2018

Zhang H et al. identified PPARβ/δ as a useful regulator for VSMC phenotypic switch and vascular remodeling following SAH, providing novel insights into the therapeutic strategies of delayed cerebral ischemia. [Read the Full Post]

Enhanced efficacy of 5-fluorouracil in combination with a dual histone deacetylase and phosphatidylinositide 3-kinase inhibitor (CUDC-907) in colorectal cancer cells

1194 | Dec 26 2018

Hamam R et al. revealed, for the first time, the enhanced inhibitory effect of CUDC-907 against CRC cells when combined with 5-FU, supporting the application of this combination as a potential therapeutic strategy in CRC treatment. [Read the Full Post]

CUDC-907 Promotes Bone Marrow Adipocytic Differentiation Through Inhibition of Histone Deacetylase and Regulation of Cell Cycle

1363 | Dec 26 2018

Ali D et al. revealed that HDAC, PI3K, and cell cycle genes are important regulators of BMA formation and demonstrate that adipocyte differentiation of hBMSCs is associated with complex changes in a number of epigenetic and genetic pathways, which can be targeted to regulate BMA formation. [Read the Full Post]

RNA Polymerase I Inhibition with CX-5461 as a Novel Therapeutic Strategy to Target MYC in Multiple Myeloma

609 | Dec 24 2018

Lee HC et al. provided a rationale for the clinical translation of CX-5461 as a novel therapeutic approach to target MYC in myeloma. [Read the Full Post]

WIP1 modulates responsiveness to Sonic Hedgehog signaling in neuronal precursor cells and medulloblastoma

0 | Dec 23 2018

Wen J et al. found that Wip1 knockdown or treatment with a WIP1 inhibitor suppressed the effects of Shh stimulation and potentiated the growth inhibitory effects of SHH pathway-inhibiting drugs in Shh-activated MB cells in vitro. [Read the Full Post]

Differential effects of histone deacetylase inhibitors on cellular drug transporters and their implications for using epigenetic modifiers in combination chemotherapy

961 | Dec 20 2018

Valdez BC et al. further implied the possibility of antagonistic effects when HDAC inhibitors are combined with anthracyclines and other MDR1 drug ligands in chemotherapy. [Read the Full Post]

FAM83A is amplified and promotes cancer stem cell-like traits and chemoresistance in pancreatic cancer

1175 | Dec 15 2018

Chen S et al. indicated that FAM83A has a vital oncogenic role to promote pancreatic cancer progression and may represent a potential clinical target. [Read the Full Post]

PPARβ/δ activation protects against corticosterone-induced ER stress in astrocytes by inhibiting the CpG hypermethylation of microRNA-181a

1570 | Dec 10 2018

Ji J et al. suggested that PPARβ/δ activation in astrocytes might be a promising target for regulating ER stress-induced astrocytic injury. [Read the Full Post]

Parthenolide inhibits the initiation of experimental autoimmune neuritis

1498 | Dec 09 2018

Zhang M et al. indicated that PAR plays dual roles in EAN and it is not proper to be applied in autoimmune diseases of nervous system. [Read the Full Post]

PARP inhibition attenuates early brain injury through NF-κB/MMP-9 pathway in a rat model of subarachnoid hemorrhage

2061 | Dec 05 2018

Chen T et al. indicated that PARP inhibition through PJ34 might be an important therapeutic drug for SAH. [Read the Full Post]

Release of Moxifloxacin from Contact Lenses Using an In Vitro Eye Model: Impact of Artificial Tear Fluid Composition and Mechanical Rubbing

615 | Nov 29 2018

Phan CM et al. suggested that sophisticated in vitro models are necessary to adequately model on-eye drug release from CL materials. [Read the Full Post]

Effects of the histone deacetylase inhibitor 'Scriptaid' on the developmental competence of mouse embryos generated through round spermatid injection

1102 | Nov 11 2018

Kong P et al. supported through grants from the National Key Research Program of China (No. 2016YFC1304800); the National Natural Science Foundation of China (Nos: 81170756, 81571486); the Natural Science Foundation of Shanghai (Nos: 15140901700, 15ZR1424900) and the Programme for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning. There are no conflicts of interest to declare. [Read the Full Post]

Identification of the Serine Biosynthesis Pathway as a Critical Component of BRAF Inhibitor Resistance of Melanoma, Pancreatic, and Non-Small Cell Lung Cancer Cells

849 | Nov 08 2018

The novel aspects of this study are the direct identification of serine biosynthesis as a critical mechanism of BRAF V600E inhibitor resistance and the first successful example of using gemcitabine + BRAFis in combination to kill previously drug-resistant cancer cells, creating the translational potential of pretreatment with gemcitabine prior to BRAFi treatment of tumor cells to reverse resistance within the mutational profile and the WT. [Read the Full Post]

Curcumin and its cyclohexanone analogue inhibited human Equilibrative nucleoside transporter 1 (ENT1) in pancreatic cancer cells

1946 | Nov 08 2018

Revalde JL et al. concluded that curcumin and A13 are inhibitors of the ENT1 transporter, but only at high concentrations (2-20µM). [Read the Full Post]

Synergistic anti-cancer effects of epigenetic drugs on medulloblastoma cells

1043 | Nov 03 2018

Yuan J et al. suggested that the application of HDACi in combination with drugs that target DNMT may represent a promising option for the treatment of medulloblastoma. [Read the Full Post]

Double-loop hairpin probe and doxorubicin-loaded gold nanoparticles for the ultrasensitive electrochemical sensing of microRNA

532 | Oct 26 2018

Tao Y et al. found that the miRNA was capable of being detected in a limit of 0.17pM and other kinds of miRNA were discriminated facilely by this method. [Read the Full Post]

Allogeneic islet cells implant on poly-l-lactide matrix to reduce hyperglycaemia in streptozotocin-induced diabetic rat

0 | Oct 22 2018

Hendrawan S et al. indicated the islet cell matrix implant reduced the blood glucose levels although complete normo-glycaemia was not established. The islet cell matrix implant may serve as an additional option for islet cell transplantation using 3D scaffold platforms for better survival and function of the islet cells. [Read the Full Post]

Allogeneic islet cells implant on poly-l-lactide matrix to reduce hyperglycaemia in streptozotocin-induced diabetic rat

678 | Oct 19 2018

Hendrawan S et al. found that 82% of seeded islet cells attached to the matrices. In the IMI group blood glucose levels were significantly reduced after implantation compared with before implantation across several time points. In the IMI group beta-cells and insulin-positive cells were identified at the implant site. [Read the Full Post]

Romidepsin induces G2/M phase arrest via Erk/cdc25C/cdc2/cyclinB pathway and apoptosis induction through JNK/c-Jun/caspase3 pathway in hepatocellular carcinoma cells

956 | Oct 13 2018

Sun WJ et al. offered proof-of-concept for use of Romidepsin as a novel class of chemotherapy in the treatment of HCC. [Read the Full Post]

Artesunate enhances the therapeutic response of glioma cells to temozolomide by inhibition of homologous recombination and senescence

902 | Oct 07 2018

Berte N et al. showed the amelioration of TMZ-induced cell death upon ART co-treatment provides a rational basis for a combination regime of TMZ and ART in glioblastoma therapy. [Read the Full Post]

Modification of tumour cell metabolism modulates sensitivity to Chk1 inhibitor-induced DNA damage

684 | Oct 05 2018

Massey AJ suggested the expression and activation of Chk1 kinase is associated with cells undergoing active DNA replication. Glutamine starvation rendered tumour cells more resistant to Chk1 inhibitor-induced DNA damage and reversal of the glutamine starvation restored the sensitivity of tumour cells to Chk1 inhibitor-induced DNA damage. Chk1 inhibitors may be a potentially useful therapeutic treatment for patients whose tumours contain a high fraction of replicating cells. [Read the Full Post]

ATM induces MacroD2 nuclear export upon DNA damage

1526 | Oct 03 2018

Golia B et al. identified a novel feedback regulation between two crucial DNA damage-induced signaling pathways: ADP-ribosylation and ATM activation. [Read the Full Post]

DW09849, a selective phosphatidylinositol 3-kinase (PI3K) inhibitor, prevents PI3K signaling and preferentially inhibits proliferation of cells containing the oncogenic mutation p110α (H1047R).

753 | Sep 22 2018

Liu JL et al. suggested that DW series compounds, especially DW09849, selectively targeting PI3Kα with less off-target effects than PIK-75, provide new clues for the design and discovery of new specific PI3Kα inhibitors for cancer therapy. [Read the Full Post]

Short-term high-fat feeding induces islet macrophage infiltration and β-cell replication independently of insulin resistance in mice

811 | Sep 21 2018

Woodland DC et al. suggested the existence of MΦ-mediated mechanisms in β-cell replication that are independent of insulin resistance. [Read the Full Post]

SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway

0 | Sep 20 2018

Wang J et al. demonstrated that SIRT1 and its activator, RSV, have clear anti-hyperuricemia functions in this mouse model. [Read the Full Post]

Triptolide decreases expression of latency-associated nuclear antigen 1 and reduces viral titers in Kaposi's sarcoma-associated and herpesvirus-related primary effusion lymphoma cells

612 | Aug 30 2018

Long C et al. indicated that triptolide impairs the expression of LANA1 and shows antitumor activity against PEL in vitro and in vivo. Triptolide may be a potential agent for treatment of PEL. [Read the Full Post]

Inhibition of PARP-1 participates in the mechanisms of propofol-induced amnesia in mice and human

976 | Aug 18 2018

Jia L et al. illustrated a potential translational research bridging animal models and human studies. [Read the Full Post]

Acquired CDK6 amplification promotes breast cancer resistance to CDK4/6 inhibitors and loss of ER signaling and dependence

0 | Aug 14 2018

Yang C et al. suggested that the clinical paradigm of sequential endocrine-based therapy may be ineffective in some settings of acquired CDK4/6 resistance. [Read the Full Post]

Characterization of cholesterol homeostasis in sphingosine-1-phosphate lyase-deficient fibroblasts reveals a Niemann-Pick disease type C-like phenotype with enhanced lysosomal Ca2+ storage

0 | Aug 08 2018

Vienken H et al. showed that both a primary defect in cholesterol trafficking and S1P lyase deficiency cause overlapping phenotypic alterations, and challenge the present view on the role of sphingosine in lysosomal Ca2+ homeostasis. [Read the Full Post]

Histone Deacetylase Inhibitor RGFP109 Overcomes Temozolomide Resistance by Blocking NF-κB-Dependent Transcription in Glioblastoma Cell Lines

0 | Aug 08 2018

Li ZY et al. showed that RGFP109, an HDAC inhibitor, in combination with TMZ may be a therapeutic candidate for patients with temozolomide-resistant GBM. [Read the Full Post]

The role of Runx2 in facilitating autophagy in metastatic breast cancer cells

1347 | Aug 05 2018

Tandon M et al. revealed a novel regulatory mechanism of autophagy via Runx2 and provide molecular insights into the role of autophagy in metastatic cancer cells. [Read the Full Post]

Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma

704 | Aug 04 2018

Mersch S et al. described for the first time the establishment and characterization of a liposarcoma cell line derived from a peritoneal sarcomatosis. Hence, in the future, the newly established cell line Lipo-DUE1 might serve as a useful in vitro and in vivo model to investigate the biological behavior of liposarcoma and to assess novel targeted therapies. [Read the Full Post]

AR-42 induces apoptosis in human hepatocellular carcinoma cells via HDAC5 inhibition

1600 | Aug 02 2018

Zhang M et al. demonstrated for the first time that AR-42 targets HDAC5 and induces apoptosis in human hepatocellular carcinoma cells. AR-42 therefore shows potential as a new drug candidate for HCC therapy. [Read the Full Post]

HDAC6 promotes cell proliferation and confers resistance to temozolomide in glioblastoma

1283 | Aug 01 2018

Wang Z et al. suggested that the inhibition of HDAC6 may be a promising strategy for the treatment of glioblastoma. [Read the Full Post]

HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions

4185 | Jul 31 2018

Yu J et al. suggested that HDAC6 inhibition is a potent therapeutic strategy against inflammatory injury to endothelial cells. [Read the Full Post]

The histone deacetylase inhibitor valproic acid inhibits NKG2D expression in natural killer cells through suppression of STAT3 and HDAC3

1220 | Jul 31 2018

Ni L et al. showed that VPA is a potent inhibitor of STAT3 phosphorylation and demonstrate that histone acetylation and STAT3 tyrosine705 phosphorylation cooperate in regulating NKG2D expression in NK cells. [Read the Full Post]

The HDAC inhibitor SB939 overcomes resistance to BCR-ABL kinase Inhibitors conferred by the BIM deletion polymorphism in chronic myeloid leukemia

1215 | Jul 22 2018

Rauzan M et al. demonstrated that SB939 overcomes BIM deletion polymorphism-induced TKI resistance, and suggest that SB939 may be useful in treating CML patients with BIM deletion-associated TKI resistance. [Read the Full Post]

Therapeutic fetal-globin inducers reduce transcriptional repression in hemoglobinopathy erythroid progenitors through distinct mechanisms

1219 | Jul 22 2018

Dai Y et al. identified clinical-stage oral therapeutics which inhibit or displace major co-repressors of γ-globin gene transcription and may suggest a rationale for combination therapy to produce enhanced efficacy. [Read the Full Post]

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay

0 | Jul 20 2018

Laporte AN, et al. indicated this assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known. [Read the Full Post]

Ribonucleotide Reductase Catalytic Subunit M1 (RRM1) as a Novel Therapeutic Target in Multiple Myeloma

709 | Jul 15 2018

Sagawa M et al. demonstrated that RRM1 is a novel therapeutic target in multiple myeloma in the preclinical setting and provide the basis for clinical evaluation of RRM1 inhibitor, alone or in combination with DNA-damaging agents, to improve patient outcome in multiple myeloma. [Read the Full Post]

Resveratrol Attenuates Aβ25-35 Caused Neurotoxicity by Inducing Autophagy Through the TyrRS-PARP1-SIRT1 Signaling Pathway

3236 | Jul 04 2018

Deng H, et al. indicated RSV attenuated neurotoxicity caused by Aβ25-35 through inducing autophagy in PC12 cells, and the autophagy was partially mediated via activation of the TyrRS-PARP1-SIRT1 signaling pathway. [Read the Full Post]

Loss of α-Tubulin Acetylation Is Associated with TGF-β-induced Epithelial-Mesenchymal Transition

4457 | Jul 03 2018

Gu S et al. demonstrated that acetylated α-tubulin can serve as a marker of EMT and that HDAC6 represents an important regulator during EMT process. [Read the Full Post]

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

0 | Jul 03 2018

Meng Z, et al. indicated that PTEN activation by inhibiting HDAC6 significantly contributed to tumour inhibition. Therefore, non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. [Read the Full Post]

Therapeutic effects of histone deacetylase inhibitors in a murine asthma model

1245 | Jun 28 2018

Ren Y, et al. suggested that treatment with HDAC inhibitors can reduce airway inflammation, airway remodeling, and airway hyperresponsiveness in chronic allergic airway disease in mice. [Read the Full Post]

LTR12 promoter activation in a broad range of human tumor cells by HDAC inhibition

1312 | Jun 28 2018

Krönung SK et al. showed that inhibition of HDAC1-3 is sufficient for LTR12 activation. Importantly, HDAC inhibitors induce LTR12 activity not only in testicular cancer cells, but also in cells derived from many additional tumor species. Finally, we characterize the transcription factor NF-Y as a mediator of LTR12 promoter activity and HDAC inhibitor-induced apoptosis, in the context of widespread genomic binding of NF-Y to specific LTR12 sequences. Thus, HDAC inhibitor-driven LTR12 activation represents a generally applicable means to induce proapoptotic genes in human cancer cells. [Read the Full Post]

HDAC5, a potential therapeutic target and prognostic biomarker, promotes proliferation, invasion and migration in human breast cancer

1319 | Jun 27 2018

Li A et al. indicated that HDAC5 is a promising prognostic marker and drug target for BC and that the combination of LMK-235 and bortezomib presents a novel therapeutic strategy for BC. [Read the Full Post]

HPOB, an HDAC6 inhibitor, attenuates corticosterone-induced injury in rat adrenal pheochromocytoma PC12 cells by inhibiting mitochondrial GR translocation and the intrinsic apoptosis pathway

1107 | Jun 26 2018

Li ZY et al. suggested that the anti-apoptotic activity of HDAC6 inhibition against the mitochondria-mediated impairment pathway might be mechanistically linked to the hyperacetylation of Hsps and consequent suppression of GR translocation to the mitochondria. [Read the Full Post]

Investigation of MTH1 activity via mismatch-based DNA chain elongation

822 | Jun 26 2018

As the method is designed directly towards the cellular function of MTH1, activity of MTH1 in different breast cancer cell lines has been detected, implying the potential application of this assay method for biomedical research and clinical diagnose in the future. [Read the Full Post]

Targeting the gyrase of Plasmodium falciparum with topoisomerase poisons

814 | Jun 23 2018

Tang Girdwood SC et al. highlighted the utility of the new methods and of fluoroquinolones as a tool for studying the in situ workings of gyrase and its plDNA substrate. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein-and-Sensitizes-the-Mitochondrial-Apoptotic-Pathway

1480 | Jun 23 2018

Yun T et al. found that histone deacetylase (HDAC) inhibitors, including butyrate, augment Lys-120 acetylation of p53 and thus Apaf-1 expression by inhibiting HDAC1. [Read the Full Post]

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay

0 | Jun 21 2018

Laporte AN et al. reported use of the proximity ligation assay to confirm the oncogenic association of SS18-SSX with its co-factor TLE1 in multiple human synovial sarcoma cell lines and in surgically-excised human tumor tissue. SS18-SSX/TLE1 interactions are disrupted by class I HDAC inhibitors and novel small molecule inhibitors. This assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known. [Read the Full Post]

HDAC6-mediated EGFR stabilization and activation restrict cell response to sorafenib in non-small cell lung cancer cells

1360 | Jun 15 2018

Wang Z et al. explained the failure of Phase III trial of sorafenib in improving overall survival of advanced NSCLC patients and bear possible implications for the improvement on the efficacy of sorafenib in treatment of NSCLC. [Read the Full Post]

N-3 polyunsaturated fatty acids increase hepatic fibroblast growth factor 21 sensitivity via a PPAR-γ-β-klotho pathway

2789 | Jun 11 2018

Yang W et al. indicated n-3 PUFAs increase hepatic FGF21 sensitivity and β-klotho expression probably through a PPAR-γ-dependent mechanism, and may thereby exert hepatic beneficial effects on lipid metabolism. [Read the Full Post]

Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity

2449 | Jun 10 2018

Szczepanowicz K et al. indicated the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity. [Read the Full Post]

Phosphoinositide 3-Kinase Is Involved in Mediating the Anti-inflammation Effects of Vasopressin

1254 | Jun 07 2018

Jan WC et al. confirmed that PI3K, especially the isoforms of PI3Kβ, PI3Kδ, and PI3Kγ, is involved in mediating the anti-inflammatory effects of vasopressin. [Read the Full Post]

Enhanced efficacy of combined HDAC and PARP targeting in glioblastoma

1147 | May 25 2018

Rasmussen RD et al. provided a pre-clinical rationale for combined administration of SAHA and olaparib, which are already individually in clinical trials. [Read the Full Post]

Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells

1251 | May 20 2018

Ma J et al. provided insight into the mechanism of action underlying the synergistic antileukemic activity of ATR inhibition in combination with cytarabine in AML. [Read the Full Post]

Nutlin-3a: A Potential Therapeutic Opportunity for TP53 Wild-Type Ovarian Carcinomas

861 | May 15 2018

Crane EK et al. found that Nutlin-3a could be a potential therapeutic agent for ovarian carcinomas expressing wild-type TP53 and warrants further investigation. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway

0 | May 12 2018

Yun T et al. found that HDAC inhibitors can induce p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]

PPARβ/δ activation protects against corticosterone-induced ER stress in astrocytes by inhibiting the CpG hypermethylation of microRNA-181a

2343 | May 06 2018

Ji J et al. suggested that PPARβ/δ activation in astrocytes might be a promising target for regulating ER stress-induced astrocytic injury. [Read the Full Post]

PPARβ/δ activation protects against corticosterone-induced ER stress in astrocytes by inhibiting the CpG hypermethylation of microRNA-181a

842 | Apr 27 2018

Ji J et al. suggested that PPARβ/δ activation in astrocytes might be a promising target for regulating ER stress-induced astrocytic injury. [Read the Full Post]

Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment

670 | Apr 17 2018

Chaudhari U et al. revealed early expression signatures of genes involved in formation of sarcomeric structures, regulation of ion homeostasis and induction of apoptosis. Eighty-four significantly deregulated genes related to cardiac functions, stress and apoptosis were validated using real-time PCR. The expression of the 84 genes was further studied by real-time PCR in hiPSC-CMs incubated with daunorubicin and mitoxantrone, further anthracycline family members that are also known to induce cardiotoxicity. A panel of 35 genes was deregulated by all three anthracycline family members and can therefore be expected to predict the cardiotoxicity of compounds acting by similar mechanisms as doxorubicin, daunorubicin or mitoxantrone. The identified gene panel can be applied in the safety assessment of novel drug candidates as well as available therapeutics to identify compounds that may cause cardiotoxicity. [Read the Full Post]

Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia

0 | Apr 11 2018

Simioni C et al. indicated that either single or combined administration of drugs against the different targets displayed inhibition of cellular viability associated with a concentration-dependent induction of apoptosis, cell cycle arrest in G0/G1 phase and autophagy, having the combined treatments a significant synergistic cytotoxic effect. Co-targeting NUP214-ABL1 fusion gene and PI3K/Akt/mTOR signaling pathway could represent a new and effective pharmacological strategy to improve the outcome in NUP214-ABL1 positive T-ALL. [Read the Full Post]

Dietary Fisetin Supplementation Protects Against Alcohol-Induced Liver Injury in Mice

1243 | Apr 04 2018

Sun Q et al. suggested that fisetin has a therapeutical potential for treating ALD. [Read the Full Post]

Novel MDM2 inhibitor SAR405838 (MI-773) induces p53-mediated apoptosis in neuroblastoma

900 | Apr 03 2018

Lu J et al. suggested that MDM2-specific inhibitors like SAR405838 may serve not only as a stand-alone therapy, but also as an effective adjunct to current chemotherapeutic regimens for treating NB with an intact MDM2-p53 axis. [Read the Full Post]

Tsc1 expression by dendritic cells is required to preserve T-cell homeostasis and response

0 | Mar 28 2018

Luo Y et al. identified Tsc1 as a crucial signaling checkpoint in DCs essential for preserving T-cell homeostasis and response. [Read the Full Post]

Significance of alpha smooth muscle actin expression in traumatic painful neuromas: a pilot study in rats

873 | Mar 28 2018

Weng W et al. provided new insights into the development of new treatment modalities for the management of intractable painful neuromas. [Read the Full Post]

Nanoformulation of Olaparib Amplifies PARP Inhibition and Sensitizes PTEN/TP53-Deficient Prostate Cancer to Radiation

1442 | Mar 24 2018

van de Ven AL et al. suggested that NanoOlaparib may be a promising new strategy for enhancing the radiosensitivity of radiation-resistant tumors lacking BRCAmutations, such as those with PTEN and TP53 deletions. [Read the Full Post]

cAMP signaling increases histone deacetylase 8 expression via the Epac2-Rap1A-Akt pathway in H1299 lung cancer cells

1310 | Mar 14 2018

Park JY et al. indicated the Epac-Rap1-Akt pathway mediates cAMP signaling-induced inhibition of JNK-dependent HDAC8 degradation, and the resulting HDAC8 increase augments cisplatin-induced apoptosis by repressing TIPRL expression in H1299 lung cancer cells. [Read the Full Post]

Panobinostat induces apoptosis via production of reactive oxygen species and synergizes with topoisomerase inhibitors in cervical cancer cells

0 | Mar 10 2018

Wasim L et al. suggest a combination therapy using inhibitors of histone deacetylase and topoisomerase together could hold the promise for an effective targeted therapeutic strategy. [Read the Full Post]

Valproic acid potentiates the anticancer activity of capecitabine in vitro and in vivo in breast cancer models via induction of thymidine phosphorylase expression

1739 | Mar 10 2018

Terranova-Barberio M et al. suggested that the combination of HDACi (e.g., VPA) and capecitabine is an innovative antitumor strategy that warrants further clinical evaluation for the treatment of metastatic breast cancer. [Read the Full Post]

In Vitro Antibacterial Activity of Rhodanine Derivatives against Pathogenic Clinical Isolates

1364 | Mar 08 2018

AbdelKhalek A et al. suggested that certain rhodanine compounds may have potential use for the treatment of several multidrug-resistant Gram-positive bacterial infections. [Read the Full Post]

Characterization of osimertinib (AZD9291)-resistant non-small cell lung cancer NCI-H1975/OSIR cell line

1586 | Mar 03 2018

Tang ZH et al. showed that EGFR could pose as one of the OSI-resistant mechanisms and navitoclax might be the candidate drug for OSI-resistant NSCLC patients. [Read the Full Post]

Kras mutations increase telomerase activity and targeting telomerase is a promising therapeutic strategy for Kras-mutant NSCLC

811 | Mar 01 2018

Liu W et al. suggested that Kras mutations increase telomerase activity and telomere length by activating the RAS/MEK pathway, which contributes to an aggressive phenotype of NSCLC. Kras mutations-induced lung tumorigenesis and chemoresistance are attenuated by telomerase inhibition. Targeting telomerase/telomere may be a promising therapeutic strategy for patients with Kras-mutant NSCLC. [Read the Full Post]

A simple, fast, label-free colorimetric method for detection of telomerase activity in urine by using hemin-graphene conjugates

992 | Feb 28 2018

Xu X et al. found a colorimetric approach affords simplicity, sensitivity and reliability in telomerase activity detection. [Read the Full Post]

Phosphorylation-mediated activation of LDHA promotes cancer cell invasion and tumour metastasis

750 | Feb 26 2018

Jin L et al. demonstrated that LDHA phosphorylation and activation provide pro-invasive, anti-anoikis and pro-metastatic advantages to cancer cells, suggesting that Y10 phosphorylation of LDHA may represent a promising therapeutic target and a prognostic marker for metastatic human cancers. [Read the Full Post]

TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2 signalling

725 | Feb 22 2018

Wang B et al. revealed a GβL-ubiquitination-dependent switch that fine-tunes the dynamic organization and activation of the mTORC2 kinase under both physiological and pathological conditions. [Read the Full Post]

Effective combinatorial immunotherapy for castration-resistant prostate cancer

1726 | Feb 21 2018

Xin Lu et al. illuminated a clinical path hypothesis for combining immune checkpoint blockade with MDSC-targeted therapies in the treatment of mCRPC. [Read the Full Post]

The PI3K/Akt/mTOR pathway is involved in CVB3-induced autophagy of HeLa cells

1663 | Feb 09 2018

Chang H et al. suggested that the PI3K/Akt/mTOR signaling pathway participates in the process of autophagy induced by CVB3 infection. This finding may provide a new perspective of CVB3-induced autophagy. [Read the Full Post]

Epigenetic Regulation of Interleukin 6 by Histone Acetylation in Macrophages and Its Role in Paraquat-Induced Pulmonary Fibrosis

3210 | Feb 06 2018

Hu L et al. indicated IL-6 functioning through EMT in PQ-induced pulmonary fibrosis was regulated dynamically by HDAC and HAT both in vitro and in vivo via epigenetically regulating chromatin accessibility. [Read the Full Post]

Inhibition of mTOR suppresses human gallbladder carcinoma cell proliferation and enhances the cytotoxicity of 5-fluorouracil by downregulating MDR1 expression

0 | Feb 03 2018

Li Q, et al. found that dual mTORC1/mTORC2 inhibitors such as OSI-027 are promising therapeutic agents in combination with 5-FU for the treatment of human gallbladder cancer. [Read the Full Post]

A novel HDAC6 inhibitor Tubastatin A: Controls HDAC6-p97/VCP-mediated ubiquitination-autophagy turnover and reverses Temozolomide-induced ER stress-tolerance in GBM cells

1966 | Jan 27 2018

Li ZY et al. showed that the balance of HDAC6-p97/VCP was crucial to ERST-associated TMZ resistance and that HDAC6 inhibition might be a synergistic target and strategy along with TMZ for the improvement of clinical glioma treatment. [Read the Full Post]

Efficacy of continuous EGFR-inhibition and role of Hedgehog in EGFR acquired resistance in human lung cancer cells with activating mutation of EGFR

0 | Jan 20 2018

Della Corte CM et al. found that EGFR-mutant NSCLC can benefit from continuous treatment with EGFR-inhibitors, indepenently from mechanisms of resistance [Read the Full Post]

Targeting DNA repair with aphidicolin sensitizes primary chronic lymphocytic leukemia cells to purine analogs

1583 | Jan 19 2018

Starczewska E et al. indicated that aphidicolin potentiates the cytotoxicity of purine analogs by inhibiting a DNA repair pathway that involves DNA polymerases, most likely NER, and provide a rationale for manipulating it to therapeutic advantage. [Read the Full Post]

Development of novel PET probes targeting phosphatidylinositol 3-kinase (PI3K) in tumors

1247 | Jan 18 2018

Makino A et al. represented the first trial of a PET tracer for detecting PI3K. Although further improvement of the probe is required prior to clinical application, these results should encourage future work. [Read the Full Post]

DNA damage response curtails detrimental replication stress and chromosomal instability induced by the dietary carcinogen PhIP

1210 | Jan 18 2018

Mimmler M et al. supported the notion that ATR plays a key role in the defense against cancer formation induced by PhIP and related HCAs. [Read the Full Post]

CQ synergistically sensitizes human colorectal cancer cells to SN-38/CPT-11 through lysosomal and mitochondrial apoptotic pathway via p53-ROS cross-talk

0 | Jan 17 2018

Chen P et al. combined treatment might represent an attractive therapeutic strategy for the treatment of CRC. [Read the Full Post]

Probing the interactions of mitoxantrone with biomimetic membranes with electrochemical and spectroscopic techniques

915 | Jan 13 2018

Dorota Nieciecka et al. showed that this approach allowed us to discriminate between the drug interactions with hydrophilic head-group region and hydrophobic alkyl chains moiety of such monolayers. [Read the Full Post]

Epigenetic silencing of miR-137 induces drug resistance and chromosomal instability by targeting AURKA in multiple myeloma

1715 | Jan 09 2018

Qin Y et al. demonstrated that miR-137 is epigenetically silenced in MM, and overexpression of miR-137 could reduce drug resistance and overcome chromosomal instability of the MM cells via affecting the apoptosis and DNA damage pathways. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway

0 | Jan 03 2018

Yun T et al. induced p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]

BCL6 modulation of acute lymphoblastic leukemia response to chemotherapy

1248 | Dec 27 2017

Slone WL et al. suggested that BCL6 is one factor, modulated by microenvironment derived cues that may contribute to regulation of ALL therapeutic response. [Read the Full Post]

Endosulfan induces cell dysfunction through cycle arrest resulting from DNA damage and DNA damage response signaling pathways

1804 | Dec 26 2017

Ni L et al. provided a new insight for mechanism of endosulfan-induced cardiovascular toxicity which will be helpful in future prevention of cardiovascular diseases induced by endosulfan. [Read the Full Post]

G-quadruplex-based fluorometric biosensor for label-free and homogenous detection of protein acetylation-related enzymes activities

1277 | Dec 26 2017

The potency of this assay is further demonstrated by detecting HAT/HDAC activity in cell lysates and evaluating HAT and HDAC-targeted inhibitors, C464 and EX 527, respectively. [Read the Full Post]

Combined use of irinotecan with histone deacetylase inhibitor belinostat could cause severe toxicity by inhibiting SN-38 glucuronidation via UGT1A1

1967 | Dec 23 2017

Wang L et al. found the potential clinical significance, as a large proportion of patients could be at risk of developing severe toxicity if irinotecan is co-administered with belinostat. [Read the Full Post]

DNA Damage Response in Human Stem Cells and Neural Descendants

1228 | Dec 23 2017

Wei J et al. demonstrated that these processes exhibit spatiotemporal evolution during cell differentiation. [Read the Full Post]

Ubiquitination and regulation of AURKA identifies a hypoxia-independent E3 ligase activity of VHL

1700 | Dec 19 2017

Hasanov E et al. identified VHL as an E3 ligase with important cellular functions under both normoxic and hypoxic conditions. [Read the Full Post]

PKCiota promotes ovarian tumor progression through deregulation of cyclin E

1868 | Dec 19 2017

Nanos-Webb A et al. identified a PI3K/PKCiota/cyclin E signaling pathway as a therapeutic target during ovarian tumorigenesis. [Read the Full Post]

Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells

1249 | Dec 17 2017

Ma J et al. provided insight into the mechanism of action underlying the synergistic antileukemic activity of ATR inhibition in combination with cytarabine in AML. [Read the Full Post]

CK2α' Drives Lung Cancer Metastasis by Targeting BRMS1 Nuclear Export and Degradation

0 | Dec 02 2017

Liu Y et al. identified a therapeutically exploitable posttranslational mechanism by which CK2α-mediated degradation of BRMS1 promotes metastases in lung cancer. [Read the Full Post]

Inflammatory CXCL12-CXCR4/CXCR7 axis mediates G-protein signaling pathway to influence the invasion and migration of nasopharyngeal carcinoma cells

0 | Nov 12 2017

Qiao N et al. provided key evidence for NPC aetiology which can be further investigated to develop novel molecular targets for NPC treatments. [Read the Full Post]

BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity

1263 | Nov 02 2017

Rasmussen RD et al. proposed that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which may represent a novel paradigm for therapeutic intervention in GBM. [Read the Full Post]

Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations

1325 | Oct 28 2017

Yalon M et al. showed that combination of vorinostat and ABT-888 could potentially prove useful for treatment of cancer with innate resistance to PARPis due to active HRR machinery, while the combination of vorinostat and 6-TG could potentially overcome innate or acquired resistance to PARPis due to secondary or reversal BRCA mutations, to decreased PARP-1 level or to increased expression of multiple drug resistant proteins. [Read the Full Post]

Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells

1039 | Oct 26 2017

Bista R et al. provided evidence that DSF/Cu2+ overcomes Ara-C and BTZ resistance in cell lines from DS-AMKL patients. A novel mutation underlying BTZ resistance was detected that may identify BTZ-resistant patients, who may not benefit from treatment with CFZ or Ara-C, but may be responsive to DSF/Cu2+. Our findings support the clinical development of DSF/Cu2+ as a less toxic efficacious treatment approach in patients with relapsed/refractory DS-AMKL. [Read the Full Post]

MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated

1526 | Oct 26 2017

Smida M et al. showed that ATM mutational status in lung cancer is a mechanistic biomarker for MEK inhibitor response, which may improve patient stratification and extend the applicability of these drugs beyond RAS and BRAF mutant tumours. [Read the Full Post]

Chemotherapy-induced Dkk-1 expression by primary human mesenchymal stem cells is p53 dependent

1673 | Oct 23 2017

Hare I et al. indicated that Dkk-1 has been shown to promote tumor growth in several models of malignancy, suggesting that MSC-derived Dkk-1 could counteract the intent of cytotoxic chemotherapy, and that pharmacologic inhibition of Dkk-1 in patients receiving chemotherapy treatment for certain malignancies may be warranted. [Read the Full Post]

ABT-888 and quinacrine induced apoptosis in metastatic breast cancer stem cells by inhibiting base excision repair via adenomatous polyposis coli

1705 | Oct 22 2017

Siddharth S et al. showed that increased APC physically interacts with PARP-1 and inhibits PARylation causing the non assembly of base excision repair (BER) multiprotein complex, resulting in an irreparable DNA damage and subsequent apoptosis. Knockdown of APC in mBCSCs inhibited DNA damage, increased BER and PARylation, reduces apoptosis while the over-expression of APC in BT20 (APC low expressing) cells reversed the effect. Thus, combination of QC and ABT-888 decreased mBCSCs growth by activating APC and inhibiting BER within the cells. [Read the Full Post]

Synthetic Lethality Exploitation by an Anti-Trop-2-SN-38 Antibody-Drug Conjugate, IMMU-132, Plus PARP Inhibitors in BRCA1/2-wild-type Triple-Negative Breast Cancer

1735 | Oct 20 2017

Cardillo TM et al. demonstrated the added benefit of combining Topo I inhibition mediated by IMMU-132 with synthetic lethality provided by PARPi in TNBC, regardless of BRCA1/2 status, thus supporting the rationale for such a combination clinically. [Read the Full Post]

The Tumor-Associated Glycosyltransferase ST6Gal-I Regulates Stem Cell Transcription Factors and Confers a Cancer Stem Cell Phenotype

1405 | Oct 14 2017

Schultz MJ et al. found that ST6Gal-I induced expression of the key tumor-promoting transcription factors, Sox9 and Slug [Read the Full Post]

Inhibition of Extracellular Calcium Influx Results in Enhanced IL-12 Production in LPS-Treated Murine Macrophages by Downregulation of the CaMKKβ-AMPK-SIRT1 Signaling Pathway

1372 | Oct 05 2017

Liu X et al. demonstrated a new role of transmembrane calcium mobilization in immunity modulation such that inhibition of calcium influx leads to impaired activation of CaMKKβ-AMPK-SIRT1 signaling pathway which lifts restriction on NF-κB activation and results in enhanced IL-12 production. [Read the Full Post]

STAT1 as a downstream mediator of ERK signaling contributes to bone cancer pain by regulating MHC II expression in spinal microglia

1866 | Oct 04 2017

Song Z et al. suggested that STAT1 contributes to bone cancer pain as a downstream mediator of ERK signaling by regulating MHC II expression in spinal microglia. [Read the Full Post]

PARP inhibitor increases chemosensitivity by upregulating miR-664b-5p in BRCA1-mutated triple-negative breast cancer

1012 | Oct 02 2017

Song W et al. showed that miR-664b-5p functions as a tumour suppressor and has an important role in the regulation of PARP inhibitors to increase chemosensitivity by targeting CCNE2. This may be one of the possible mechanisms by which PARP inhibitors increase chemosensitivity in BRCA1-mutated TNBC. [Read the Full Post]

Preparation and Biochemical Analysis of Classical Histone Deacetylases

0 | Sep 28 2017

Mohseni J et al. established methods for assaying HDAC activities, as well as introduces more recently developed nontraditional assays. [Read the Full Post]

Preparation and Biochemical Analysis of Classical Histone Deacetylases

0 | Sep 28 2017

Villagra A et al. reviewed some of the older established methods for assaying HDAC activities, as well as introduces more recently developed nontraditional assays. [Read the Full Post]

In Silico Analysis Guides Selection of BET Inhibitors for Triple-Negative Breast Cancer Treatment

0 | Sep 27 2017

Perez-Peña J et al. demonstrated the antitumor effect of this new family of compounds in TNBC, paving the way for its future clinical development. [Read the Full Post]

Evaluation of the Therapeutic Potential of the Novel Isotype Specific HDAC Inhibitor 4SC-202 in Urothelial Carcinoma Cell Lines.

1835 | Sep 17 2017

Pinkerneil M et al. combined inhibition of HDAC1, HDAC2 and HDAC3 seems to be a promising treatment strategy for UC. [Read the Full Post]

Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients

0 | Sep 16 2017

Mohseni J et al. showed that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene. [Read the Full Post]

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay

2011 | Aug 27 2017

Laporte AN et al. report use of the proximity ligation assay to confirm the oncogenic association of SS18-SSX with its co-factor TLE1 in multiple human synovial sarcoma cell lines and in surgically-excised human tumor tissue. SS18-SSX/TLE1 interactions are disrupted by class I HDAC inhibitors and novel small molecule inhibitors. This assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known. [Read the Full Post]

Brain-Penetrating Histone Deacetylase Inhibitor RG2833 Reduces the Viability of Human Malignant Melanoma Cell Lines SK-MEL-5 and SK-MEL-28 in vitro

1974 | Aug 24 2017

Lauren Green found that concentrations of RG2833 that effectively inhibited HDAC activity also resulted in reduced melanoma cell growth and viability. These results demonstrate the effectiveness of RG2833 in reducing the growth and viability of malignant melanoma cells in vitro and warrant further investigation of the potential therapeutic use of RG2833 and related compounds in the battle against cancer. [Read the Full Post]

Sodium phenylbutyrate antagonizes prostate cancer through the induction of apoptosis and attenuation of cell viability and migration

2062 | Aug 23 2017

Xu Y et al. found that the viability of PCa cells was significantly inhibited by SPB treatment. As illustrated by flow cytometry, for DU145 cell line the average apoptotic rate of SPB-treated cells was significantly lower than that of the control group (P<0.05); similar results were also seen for PC3 (P<0.05). SPB administration also attenuated the colony formation and migration abilities in both cell lines. The expression level of survivin in SPB-treated cells was significantly downregulated, while the phosphorylation of p-38 and ERK was enhanced. Furthermore, in vivo tumor formation of both cell lines was suppressed by SPB as well. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway

2418 | Aug 23 2017

Yun T et al. found that histone deacetylase (HDAC) inhibitors, including butyrate, augment Lys-120 acetylation of p53 and thus Apaf-1 expression by inhibiting HDAC1. In p53-null cells, transfection of wild-type but not K120R mutant p53 can restore the p53-dependent sensitivity to butyrate. Strikingly, transfection of acetylation-mimicking K120Q mutant p53 is sufficient to up-regulates Apaf-1 in a manner independent of butyrate treatment. Therefore, HDAC inhibitors can induce p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]

Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

2010 | Aug 20 2017

Isono M et al. showed that AZD7762 enhanced sensitivity of urothelial carcinoma cells to gemcitabine by inhibiting DNA repair and disturbing checkpoints. Combining gemcitabine with CHK1 inhibition holds promise for urothelial cancer therapy. [Read the Full Post]

Plasmonic nanocarrier grid-enhanced Raman sensor for studies of anticancer drug delivery

1516 | Aug 20 2017

Kurzątkowska K et al. demonstrated that the proposed nanocarrier SERS sensor can be utilized to investigate attachment of targeting ligands to nanocarriers (attachment of folic acid ligand recognized by folate receptors of cancer cells is described). Further testing of the nanocarrier SERS sensor involved drug release induced by lowering pH and increasing GSH levels, both occurring in cancer cells. The proposed sensor can be utilized for a variety of drugs and targeting ligands, including those which are Raman inactive, since the linkers can act as the Raman markers, as illustrated with mercaptobenzoic acid and para-aminothiophenol. [Read the Full Post]

Hyperactivation of ATM upon DNA-PKcs inhibition modulates p53 dynamics and cell fate in response to DNA damage

0 | Aug 19 2017

Finzel A et al. revealed a new regulatory interplay in which loss of DNA-PKcs function leads to hyperactivation of ATM and amplification of the p53 response, sensitizing cells for damage-induced senescence. [Read the Full Post]

Nuclear PTEN interferes with binding of Ku70 at double-strand breaks through post-translational poly(ADP-ribosyl)ation

1122 | Aug 14 2017

Guan J, et al. provided contributes to understanding the effect of PTEN in repair of DSB and using defined anti-tumor DSB drugs to treat tumor cells with aberrant PTEN. [Read the Full Post]

Cestrum nocturnum Flower Extracts Attenuate Proliferation and Induce Apoptosis in Malignant Cells through Inducing DNA Damage and Inhibiting Topoisomerase II Activity

1109 | Jul 30 2017

Wu DP et al. suggested that fractions C4 and C5 may represent important sources of potential antitumor agents due to their pronounced antitumor effects and low immune toxicity. [Read the Full Post]

Reconstructing the temporal progression of HIV-1 immune response pathways.

0 | Jul 29 2017

Jain S et al. experimentally validated several of TimePaths' predictions highlighting the usefulness of temporal models. [Read the Full Post]

Common and unique genetic interactions of the poly(ADP-ribose) polymerases PARP1 and PARP2 with DNA double-strand break repair pathways.

0 | Jul 22 2017

Ghosh R et al. highlighted specific nonoverlapping functions of PARP1 and PARP2 at H2AX-deficient chromatin during replicative phases of the cell cycle and uncover a unique requirement for PARP1 in NHEJ-deficient cells. [Read the Full Post]

Panobinostat induces apoptosis via production of reactive oxygen species and synergizes with topoisomerase inhibitors in cervical cancer cells

2163 | Jul 20 2017

Wasim L et al. suggested a combination therapy using inhibitors of histone deacetylase and topoisomerase together could hold the promise for an effective targeted therapeutic strategy. [Read the Full Post]

Persistent GP130/STAT3 Signaling Contributes to the Resistance of Doxorubicin, Cisplatin, and MEK Inhibitor in Human Rhabdomyosarcoma Cells

0 | Jul 19 2017

Wu X et al. demonstrated that GP130/STAT3 signaling contributes to the resistance of these drugs in rhabdomyosarcoma cells. They also suggested a potentially novel cancer therapeutic strategy using the combination of inhibitors of GP130/STAT3 signaling with doxorubicin, cisplatin, or AZD6244 for rhabdomyosarcoma treatments. [Read the Full Post]

Histone deacetylase inhibitor panobinostat induces calcineurin degradation in multiple myeloma

2433 | Jul 19 2017

Imai Y et al. findings underscore the usefulness of calcineurin-targeted therapy in MM patients, including patients who are resistant to bortezomib. [Read the Full Post]

MiR-193a-5p Targets the Coding Region of AP-2α mRNA and Induces Cisplatin Resistance in Bladder Cancers

2722 | Jul 18 2017

Zhou J et al. concluded that miR-193a-5p induced cisplatin resistance by repressing AP-2α expression in bladder cancer cells. [Read the Full Post]

MiR-335 regulates the chemo-radioresistance of small cell lung cancer cells by targeting PARP-1

1669 | Jul 12 2017

Luo Y et al. indicated that miR-335 may serve as a critical regulator of chemo-radiotherapy resistance in SCLC and a new potential therapeutic target. [Read the Full Post]

Persistent GP130/STAT3 Signaling Contributes to the Resistance of Doxorubicin, Cisplatin, and MEK Inhibitor in Human Rhabdomyosarcoma Cells

2149 | Jul 10 2017

Wu X et al. demonstrated that GP130/STAT3 signaling contributes to the resistance of these drugs in rhabdomyosarcoma cells. They also suggested a potentially novel cancer therapeutic strategy using the combination of inhibitors of GP130/STAT3 signaling with doxorubicin, cisplatin, or AZD6244 for rhabdomyosarcoma treatments. [Read the Full Post]

HBXIP, a binding protein of HBx, regulates maintenance of the G2/M phase checkpoint induced by DNA damage and enhances sensitivity to doxorubicin-induced cytotoxicity

1940 | Jul 10 2017

Fei HR et al. suggested that HBXIP can function as a mediator protein for DNA damage response signals to activate the G2/M checkpoint to maintain genome integrity and prevent cell death. [Read the Full Post]

IFN-α potentiates the direct and immune-mediated antitumor effects of epigenetic drugs on both metastatic and stem cells of colorectal cancer

0 | Jul 07 2017

Buoncervello M et al. opened a new frontier on the suitability of IFN-α in association with epigenetics as a novel and promising therapeutic approach for CRC management. [Read the Full Post]

Impact of CTLA-4 blockade in conjunction with metronomic chemotherapy on preclinical breast cancer growth

1822 | Jun 28 2017

Parra K et al. proved Sequential therapy of anti-CTLA-4 followed by gemcitabine is effective in chemotherapy-naive tumours, although tumour relapses can occur, in some cases accompanied by the development of spontaneous metastases. [Read the Full Post]

Phospho-Akt overexpression is prognostic and can be used to tailor the synergistic interaction of Akt inhibitors with gemcitabine in pancreatic cancer

2161 | Jun 27 2017

Massihnia D et al. found that inhibition of Glut1 might overcome resistance to these therapies and warrants further studies. [Read the Full Post]

The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells.

2407 | Jun 26 2017

Nunn AD et al. demonstrated the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome. [Read the Full Post]

Effects of inhibiting PI3K-Akt-mTOR pathway on lipid metabolism homeostasis in goose primary hepatocytes

2358 | Jun 25 2017

Liu DD et al. suggested that the reduction of lipids accumulation induced-by inhibiting PI3K-Akt-mTOR pathway was closely linked to the decrease of lipogenesis, the increase of fatty acids oxidation, and the increase of VLDL assembly and secretion in goose hepatocytes. [Read the Full Post]

BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells

3738 | Jun 25 2017

The immunoblot analysis showed that BEZ235 treatment decreased pAKT, pmTOR and pERK whereas AZD2014 decreased only pmTOR. [Read the Full Post]

Histone Deacetylase Inhibitor RGFP109 Overcomes Temozolomide Resistance by Blocking NF-κB-Dependent Transcription in Glioblastoma Cell Lines

5737 | Jun 18 2017

Li ZY et al. showed that RGFP109, an HDAC inhibitor, in combination with TMZ may be a therapeutic candidate for patients with temozolomide-resistant GBM. [Read the Full Post]

PARP Inhibitor Activity Correlates with SLFN11 Expression and Demonstrates Synergy with Temozolomide in Small Cell Lung Cancer

1359 | Jun 18 2017

Lok BH et al. found that SLFN11 is a relevant predictive biomarker of sensitivity to PARP inhibitor monotherapy in SCLC and we identify combinatorial therapy with TMZ as a particularly promising therapeutic strategy that warrants further clinical investigation. [Read the Full Post]

A role of KIT receptor signaling for proliferation and differentiation of rat stem Leydig cells in vitro

2785 | Jun 15 2017

Liu S et al. found KITL is a growth factor that regulates the development of the stem Leydig cell. [Read the Full Post]

PRRT2 inhibits the proliferation of glioma cells by modulating unfolded protein response pathway

2257 | Jun 12 2017

Bi G et al. found that PRRT2 as a tumor suppressor in glioma and provide a promising target for potential therapeutic intervention. [Read the Full Post]

Registered report: Systematic identification of genomic markers of drug sensitivity in cancer cells

1787 | Jun 10 2017

Vanden Heuvel JP et al. found that cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife. [Read the Full Post]

MiR-335 regulates the chemo-radioresistance of small cell lung cancer cells by targeting PARP-1

1174 | Jun 07 2017

Luo Y et al.found that miR-335 may serve as a critical regulator of chemo-radiotherapy resistance in SCLC and a new potential therapeutic target. [Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

0 | Jun 01 2017

Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]

Levetiracetam mitigates doxorubicin-induced DNA and synaptic damage in neurons

0 | May 29 2017

Manchon JF et al. found that levetiracetam might be part of a valuable new approach for mitigating synaptic damage and, perhaps, for treating cognitive disturbances in cancer patients and survivors. [Read the Full Post]

Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ

0 | May 23 2017

Lin YH et al. showed that PE treatment of NRVMs results in decreased binding of HDAC3 to myofibrils, suggesting a signal-dependent mechanism for the regulation of sarcomere-associated CapZβ1 acetylation. [Read the Full Post]

Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3.

0 | May 10 2017

Leng Y et al. provided a new mechanism via which histone deacetylase 2 and 3 participate in upregulating fibroblast growth factor 21 transcription and extending process outgrowth in glia. [Read the Full Post]

Effect of the BRCA1-SIRT1-EGFR axis on cisplatin sensitivity in ovarian cancer.

0 | May 10 2017

Those results improve Li Det al.'s understanding of the basic molecular mechanism underlying BRCA1-related cisplatin resistance in ovarian cancer. [Read the Full Post]

Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3.

0 | May 09 2017

Leng Y et al. provided a new mechanism via which histone deacetylase 2 and 3 participate in upregulating fibroblast growth factor 21 transcription and extending process outgrowth in glia. [Read the Full Post]

Inhibitory effects of SRT1720 on the apoptosis of rabbit chondrocytes by activating SIRT1 via p53/bax and NF-κB/PGC-1α pathways

1921 | May 02 2017

Liu B et al. suggested that SRT1720 inhibits chondrocyte apoptosis by activating the expression of SIRT1 via p53/bax and NF-κB/PGC-1α pathways. [Read the Full Post]

The histone deacetylase inhibitor PCI-24781 as a putative radiosensitizer in pediatric glioblastoma cell lines

0 | May 01 2017

de Andrade PV et al demonstrate that HDACi PCI-24781 has a radiosensitizing profile that compromises the repair of double-strand DNA breaks in cells of pediatric GBM treated with radiotherapy. [Read the Full Post]

Enhancing glioblastoma cell sensitivity to chemotherapeutics: a strategy involving survivin gene silencing mediated by gemini surfactant-based complexes

0 | Apr 26 2017

Cruz RQ et al showed that survivin downregulation combined with administration of the chemotherapeutic agents temozolomide or etoposide resulted in a synergistic cytotoxic effect, thus revealing to be a promising strategy to reduce the chemotherapeutic doses for GBM treatment. [Read the Full Post]

Inhibitory effects of SRT1720 on the apoptosis of rabbit chondrocytes by activating SIRT1 via p53/bax and NF-κB/PGC-1α pathways

1859 | Apr 25 2017

Liu B et al. suggested that SRT1720 inhibits chondrocyte apoptosis by activating the expression of SIRT1 via p53/bax and NF-κB/PGC-1α pathways. [Read the Full Post]

The PARP inhibitor PJ-34 sensitizes cells to UVA-induced phototoxicity by a PARP independent mechanism

1614 | Apr 22 2017

Lakatos P et al. found that PJ-34 is a photosensitizer and PJ-34+UVA causes DNA damage and caspase-mediated cell death independently of PARP-1 inhibition. [Read the Full Post]

Developmental expression of STATs, nuclear factor-κB and inflammatory genes in the jejunum of piglets during weaning

2751 | Apr 18 2017

Yi H et al found weaning caused severe inflammation associated with activation of the NF-κB and STAT-3 pathways and suppression of STAT-1 and STAT-6 in the jejunum of piglets. [Read the Full Post]

Phosphatidylinositol 3-Kinase/Akt Mediates Integrin Signaling To Control RNA Polymerase I Transcriptional Activity

7246 | Apr 09 2017

Collectively, Wu C et al revealed, for the first time, a pivotal role of integrin signaling in regulation of RNA polymerase I transcriptional activity and shed light on the downstream signaling axis that participates in regulation of this key aspect of cell growth. [Read the Full Post]

A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition

2448 | Apr 06 2017

Kim H et al. demonstrated that CX-4945 is a potent DYRK1A inhibitor and also suggested that it has therapeutic potential for DYRK1A-associated diseases. [Read the Full Post]

Activation of the miR-34a/SIRT1/p53 Signaling Pathway Contributes to the Progress of Liver Fibrosis via Inducing Apoptosis in Hepatocytes but Not in HSCs

1720 | Apr 04 2017

Tian XF et al. found that the miR-34a/SIRT1/p53 signaling pathway might be a promising therapeutic target for liver fibrosis. [Read the Full Post]

Heterogeneous Nuclear Ribonucleoprotein L is required for the survival and functional integrity of murine hematopoietic stem cells

0 | Apr 01 2017

Gaudreau MC et al suggested that hnRNP L is critical for the survival and functional integrity of HSCs by restricting the activation of caspase-dependent death receptor pathways. [Read the Full Post]

Linifanib (ABT-869) Potentiates the Efficacy of Chemotherapeutic Agents through the Suppression of Receptor Tyrosine Kinase-Mediated AKT/mTOR Signaling Pathways in Gastric Cancer

1228 | Mar 23 2017

Chen J et al. suggested that the addition of ABT-869 to traditional chemotherapies may be a promising strategy for the treatment of human gastric cancer. [Read the Full Post]

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

0 | Mar 23 2017

Meng Z et al indicated that PTEN activation by inhibiting HDAC6 significantly contributed to tumour inhibition. Therefore, non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. [Read the Full Post]

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ

2951 | Mar 16 2017

Zhao D et al found that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ. [Read the Full Post]

HDAC4 mediates IFN-γ induced disruption of energy expenditure-related gene expression by repressing SIRT1 transcription in skeletal muscle cells

3488 | Mar 13 2017

Fang M et al revealed a role for HDAC4 in regulating cellular energy output and as such provide insights into rationalized design of novel anti-diabetic therapeutics. [Read the Full Post]

Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways

0 | Mar 13 2017

Sampson VB et al suggested that potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS. [Read the Full Post]

1 | Mar 03 2017

[Read the Full Post]

Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites

2457 | Feb 19 2017

Douglass AN, et al.'s data demonstrate that host-based prophylaxis could be developed into an effective intervention strategy that eliminates LS parasites before the onset of clinical disease and thus opens a [Read the Full Post]

Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition

0 | Feb 17 2017

When compared to the SW13- subtype, SW13+ cells have restored BRM expression, increased metastatic capacity, and significantly different expression of a variety of chromatin remodeling factors including those involved with histone acetylation and methylation. These data are consistent with a multistep mechanism of SW13- to SW13+ conversion and subtype stabilization: histone hypermodification results in the altered expression of chromatin remodeling factors and chromatin epigenetic enzymes and the re-expression of BRM which results in restoration of SWI/SNF complex function and leads to changes in chromatin structure and gene expression that stabilize the SW13+ phenotype. [Read the Full Post]

RNA polymerase I transcription is modulated by spatial learning in different brain regions.

1456 | Feb 08 2017

Capitano F, et al.'s results suggest that de novo rRNA transcription is a necessary step for spatial memory consolidation and that after learning it occurs in several brain regions with a complex spatio-temporal dynamic. This article is protected by copyright. All rights reserved. [Read the Full Post]

Inflammatory CXCL12-CXCR4/CXCR7 axis mediates G-protein signaling pathway to influence the invasion and migration of nasopharyngeal carcinoma cells

0 | Feb 07 2017

Qiao N, et al.'s conclusions may provide key evidence for NPC aetiology which can be further investigated to develop novel molecular targets for NPC treatments. [Read the Full Post]

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

2950 | Jan 27 2017

Meng Z et al. found that non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. [Read the Full Post]

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ

1478 | Jan 23 2017

Zhao D, et al.'s data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ. [Read the Full Post]

Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways

0 | Jan 21 2017

In Sampson VB, et al.'s summary, potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS. [Read the Full Post]

Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites

2758 | Jan 08 2017

Douglass AN, et al.‘’s data demonstrate that host-based prophylaxis could be developed into an effective intervention strategy that eliminates LS parasites before the onset of clinical disease and thus opens a new avenue to prevent malaria. [Read the Full Post]

Inflammatory CXCL12-CXCR4/CXCR7 axis mediates G-protein signaling pathway to influence the invasion and migration of nasopharyngeal carcinoma cells

1703 | Jan 03 2017

Qiao N et al. provided key evidence for NPC aetiology which can be further investigated to develop novel molecular targets for NPC treatments. [Read the Full Post]

RNA polymerase I transcription is modulated by spatial learning in different brain regions.

0 | Jan 03 2017

J Neurochem's results suggested that de novo rRNA transcription is a necessary step for spatial memory consolidation and that after learning it occurs in several brain regions with a complex spatio-temporal dynamic. [Read the Full Post]

The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells

2568 | Dec 27 2016

The results of Nunn AD, et al. demonstrated the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome. [Read the Full Post]

IFN-α potentiates the direct and immune-mediated antitumor effects of epigenetic drugs on both metastatic and stem cells of colorectal cancer

2945 | Dec 22 2016

The findings of Buoncervello M et al. open a new frontier on the suitability of IFN-α in association with epigenetics as a novel and promising therapeutic approach for CRC management. [Read the Full Post]

Common and unique genetic interactions of the poly(ADP-ribose) polymerases PARP1 and PARP2 with DNA double-strand break repair pathways

2232 | Dec 14 2016

Ghosh R et al.'s findings highlight specific nonoverlapping functions of PARP1 and PARP2 at H2AX-deficient chromatin during replicative phases of the cell cycle and uncover a unique requirement for PARP1 in NHEJ-deficient cells. [Read the Full Post]

Hyperactivation of ATM upon DNA-PKcs inhibition modulates p53 dynamics and cell fate in response to DNA damage

2618 | Dec 06 2016

The results of Finzel A et al. revealed a new regulatory interplay in which loss of DNA-PKcs function leads to hyperactivation of ATM and amplification of the p53 response, sensitizing cells for damage-induced senescence. [Read the Full Post]

Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients.

0 | Nov 29 2016

With the exception on the effect of Dacinostat in Type II cells, Mohseni J, et al have shown that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene. [Read the Full Post]

Evaluation of the Therapeutic Potential of the Novel Isotype Specific HDAC Inhibitor 4SC-202 in Urothelial Carcinoma Cell Lines

2862 | Nov 28 2016

Specific pharmacological inhibition of class I HDACs by 4SC-202 impairs UC cell viability, inducing cell cycle disturbances and cell death. Combined inhibition of HDAC1, HDAC2 and HDAC3 seems to be a promising treatment strategy for UC. [Read the Full Post]

Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients

4131 | Nov 25 2016

With the exception on the effect of Dacinostat in Type II cells, Mohseni J et al showed that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene. [Read the Full Post]

Preparation and Biochemical Analysis of Classical Histone Deacetylases

2992 | Nov 24 2016

Villagra A et al. reviewed some of the older established methods for assaying HDAC activities, as well as introduces more recently developed nontraditional assays. [Read the Full Post]

Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer

2196 | Nov 17 2016

Ju HQ et al. revealed a novel regulatory mechanism for Nampt in PDAC and suggested that Nampt inhibition may override gemcitabine resistance by decreasing the NAD level and suppressing glycolytic activity, warranting further clinical investigation for pancreatic cancer treatment. [Read the Full Post]

The Tumor-Associated Glycosyltransferase ST6Gal-I Regulates Stem Cell Transcription Factors and Confers a Cancer Stem Cell Phenotype

1983 | Nov 13 2016

Schultz MJ et al. highlighted a previously unrecognized role for a specific glycosyltransferase in driving a CSC state. [Read the Full Post]

Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations

2084 | Nov 11 2016

Yalon M et al. found that drugs which increase phosphorylation of eIF2α may mimic the sensitizing effect of vorinostat on cellular response to PARPis or to 6-TG, without activating all of its downstream effectors. [Read the Full Post]

Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition.

2859 | Nov 08 2016

Davis MR, et al. found that The efficacy of HDAC inhibitors in inducing subtype switching was determined by immunofluorescence and qPCR. [Read the Full Post]

Combinatorial Study of a Novel Poly (ADP-ribose) Polymerase Inhibitor and an HDAC Inhibitor, SAHA, in Leukemic Cell Lines

2283 | Nov 02 2016

Hegde M et al. revealed that coadministration of PARP inhibitor with SAHA could be used as a combination therapy against leukemic cells that possess high levels of intrinsic PARP activity. [Read the Full Post]

Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests

2890 | Oct 31 2016

Shinde V, et al. found that the concept based on the indices D p and D i offers the possibility to quantitatively express the propensity of test compounds to interfere with normal development. [Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

5728 | Oct 27 2016

Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]

Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ

3122 | Oct 20 2016

Lin YH et al. showed that PE treatment of NRVMs results in decreased binding of HDAC3 to myofibrils, suggesting a signal-dependent mechanism for the regulation of sarcomere-associated CapZβ1 acetylation. [Read the Full Post]

Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3

3191 | Oct 09 2016

Leng Y et al. provided a new mechanism via which histone deacetylase 2 and 3 participate in upregulating fibroblast growth factor 21 transcription and extending process outgrowth in glia. [Read the Full Post]

Effect of the BRCA1-SIRT1-EGFR axis on cisplatin sensitivity in ovarian cancer

2758 | Oct 09 2016

Li D et al. improved the understanding of the basic molecular mechanism underlying BRCA1-related cisplatin resistance in ovarian cancer. [Read the Full Post]

The histone deacetylase inhibitor PCI-24781 as a putative radiosensitizer in pediatric glioblastoma cell lines

2827 | Sep 28 2016

De Andrade PV et al demonstrated that HDACi PCI-24781 has a radiosensitizing profile that compromises the repair of double-strand DNA breaks in cells of pediatric GBM treated with radiotherapy. [Read the Full Post]

Heterogeneous Nuclear Ribonucleoprotein L is required for the survival and functional integrity of murine hematopoietic stem cells

2328 | Sep 06 2016

Gaudreau MC, et al. suggested that hnRNP L is critical for the survival and functional integrity of HSCs by restricting the activation of caspase-dependent death receptor pathways. [Read the Full Post]

HDAC4 mediates IFN-γ induced disruption of energy expenditure-related gene expression by repressing SIRT1 transcription in skeletal muscle cells

5143 | Sep 02 2016

Fang M, et al. revealed a role for HDAC4 in regulating cellular energy output and as such provide insights into rationalized design of novel anti-diabetic therapeutics. [Read the Full Post]

The role of nuclease FAN1 in DNA crosslink repair in Arabidopsis thaliana

2796 | Mar 26 2015

Herrmann et al. demonstrated that FAN1 homolog is present in plants and is proved to be involved in Arabidopsis thaliana CL repair. [Read the Full Post]

The interferon-related developmental regulator 1 is a key factor for human papillomavirus-induced NFкB inhibition

5159 | Mar 24 2015

Tummers et al. found hrHPV impairs immune response by inhibiting the acetylation of NFкB/RelA K310 in keratinocytes. [Read the Full Post]

Bromodomain and extra-terminal proteins are required in STAT5-mediated transcription

5529 | Mar 23 2015

Pinz et al. found deacetylase inhibitors lead to the delocalization of the bromodomain and extra-terminal (BET) protein Brd2, as well as Brd2-related factor TBP to hyperacetylated chromatin, via the global upregulation of histone acetylation. [Read the Full Post]

CY190602, a novel DNA/HDAC dual-targeting drug with enhanced anti-cancer potency

9773 | Mar 19 2015

Liu et al. demonstrated a novel bendamustine-derived drug, CY190602, enhanced anticancer potency. [Read the Full Post]

Histone deacetylase inhibitors have negative effects on the elimination of HIV-infected cells by cytotoxic T-Lymphocytes

5210 | Mar 02 2015

Jones et al. tested the impact of three HDACis, suberanilohydroxamic acid (SAHA), romidepsin and panobinostat, in clinical development on immune effectors functions, such as T-cell effector. [Read the Full Post]

An inverse correlation between homologous recombination and Polθ in epithelial ovarian cancers

4312 | Feb 27 2015

Ceccaldi et al. reported that HR activity inversely correlated with Polθ expression in EOCs. [Read the Full Post]

The combination of broadly neutralizing antibodies and viral inducers can suppress the establishment of HIV-1 latent reservoir

6522 | Feb 13 2015

Halper-Stromerg et al. demonstrated that broadly neutralizing antibodies (bNAbs) can suppress the establishment of a silent reservoir in humanized mice. [Read the Full Post]

Magnetic resonance imaging-visible amonafide-eluting alginate microspheres, a novel drug carrier for targeted arterial-infusion chemotherapy for liver tumors

2732 | Feb 12 2015

Kim et al. demonstrated a novel approach that facilitates arterial-infusion chemotherapy with magnetic resonance imaging (MRI)-visible amonafide-eluting alginate microspheres, and tested this approach on a xenograft rodent model. [Read the Full Post]

Recently identified CHEK2 Y390C mutation facilitates early breast cancer development

6777 | Feb 05 2015

Wang et al. identified a missense variant Y390C of CHEK2 that related to tumorigenesis in high-risk breast cancer patients. [Read the Full Post]

P2X7 receptor is a key upstream regulator for main signaling pathways involved in neuroblastoma progression

6484 | Feb 04 2015

Amoroso et al. demonstrated that P2X7 plays a key role in regulating the PI3K/Akt/GSK3β/MYCN and HIF1α/VEGF pathways, two main signaling pathways involved in NB progression. [Read the Full Post]

The inhibition of class I histone deacetylases by butyrate can suppress acute gout arthritis

5125 | Jan 22 2015

Cleophas et al. found high concentration of short-chain fatty acid butyrate provides anti-inflammatory effect by inhibiting of histone deacetylases (HDACs) in acute gout arthritis. [Read the Full Post]

Butyrate acts as an suppressor against colonic tumor in gnotobiotic mouse models

5386 | Jan 19 2015

Donohoe et al. demonstrated dietary fiber suppress tumor progress in a microbiota- and butyrate-dependent manner. [Read the Full Post]

Snail also acts as a transactivator for the expression of tumor-associated cytokines

6843 | Jan 16 2015

Hsu et al. demonstrated the underlying mechanism of Snail-mediated target gene transactivation, and also identified several target genes. [Read the Full Post]

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

12588 | Jan 07 2015

Winter et al. identified the underlying mechanism of the emerging JAK2 inhibitor therapy resistance in MPNs patients, and found the RAS and pathways mediated by AKT and ERK contribute to the resistance. [Read the Full Post]

Resvertrol targets a human tRNA synthetase for activation of NAD+-dependent PARP1

5432 | Jan 05 2015

Mathew Sajish and Paul Schimmel found resvertrol interacts with tyrosyl transfer-RNA (tRNA) synthetase (TyrRS), which translocates to the nucleus in response to stress, to initiating its effect in nuclear. [Read the Full Post]

IncRNA BCAR4 regulates cancer development cooperated with chemokine signals

7409 | Dec 09 2014

Xing et al. demonstrated the mechanism of BCAR4, a disease-related Inc RNA, in regulation signaling pathways in breast cancer metastasis. [Read the Full Post]

ERK/Cdk5 axis regulates diabetes-related PPARγ phosphorylation

8094 | Nov 21 2014

Recently, Banks et al. discovered that ERK/Cdk5 axis is involved in regulation PPARγ activities, and the inhibition of ERK and MEK leads to the improvement of insulin resistance. [Read the Full Post]

High-fat diet and NAD+ replenishment can rescue Cockayne Syndrome

5747 | Nov 07 2014

Scheibye-Knudsen et al. demonstrated high-fat diet, the inhibition of β-OHB, and the elevation of NAD+ levels, may have the effect to rescue CS-associated phenotype through activating SIRT 1 signaling. [Read the Full Post]

The effect of panobinostat on HIV latency disruption in a phase 1/2 clinical trial

5830 | Oct 22 2014

Rasmussen et al. found panobinostat, a histone deacetylase inhibitor, has the ability to activate infected cells from HIV latency. They also tested the safety of this strategy on phase 1/2 clinical trial. The effect of panobinostat treatment was not significant in reducing the number of latently infected cells. However, panobinostat effectively disrupt HIV latency in vivo. [Read the Full Post]

PCI34051 is a potent histone deacetylase 8 inhibitor

4398 | Mar 06 2014

PCI-34051 is a potent and specific HDAC8 inhibitor with IC50 of 10 nM. It has greater than 200-fold selectivity over HDAC1 and 6. [Read the Full Post]

AZD2281 is an experimental chemotherapeutic agent

4225 | Feb 27 2014

Olaparib (AZD2281, KU0059436) is a selective inhibitor of PARP1/2 with IC50 of 5 nM/1 nM [Read the Full Post]

PCI 24781 is a broad spectrum hydroxamic acid based inhibitor of HDAC

4290 | Feb 25 2014

HDAC activity is measured using a continuous trypsin-coupled assay. [Read the Full Post]

SB939 is a novel histone deacetylase inhibitor with improved

4438 | Feb 11 2014

SB939 has a 100-fold greater selectivity for HDACs than for Zn-binding non-HDAC enzymes, receptors, and ion channels. [Read the Full Post]

Adriamycin is an anti cancer chemotherapy drug

0 | Jan 27 2014

Doxorubicin (Adriamycin) is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage and apoptosis. [Read the Full Post]

MS 275 is a benzamide histone deacetylase inhibitor undergoing clinical trials

4424 | Jan 22 2014

MS-275 shows inhibitory to HDACs by 2-amino group. MS-275 induces accumulation of p21WAF1/CIP1 and gelsolin in K562 cell. [Read the Full Post]

MS 275 is a benzamide histone deacetylase inhibitor

4287 | Jan 21 2014

MS-275 shows inhibitory to HDACs by 2'-amino group. MS-275 induces accumulation of p21WAF1/CIP1 and gelsolin in K562 cell. [Read the Full Post]

Adriamycin is photosensitive and containers

2876 | Jan 10 2014

Doxorubicin (Adriamycin) is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage and apoptosis. [Read the Full Post]

NU7441 is a potent novel DNA PK inhibitor

2851 | Dec 26 2013

NU7441 is a highly potent and selective DNA-PK inhibitor with IC50 of 14 nM and also inhibits PI3K with IC50 of 5 μM. [Read the Full Post]

SB939 is a novel histone deacetylas inhibitor with improved

4329 | Dec 23 2013

SB939 is a potent pan-HDAC inhibitor with IC50 of 40-140 nM with exception for HDAC6. It has no activity against the class III isoenzyme SIRT I. [Read the Full Post]

ABT 888 is a potential anti cancer drug acting as a PARP inhibitor

4540 | Dec 20 2013

ABT-888 is inactive to SIRT2 (>5 μM) .ABT-888 inhibits the PARP activity with EC50 of 2 nM in C41 cells. [Read the Full Post]

Givinostat is a histone deacetylase inhibitor with potential

4045 | Dec 17 2013

Givinostat (ITF2357) is a potent HDAC inhibitor for HDAC2, HDAC1B and HDAC1A with IC50 of 10 nM, 7.5 nM and 16 nM. [Read the Full Post]

Olaparib is an experimental chemotherapeutic agent

0 | Dec 12 2013

Olaparib could ablate the PARP-1 activity at concentrations of 30-100 nM in SW620 cells. [Read the Full Post]

Adriamycin is an anti cancer chemotherapy drug

3114 | Dec 02 2013

Doxorubicin (Adriamycin) is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage and apoptosis. [Read the Full Post]

CUDC 101 is a potent inhibitor of histone deacetylase

4113 | Nov 25 2013

CUDC-101 is a potent multi-targeted inhibitor against HDAC, EGFR and HER2 with IC50 of 4.4 nM, 2.4 nM, and 15.7 nM, and inhibits class I/II HDACs, but not class III, Sir-type HDACs. [Read the Full Post]

Decitabine is a drug for the treatment of myelodysplastic syndromes

3077 | Nov 22 2013

Decitabine is a potent inhibitor of DNA methylation with IC50 of 438 nM and 4.38 nM in HL-60 and KG1a cells, respectively. [Read the Full Post]

AG 014699 is a PARP inhibitor being investigated as a potential anti cancer agent

4335 | Nov 21 2013

Rucaparib is a potent inhibitor of purified full-length human PARP-1 and shows higher inhibition of cellular PARP in LoVo and SW620 cells. [Read the Full Post]

BMN 673 was generally well tolerated

4279 | Nov 08 2013

BMN-673 selectively binds to PARP and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. [Read the Full Post]

Olaparib is an experimental chemotherapeutic agent

4096 | Nov 07 2013

Olaparib would act against BRCA1 or BRCA2 mutations. Olaparib is not sensitive to tankyrase-1 (IC50 >1 μM). [Read the Full Post]

BMN 673 is an orally bioavailable inhibitor of the nuclear

3649 | Nov 04 2013

BMN 673 is a novel PARP inhibitor with IC50 of 0.58 nM. It is also a potent inhibitor of PARP-2, but does not inhibit PARG and is highly sensitive to PTEN mutation. [Read the Full Post]

SB939 is a pan histone deacetylase inhibitor binding

4229 | Nov 04 2013

SB939 has a 100-fold greater selectivity for HDACs than for Zn-binding non-HDAC enzymes, receptors, and ion channels. [Read the Full Post]

Trichostatin A is an organic compound that serves as an antifungal antibiotic

3964 | Oct 25 2013

Trichostatin A (TSA) is an HDAC inhibitor with IC50 of ~1.8 nM – HDAC8 is the only known member of the HDAC-family that is not affected by TSA. [Read the Full Post]

CGK733 was a synthetic chemical substance which was reported in 2006

4200 | Oct 23 2013

CGK733 is able to confer robust growth to senescent cells that have ceased proliferation. [Read the Full Post]

Veliparib is a potential anti cancer drug acting as a PARP inhibitor

0 | Oct 09 2013

ABT-888 is a potent inhibitor of PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM, respectively. It is inactive to SIRT2. [Read the Full Post]

STA9090 is a novel synthetic small molecule inhibitor of heat shock protein 90

2602 | Aug 31 2013

Ganetespib is an HSP90 inhibitor with IC50 of 4 nM in OSA 8 cells, induces apoptosis of OSA cells while normal osteoblasts are not affected; active metabolite of STA-1474. [Read the Full Post]

MS275 strongly inhibits HDAC1 and HDAC3 with IC50

3917 | Aug 29 2013

MS-275 exhibits great antitumor activity against human tumor xenografts except HCT-15 at 49 mg/kg. [Read the Full Post]

Veliparib is a potential anti cancer drug acting as a PARP inhibitor

3690 | Jun 17 2013

ABT-888 inhibits the PARP activity with EC50 of 2 nM in C41 cells. ABT-888 could decrease the PAR levels in both irradiated and nonirradiated H460 cells. ABT-888 also reduces clonogenic survival and inhibits DNA repair by PARP-1 inhibition in H460 cells. [Read the Full Post]

Rucaparib is a PARP inhibitor being investigated as a potential anticancer agent

3498 | May 20 2013

Rucaparib also reduces the migration of some cancer and normal cells in culture.It can be taken orally in tablet form. [Read the Full Post]

Tubastatin A was substantially more selective than the known HDAC6 inhibitor

4139 | Apr 28 2013

Tubastatin A is substantially selective for all 11 HDAC isoforms and maintains over 1000-fold selectivity against all isoforms excluding HDAC8, where it has approximately 57-fold selectivity. [Read the Full Post]

Vorinostat is a member of a larger class of compounds that inhibit histone deacetylases

4057 | Mar 06 2013

A total of 155 children were screened for enrollment in the study, with 110 children being excluded on the basis of the enrollment criteria. The predominant reasons for exclusion were based on either the age or the weight criterion. Forty-five Vorinostat children meeting enrollment criteria for the PK substudy were enrolled: 23 in the AL arm and 22 in the AQ-AS arm. [Read the Full Post]

Cells subjected to ATM inhibitor Ku55933

3951 | Dec 18 2012

Antineoplastic drugs play an important role in cancer therapy. A growing number of patients and new fields of application have resulted in an increasing use of these agents. Most ATM inhibition antineoplastic drugs have carcinogenic, mutagenic and teratogenic properties. [Read the Full Post]

DNA PK Inhibitors is a trimeric nuclear serine kinase composed of a large catalytic subunit

3970 | Dec 11 2012

Over the past year, multiple new systemic therapy agents have become available to treat men with metastatic castration resistant prostate cancer mCRPC that provide modest but much needed benefits Table . [Read the Full Post]

The importance of Topotecan in cancer

3283 | Dec 05 2012

The importance of HER2 in cancer was realized in the early 1980s when a mutationaly activated form of its rodent homologue neu was identified in a search for oncogenes in a carcinogen induced rat tumorigenesis Topotecan model (Shih et al. 1981). Its human homologue HER2 was simultaneously cloned and found to be amplified in a GS-1101 breast cancer cell line (King et al. 1985). [Read the Full Post]

HDAC is also shown to occur in an inhibitor

4402 | Oct 24 2012

These include KIT, RET, STK11 LKB1. These are all known cancer associated kinases that have dysregulated signaling in various human cancers, including GIST and hematological malignancies, papillary thyroid cancer and lung cancer [Read the Full Post]

PARP INHIBITOR: STROKE ISCHEMIA AND CANCER

4235 | Sep 27 2012

DEREGULATION OF PARP CASCADE: In humans, Poly (ADP-ribose) polymerase or PARP enzymes are encoded by PARP gene and regulate some crucial processes in the cells for example programmed cell death or the DNA repair system. They play their role in DNA repair process by repairing the ssDNA or single stranded DNA breaks on DNA. The interaction of BRCA1 and BRCA2 with them is very well documented which links the deregulation of PARP with ovarian and breast cancer because many of these types of cancers are associated with the mutations in BRCA1 and BRCA2 genes. For this reason, the inhibition of PARP is found to be an attractive therapeutic approach due to the specificity and effectiveness of PARP specific inhibitors against the cancers caused by BRCA genes. An inhibitor having specificity for PARP exhibits good results due to high sensitivity of cancer cells against PARP inhibiting drugs leaving the healthy cells unaffected. Hence the PARP inhibition mechanism has made them an attractive and better choice as compared to the conventional therapies affecting all the healthy cells as well. [Read the Full Post]

VORINOSTAT: A HYDROXAMIC ACID

5001 | Sep 10 2012

VORINOSTAT OR SAHA (SUBEROYLANILIDE HYDROXAMIC ACID): Histone deacetylase inhibitors or HDACi perform functions in the regulation of gene expression, cell cycle arrest, apoptosis stimulation in cancer cells and variation of different pathways in cancer cells such as cellular proliferation due to hyperacetylating the histone proteins. HDAC inhibitors are one of the leading approach for the treatment of cancers and tumors and among these inhibitors Vorinostat SAHA is the important one. This inhibitor is found to have strong anti-oncogenic properties and the Vorinostat structure contains a molecules having hydroxamic acid. For both classes of HDAC inhibitors that is class I and II the Vorinostat IC50 is about 50nM. The solubility of Vorinostat is around 2mg/ml in ethanol where it is highly soluble in DMSO in which 65mg/ml is Vorinostat solubility but it is poorly soluble in water. Stability of Vorinostat is of about 24 months when stored at -20 ºC. One can purchase Vorinostat for research purpose from any of the Vorinostat supplier by spending Vorinostat price that is $26 for a vial of 100mg however the prices are variably depending upon purity of the salt and supplier. Amongst different HDAC inhibitors the first FDA approved such inhibitor is Vorinostat HDAC inhibitor for the treatment of T-cell lymphoma. [Read the Full Post]

PARP INHIBITOR: TREATMENT OF STROK, ISCHEMIA AND CANCER

3607 | Sep 09 2012

DEREGULATION OF PARP CASCADE AND ITS APPLICATIONS: Poly ADP-ribose polymerases or PARP are the translated product of PARP genes located in human genome. These proteins play some of the vital roles in the cell such as apoptosis and DNA repair mechanism. The repair mechanism of DNA is specific for the single stranded DNA (ss DNA) breaks. A reasonable work has been reported about the interaction of BRCA1 and BRCA2 and this knowledge leads to the understanding of PARP deregulation causes or links with ovarian and breast cancer as different research reports concluded the mutations of these two genes are present in these cancers. Due to these reasons the PARP inhibition mechanism has become an efficient therapeutic tool for cancer treatment [1]. The specific PARP inhibitors may have efficient results against tumors and cancers with BRCAness. The beauty of these PARP inhibitors is that the normal cells are not affected where tumors cells are only targeted. Mechanism of PARP inhibitor tells about the efficacy of these inhibitors in treatment of cancers and because of their efficient actions the old therapies are becoming less popular as they affect the normal cells as well. [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS BEYOND CANCER TREATMENT

4581 | Sep 02 2012

EPIGENEITIC MODULATION AND HDAC INHIBITORS In cellular genome a major part comprises of histone proteins and these proteins upon addition of acetyle group perform some of the most important cellular pathways are controlled by these proteins, these pathways include cell growth and proliferation and programmed cell death. When the acetyle group is detached from histones the process of apoptosis starts because most of the genetic expression of some vital proteins is ceased due to deacetylation and in addition to this the DNA condensation is also increased due to increased DNA binding capacity. It has been noticed that during neurodegenerative diseases the process of deacetylation is disturbed which leads to different types of cancers and tumors which is characterized by uncontrolled cell proliferation. These studies encouraged the discoveries of HDAC inhibitors and also enlighten the HDAC inhibition process. In preclinical and clinical evaluations HDAC inhibitions have been applied which leads to the successful and detailed use of this process by good number of researchers. Various activity assays are available for the estimation of HDACs levels. Kits are available for such assays however these can also be performed manually in the lab. HDAC inhibitors analysis can also be done by a nonisotopic assay which is microplate reader compatible and test for robotic screening and compound profiling is also available or another assay which is suitable for high throughput screening. [Read the Full Post]

HDAC INHIBITORS AGAINST TOMORS

4764 | Aug 22 2012

HDAC INHIBITION: A SOURCE OF EPIGENETIC MODULATION Histone acetylation is an essential process in functions like cell growth and cellular death by causing the inhibition of transcription of proteins caused by removal of the acetyl groups from the histone proteins, as a result of which the binding of DNA is increased, causing it to be condensed. A disturbance in this phenomenon leads to an uncontrolled growth of the cells that leads to the production of tumors and neurodegenerative diseases as well. HDAC inhibition is performed to treat various forms of tumors by using HDAC-2 inhibitors. Different successful studies at various levels have elucidated the mechanism of action of HDAC inhibitors leading to their enormous applications in various preclinical and clinical trials. The levels of HDAC inhibitors can be assessed by the use of different sort of assays specially developed for this reason. These chemical assays can be performed in laboratory by using various kits. The researchers can perform nonisotopic HDAC inhibitor and microplate reader compatible assay and the one for the robotic screening and compound profiling. In addition to it a simple flourogenic assay can also be used for the high-throughput screening process. [Read the Full Post]

HDAC INHIBITORS AGAINST CANCERS

4520 | Aug 15 2012

HDAC INHIBITION AND EPIGENETIC MODULATION An important process; histone acetylation is related to cellular functions for example cell death and cell growth stimulating the protein transcription inhibition by removing the acetyl groups from the related proteins hence causing the increase in DNA binding and making it more condensed. Any disturbance in this process leads to the uncontrolled cellular growth that further leads to the tumor production and also the neurodegenerative diseases. Histone deacetylase inhibition is carried out for the treatment of different types of tumors by using the HDAC-6 inhibitors. Various successful studies at different levels have exhibited the mode of action of histone deacetylase inhibitors further leading to their vast area of applications in different clinical and pre-clinical studies. The HDAC inhibitors levels can be analyzed by using various types of assays specifically developed for this purpose. These assays can be carried out in the labs through different kits. Researchers can perform microplate reader compatible assay and the nonisotopic HDAC inhibitor assay and also the one for compound profiling and robotic screening. In addition to this simple flourogenic assay may also be carried out for the process of high-throughput screening. [Read the Full Post]

HDAC INHIBITORS AGAINST CANCERS

4485 | Aug 01 2012

EPIGENETIC MODULATION VIA HDAC INHIBITION: Histones acetylation is vital process in the functions like cellular growth and cell death by inhibiting the transcription of proteins which is caused by the removal of acetyl groups from histones as a result the DNA binding increases and DNA is condensed. When this process is disturbed it leads to uncontrolled growth of cells leading to the formation of cancers and also neurodegenerative diseases. HDAC inhibition for the treatment of cancer comes by the use of HDAC inhibitors. Successful studies elucidating mechanisms of HDAC inhibitors led to their vast applications in different clinical and preclinical studies. HDAC levels can be assessed by using various assays developed for this purpose. These assays can be performed in lab by the help of kits. Researchers can perform microplate reader compatible and nonisotopic HDAC inhibitor assay and one for compound profiling and robotic screening and in addition to this simply a flourogenic assay can be performed for high-throughput screening. [Read the Full Post]

PARP INHIBITOR: A MULTI PURPOSE AGENT

3844 | Jul 23 2012

PARP INHIBITOR AND ITS APPLICATIONS: Poly ADP-ribose polymerases or PARP are translated by the PARP genes which are a part of human genome. PARP are vital proteins for some of the most important functions such as DNA repair mechanism and apoptosis. There are many reports of research in which a close relation of PARP inhibition is noted with BRCA1 and BRCA2 which are associated with onset of ovarian and breast cancer. Based on these research reports PARP inhibition has become a novel tool for the treatment of different types of cancers and tumors. PARP inhibitors have shown efficient results against BRCA genes. PARP protein inhibitor has unique property of not affecting normal cell; therefore these inhibitors are specific for cancer cells. The choice for cancer treatment with least side effects is becoming famous due to PARP inhibitors which are potent anti cancer agents. [Read the Full Post]

PARP INHIBITOR: A THERAPEUTIC AGENT FOR ISCHEMIA, STROK AND CANCER

3858 | Jul 15 2012

USES OF PARP INHIBITOR AND DOWNREGULATION OF PARP CASCADE Human genome consists of different genes one of which is PARP gene which translates to produce PARP or Poly ADP-ribose polymerases. Important functions of cells like programmed cell death and mechanism of DNA repair is being controlled by these proteins. Breaks in single strand of DNA are specifically repaired by these proteins. Since BRCA1 and BRCA2 are involved in breast and ovarian cancer onset their associations with PARP inhibition have been reported in a number of researches. Because of these details inhibition of PARP has become a vital tool for therapy of various cancers [1]. Against these BRCA genes inhibitors of PARP have shown effective results. PARP inhibitors specifically targets only the cancer cells not normal cells which is their edge point. Conventional therapies have become less famous because mode of action of PARP inhibitor has shown that it is very good against different cancers. [Read the Full Post]

INHIBITORS OF HISTONE DEACETYLASE

3627 | Jul 13 2012

HDAC INHIBITORS AND EPIGENEITIC VARIATION Different functions of the cell like apoptosis, cell multiplication and growth is controlled by genes present in cell histone proteins comprise the large portion these genes. These histone proteins act when they are being acetylated. When these histone proteins get deacetylated they trigger apoptosis because translation of vital proteins gets stopped when they are being deacetylated and also binding capability of DNA is increased due its condensation. Studies showed that in neurodegenerative diseases deacetylation process is seemed blocked which ultimately gave rise to unchecked growth of cells which is characteristic of various kinds of carcinomas and malignancies. These findings forced scientists to discover HDAC inhibitors brought into light the process of HDAC inhibition. Quite large number of researchers described in detail the process of inhibition by administering HDAC inhibitors in clinical as well as pre-clinical trials. Different activity estimation assays are present to assess levels of HDACs. [Read the Full Post]

PARP INHIBITOR: TREATMENT OF STROK, ISCHEMIA AND CANCER

3600 | Jul 08 2012

DEREGULATION OF PARP CASCADE AND ITS APPLICATIONS: Poly ADP-ribose polymerases or PARP are the translated product of PARP genes located in human genome. These proteins play some of the vital roles in the cell such as apoptosis and DNA repair mechanism. The repair mechanism of DNA is specific for the single stranded DNA (ss DNA) breaks. A reasonable work has been reported about the interaction of BRCA1 and BRCA2 and this knowledge leads to the understanding of PARP deregulation causes or links with ovarian and breast cancer as different research reports concluded the mutations of these two genes are present in these cancers. Due to these reasons the PARP inhibition mechanism has become an efficient therapeutic tool for cancer treatment. The specific PARP inhibitors may have efficient results against tumors and cancers with BRCAness. The beauty of these PARP inhibitors is that the normal cells are not affected where tumors cells are only targeted. Mechanism of PARP inhibitor tells about the efficacy of these inhibitors in treatment of cancers and because of their efficient actions the old therapies are becoming less popular as they affect the normal cells as well. [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS – CANCERS AND BEYOND

4711 | Jun 26 2012

HDAC INHIBITIORS AND EPIGENEITIC MODULATION: Histone proteins are major part of cellular genome and acetylation of these proteins plays a mile stone role in some of the most important cellular mechanisms such as growth of cell and cell death by apoptosis. The process which controls apoptosis process is carried out by checking the gene transcription of different important proteins by removing acetyl groups from histones, this deacetylation leads to condensation of DNA due to increasing capacity of DNA binding. In neurodegenerative diseases this mechanism of deacetylation goes wrong leading to various types of cancers in which cell proliferation is uncontrolled. This problem leads to the HDAC inhibitor pathway and smoothes the process of HDAC inhibition. HDAC inhibitions have been employed in preclinical and clinical studies due to which extensive and successful use of this process is targeted by many researchers. HDACs levels estimation has been developed by different activity assays. These assays are carried out by manually in the research lab or by kit methods. A nonisotopic assay that is microplate reader compatible can also be performed by researchers for the analysis of HDAC inhibitors, an appropriate test for compound profiling and robotic screening or a suitable fluorescence assay for high-throughput screening. [Read the Full Post]

PARP INHIBITOR: ISCHEMIA, STROK AND CANCER

4227 | Jun 24 2012

PARP CASCADE DEREGULATION AND ITS IMPLICATION: PARP are Poly ADP-ribose polymerases and translated by PARP genes present in human genome. These proteins are important for the regulation of critical processes such as DNA repair mechanism and programmed cell death. The DNA repair mechanism based on these enzymes is specific for ssDNA (single stranded DNA) breaks. A sufficient data is available on the BRCA1 and BRCA2 interaction which leads to the concept of PARP deregulation link with breast and ovarian cancer because many cases of these cancers reported about the mutations present in these two genes. Because of this reason PARP inhibition mechanism has proved as an effective therapeutic tool [1] where inhibitors specific for PARP may have effective results against cancers and tumors with BRCAness. PARP inhibitors are mostly specific as the tumor cells are targeted by these molecules therefore the normal cells remain un-affected. The mechanism of PARP inhibitor is so effective against cancer and due to this reason conventional therapies are becoming less useable due to their effects on healthy cells as well. [Read the Full Post]

VORINOSTAT: THE FAMOUS HYDROXAMIC ACID

4025 | May 15 2012

SUBEROYLANILIDE HYDROXAMIC ACID (SAHA) OR VORINOSTAT: Functions of HDACi (HDAC inhibitors) is to regulate the gene expression, induction of cell cycle arrest, stimulate apoptosis in cancer cells and modulation of various pathways in tumor cells for example cell proliferation, by hyperacetylating the histone proteins. Due to possessing these abilities, HDAC inhibitors are being used as a very valuable chemotherapeutic anti-cancer agents and SAHA or Vorinostat SAHA is important among them [1]. Vorinostat has found to be possessing strong anti-cancer properties [2] and Vorinostat structure reveals that this molecule is a derivative of hydroxamic acid. For HDAC inhibitors class I and HDACi class II Vorinostat IC50 is found to be near 50 nM. Vorinostat is soluble is ethanol up to 2 mg/ml and in DMSO 65 mg/ml but Vorinostat solubility is found to be very poor in water. [Read the Full Post]

PARP INHIBITOR: CANCER, ISCHEMIA AND STROKE

3104 | May 15 2012

IMPLICATION OF DEREGULATION OF PARP CASCADE: PARP or Poly ADP-ribose polymerase enzymatic proteins are encoded by PARP genes in human, and are responsible of regulating the critical cellular processes for example, programmed cell death and DNA repair channel. They play their role in DNA repair pathway by repairing the single-stranded DNA breaks (ssDNA). The interaction of BRCA1 and BRCA2 with them is very well documented that describes a link between PARP deregulation and ovarian and breast cancer, as many among these cancers are associated with the mutations inside these two genes. This is why the PARP inhibition process has proved to be an attractive therapeutic tool [1] and PARP specific inhibitor molecule may prove highly effective against tumors with BRCAness. Generally PARP selective inhibitor exhibits good results due to the tumor cells beings highly sensitive for PARP inhibitor drug leaving the remaining healthy cells. Hence PARP inhibitor mechanism has made them a better choice as compare to the conventional therapies that must affect all the cells irrespective of their status. [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS – TUMORS AND BEYOND

3813 | May 06 2012

EPIGENETIC MODULATION BY HDAC INHIBITIORS: Acetylation process of histone proteins performs a major role in various cellular processes for example cellular growth and apoptosis by preventing the transcription of various proteins by the removal of acetyl groups from the histones hence increasing their DNA binding capacity which leads to the formation of a condensed DNA. This strategy goes wrong in case of neurodegenerative diseases and many types of cancers in which any abnormality in this process causes the removal of this block leading to the cells to proliferate in an uncontrolled manner. Then an HDAC inhibitor pathway comes into light and smoothes the progress of HDAC inhibition. The successful revelation of mechanism of HDAC inhibition has led to their extensive use in different clinical and preclinical studies. [Read the Full Post]

VORINOSTAT – AN ANTI HISTONE MODIFYING AGENT

3991 | Apr 17 2012

CHROMATIN REMODELLING INHIBITION IN CANCER THERAPY Histone modification is a very important phenomenon regarding regulation of expression of genes. Acetylation and deacetylation of histones in attached to the genetic material i.e., DNA is done with the help of specific proteins, therefore, in order to inhibit or stimulate the expression of specific genes histone tail modifying proteins can be modified. Histone deacetylating Complexes (HDACs) are one of these modifying proteins which inhibit the expression of some genes by de-acetylating them. Inhibiting these proteins may function in the modulation of gene expression by hyperacetylating them. HDAC inhibitors hence modulate the aberrant expression of genes in cancerous cells. They may inhibit cell division, arrest cell cycle or stimulate apoptosis. A lot of research is being done on different types of HDAC inhibitors in order to use them as anti-cancer therapeutics. Vorinostat is one of such HDAC inhibitors. It is also known as Suberoylanilide Hydroxamic Acid (SAHA). [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS – TUMORS AND BEYOND

3567 | Apr 16 2012

EPIGENETIC MODULATION BY HDAC INHIBITIORS: Acetylation process of histone proteins performs a major role in various cellular processes for example cellular growth and apoptosis by preventing the transcription of various proteins by the removal of acetyl groups from the histones hence increasing their DNA binding capacity which leads to the formation of a condensed DNA. This strategy goes wrong in case of neurodegenerative diseases and many types of cancers in which any abnormality in this process causes the removal of this block leading to the cells to proliferate in an uncontrolled manner. Then an HDAC inhibitor pathway comes into light and smoothes the progress of HDAC inhibition. The successful revelation of mechanism of HDAC inhibition has led to their extensive use in different clinical and preclinical studies. Various assays for HDACs have been developed that are used for the analysis of HDAC levels. [Read the Full Post]

OLAPARIB: THE FIRST PARP INHIBITOR

5087 | Mar 19 2012

Introduction: PARP Inhibition Signaling activities within the cell are conducted along set pathways of protein – protein interactions. Depending on the cell status and the ligands triggering the signaling cascade to what function is carried out in the nucleus. A protein located in the nucleus has been established to be the principle regulator of the apoptosis and repair functions of certain DNA damage. This protein is called “Poly (ADP-ribose) polymerase” or it is abbreviated to “PARP”. The PARP family of proteins is extensive with 17 members currently known and the range of effects of PARP activity is large. The general structure of the PARP series of proteins contains four different types of binding domains which dictate the activity, one of the domains is referred to as the catalytic domain contains an amino acid sequence that is identical between all the members of the protein family. The mechanism of action of PARP proteins is to add a series of ADP ribose molecules to the protein ligands, the number and site of this addition controls the response of the affected protein. [Read the Full Post]

PANOBINOSTAT

5622 | Mar 19 2012

Introduction: Inhibition of HDAC Of the 18 isoforms of the histone deacetylase enzyme the class one and class two proteins are the most frequently found to be over expressed in tumor tissue. The activity of the HDAC enzyme is to remove an acetyl group from a target protein which induces a conformational change so that further protein binding is induced or inhibited. The signal begins in the cellular cytosole and is transmitted to the nucleus. This signaling transfer results eventually in the regulation of a cellular growth activity, be that life or death! The class 1 & 2 enzymes function by binding their target protein to a binding domain which has a zinc atom as a functional part. This zinc atom catalysis the deacetylation process and is the target of inhibition for most known HDAC inhibitors. [Read the Full Post]

MS-275

4281 | Mar 19 2012

Introduction: HDAC inhibition In most cancerous tissue there exists an imbalance between regulatory pathways that came be exploited for chemotherapeutic activity. One of the pathways that exhibits such activity is the acetylation / de-acetylation pathway. The regulatory enzyme in this pathway is referred to as Histone deacetylase (HDAC) and it operates in balance with Histone acetyl transferase. The addition or removal of an acetyl group causes the protein conformational shape to change and this in turn triggers either an attraction or inhibition of a protein complex formation. This action sends a signal to the nucleus to being or stop growth actions. There are many HDAC enzymes located in the cellular cytosole or within the nucleus membrane and most activity is controlled by a zinc catalyst, one small group requires NAD+ to function instead. [Read the Full Post]

HDAC INHIBITORS – CANCERS AND BEYOND

3931 | Mar 19 2012

Introduction: Histone deacetylases Cellular growth is regulated via many different mechanisms in the mammalian species, depending on the mechanism or pathway that is triggered to what effect is seen in the body. One of these regulatory compounds is called histone deacetylase or abbreviated to HDAC. As it name indicates this enzymes function is to remove an acetyl group from a target, this can be either a protein or a non-protein molecule. The removal of the acetyl group results in a conformational change in the target protein that triggers further signaling down a “pathway” that results in the induction or inhibition of carious growth related activities in the cell. HDAC is not a single protein but exists in 18 different isoforms which are classified into four groups based on their activity and physical nature. Located in the nucleus are HDAC’s 1, 2, 3 & 8 responsible for mostly transcription activities. In the cytosole are the HDAC’s 4, 5, 7 & 9, these transmit signals between extracellular sources and the nucleus. HDAC 11 and HDAC’s 6 & 10 are located in between cytosole and nucleus, their function varies. [Read the Full Post]

CUDC -101: HDAC inhibitor

4195 | Mar 20 2012

Introduction: HDAC inhibition Regulation of the activity of the proteins that initiate and transmitted signals for the cellular growth or gene transcription is a vital process in the mammalian system. There are many different mechanisms that perform this task but o of the more significant is the addition or removal of an acetyl group. The enzyme’s most responsible for this activity is known as “Histone deacetylase” and “Histone transferase” or more commonly known as HDAC and HAT respectively. In a normal situation these two enzymes operate in a balanced mechanism but genetic aberrations can significantly affect this balance in one way or another. Most typically it is observed that the HDAC is over expressed or in a permanent “on” condition in most diseased states. With over 18 currently known isoforms of HDAC divided into class’s based on the mechanism of action this represents a major target for chemotherapeutic action To target HDAC an inhibitor should be able to interfere with the ligand – enzyme binding which occurs in the tyrosine kinase domain and two classes out of 4 HDAC’s require Zinc to catalyse the reaction. [Read the Full Post]

PARP INHIBITOR IN CANCER, STROKE AND ISCHEMIA

3287 | Mar 18 2012

Introduction: Mechanism of Action of Poly (ADP-ribose) polymerase (PARP) Within any cellular growth process there must be facilities for the replication of DNA, however, this process is not always 100% accurate. In addition mechanisms for the repair of incorrect sequences or the repair of cytotoxic damaged DNA must exist in tandem. PARP is not part of a repair mechanism but it does function as one of the regulatory enzymes controlling the mechanisms that do repair DNA such as the BER/SSER pathway. As well as regulating DNA repair PARP is a true multi-tasking protein since it also regulates the normal processes of cell disposal (ie cell death, apoptosis), development of neuro-functions and many other cell proliferation processes. PARP is typically located in the cell nucleus where in combination with other proteins recognizes minor DNA strand damage, forms skeletal structures around the site of the damage and enrolls specific proteins to remove the damaged section and replace the missing part. [Read the Full Post]

U0126: THE MOST POTENT MEK INHIBITOR

5868 | Mar 18 2012

The MAPK pathways In ever cells life span there are circumstances when the cell is placed in a stressful situation, such toxic shock, injury to the surrounding tissue or old age. In such circumstances the cells must react either to die or to live and grow. The regulation of this process is the responsibility of the “Mitogen-activated protein kinases (MAPK)”. The MAP kinases are involved in a broad spectrum of processes covering proliferation (mitosis), apoptosis, cell migration/motility and gene expression. The MAP kinases are located in the cell membrane and on receipt of an external extracellular signal any one of three pathways can be stimulated, these are the ERK, JNK or the P38MAPK pathways. [Read the Full Post]

HDAC INHIBITOR AND ITS EEFICACY IN CANCER

3895 | Mar 19 2012

Introduction: Inhibition of Histone deacetylase function Checks and balances are key terms used when describing the modulation of the cell growth pathways and quality assurance mechanisms. Verification of every stage in the process is checked for completion and there should be a balance between cell growth & cell death depending on the circumstances. Balance is maintained via the signaling pathways, which require a chemical change to transmit their signals down the line. Typically, this is the phosphorylation of the tyrosine kinase-binding domain. This domain is found in the large super family of protein kinases that dominate the regulation of cell growth. However, phosphorylation is not the only mechanism of activation, acetylation can also be utilized and this is where the histone deacetylase proteins comes into play. HDAC´s have been classified into four categories of which class 1 HDAC´s are primarily located in the nucleus, and are linked to transcriptional activation. Class 2 HDAC´s carry signals from cytosole into the nucleus were transcriptional activities are triggered. Classes 3 and 4 are not well defined and have not been associated with cancer chemotherapy or any metabolic disorders to date. [Read the Full Post]

OLAPARIB FOR PARP-1 INHIBITION

4413 | Mar 13 2012

PARP-1 Inhibition and its Implications in Cancer: The Poly [ADP-ribose] polymerase 1 or PARP-1 proteins have been well documented to be linked with cancers affecting their differentiation, proliferation and transformation. On the other hand, BRCA1 and BRCA2 genes are also well linked with the highly proliferating ovarian and breast cancer and hence the development of PARP-1 inhibitors that can target the aforementioned genes effectively in breast and ovarian cancer cells has been considered as a very attractive and feasible approach. The increasing popularity of PARP-1 inhibitors can be attributed to their specific action against cancer cells while sparing normal cells. [Read the Full Post]

AZD2281: THE FIRST PARP INHIBITOR

4552 | Mar 13 2012

Introduction: PARP Inhibition Poly (ADP-ribose) polymerase (PARP) is an enzyme located in the cell nucleus that regulates apoptosis and controls repair of minor damaged DNA strands. Since DNA mutations are a common function of many clinical diseases PARP is a significant target for chemotherapeutic action. With 17 known members of the PARP family the mechanism of action for PARP’s activity is important to understand. The PARP protein consists of 4 important area’s; the Zinc figures where DNA repair takes place, a caspase cleavage function, a catalytic domain and a modification domain. Chemotherapeutic action is considered to be via the caspase domain or via the DNA repair domain. Inhibiting the repair of DNA strands triggers the automatic functions of cell death. Inhibitors for PARP have been developed and tested pre-clinically demonstrating the effectiveness of this approach. [Read the Full Post]

BELINOSTAT: THE UNUSUAL HDAC INHIBITOR

5223 | Mar 13 2012

Introduction: HDAC inhibition In humans, histone deacetylase (HDAC) is a regulatory enzyme located both in the cellular cytoplasm and in the nucleus. Its function is the removal of an acetyl group from both protein and non-protein targets, this removal is usually part of a signaling pathway inducing or reducing various activities within the cell. There are currently 18 isoforms of HDAC known which are classified into four classes. Class 1 are the nucleus HDAC´s (1,2,3&8); Class II HDAC´s (4, 5, 7 & 9) are located in either the cytoplasm, the nuclease or a transitional state between the two. These two classes of enzymes are related by the fact that they require a zinc catalyst for activity. Class III (6&10) and IV HDAC´s (11) do not require zinc for their activity but instead rely on NAD+ for their activity. [Read the Full Post]

Roles of sirtuins in the nervous system diseases

7048 | Nov 16 2011

As is reported in some studies, SIRT1 is expressed in the adult brain, with high levels in the cortex, hippocampus, cerebellum, and hypothalamus. In brain, SIRT2 is a cytoplasmic protein and plays an important role in the formation of myelin sheath and in the myelin-axon interaction. Other members of sirtuins is also found to exist in brain in various forms. Recent research indicates that a neuroprotective role of sirtuins, especially SIRT1 has been observed[1]. In fact, the effects of sirtuins on common neurological disorders has been described previously. [Read the Full Post]

Expression and activity of Sirtuins

6057 | Nov 15 2011

Sirtuins are a class of proteins that possess either histone deacetylase or mono-ribosyltransferase activity, and the activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD+). Until now, seven members have been identified as sirtuin 1 (SIRT1) through SIRT 7. Of which, is considered to be one of the determining factors in longevity induced by calorie restriction. [Read the Full Post]

The antifungi activity of DNA topoisomerase inhibitors

4305 | Nov 10 2011

Fungal infections represent the invasion of tissues by one or more species of fungi, such as Aspergillus and yeasts. Some fungal infections will trigger the body’s immune system, cause inflammation and tissue damage, and even lead to serious lung, blood (septicemia) or systemic diseases. [Read the Full Post]

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

12461 | Sep 20 2011

Ovarian cancer is a cancerous growth arising from the ovary, and remains the leading cause of death from gynecological cancer, accounting for more than 140,000 deaths per year worldwide. The risk of developing ovarian cancer appears to be affected by several factors, and 10% of ovarian cancer patients have a family history of the disease. Certain genes defects (BRCA1 and BRCA2) are considered to be responsible for a small number of ovarian cancer cases. [Read the Full Post]

HDACs, play important roles in kidney development

6260 | Sep 08 2011

Histone deacetylases (HDACs) regulate fundamental biological processes such as cellular proliferation, differentiation, and survival via genomic and non-genomic effects. Some data suggest that HDACs may play a important role in kidney development. [Read the Full Post]

Kong, X., Y. Shen, et al. (2011). "Emerging roles of DNA-PK besides DNA repair." Cell Signal 23(8): 1273-1280.

5176 | Aug 19 2011

This article reviews the role of DNA-PK from two aspects. It not only introduces the regulation of DNA-PK activity and the roles of DNA-PK in non-homologous end-joining (NHEJ) repair and homologous recombinant (HR) repair, but also introduces the involvement of DNA-PK in the inflammatory response, in metabolic gene regulation, and in the homeostasis of cell proliferation as well. [Read the Full Post]

Nitiss, J. L. (2009). "Targeting DNA topoisomerase II in cancer chemotherapy." Nat Rev Cancer 9(5): 338-350.

3284 | Jun 12 2011

The molecular tools that have allowed an understanding of the biological functions of TOP2 are also being applied to understanding the details of drug action. These studies promise refined targeting of TOP2 as an effective anticancer strategy. [Read the Full Post]

Pommier, Y. (2006). "Topoisomerase I inhibitors: camptothecins and beyond." Nat Rev Cancer 6(10): 789-802.

3981 | May 27 2011

The mechanisms and molecular determinants of tumour response to TOP1 inhibitors are reviewed, and rational combinations of TOP1 inhibitors with other drugs are considered based on current knowledge of repair and checkpoint pathways that are associated with TOP1-mediated DNA damage. [Read the Full Post]

Burma, S. and D. J. Chen (2004). "Role of DNA-PK in the cellular response to DNA double-strand breaks." DNA Repair (Amst) 3(8-9): 909-918.

4816 | May 11 2011

This review introduces DNA-PK as a kinase in the cellular response to DNA double-strand breaks with many details including autophosphorylation of DNA–PKcs, role of DNA–PK in the signaling of DNA damage, and the manifold functions of DNA–PK at the mammalian telomere. I t also mentions the innate immune response which DNA-PK is related to. [Read the Full Post]

Ekwall, K. (2005). "Genome-wide analysis of HDAC function." Trends Genet 21(11): 608-615.

3923 | Apr 19 2011

This review is about genome-wide analysis of HDAC functions. It is a review of systematic study of HDACs and introduces the related targets such as Rpd3, Hos1, Hos2 , Hos3 and so on. [Read the Full Post]

de Ruijter, A. J., A. H. van Gennip, et al. (2003). "Histone deacetylases (HDACs): characterization of the classical HDAC family." Biochem J 370(Pt 3): 737-749.

3993 | Mar 20 2011

This is an article which give us the detail of HDAC family member proteins. It introduce the members of HDAC family one by one. You can make different HDACs clear after reading this article. [Read the Full Post]