Cytoskeletal Signaling

Plasmodium falciparum formins are essential for invasion and sexual stage development

36 | Feb 16 2024

"By elucidating the distinct roles of Plasmodium falciparum formins 1 and 2 (FRM1 and FRM2) in various stages of the malaria parasite's lifecycle and demonstrating the efficacy of the small molecule inhibitor SMIFH2 in blocking multiple stages of parasite development, this research presents promising avenues for targeted intervention and a deeper comprehension of malaria pathogenesis." [Read the Full Post]

ROCK Inhibitors as an Alternative Therapy for Corneal Grafting: A Systematic Review

123 | Feb 15 2024

The review on ROCK inhibitors for corneal wound healing showcases their diverse therapeutic potential across various ocular conditions, offering promise as an effective alternative to human donor tissue for addressing the significant unmet medical need in corneal blindness. [Read the Full Post]

Proteomic and Phosphoproteomic Profiling Reveals the Oncogenic Role of Protein Kinase D Family Kinases in Cholangiocarcinoma

92 | Feb 15 2024

The comprehensive analysis of protein and phosphorylation signatures in cholangiocarcinoma revealed the PRKD family's pivotal role, highlighting their potential as novel treatment targets validated by the inhibitory effects of 1-naphthyl PP1 on CCA cell proliferation, migration, and invasion. [Read the Full Post]

Hypoxia-activated glutamine antagonist prodrug combined with combretastatin A4 nanoparticles for tumor-selective metabolic blockade

55 | Feb 13 2024

The development of HDON, a hypoxia-activated prodrug derived from DON, coupled with combretastatin A4 nanoparticles, demonstrates exceptional tumor selectivity and efficacy, achieving remarkable tumor suppression rates and cure rates in murine liver, colon, and breast cancer models. [Read the Full Post]

Cell-Penetrating Peptide-Bismuth Bicycles

44 | Feb 09 2024

The development of peptide-bismuth bicycles as cell-penetrating peptides showcases a groundbreaking leap in cellular uptake efficiency, offering a promising avenue for diverse biomedical applications. [Read the Full Post]

Alignment of actin filament streams driven by myosin motors in crowded environments

31 | Feb 06 2024

In a crowded cellular environment, the interplay between myosin-driven actin filament movement and ionic strength unveils a remarkable spatial patterning, offering profound insights into cytoskeletal organization within living cells. [Read the Full Post]

225Ac-iPSMA-RGD for Alpha-Therapy Dual Targeting of Stromal/Tumor Cell PSMA and Integrins

24 | Jan 30 2024

The preclinical evaluation of 225Ac-iPSMA-RGD demonstrates its cytotoxicity, biodistribution, and therapeutic potential, suggesting promise for targeted alpha therapy in treating colorectal cancer. [Read the Full Post]

Assessing safety concerns of interstitial lung disease associated with antibody-drug conjugates: a real-world pharmacovigilance evaluation of the FDA adverse event reporting system

56 | Jan 29 2024

The identification of significant safety signals for interstitial lung disease associated with several FDA-approved antibody-drug conjugates underscores the critical need for heightened clinician awareness and early patient monitoring, prompting further research and potential adjustments in clinical practice guidelines. [Read the Full Post]

Axillary Nodal Response to Neoadjuvant T-DM1 Combined with Pertuzumab in a Prospective Phase II Multi-Institution Clinical Trial

49 | Jan 29 2024

In HER2-positive breast cancer patients undergoing neoadjuvant dual HER2-targeted therapy, achieving a pathologic complete response or residual cancer burden I in the breast strongly correlates with a high probability of having no residual disease in the axillary lymph nodes, suggesting a potential consideration for omitting axillary surgical staging in future trials for those demonstrating these favorable responses. [Read the Full Post]

RGCC-mediated PLK1 activity drives breast cancer lung metastasis by phosphorylating AMPKα2 to activate oxidative phosphorylation and fatty acid oxidation

27 | Jan 25 2024

The study reveals that RGCC overexpression drives a signaling cascade, involving PLK1 and AMPKα2, enhancing metabolic adaptations in TNBC cells, providing crucial insights and potential therapeutic targets for combating lung-specific metastasis in triple-negative breast cancer. [Read the Full Post]

Chaetocin-mediated SUV39H1 inhibition targets stemness and oncogenic networks of diffuse midline gliomas and synergizes with ONC201

65 | Jan 22 2024

Targeting the SUV39H1-H3K9me3 pathway in DIPG cells with chaetocin, and combining it with a DRD2 antagonist like ONC201, presents a promising strategy for effective treatment by exploiting vulnerabilities and overcoming resistance mechanisms. [Read the Full Post]

Contribution of Telomere Length to Systemic Sclerosis Onset: A Mendelian Randomization Study

48 | Jan 21 2024

The study utilizing Mendelian randomization suggests a causal link between longer leukocyte telomere length and a reduced risk of systemic sclerosis, implicating the influence of specific genetic variants in TERC and TERT genes. [Read the Full Post]

Regulation of the integrin αVβ3- actin filaments axis in early osteogenic differentiation of human mesenchymal stem cells under cyclic tensile stress

20 | Jan 20 2024

Cyclic tensile stress influences early osteogenesis in human mesenchymal stem cells through the integrin αVβ3-actin filaments axis while involving nuclear localization of YAP. [Read the Full Post]

AT7867 promotes pancreatic progenitor differentiation of human iPSCs

47 | Jan 18 2024

AT7867 treatment significantly enhances the differentiation of pancreatic progenitor cells, resulting in increased expression of key markers and accelerated diabetes reversal upon transplantation into diabetic mice. [Read the Full Post]

Leukadherin-1 inhibits NLRP3 inflammasome by blocking inflammasome assembly

32 | Jan 15 2024

Leukadherin-1 (LA-1) demonstrates potent inhibition of NLRP3 inflammasome activation through specific mechanisms, suggesting its potential as a targeted treatment for NLRP3-associated inflammatory diseases. [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]

Target-based virtual screening, computational multiscoring docking and molecular dynamics simulation of small molecules as promising drug candidate affecting kinesin-like protein KIFC1

33 | Jan 09 2024

The computational analysis identified mcule-4895338547 as a promising small-molecule inhibitor targeting KIFC1, showing strong binding affinity and favorable properties, holding potential for further exploration in cancer treatment. [Read the Full Post]

Synthesis, Screening and Characterization of Novel Potent Arp2/3 Inhibitory Compounds Analogous to CK-666

33 | Jan 07 2024

A comprehensive screening of 74 compounds related to CK-666 revealed two potent Arp2/3 inhibitors, compounds 59 and 69, which displayed improved in vivo efficiency despite being slightly less effective in vitro, validating original assays for Arp2/3 activity while offering promising candidates for further study. [Read the Full Post]

Wnt signaling pathway inhibitor promotes mesenchymal stem cells differentiation into cardiac progenitor cells in vitro and improves cardiomyopathy in vivo

34 | Jan 04 2024

"IWP-4 treatment of mesenchymal stem cells from human umbilical cord tissue enhances cardiac differentiation, leading to improved myocardial regeneration and functional recovery in a myocardial infarction rat model." [Read the Full Post]

Comprehensive analysis of angiogenesis pattern and related immune landscape for individual treatment in osteosarcoma

32 | Jan 01 2024

The ANGscore, a novel prognostic model based on angiogenesis patterns in osteosarcoma, not only accurately predicts patient outcomes and immune characteristics but also holds promise in guiding personalized treatment strategies and immunotherapy responses for better clinical management. [Read the Full Post]

CCT251545 enhances drug delivery and potentiates chemotherapy in multidrug-resistant cancers by Rac1-mediated macropinocytosis

57 | Dec 30 2023

The study's findings suggest that CCT251545 in combination with chemotherapy demonstrates a potent synergistic effect by enhancing drug uptake through Rac1-dependent macropinocytosis and elevating NAD levels, providing a promising avenue for managing multidrug-resistant cancers. [Read the Full Post]

PM2.5 induces cardiac malformations via PI3K/akt2/mTORC1 signaling pathway in zebrafish larvae

85 | Dec 27 2023

Exposure to PM2.5 triggers a complex cascade involving PI3K/akt2/mTORC1 signaling through AHR/ROS-induced PTEN suppression, leading to mitochondrial-mediated intrinsic apoptosis, Wnt signaling suppression, and ultimately contributing to cardiac defects in zebrafish larvae. [Read the Full Post]

Development and Validation of a Novel UHPLC-MS/MS Method for the Quantification of Plinabulin in Plasma and Its Application in a Pharmacokinetic Study with Leukopenic Rats

41 | Dec 25 2023

This study on plinabulin's pharmacokinetics in rats suggests no significant differences between leukopenia and control groups, indicating its potential as a candidate for treating chemotherapy-induced leukopenia pending further human clinical trials. [Read the Full Post]

Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma

48 | Dec 22 2023

This study employs a bioinformatics screening protocol integrating drug-sensitivity data and basal gene expression to predict synergistic combinations of histone deacetylase inhibitors (HDACi), identifying the sphingolipid signaling pathway as a promising target; further experimental validation reveals novel synergisms between HDACi and a Rho-associated protein kinase (ROCK) inhibitor RKI-1447, as well as between HDACi and a sphingosine 1-phosphate (S1P) receptor agonist fingolimod in the treatment of pancreatic ductal adenocarcinoma (PDAC). [Read the Full Post]

Identification of potential biomarkers and immune infiltration characteristics in recurrent implantation failure using bioinformatics analysis

39 | Dec 20 2023

This study reveals altered immune cell infiltration, identifies key signaling pathways, and proposes potential diagnostic markers and therapeutic compounds for recurrent implantation failure, offering valuable insights for improving endometrial receptivity in reproductive medicine. [Read the Full Post]

Enhancing reporting quality and impact of early phase dose-finding clinical trials: CONSORT Dose-finding Extension (CONSORT-DEFINE) guidance

37 | Dec 18 2023

CONSORT-DEFINE provides international, consensus-driven guidelines for reporting early phase dose-finding trials, emphasizing essential items to enhance transparency, completeness, and reproducibility, thereby promoting clear interpretation and informed decision-making in medical research and practice. [Read the Full Post]

GRP78 acts as a cAMP/PKA signaling modulator through the MC4R pathway in porcine embryonic development

55 | Dec 17 2023

In this study, inhibiting Glucose-regulated protein 78 (GRP78) function using HA15 during porcine embryonic development disrupted the MC4R pathway, downregulated cAMP/PKA signaling, inhibited cell cycle progression, and induced mitochondrial dysfunction, revealing the crucial role of GRP78 in regulating these processes. [Read the Full Post]

5-HT6 receptor antagonists. Design, synthesis, and structure-activity relationship of substituted 2-(1-methyl-4-piperazinyl)pyridines

63 | Dec 16 2023

The study presents a novel series of 6-piperazinyl-7-azaindoles demonstrating potent 5-HT6 receptor antagonism, with a focus on optimizing the lead structure and exploring structure-activity relationships, highlighting Compound 29 as a promising candidate for further drug development. [Read the Full Post]

Glucose metabolic upregulation via phosphorylation of S6 ribosomal protein affects tumor progression in distal cholangiocarcinoma

68 | Dec 13 2023

In summary, the study reveals that inhibiting phosphorylated S6 ribosomal protein, a marker of mTORC1 activity, suppresses glucose metabolism pathways and reduces cell proliferation, suggesting mTORC1 as a potential therapeutic target in distal cholangiocarcinoma. [Read the Full Post]

Optimization of the Lead Compound NVP-BHG712 as a Colorectal Cancer Inhibitor

30 | Dec 12 2023

In this study, a series of EPHA2 kinase inhibitors, including derivatives of NVP-BHG712 and triazine-based compounds, were synthesized and evaluated, revealing eight inhibitors with low-nanomolar affinities (KD <10 nM) that demonstrated promising effects in controlling human colon carcinoma, highlighting their potential as therapeutic tools in cancer research. [Read the Full Post]

Retinoic acid delays murine palatal shelf elevation by inhibiting Wnt5a-mediated noncanonical Wnt signaling and downstream Cdc-42/F-actin remodeling in mesenchymal cells

40 | Dec 10 2023

This study elucidates the mechanism by which retinoic acid disrupts palate development, causing cleft palate in mice, revealing the crucial role of Wnt5a-mediated noncanonical Wnt signaling downstream of Rho GTPase Cdc42 in regulating cytoskeletal remodeling and cell migration during the process. [Read the Full Post]

Transcriptomics-Guided In Silico Drug Repurposing: Identifying New Candidates with Dual-Stage Antiplasmodial Activity

57 | Dec 08 2023

The research effort identified two promising compounds, HSP-990 and silvestrol aglycone, demonstrating potent inhibitory activity at nanomolar concentrations against the asexual blood stage of Plasmodium falciparum, with silvestrol aglycone showing low cytotoxicity and transmission-blocking potential, indicating their potential as dual-acting antimalarial and transmission-blocking candidates for malaria control. [Read the Full Post]

Anticancer effects of ABTL0812, a clinical stage drug inducer of autophagy-mediated cancer cell death, in glioblastoma models

66 | Dec 07 2023

The study demonstrates that ABTL0812, an oral anticancer compound, inhibits GBM cell proliferation, reverses proneural to mesenchymal transition, induces cell differentiation, and promotes autophagy-mediated cell death, providing compelling evidence for its potential as a novel therapy, either alone or in combination with standard treatments, for glioblastoma multiforme. [Read the Full Post]

Pyrintegrin Induces Soft Tissue Formation by Transplanted or Endogenous Cells

26 | Dec 06 2023

The experimental study demonstrates that Pyrintegrin (Ptn) promotes robust adipogenesis both in vitro and in vivo, suggesting its potential therapeutic application in soft tissue reconstruction and augmentation by inducing the formation of adipose tissue from transplanted and endogenous cells. [Read the Full Post]

Preclinical Efficacy of Covalent-Allosteric AKT Inhibitor Borussertib in Combination with Trametinib in KRAS-Mutant Pancreatic and Colorectal Cancer

23 | Dec 01 2023

The discovery of borussertib, a covalent-allosteric AKT inhibitor, and its demonstrated efficacy in combination with the MEK inhibitor trametinib in patient-derived xenograft models represent a promising advancement in targeted cancer therapy for individuals with specific genetic alterations in the PTEN, PI3K, and RAS signaling pathways. [Read the Full Post]

Indication for a Pneumocystis Prophylaxis Therapy in Patients with Vascular Anomalies Treated with PIK3/AKT/mTOR Pathway Inhibitors: Experts' Opinion and Systematic Review from the Literature

22 | Nov 27 2023

The study underscores the rare but existing risk of Pneumocystis jirovecii pneumonia in patients with vascular anomalies treated with mTOR inhibitors, indicating the potential benefit of prophylaxis, particularly with trimethoprim-sulfamethoxazole, for specific high-risk patient groups. [Read the Full Post]

Cytoplasmic Hsp70s promote EcR transport into the nucleus by responding to various stimuli

58 | Nov 27 2023

This study reveals that cytoplasmic Hsp70s facilitate the transport of the ecdysone receptor (EcR) into the nucleus in response to diverse stimuli, shedding light on the intricate mechanisms underlying insect metamorphosis and highlighting potential applications in pest control and broader biological research. [Read the Full Post]

Indole derivatives targeting colchicine binding site as potential anticancer agents

35 | Nov 27 2023

Research on indole derivatives targeting the colchicine-binding site (CBS) of microtubules holds significant promise for the development of novel and effective anticancer therapies with improved efficacy and reduced toxicity. [Read the Full Post]

Overfit deep neural network for predicting drug-target interactions

105 | Nov 27 2023

The OverfitDTI framework utilizes intentionally overfitted deep neural networks to accurately capture the intricate relationships between drugs and targets, enabling precise drug-target interaction predictions, as demonstrated by the successful identification and experimental validation of TEK inhibitors. [Read the Full Post]

TTK Protein Kinase promotes temozolomide resistance through inducing autophagy in glioblastoma

40 | Nov 26 2023

Inhibition of TTK Protein Kinase (TTK) using specific inhibitors, in combination with Temozolomide (TMZ) chemotherapy, overcomes TMZ resistance in glioblastoma multiforme (GBM) cells by suppressing autophagy, suggesting a promising therapeutic strategy for improving treatment outcomes in GBM patients. [Read the Full Post]

Oridonin Synergistically Enhances the Pro-Apoptotic Effect of Venetoclax on Acute Myeloid Leukemia Cells by Inhibiting AKT Signaling

30 | Nov 23 2023

**Synergistic inhibition of AKT signaling by oridonin enhances the apoptotic effects of venetoclax, offering a promising combination therapy to overcome resistance and improve outcomes in acute myeloid leukemia.** [Read the Full Post]

Target Residence Time-Guided Optimization on TTK Kinase Results in Inhibitors with Potent Anti-Proliferative Activity

43 | Nov 22 2023

The study reveals that TTK inhibitors, particularly those inducing a shift in the glycine-rich loop by binding to the catalytic lysine at position 553, disrupt the catalytic machinery, leading to potent anti-proliferative effects, offering promising avenues for cancer treatment. [Read the Full Post]

High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers

47 | Nov 22 2023

BOS172722 is a potent spindle assembly checkpoint kinase MPS1 inhibitor that, in combination with paclitaxel, demonstrates significant synergistic effects, inducing chromosomal segregation defects and robust tumor regressions in preclinical models of triple-negative breast cancer, indicating its potential as a promising therapeutic approach for this patient population. [Read the Full Post]

Identifying promising GSK3β inhibitors for cancer management: a computational pipeline combining virtual screening and molecular dynamics simulations

46 | Nov 21 2023

The computational screening study identified BMS-754807 and GSK429286A as promising GSK3β inhibitors with high binding affinities, suggesting their potential as novel anticancer drugs pending experimental validation. [Read the Full Post]

Identification of circRNA-miRNA-mRNA network regulated by Hsp90 in human melanoma A375 cells

48 | Nov 21 2023

The study reveals that targeting the ECM-receptor interaction pathway, specifically the integrin (ITG) and collagen (COL) network, following Hsp90 inhibition by SNX-2112, offers a promising and novel therapeutic approach for melanoma treatment. [Read the Full Post]

Heat shock factor 1 is a promising therapeutic target against adult T-cell leukemia

73 | Nov 18 2023

Targeting the overexpressed heat shock factor 1 (HSF1) with the inhibitor KRIBB11 inhibits proliferation, induces apoptosis, disrupts essential signaling pathways, and sensitizes adult T-cell leukemia cells to HSP90 inhibition, offering a potential therapeutic approach for ATL. [Read the Full Post]

Virtual screening indicates potential inhibitors of the P2X7 receptor

27 | Nov 14 2023

The passage discusses the search for natural and synthetic anti-inflammatory compounds, highlighting the identification of potential P2X7 receptor inhibitors, including flavonoids and drugs, through virtual screening and subsequent in vitro validation. [Read the Full Post]

HSP70 attenuates neuronal necroptosis through the HSP90α-RIPK3 pathway following neuronal trauma

49 | Nov 14 2023

Activation of HSP70 protects against necroptosis in neuronal trauma, with HSP90α-mediated regulation of RIPK3 and MLKL contributing to this protective effect. [Read the Full Post]

Scutellarin suppresses the metastasis of triple-negative breast cancer via targeting TNFα/TNFR2-RUNX1-triggered G-CSF expression in endothelial cells

139 | Nov 13 2023

Scutellarin (SC) inhibits metastasis in triple-negative breast cancer (TNBC) by disrupting the TNFα/TNFR2-initiated RUNX1 activation and subsequent G-CSF production in TNBC-associated endothelial cells (ECs). [Read the Full Post]

Physalis Mottle Virus-Like Nanocarriers with Expanded Internal Loading Capacity

40 | Nov 10 2023

The engineering of cysteine-added mutants of PhMV VLPs has significantly improved their reactivity and cargo-loading capacity, making them promising nanocarriers for precise delivery of small-molecule drugs and imaging reagents in vivo. [Read the Full Post]

The Anti-Breast Cancer Stem Cell Potency of Copper(I)-Non-Steroidal Anti-Inflammatory Drug Complexes

33 | Nov 10 2023

A series of copper(I) complexes combining non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine ligands demonstrated potent anti-breast cancer stem cell activity, reducing cell viability and increasing intracellular reactive oxygen species (ROS) levels, potentially opening new avenues for breast cancer treatment. [Read the Full Post]

Combined inhibition of aurora kinases and Bcl-xL induces apoptosis through select BH3-only proteins

0 | Nov 08 2023

The study demonstrates that combining small-molecule inhibitors of AURK with BH3-mimetic inhibitors targeting Bcl-xL potently induces apoptosis and may overcome resistance to AURK inhibitors in colon cancer cells. [Read the Full Post]

GRP78 Inhibitor YUM70 Suppresses SARS-CoV-2 Viral Entry, Spike Protein Production and Ameliorates Lung Damage

27 | Nov 04 2023

The study demonstrated that the small molecule inhibitor YUM70, which targets the GRP78 protein, effectively blocked SARS-CoV-2 viral entry and infection in vitro and in vivo, suggesting its potential as a promising therapeutic approach against COVID-19 and its variants. [Read the Full Post]

Dynamic expression of IGFBP3 modulate dual actions of mineralization micro-environment during tooth development via Wnt/beta-catenin signaling pathway

60 | Oct 31 2023

This study demonstrates that IGFBP3 regulates the mineralization microenvironment during tooth development through its modulation of the DKK1-Wnt/beta-catenin axis, highlighting its potential importance in tooth regeneration and dental care. [Read the Full Post]

CX3CL1 in the red bone marrow promotes renal cell carcinoma to metastasize to the spine by involving the Src-related pathway

46 | Oct 30 2023

CX3CL1 promotes migration and invasion of renal cell carcinoma (RCC) cells, potentially facilitating RCC metastasis to the spine, through activation of the Src/FAK signaling pathway. [Read the Full Post]

Identification of Tau-Tubulin Kinase 1 Inhibitors by Microfluidics-based Mobility Shift Assay from a Kinase Inhibitor Library

73 | Oct 29 2023

This study identified a peptide substrate for human TTBK1 and developed a microfluidics-based assay, enabling the screening of kinase inhibitors and the potential development of novel hTTBK1 inhibitors for Alzheimer's disease prevention. [Read the Full Post]

A novel denoising method for low-dose CT images based on transformer and CNN

77 | Oct 28 2023

The paper proposes a novel LDCT image denoising method based on a transformer combined with a convolutional neural network (CNN), which effectively removes noise and improves image quality, outperforming state-of-the-art models in evaluation metrics such as PSNR, SSIM, and RMSE. [Read the Full Post]

Traf2 and NCK Interacting Kinase Is a Critical Regulator of Procollagen I Trafficking and Hepatic Fibrogenesis in Mice

113 | Oct 27 2023

The study identified TNIK as a key kinase involved in procollagen I trafficking and demonstrated its potential as a therapeutic target for hepatic fibrosis. [Read the Full Post]

YAP and β-catenin cooperate to drive H. pylori-induced gastric tumorigenesis

77 | Oct 26 2023

This study provides evidence that the interaction between Yes-associated protein 1 (YAP) and β-catenin synergistically promotes H. pylori-induced gastric carcinogenesis and identifies shared downstream genes, CDX2, LGR5, and RUVBL1, potentially contributing to the pathogenesis of H. pylori-associated gastric cancer. [Read the Full Post]

Pak1 pathway hyper-activation mediates resistance to endocrine therapy and CDK4/6 inhibitors in ER+ breast cancer

62 | Oct 23 2023

This study demonstrates that p21-activated kinase 1 (Pak1) plays a crucial role in resistance to estrogen receptor antagonists and CDK4/6 inhibitors in estrogen receptor-positive (ER+) breast cancer, suggesting the potential for Pak1 inhibitors as a therapeutic approach for patients with ER+ breast cancer who have become resistant to current treatments. [Read the Full Post]

[p53 regulates primordial follicle activation through the mTOR signaling pathway]

74 | Oct 22 2023

This study demonstrated that p53 inhibits primordial follicle activation through the mTOR signaling pathway, thereby maintaining the reserve of primordial follicles. [Read the Full Post]

Double crosslinked biomimetic composite hydrogels containing topographical cues and WAY-316606 induce neural tissue regeneration and functional recovery after spinal cord injury

34 | Oct 21 2023

The study presents a multifunctional biomaterial system composed of acellularized spinal cord matrix, gelatin-acrylated-β-cyclodextrin-polyethene glycol diacrylate hydrogel, and aligned polycaprolactone microfibers, loaded with WAY-316606, which effectively promotes neural tissue regeneration and significantly improves motor function in rats with spinal cord injury. [Read the Full Post]

PTK2B regulates immune responses of neutrophils and protects mucosal inflammation in ulcerative colitis

62 | Oct 14 2023

Proline-rich tyrosine kinase 2B (PTK2B) plays a role in the pathogenesis of ulcerative colitis (UC) by promoting neutrophil migration and inhibiting mucosal inflammation, making it a potential therapeutic target for UC treatment. [Read the Full Post]

Olverembatinib Treatment in Pediatric Patients With Relapsed Philadelphia-Chromosome-Positive Acute Lymphoblastic Leukemia

68 | Oct 13 2023

In this study, olverembatinib demonstrated both safety and efficacy in children with relapsed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), including some achieving complete remission as a single agent. [Read the Full Post]

The Novel Cardiac Myosin Activator Danicamtiv Improves Cardiac Systolic Function at the Expense of Diastolic Dysfunction In Vitro and In Vivo: Implications for Clinical Applications

44 | Oct 13 2023

Danicamtiv, a direct myosin activator, has demonstrated positive effects on cardiac systolic function but may impair diastolic performance, particularly at higher concentrations, indicating a need for cautious dosing and monitoring. [Read the Full Post]

Pharmacological Inhibition of p-21 Activated Kinase (PAK) Restores Impaired Neurite Outgrowth and Remodeling in a Cellular Model of Down Syndrome

79 | Oct 12 2023

In a cellular model of Down syndrome, overexpression of APP and subsequent PAK1 hyperphosphorylation impair neurite outgrowth and remodeling, suggesting PAK1 as a potential pharmacological target for intervention. [Read the Full Post]

Apatinib Inhibits Stem Properties and Malignant Biological Behaviors of Breast Cancer Stem Cells by Blocking Wnt/β-catenin Signal Pathway through Downregulating LncRNA ROR

15 | Oct 12 2023

Apatinib effectively inhibits the stem-like properties and malignant behaviors of breast cancer stem cells (BCSCs) by suppressing the Wnt/β-catenin pathway through downregulation of lncRNA ROR. [Read the Full Post]

CRIP1 supports the growth and migration of AML-M5 subtype cells by activating Wnt/β-catenin pathway

67 | Oct 10 2023

CRIP1, an oncogene overexpressed in AML cells, promotes cell survival and migration through the activation of the Wnt/β-catenin pathway, making it a potential therapeutic target for AML-M5 treatment. [Read the Full Post]

Screening and Analysis of Possible Drugs Binding to PDGFRα: A Molecular Modeling Study

69 | Oct 09 2023

This study aimed to identify new ligands for the platelet-derived growth factor receptor (PDGFR) through screening of thousands of compounds, resulting in the selection of potential drugs and natural compounds with high affinity, providing valuable insights for the development of more effective treatments for PDGFR-related diseases. [Read the Full Post]

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

74 | 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]

The First Case of Human Hepatic Fasciolosis Presented as Hepatic Pseudotumor Histopathologically Diagnosed in Romania-A Case Report

35 | Oct 05 2023

The case report highlights the importance of considering fasciolosis as a potential diagnosis even in areas where it is not commonly observed, emphasizing the need for careful evaluation in patients presenting with relevant symptoms. [Read the Full Post]

Preparation and Properties of Natural Polysaccharide-Based Drug Delivery Nanoparticles

85 | Oct 05 2023

The paper presents the development of RGD-(NPGP/CS)3NPGP nanoparticles through layer-by-layer assembly, which demonstrate high encapsulation efficiency, pH-sensitive release, and effective targeting to integrin receptor-expressing tumor cells, making them promising as novel anticancer drug carriers. [Read the Full Post]

Effectiveness of netarsudil 0.02% in lowering intraocular pressure in patients with secondary glaucoma

62 | Oct 01 2023

Netarsudil, 0.02%, was found to be effective in lowering intraocular pressure (IOP) in patients with secondary forms of glaucoma, especially uveitic glaucoma. [Read the Full Post]

Bone impact after two years of low-dose oral contraceptive use during adolescence

62 | Sep 29 2023

The present study indicates that the use of combined hormonal contraceptives in healthy adolescents is associated with compromised bone mass acquisition, with a more pronounced negative impact observed in those using contraceptives containing 30 μg of Ethinylestradiol. [Read the Full Post]

RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer

84 | Sep 27 2023

RNF112 suppresses gastric cancer progression by directly ubiquitinating FOXM1, making the RNF112/FOXM1 axis a potential prognostic biomarker and therapeutic target in gastric cancer. [Read the Full Post]

Effectiveness of netarsudil 0.02% in lowering intraocular pressure in patients with secondary glaucoma

109 | Sep 27 2023

Netarsudil, 0.02%, was found to effectively lower intraocular pressure in patients with secondary forms of glaucoma, particularly uveitic glaucoma, based on a retrospective study. [Read the Full Post]

A randomized trial of eribulin monotherapy versus eribulin plus anlotinib in patients with locally recurrent or metastatic breast cancer

108 | Sep 08 2023

The combination of eribulin and anlotinib demonstrated improved progression-free survival and disease control rates compared to eribulin monotherapy in patients with HER2-negative locally recurrent or metastatic breast cancer, suggesting it as a potential alternative treatment option. [Read the Full Post]

Current and emerging pharmacotherapy for the management of hypertrophic cardiomyopathy

77 | Sep 03 2023

The emerging cardiac myosin inhibitors (CMIs) and ongoing research into targeted therapies and gene therapy hold promise for improving the management and treatment of hypertrophic cardiomyopathy (HCM). [Read the Full Post]

Effect of chronopharmacology and food on in vivo pharmacokinetic profile of mavacamten

87 | Sep 03 2023

This study found that circadian rhythms significantly impact the pharmacokinetics of mavacamten in rats, while food intake has a minimal effect, highlighting the importance of considering chronopharmacology in optimizing dosing time for this drug. [Read the Full Post]

Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases

96 | Aug 25 2023

This comprehensive review highlights the structure, biological functions, and therapeutic potential of CLKs and their inhibitors, shedding light on their significance in various human diseases and paving the way for future clinical treatments. [Read the Full Post]

Comparison of multiple synthetic chondroinductive factors in pellet culture against a TGF-β positive control

105 | Aug 25 2023

The current study found that, despite the promising potential of CM10, CK2.1, kartogenin, and SM04690 as chondroinductive agents, they did not exhibit higher gene expression of chondrogenic markers compared to the positive control TGF-β3, suggesting the need for further research and identification of new chondroinductive factors. [Read the Full Post]

Pro-inflammatory role of Wnt/β-catenin signaling in endothelial dysfunction

119 | Aug 21 2023

The inhibition of the Wnt/β-catenin signaling pathway with iCRT-14 improved endothelial function by reducing inflammation and monocyte adhesion but also exhibited pro-coagulatory effects and hindered wound healing, which may impact its suitability as a therapy for atherosclerosis and vein graft failure. [Read the Full Post]

Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib

43 | Aug 11 2023

This study proposes the use of AI-designed gamma-tocotrienol (AIGT) as a potential therapeutic option for chronic myeloid leukemia (CML) by targeting the BCR-ABL1 fusion protein, exhibiting promising efficacy and potential hepatoprotective properties compared to existing medications. [Read the Full Post]

The EMA Assessment of Asciminib for the Treatment of Adult Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Who Were Previously Treated With At Least 2 Tyrosine Kinase Inhibitors

78 | Aug 11 2023

Asciminib, an allosteric high-affinity tyrosine kinase inhibitor, received marketing authorization from the European Commission for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase after evaluating its clinical efficacy and safety in the phase III ASCEMBL study. [Read the Full Post]

A phase II trial of GSK2256098 and trametinib in patients with advanced pancreatic ductal adenocarcinoma

67 | Aug 08 2023

The combination of GSK2256098 and trametinib did not show significant clinical benefit in advanced pancreatic ductal adenocarcinoma (PDAC) patients, with short median progression-free survival and overall survival observed in the study. [Read the Full Post]

Progress in on-line, at-line, and in-line coupling of sample treatment with capillary and microchip electrophoresis over the past 10 years: A review

83 | Aug 05 2023

The review evaluates the progress of on-line, at-line, and in-line sample treatment coupled with capillary and microchip electrophoresis over the past decade, focusing on the development of flow-gating interfaces, the coupling of extraction techniques, and the design of sequential analyzers, with applications in studying living organisms and monitoring substances in diverse samples. [Read the Full Post]

Prostate cancer cell‑derived spondin 2 boosts osteogenic factor levels in osteoblasts via the PI3K/AKT/mTOR pathway

78 | Aug 04 2023

Spondin 2 promotes osteogenesis in prostate cancer by activating the PI3K/AKT/mTOR pathway and involving the integrin receptor α5β1. [Read the Full Post]

Modulation of gene expression on a transcriptome-wide level following human neural stem cell transplantation in aged mouse stroke brains

19 | Aug 04 2023

This study demonstrates that transplantation of human neural stem cells (NSCs) in aged mice after stroke reduces infarct size, modulates proinflammatory factors and matrix metalloproteases, and induces differential expression of genes and pathways associated with neuroinflammation, cell adhesion, and matrix remodeling. [Read the Full Post]

NAD + Metabolism Generates a Metabolic Vulnerability in Endocrine-Resistant Metastatic Breast Tumors in Females

103 | Aug 03 2023

The study revealed that combining a NAMPT inhibitor with fulvestrant showed a synergistic effect in reducing metastatic tumor burden and reversing gene expression associated with aggressive tumor phenotypes in ER+ metastatic breast cancer, offering a promising strategy for treatment. [Read the Full Post]

KIF11 is a potential prognostic biomarker and therapeutic target for adrenocortical carcinoma

65 | Aug 02 2023

The study demonstrated that the overexpression of KIF11 in adrenocortical carcinoma (ACC) is associated with poor prognosis and suggests that KIF11 may serve as a potential therapeutic target for ACC. [Read the Full Post]

Diminishing the Pathogenesis of the Food-Borne Pathogen Serratia marcescens by Low Doses of Sodium Citrate

33 | Jul 24 2023

Sodium citrate, when used at low concentrations, exhibits significant anti-virulence and anti-biofilm activity against Serratia marcescens, making it a safe and effective food additive for preventing contamination and spoilage. [Read the Full Post]

Inflammatory Response and Exosome Biogenesis of Choroid Plexus Organoids Derived from Human Pluripotent Stem Cells

55 | Jul 22 2023

This study investigates the impact of Wnt signaling on inflammatory response and extracellular vesicle biogenesis in choroid plexus organoids derived from human-induced pluripotent stem cells, providing a model for drug screening and designing drug delivery systems for neurological disorders such as Alzheimer's disease and ischemic stroke. [Read the Full Post]

Targeting FLT3 Mutation in Acute Myeloid Leukemia: Current Strategies and Future Directions

28 | Jul 16 2023

FLT3 inhibitors have improved clinical outcomes for acute myeloid leukemia patients with FLT3 mutations, but the emergence of resistance and the need for novel therapeutic strategies remain ongoing challenges. [Read the Full Post]

Dynamin-independent CaV1.2 and KCa1.1 channels regulation and vascular tone modulation by the mitochondrial fission inhibitors dynasore and dyngo-4a

44 | Jul 15 2023

The study raises caution regarding the use of dynasore, mdivi-1, and dyngo-4a as tools to investigate the role of mitochondrial fission in vascular contraction, emphasizing the need for a selective dynamin inhibitor and/or alternative experimental approaches. [Read the Full Post]

Specific gene module pair-based target identification and drug discovery

0 | Jul 14 2023

The GMPTI method extracts target-induced gene modules to identify target signatures and predict novel compound-target interactions, leading to the discovery of novel inhibitors for three proteins in the PI3K pathway. [Read the Full Post]

Molecular insights into the behavior of the allosteric and ATP-competitive inhibitors in interaction with AKT1 protein: A molecular dynamics study

25 | Jul 12 2023

This computational study investigated the effects of various AKT1 inhibitors on the inactive and active conformations of the protein, revealing stable complexes and highlighting MK-2206 as having the strongest binding affinity in the inactive conformation and van der Waals interactions as the main contributors to binding energy. [Read the Full Post]

Cell recognitive bioadhesive-based osteogenic barrier coating with localized delivery of bone morphogenetic protein-2 for accelerated guided bone regeneration

93 | Jul 11 2023

A bioengineered mussel adhesive protein (MAP) fused with an Alg-Gly-Asp (RGD) peptide coating on titanium mesh (Ti-mesh) enables effective cell occlusion, localized delivery of bone morphogenetic protein-2 (BMP-2), and accelerated bone regeneration, making it a promising approach for guided bone regeneration (GBR) treatments. [Read the Full Post]

Synthesis of Novel Carborane-Containing Derivatives of RGD Peptide

78 | Jul 11 2023

Carborane derivatives of the N- and C-protected RGD peptide containing a glutaric acid residue as a linker fragment have demonstrated potential as starting compounds for the synthesis of unprotected or selectively protected peptides and as building blocks for the development of more complex boron-containing derivatives of the RGD peptide for targeted delivery in tumor treatment, such as glioblastoma. [Read the Full Post]

Topical Ripasudil for the Treatment of Segmental Corneal Edema: A Case Series

128 | Jul 10 2023

Topical ripasudil has shown promising results in improving vision and resolving corneal edema in patients with focal corneal edema following anterior segment surgeries, serving as an effective treatment option that may reduce the need for endothelial transplantation. [Read the Full Post]

Ripasudil-Brimonidine Fixed-Dose Combination vs Ripasudil or Brimonidine: Two Phase 3 Randomized Clinical Trials

66 | Jul 10 2023

The results of the study demonstrated that the ripasudil-brimonidine fixed-dose combination (RBFC) had a greater ability to lower intraocular pressure (IOP) compared to ripasudil or brimonidine alone. [Read the Full Post]

Apoptotic cell death in disease-Current understanding of the NCCD 2023

151 | Jul 09 2023

The Nomenclature Committee on Cell Death (NCCD) critically summarizes the extensive pre-clinical literature linking the core apoptotic apparatus to organismal homeostasis in various disease contexts, highlighting its role in both disease etiology and potential therapeutic interventions. [Read the Full Post]

FUT8-Mediated Core Fucosylation Promotes the Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

24 | Jul 08 2023

This study highlights the significant involvement of FUT8-mediated core fucosylation in pulmonary vascular remodeling in pulmonary arterial hypertension (PAH), suggesting FUT8 as a potential novel therapeutic target for PAH. [Read the Full Post]

Comparative transcriptome profile of mouse macrophages treated with the RhoA/Rock pathway inhibitors Y27632, Fingolimod (Gilenya), and Rezurock (Belumosudil, SLx-2119)

38 | Jul 07 2023

The transcriptome profiling study comparing macrophages treated with Y27632, Fingolimod, and Rezurock revealed distinct downregulation of GTPase and actin pathways in cell migration for Y27632 and Fingolimod, while Rezurock specifically downregulated fibrosis-related genes, providing insights into the differences in their anti-chronic rejection properties and aiding in the development of targeted therapies. [Read the Full Post]

Discovery of indoline-based derivatives as effective ROCK2 inhibitors for the potential new treatment of idiopathic pulmonary fibrosis

91 | Jul 07 2023

A new series of selective ROCK2 inhibitors based on indoline, particularly compound 9b, showed promising results in inhibiting collagen gel contraction, suppressing fibrotic markers, and exhibiting anti-pulmonary fibrosis effects in a bleomycin-induced IPF rat model, suggesting its potential as a lead compound for IPF treatment. [Read the Full Post]

Isoxazole 9 (ISX9), a small molecule targeting Axin, activates Wnt/β-catenin signalling and promotes hair regrowth

77 | Jul 05 2023

The study identified ISX9 as a novel activator of the Wnt/β-catenin pathway, promoting hair regrowth and suggesting its potential as a therapeutic agent for alopecia treatment. [Read the Full Post]

ISX-9 potentiates CaMKIIδ-mediated BMAL1 activation to enhance circadian amplitude

46 | Jul 05 2023

ISX-9, a neurogenic small molecule, has shown promising effects in improving circadian amplitude, metabolic rhythms, sleep homeostasis, and locomotive activity, making it a potential candidate for treating circadian-related disorders. [Read the Full Post]

The effect of sex on retinopathy of prematurity severity among premature mixed-sex multiple gestation infants

42 | Jun 29 2023

This retrospective study of 68 premature infants found no significant difference between male and female mixed-sex multiple gestation infants in terms of the most severe stage of retinopathy of prematurity (ROP) developed or the need for ROP treatment, but males received treatment at an earlier postmenstrual age (PMA) despite females having lower birthweight and slower growth velocity. [Read the Full Post]

Identifying a selective inhibitor of autophagy that targets ATG12-ATG3 protein-protein interaction

47 | Jun 29 2023

Compound 189, identified through a high throughput compound screen, selectively inhibits the ATG12-ATG3 protein-protein interaction involved in autophagy, demonstrating potential as a therapeutic drug for autophagy-dependent tumors and inflammation. [Read the Full Post]

Runx3-overexpression cooperates with ex vivo AKT inhibition to generate receptor-engineered T cells with better persistence, tumor-residency, and antitumor ability

110 | Jun 28 2023

Combining Runx3 overexpression with ex vivo AKT inhibition generates CAR-T cells with both tissue-resident and central memory characteristics, enhancing their persistence, cytotoxic potential, and tumor-residency ability for the treatment of solid tumors. [Read the Full Post]

Modulation of blood-brain tumor barrier for delivery of magnetic hyperthermia to brain cancer

70 | Jun 25 2023

This proposed approach utilizes a polymeric nanocarrier to deliver fingolimod and modulate the blood-brain tumor barrier, allowing for targeted accumulation of magnetic nanoclusters and synergistic magnetic hyperthermia therapy for the treatment of glioblastoma [Read the Full Post]

Short-term follow-up pilot study of sole middle meningeal artery embolization for chronic subdural hematoma: influence of internal architecture on the radiological outcomes

83 | Jun 24 2023

The study found that patients with separated chronic subdural hematoma (CSDH) architecture had a lower rate of achieving the radiological endpoint and a slower rate of volume reduction compared to other CSDH types when treated with middle meningeal artery embolization (MMAE). [Read the Full Post]

Prognostic implication and immunotherapy response prediction of a ubiquitination-related gene signature in breast cancer

54 | Jun 23 2023

[Read the Full Post]

Molecular Docking, Molecular Dynamics Simulations, and Free Energy Calculation Insights into the Binding Mechanism between VS-4718 and Focal Adhesion Kinase

110 | Jun 21 2023

This research work elucidates the binding mechanism between VS-4718 and focal adhesion kinase (FAK), providing valuable insights for optimizing the design of FAK inhibitors in cancer therapy. [Read the Full Post]

Exploring MicroRNA and Exosome Involvement in Malignant Pleural Mesothelioma Drug Response

49 | Jun 20 2023

The study revealed that transfection of specific microRNAs enhanced the sensitivity of malignant pleural mesothelioma cells to chemotherapy and a FAK inhibitor, while also demonstrating that YM155-resistant cells showed increased exosome secretion and upregulation of drug transporter genes ABCA6 and ABCA10, which correlated with poor sensitivity to YM155. [Read the Full Post]

High-Content Drug Discovery Targeting Molecular Bladder Cancer Subtypes

51 | Jun 14 2023

This study utilized high-content screening drug discovery to identify subtype-specific therapies for muscle-invasive bladder cancer (MIBC), uncovering sensitivities to HDAC and CHK inhibitors in basal subtype, MDM2 inhibitors in luminal subtype, and an ITGAV inhibitor in mesenchymal-like subtype, with potential implications for personalized treatment strategies in clinical trials. [Read the Full Post]

Targeting Akt/PKB in pediatric tumors: A review from preclinical to clinical trials

0 | Jun 13 2023

Akt inhibitors show promise as a feasible and potentially effective approach for treating pediatric tumors by targeting the PI3K/Akt/mTOR signaling pathway. [Read the Full Post]

Azeliragon inhibits PAK1 and enhances the therapeutic efficacy of AKT inhibitors in pancreatic cancer

57 | Jun 12 2023

The study identified azeliragon as a potent inhibitor of PAK1 and demonstrated its ability to promote apoptosis in pancreatic cancer cells, inhibit tumor growth in a xenograft model, and exhibit a synergistic effect when combined with afuresertib, suggesting its potential as a novel treatment strategy for pancreatic cancer. [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]

Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma

52 | Jun 01 2023

The study found that copy number gains of loci containing the STAT3/5 oncogenes are present in 74% of L-CTCL cases and identified the STAT3/5 and PAK kinase interaction as a potential therapeutic target for L-CTCL. [Read the Full Post]

Aerobic exercise alleviates ventilator-induced lung injury by inhibiting NLRP3 inflammasome activation

35 | May 29 2023

The study found that exercise can reduce ventilator-induced lung injury by inhibiting PKCɑ and NLRP3 activation. [Read the Full Post]

Temperature sensing by the calcium-sensing receptor

48 | May 29 2023

The study suggests that CaSRs, a type of GPCR, may contribute to temperature sensing through a mechanism dependent on repetitive phosphorylation and dephosphorylation. [Read the Full Post]

CD137 signaling aggravates myocardial ischemia-reperfusion injury by inhibiting mitophagy mediated NLRP3 inflammasome activation

49 | May 26 2023

CD137 signaling exacerbates myocardial ischemia-reperfusion injury by suppressing mitophagy and promoting NLRP3 inflammasome activation via increased mitochondrial ROS generation. [Read the Full Post]

The off-target effects of dynamin inhibitor Dyngo-4a during the internalization of dextran by bone marrow mesenchymal stem cells in rat

54 | May 26 2023

The study concludes that the off-target effects of dynamin inhibitor Dyngo-4a are observed in the internalization of dextran by BMSCs. [Read the Full Post]

Commiphora myrrha stimulates insulin secretion from β-cells through activation of atypical protein kinase C and mitogen-activated protein kinase

60 | May 22 2023

The study investigated the molecular mechanism of action of Commiphora myrrha (CM)-induced insulin secretion and found that CM directly stimulates insulin secretion through activating known downstream effectors of insulin-stimulus secretion coupling, which is completely dependent on protein kinase activation, particularly the phosphorylation and activation of PKCζ and ERK1/2. [Read the Full Post]

Coronarin A modulated hepatic glycogen synthesis and gluconeogenesis via inhibiting mTORC1/S6K1 signaling and ameliorated glucose homeostasis of diabetic mice

23 | May 21 2023

Coronarin A, a natural compound isolated from Hedychium gardnerianum, has potential therapeutic effects in the treatment of type 2 diabetes mellitus by stimulating glycogen synthesis and suppressing gluconeogenesis via activation of the PI3K/Akt/GSK3β and ERK/Wnt/β-catenin pathways and inhibition of mTORC1/S6K1 signaling. [Read the Full Post]

Functional Assessment of Kinesin-7 CENP-E in Spermatocytes using In Vivo Inhibition, Immunofluorescence and Flow Cytometry

0 | May 21 2023

The article describes a practical and efficient in vivo inhibition method for kinesin-7 CENP-E in mouse spermatocytes via testicular injection, facilitating mechanistic studies of meiosis and potential clinical applications. [Read the Full Post]

Smoking-related epigenetic modifications are associated with the prognosis and chemotherapeutics of patients with bladder cancer

34 | May 19 2023

The study identified smoking-related epigenetic modifications in bladder cancer and constructed a corresponding prognostic model, which was linked to different sensitivities to chemotherapeutics. [Read the Full Post]

Allosteric inhibition of HSP70 in collaboration with STUB1 augments enzalutamide efficacy in antiandrogen resistant prostate tumor and patient-derived models

40 | May 13 2023

The study suggests that targeting HSP70 using small-molecule inhibitors, in combination with ARSI drugs, could be a promising approach to overcome resistance to ARSI in advanced prostate cancer. [Read the Full Post]

PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain

36 | May 13 2023

The study found that LRRK1 is activated by PKC-dependent phosphorylation of a cluster of conserved residues within a region of the CORB domain, which promotes interaction and stabilization of the αC-helix on the kinase domain, revealing a novel activation mechanism. [Read the Full Post]

A Phase Ib Study of Sotrastaurin, a PKC Inhibitor, and Alpelisib, a PI3Kα Inhibitor, in Patients with Metastatic Uveal Melanoma

64 | May 13 2023

The phase Ib study found that the combination of sotrastaurin and alpelisib was tolerable but showed limited clinical activity in patients with metastatic uveal melanoma or GNAQ/11 mutant cutaneous melanoma. [Read the Full Post]

ETC-159, an Upstream Wnt inhibitor, Induces Tumour Necrosis via Modulation of Angiogenesis in Osteosarcoma

75 | May 09 2023

ETC-159, a PORCN inhibitor, has shown potential as a treatment for osteosarcomas by inhibiting the Wnt pathway and leading to increased tumour necrosis and reduced vascularity, providing a new window of vulnerability for therapy development. [Read the Full Post]

Immune checkpoint inhibitors modulate the cytotoxic effect of chemotherapy in lung adenocarcinoma cells

133 | Apr 24 2023

The study found that immune checkpoint inhibitors can either potentiate or depotentiate the cytotoxic effects of chemotherapy in lung adenocarcinoma cell lines with different PD-L1 expression levels, and the specific effects vary depending on the ICIs and chemotherapy agents used. [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

148 | 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]

O-linked N-acetylglucosamine modification induced by lipopolysaccharide is involved in inflammatory signaling pathway in endothelial cells

33 | Apr 12 2023

The study investigated the involvement of O-GlcNAc modification in the inflammatory signaling pathway of endothelial cells under LPS stimulation and found that increasing OGT expression could inhibit the activation of the inflammatory signal pathway and reduce inflammatory cytokine expression, and that the PI3K/Akt pathway is involved in regulating O-GlcNAc modification in response to LPS stimulation. [Read the Full Post]

Distinct Protein Kinase C isoforms drive the cell cycle re-entry of two separate populations of neonatal rat ventricular cardiomyocytes

30 | Apr 06 2023

The study found that distinct PKC isoforms are responsible for the preferential appearance of nestin(+)- or nestin(-)-NNVMs that re-enter the cell cycle in the presence of SB203580. [Read the Full Post]

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

175 | 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]

Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the GEOMETRY mono-1 study

47 | Apr 05 2023

Capmatinib showed meaningful improvements in cough and preserved quality of life in patients with METex14-mutated advanced non-small cell lung cancer, as reported by patient-reported outcomes in the GEOMETRY mono-1 study. [Read the Full Post]

Real-world outcomes in non-small-cell lung cancer patients with MET Exon 14 skipping mutation and brain metastases treated with capmatinib

92 | Apr 05 2023

This retrospective medical record review study demonstrated that capmatinib is effective in treating non-small-cell lung cancer patients with MET exon 14 skipping mutation and brain metastases in a real-world setting, with high response rates and progression-free survival. [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]

Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent

58 | Mar 31 2023

The passage describes the pharmacokinetics of geldanamycin in mice and a dog and highlights the potential for acute hepatotoxic reactions, indicating a need for further pharmacological and therapeutic information before considering the drug for clinical development. [Read the Full Post]

Identification of significant gene expression changes in multiple perturbation experiments using knockoffs

111 | Mar 30 2023

The approach described uses the model-X knockoffs framework and Deep Neural Networks to identify significant gene expression changes in multiple perturbation experiments, allowing for better understanding of underlying mechanisms of disease and identification of new drug targets. [Read the Full Post]

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

139 | 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

118 | 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]

WP1130 relieves septic shock in mice by inhibiting NLRP3 inflammasome activation

56 | Mar 20 2023

WP1130 specifically inhibits NLRP3 inflammasome activation and alleviates septic shock in mice. [Read the Full Post]

USP9x promotes CD8 + T-cell dysfunction in association with autophagy inhibition in septic liver injury

66 | Mar 20 2023

This study suggests that USP9x inhibition could be a potential therapeutic target for septic liver injury by promoting CD8+ T-cell function via autophagy regulation. [Read the Full Post]

Endothelial-specific targeting of RhoA signaling via CD31 antibody-conjugated nanoparticles

136 | Feb 26 2023

The study aimed to develop a CD31-targeting liposome with Fasudil, a clinically-relevant Rho kinase inhibitor, to target the RhoA signaling in endothelial cells for potential anti-angiogenic therapy by minimizing toxicity. [Read the Full Post]

Predictive factors for improvement of symptomatic cerebral vasospasm following subarachnoid hemorrhage by selective intra-arterial administration of fasudil hydrochloride

161 | Feb 26 2023

Selective intra-arterial administration of fasudil improves neurological findings in 72.2% of patients with cerebral vasospasm following subarachnoid hemorrhage and is most effective when the spasm is limited to peripheral vessels and the patient is younger and does not have a large cerebral infarction in the spasm artery perfusion area. [Read the Full Post]

Case report: Ponatinib as a bridge to CAR-T cells and subsequent maintenance in a patient with relapsed/refractory Philadelphia-like acute lymphoblastic leukemia

77 | Feb 22 2023

A young patient with relapsed/refractory Ph-like ALL was successfully treated with chimeric antigen receptor T (CAR-T) cells after bridging with compassionate-use ponatinib and low-dose prednisone, and maintained with low-dose ponatinib, resulting in measurable residual disease negativity and B-cell aplasia 20 months later, marking this as the first reported use of ponatinib in Ph-like ALL as a bridge to and maintenance after CAR-T cell therapy. [Read the Full Post]

Staurosporine analogues from microbial and synthetic sources and their biological activities

95 | Feb 20 2023

Staurosporine and its analogues have strong inhibitory effects against a variety of kinases and have various biological properties such as antifungal, antibacterial, and immunosuppressive activities, but have limited clinical effectiveness due to cross-reactivity and poor selectivity. [Read the Full Post]

Drug resistance dependent on allostery: A P-loop rigor Eg5 mutant exhibits resistance to allosteric inhibition by STLC

33 | Feb 20 2023

Resistance to Eg5 inhibitors, a potential target for cancer chemotherapy, was explored using the HCT116 cell line and found to arise from a dominant point mutation in the P-loop of the ATP binding domain of Eg5, Eg5(T107N), causing strong non-exchangeable binding to microtubules and resistance to loop-L5 binding inhibitors, but potentially overcome by inhibitors that bind to sites other than the loop-L5 binding site. [Read the Full Post]

Single-cell transcriptomics reveals the role of Macrophage-Naïve CD4 + T cell interaction in the immunosuppressive microenvironment of primary liver carcinoma

73 | Feb 20 2023

The study investigates the important interactions between immune cells and their targeting drugs in liver carcinoma using single-cell and bulk transcriptomic data, revealing the crucial role of macrophage-naive CD4 + T cell interaction in the immunosuppressive microenvironment of liver carcinoma and identifying five predictive drugs that may help improve the immunosuppressive microenvironment and prevent immune evasion. [Read the Full Post]

Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent

103 | Feb 18 2023

Rigosertib, a dual PLK1 and PI3K inhibitor, showed dose- and time-dependent efficacy against 5 human tumor cell lines in vitro, with A549 cells being the most sensitive and U87-MG cells the most resistant, with p53 levels affecting the efficacy, making Rigosertib a potential antineoplastic agent against lung cancer in humans. [Read the Full Post]

PLK1-ELAVL1/HuR-miR-122 signaling facilitates hepatitis C virus proliferation

83 | Feb 18 2023

Rigosertib, an anticancer agent under clinical trials, targets PLK1 and modulates ELAVL1/HuR-miR-122 signaling to effectively inhibit the proliferation of wild-type and sofosbuvir resistance-associated HCVs, suggesting it could be useful for treating HCV and HCV-associated diseases. [Read the Full Post]

Lithium affects the circadian clock in the choroid plexus - A new role for an old mechanism

38 | Feb 14 2023

Lithium affects the circadian clock in the choroid plexus of the ventricle barrier complex, influencing brain function and potentially improving it in psychiatric patients by aligning the clock with the sleep-wake cycle, with potential for personalized timing of treatment. [Read the Full Post]

Effect of Gubenyiliu formula II and its disassembled prescriptions on cell autophagy in breast cancer through PI3K/AKT/mTOR pathway

145 | Feb 12 2023

This study confirmed that GYII can effectively treat breast cancer by inhibiting the PI3K/AKT/mTOR signaling pathway-mediated autophagy, while QX and FZ have different effects on tumor growth and metastasis. [Read the Full Post]

Specific gene module pair-based target identification and drug discovery

176 | Feb 12 2023

A novel method called "gene module pair-based target identification (GMPTI)" was developed to predict the targets of new compounds using consensus gene modules extracted from transcriptional profiles induced by perturbagens of known targets, resulting in the discovery of novel inhibitors for three PI3K pathway proteins. [Read the Full Post]

Successful Treatment of Patient With Ewing Sarcoma in the Setting of Inherited Cholestatic Liver Disease

76 | Feb 12 2023

Treatment of Ewing sarcoma in a patient with PFIC1 presents a challenge due to the reliance of standard chemotherapy on intact hepatic metabolism, which results in prolonged lymphopenia and severe infectious complications in this patient. [Read the Full Post]

Effect of hyperthermia alone and in combination with anticancer drugs on the viability of P388 leukemic cells

70 | Feb 12 2023

Local tumor hyperthermia (42°C) for 1 hour with antineoplastic drugs Adriamycin, Vincristine, or 5-Fluorouracil showed synergistic cell killing action against P388 murine lymphocytic leukemia cells in vitro, while Cyclophosphamide and Cytosine Arabinoside did not show enhanced therapeutic effects. [Read the Full Post]

Zearalenone and its metabolite exposure directs oestrogen metabolism towards potentially carcinogenic metabolites in human breast cancer MCF-7 cells

74 | Feb 11 2023

Mycoestrogens increase the production of CYP1B1-mediated oestrogen catechol metabolites, directing the biotransformation of E2 towards 4-OHE2, a crucial factor in oestrogen-induced tumour initiation. [Read the Full Post]

Synthesis and antiproliferative activity evaluation of B-norcholesterol-6-amide compounds

69 | Feb 10 2023

The study found that introducing chloroalkyl acyl groups into the 6-position of 6-amino-B-norcholesterol greatly enhanced the cytotoxicity of the resulting B-norcholesterol-6-amide compounds, with compound 20 having an IC50 value of 3.9 μM on HeLa cells. [Read the Full Post]

In Vitro Characterization of 177Lu-DOTA-M5A Anti-Carcinoembryonic Antigen Humanized Antibody and HSP90 Inhibition for Potentiated Radioimmunotherapy of Colorectal Cancer

35 | Feb 02 2023

The combination therapy of 177Lu-radiolabeled anti-CEA hT84.66-M5A mAb (M5A) and the heat shock protein 90 inhibitor onalespib showed enhanced therapeutic effects over individual monotherapies for the potential treatment of colorectal cancer. [Read the Full Post]

Neoadjuvant chemotherapy with weekly cisplatin and paclitaxel followed by chemoradiation for locally advanced cervical cancer

150 | Feb 01 2023

The study found that neoadjuvant chemotherapy with weekly cisplatin and paclitaxel followed by concurrent chemoradiation was a feasible, safe and effective treatment for cervical cancer, with a high response rate and good overall survival. [Read the Full Post]

Preparation and evaluation of paclitaxel-loaded reactive oxygen species and glutathione redox-responsive poly(lactic-co-glycolic acid) nanoparticles for controlled release in tumor cells

102 | Feb 01 2023

The study found that PLGA copolymer with thioether and disulfide groups can effectively deliver paclitaxel to tumors, leading to increased drug accumulation at the site and offering a promising approach for intelligent and responsive drug delivery. [Read the Full Post]

Upregulation of TGF-β-induced HSP27 by HSP90 inhibitors in osteoblasts

52 | Feb 01 2023

The study found that HSP90 inhibitors increased TGF-β-induced HSP27 expression in mouse osteoblastic MC3T3-E1 cells through the SAPK/JNK pathway. [Read the Full Post]

Exosomal LOC85009 inhibits docetaxel resistance in lung adenocarcinoma through regulating ATG5-induced autophagy

63 | Jan 30 2023

Zhengyuan Yu et al. suggested that LOC85009 might be a potential target to reverse DTX resistance in the treatment of LUAD. [Read the Full Post]

Intraperitoneal Chemotherapy for Unresectable Peritoneal Surface Malignancies

26 | Jan 30 2023

Niels A D Guchelaar et al. provided a systematic overview of intraperitoneal used drugs, the performed clinical studies so far, and the complications of the peritoneal implemental ports. [Read the Full Post]

Rescue of Misfolded Organic Cation Transporter 3 Variants

94 | Jan 27 2023

Thomas J F Angenoorth et al. found that folding-deficient SLC22 transporter variants, in particular those of OCT3, were amenable to rescue by chaperones. [Read the Full Post]

Heat shock protein 90 inhibitors induce cell differentiation via the ubiquitin-dependent aurora kinase A degradation in a MPLW515L mouse model of primary myelofibrosis

38 | Jan 27 2023

Fuping Wang et al. demonstrated that combined therapy showed superior activity in acute megakaryocytic leukemia mouse model than single therapy. [Read the Full Post]

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

52 | 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]

Interactive webtool for analyzing drug sensitivity and resistance associated with genetic signatures of cancer cell lines

128 | Jan 19 2023

Myriam Boeschen et al. found support for the described sensitivity of H1047 mutants to GSK690693 targeting the AKT pathway. [Read the Full Post]

Guhong Injection Alleviates Cerebral Ischemia-Reperfusion Injury via the PKC/HIF-1α Pathway in Rats

86 | Jan 08 2023

Li Yu et al. confirmed GHI could ameliorate cerebral I/R injury in MCAO rats possibly via the PKC/HIF-1α pathway. [Read the Full Post]

PKCβ Facilitates Leukemogenesis in Chronic Lymphocytic Leukaemia by Promoting Constitutive BCR-Mediated Signalling

43 | Jan 08 2023

Jodie Hay et al. demonstrated that PKCβ expression facilitates leukemogenesis and identified that BCR-mediated signalling was a key driver of CLL development in the PKCα-KR model. [Read the Full Post]

A Novel Cuproptosis-Related Prognostic Model and the Hub Gene FDX1 Predict the Prognosis and Correlate with Immune Infiltration in Clear Cell Renal Cell Carcinoma

64 | Jan 07 2023

Kenan Zhang et al. constructed a CRGs prognostic model and revealed that FDX1 could serve as a prognostic biomarker and predict therapeutic response in ccRCC. [Read the Full Post]

Identification of cuproptosis-related long non-coding ribonucleic acid signature as a novel prognosis model for colon cancer

60 | Jan 07 2023

Rong Xu et al. found that inhibition of AL512306.3 and ZEB1-AS1 significantly suppressed the cell proliferation in colon cancer cells. [Read the Full Post]

Single-cell profiling reveals molecular basis of malignant phenotypes and tumor microenvironments in small bowel adenocarcinomas

65 | Jan 06 2023

Jingwei Yang et al. showed that the duodenal subtype of SBA exhibited molecular features more similar to gastric cancer whereas jejunal subtype of SBA more similar to colorectal cancer. [Read the Full Post]

Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells

17 | Jan 02 2023

Barbora Adamová et al. thought that the combined therapy of perifosine and ABT-737 could be considered as a potential treatment strategy for colon cancer. [Read the Full Post]

Akt Pathway Inhibitors

71 | Jan 02 2023

Nne E Uko et al. suggested a mechanistic basis involving hyperactivated Akt signaling. Allosteric inhibitors were known to alter the activity of kinases. [Read the Full Post]

Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington's Disease Patients

76 | Dec 31 2022

Karen E Anderson et al. explored the effects of a low dose of nilotinib (150 mg) on behavioral changes and motor symptoms in manifest HD patients. [Read the Full Post]

The Economic Burden of Chronic Myeloid Leukemia in Patients with Later Lines: Findings from a Real-World Analysis in Italy

95 | Dec 30 2022

Massimo Breccia et al. suggested that further efforts were needed to improve the therapeutic management of later lines of CML. [Read the Full Post]

Attenuated Dose Dasatinib in Newly Diagnosed Chronic Myeloid Leukemia Chronic Phase Patients in India

23 | Dec 29 2022

Rayaz Ahmed et al. thought that low dose dasatinib was safe and effective as an upfront therapy in CML-CP. [Read the Full Post]

Combined use of dasatinib and quercetin alleviates overtraining-induced deficits in learning and memory through eliminating senescent cells and reducing apoptotic cells in rat hippocampus

56 | Dec 28 2022

Chenkang Wang found that D+Q alleviated overtraining-induced deficits in learning and memory through elimination of senescent cells and reduction of apoptotic cell number. [Read the Full Post]

Clinical impact of minimal residual disease and genetic subtypes on the prognosis of childhood acute lymphoblastic leukemia

92 | Dec 27 2022

Chih-Hsiang Yu et al. found that MRD-directed therapy improved the outcomes for pediatric ALL, especially standard-risk patients. [Read the Full Post]

A mitophagy-related gene signature associated with prognosis and immune microenvironment in colorectal cancer

133 | Dec 24 2022

Cong Zhang et al. developed a novel mitophagy-related gene signature that could be utilized not only as an independent predictive biomarker but also as a tool for tailoring personalizing treatment for CRC patients. [Read the Full Post]

Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial

74 | Dec 23 2022

Keiko Imamura et al. found that the treatment-responsive patients could be distinguished by lower levels of plasma NFL. [Read the Full Post]

Recent updates on Wnt signaling modulators: a patent review (2014-2020)

24 | Dec 14 2022

Vishalgiri G Goswami et al. thought that targeting Wnt pathway could be a potential approach to design and develop novel therapeutic classes. [Read the Full Post]

Novel biallelic mutations in TTC29 cause asthenoteratospermia and male infertility

27 | Dec 10 2022

Siyu Dai et al. found the novel biallelic mutations in TTC29 in a MMAF patient, which findings expand the mutational spectrum of TTC29. [Read the Full Post]

Protein kinase C-β distinctly regulates blood-brain barrier-forming capacity of Brain Microvascular endothelial cells and outgrowth endothelial cells

38 | Dec 06 2022

Rais Reskiawan A Kadir et al. thought that targeting PKC-β signalling pathway in ischaemic settings required close attention while using OECs as cellular therapeutic. [Read the Full Post]

PKCβ Inhibition Promotes TXNIP Degradation to Ameliorate Pancreatic β-Cell Dysfunction

50 | Dec 05 2022

Shijun He et al. suggested that KCβ inhibitor was a promising agent for ameliorating β-cell dysfunction through TXNIP. [Read the Full Post]

Inhibition of focal adhesion turnover prevents osteoblastic differentiation through β-catenin mediated transduction of pro-osteogenic substrate

41 | Nov 26 2022

Otto J Juhl 4th et al. suggested that the observed β-catenin translocation is a result of focal adhesion turnover, providing evidence for a focal adhesion initiated, β-catenin mediated mechanism of substrate surface signal transduction. [Read the Full Post]

Hepatic ER stress suppresses adipose browning through ATF4-CIRP-ANGPTL3 cascade

37 | Nov 20 2022

Sihan Lv et al. identified a communication mechanism to link hepatic ER stress and adipose browning that might imply a reciprocal regulation of obesity and liver steatosis. [Read the Full Post]

Phase 1 multicenter study of the HSP90 inhibitor SNX-5422 plus carboplatin and paclitaxel in patients with lung cancers

0 | Nov 10 2022

Martin Gutierrez et al. found that the triplet combination of SNX-5422, carboplatin and paclitaxel followed by maintenance SNX-5422 therapy was well-tolerated and showed anti-tumor activity [Read the Full Post]

Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells

0 | Nov 09 2022

Ria Goswami et al. found that an orally bioavailable Hsp90 inhibitor, SNX-5422, currently in clinical trials as an anti-cancer therapeutic, inhibited SARS-CoV-2 replication in vitro at a high selectivity index. [Read the Full Post]

Ganetespib selectively sensitizes cancer cells for proximal and distal spread-out Bragg peak proton irradiation

107 | Oct 30 2022

Simon Deycmar et al. provided additional experimental data on cellular response and a rational for future combinatorial approaches with proton radiotherapy. [Read the Full Post]

Hsp90 Inhibitor STA9090 induced VPS35 related extracellular vesicle release and metastasis in hepatocellular carcinoma

43 | Oct 29 2022

Wenchong Tan et al. found that therapeutic strategy to inhibit the metastasis of HCC caused by N-terminal Hsp90 inhibitor induced extracellular vesicles. [Read the Full Post]

Spleen tyrosine kinase (SYK) inhibitor PRT062607 protects against ovariectomy-induced bone loss and breast cancer-induced bone destruction

0 | Oct 25 2022

Gang Xie et al. suggested the potential value of PRT in managing osteolytic diseased mediated by osteoclasts. [Read the Full Post]

The Role of Syk in Inflammatory Response of Human Abdominal Aortic Aneurysm Tissue

0 | Oct 25 2022

Ryo Kanamoto et al. found an important role of Syk for IgG-dependent inflammatory response in human AAA. [Read the Full Post]

URMC-099 prophylaxis prevents hippocampal vascular vulnerability and synaptic damage in an orthopedic model of delirium superimposed on dementia

59 | Oct 19 2022

Patrick Miller-Rhodes et al. linked post-surgical endothelial activation, microglial MafB immunoreactivity, and synapse loss as key substrates for DSD, all of which could be prevented by URMC-099. [Read the Full Post]

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

56 | 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]

Vascular Disruptive Hydrogel Platform for Enhanced Chemotherapy and Anti-Angiogenesis through Alleviation of Immune Surveillance

37 | Oct 13 2022

Fasheng Li et al. provided a new treatment strategy through the mediation of the tumor immune microenvironment by vascular disruption to fulfill enhanced chemotherapy and immunotherapy. [Read the Full Post]

The Efficacy of Fosbretabulin Disodium Combined with Radiofrequency Ablation in Lung Cancer

20 | Oct 12 2022

Jieli Kou et al. found that FBTD promoted the antitumor effects of RFA in lung tumor-bearing mice in the study. [Read the Full Post]

Design, synthesis and biological evaluation of conformationnally-restricted analogues of E7010 as inhibitors of tubulin assembly (ITA) and vascular disrupting agents (VDA)

21 | Oct 12 2022

Vassili Prudhomme et al. found that indole 4j exhibited good potency against HUVEC and HIG-82 cell lines, as well as a good ability to inhibit tubulin assembly. [Read the Full Post]

Targeting Akt/PKB in pediatric tumors: A review from preclinical to clinical trials

54 | Sep 29 2022

Bruno Toson et al. demonstrated the impact that Akt inhibition provided in tumorigenesis, and suggested targeting the PI3K/Akt/mTOR signaling pathway, alone or in combination with other inhibitors, was a feasible tool to achieve better outcomes in pediatric tumors. [Read the Full Post]

HGF-mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c-MET

48 | Sep 25 2022

Tongyue Zhang et al. uncovered functional and prognostic roles for ETV1 in HCC and exposed a positive feedback loop of HGF-ERK1/2-ETV1-c-MET. [Read the Full Post]

FLT3 Inhibitors as Maintenance Therapy after Allogeneic Stem-Cell Transplantation

125 | Sep 23 2022

Amanda Blackmon et al. reviewed the toxicities and efficacy of FLT3 inhibitors as posttransplant maintenance, recommendations on the use of FLT3 inhibitors by international consensus guidelines, and highlighted key remaining questions. [Read the Full Post]

[Correlation between low expression of Hsp90 protein in keratinocytes and the number of small extracellular vesicles and its potential clinical significance]

92 | Sep 17 2022

Jun Chen et al. found that the secretion of sEVs in HaCaT cells. sEVs may be involved in the transfer of molecules between epithelial cells and immune cells. [Read the Full Post]

Identification of potential immunotherapy biomarkers for breast cancer by bioinformatics analysis

96 | Sep 16 2022

Yao Song et al. found that CD24, MMP1, SDC1, and SPP1 were potentially associated with five immune cell types infiltration (CD8+ T cells, CD4+ T cells, neutrophils, macrophages,and dendritic cells) by TIMER. [Read the Full Post]

Non-small cell lung cancer with EGFR exon 20 insertion mutation: a systematic literature review and meta-analysis of patient outcomes

69 | Sep 05 2022

Christina Soeun Kwon et al. found EGFR exon 20 insertion mutations as the availability of new targeted treatments might offer additional therapeutic options to these patients. [Read the Full Post]

A Low Membrane Hsp70 Expression in Tumor Cells With Impaired Lactate Metabolism Mediates Radiosensitization by NVP-AUY922

76 | Sep 05 2022

Melissa Schwab et al. found that the membrane Hsp70 density, but not cytosolic HSP levels determined the radiosensitizing effect of the Hsp90 inhibitor NVP-AUY922 in LDH-/- cells. [Read the Full Post]

Design, synthesis, and biological evaluation of potent FAK-degrading PROTACs

59 | Sep 03 2022

Qiaohua Qin et al. found that PROTAC A13 could be useful as expand tool for studying functions of FAK in biological system and as potential therapeutic agents. [Read the Full Post]

Cebpb Regulates Skeletal Stem Cell Osteogenic Differentiation and Fracture Healing via the WNT/ β-Catenin Pathway

44 | Aug 30 2022

Jiansong Wang et al. proved that Cebpb knockdown promoted SSC osteogenic differentiation and fracture healing via the WNT/β-catenin signaling pathway. [Read the Full Post]

Differential prognostic impact of stratified additional chromosome abnormalities on disease progression among Malaysian chronic myeloid leukemia patients undergoing treatment with imatinib mesylate

64 | Aug 29 2022

Ismail Siti Mariam et al. concluded that the stratification based on individual ACAs had a differential prognostic impact and might be a potential novel risk predictive system to prognosticate and guided the treatment of CML patients at diagnosis and during treatment. [Read the Full Post]

Protein kinase C targeting of luminal (T-47D), luminal/HER2-positive (BT474), and triple negative (HCC1806) breast cancer cells in-vitro with AEB071 (Sotrastaurin) is efficient but mediated by subtype specific molecular effects

40 | Aug 12 2022

Veruschka Albert et al. thought that a combined targeting of PKC and a subtype specific driver molecule might complement specified breast cancer treatment. [Read the Full Post]

Inhibiting SRC activity attenuates kainic-acid induced mouse epilepsy via reducing NR2B phosphorylation and full-length NR2B expression

42 | Aug 12 2022

Lu Liu et al. found that the early application of SRC inhibitors exerted protective effects on seizure severity, loss of neurons, and sprouting of mossy fibres in KA-induced mouse epilepsy. [Read the Full Post]

The CBP/β-Catenin Antagonist, ICG-001, Inhibits Tumor Metastasis via Blocking of the miR-134/ITGB1 Axis-Mediated Cell Adhesion in Nasopharyngeal Carcinoma

45 | Aug 11 2022

Luo Chen et al. showed that ICG-001 transient overexpression of miR-134 or stable overexpression of miR-134 could significantly reduce the lung metastasis of NPC cells. [Read the Full Post]

Inhibition of CBP/β-catenin signaling ameliorated fibrosis in cholestatic liver disease

43 | Aug 07 2022

Masamichi Kimura et al. highlighted the therapeutic effect of CBP/β-catenin inhibition in cholestatic liver diseases. [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

80 | 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]

Ipatasertib, an oral AKT inhibitor, inhibits cell proliferation and migration, and induces apoptosis in serous endometrial cancer

163 | Jul 12 2022

Lindsey Buckingham et al. found that IPAT significantly inhibited cell proliferation and colony formation in a dose-dependent manner in USC cells. [Read the Full Post]

The close interaction between hypoxia-related proteins and metastasis in pancarcinomas

161 | Jul 11 2022

Andrés López-Cortés et al. identified 23 drugs enrolled in clinical trials focused on metastatic disease treatment. [Read the Full Post]

MicroRNA-26b regulates BMSC osteogenic differentiation of TMJ subchondral bone through β-catenin in osteoarthritis

64 | Jul 10 2022

Jinlu Yang et al. thought that miR-26b might modulate subchondral bone loss induced by abnormal occlusion and influence the osteogenic differentiation of subchondral BMSCs through β-catenin in the context of TMJ-OA progression. [Read the Full Post]

Reengineering Ponatinib to Minimize Cardiovascular Toxicity

232 | Jul 03 2022

Anna Pavlovna Hnatiuk et al. suggested that ponatinib cardiotoxicity was mediated by a few kinases, some of which were previously unassociated with cardiovascular disease. [Read the Full Post]

Synthesis, structural characterization, DFT calculations, molecular docking, and molecular dynamics simulations of a novel ferrocene derivative to unravel its potential antitumor activity

381 | Jun 12 2022

Mohamed M Hammoud et al. revealed the antitumor potential of ferrocene derivative (10) through targeting and inhibiting mitogen-activated protein (MAP) kinases interacting kinase (Mnk) 1.Communicated by Ramaswamy H. Sarma. [Read the Full Post]

RNF43 R117fs mutant positively regulates Wnt/β-catenin signaling by failing to internalize FZD expressed on the cell surface

115 | Jun 07 2022

A-Ri Cho et al. demonstrated that RNF43 frameshift mutations retained normal functionality; thus, targeted anti-cancer therapy could be developed according to the mutation type of RNF43. [Read the Full Post]

Vasorelaxant effect of curcubisabolanin A isolated from Curcuma longa through the PI3K/Akt/eNOS signaling pathway

189 | May 25 2022

Jin-Feng Chen et al. demonstrated that the vasorelaxant effect of curcubisabolanin A was partially endothelium-dependent. [Read the Full Post]

Premise and peril of Wnt signaling activation through GSK-3β inhibition

225 | May 19 2022

Samuel M Law et al. thought that caution was required when micromolar levels of CHIR-99021 were used for the purpose of activating the canonical Wnt signaling pathway. [Read the Full Post]

ARHGAP29 Regulates Keratinocyte Migration through the RhoA/ROCK Pathway

235 | May 15 2022

Lindsey Rhea et al. demonstrated that ARHGAP29 regulated keratinocyte morphology and promoted migration speed and directionality through the RhoA/ROCK pathway, providing potential insight into its importance in craniofacial development. [Read the Full Post]

Phase II Clinical and Translational Study of Everolimus ± Paclitaxel as First-Line Therapy in Cisplatin-Ineligible Advanced Urothelial Carcinoma

257 | Apr 25 2022

Tomi Jun et al. thought that everolimus plus paclitaxel demonstrated clinical activity in cisplatin-ineligible patients with metastatic UC, although the specific contribution of everolimus could not be delineated. [Read the Full Post]

Individualization in the first-line treatment of advanced ovarian cancer based on the mechanism of action of molecularly targeted drugs

386 | Apr 23 2022

Hidekatsu Nakai et al, found that the importance of achieving complete surgery and aiming for cure in the treatment of ovarian cancer and how the use of bevacizumab, olaparib, and niraparib should be individualized. [Read the Full Post]

B7-H4 expression is upregulated by PKCδ activation and contributes to PKCδ-induced cell motility in colorectal cancer

310 | Apr 13 2022

Bin Zhou et al. found that B7-H4 expression was upregulated by STAT3 activation via PKCδ and played roles in PKCδ-induced cancer cell motility and metastasis, suggesting that the PKCδ/STAT3/B7-H4 axis might be a potential therapeutic target for CRC. [Read the Full Post]

Effect of Maternal Docosahexaenoic Acid Supplementation on Very Preterm Infant Growth: Secondary Outcome of a Randomized Clinical Trial

256 | Apr 13 2022

Georgina Angoa et al. showed that DHA positively affected female infants' neonatal weight profile and velocity and negatively affected male infants' weight at 36 weeks' PMA. [Read the Full Post]

Inhibition of the PINK1-Parkin Pathway Enhances the Lethality of Sorafenib and Regorafenib in Hepatocellular Carcinoma

277 | Apr 05 2022

Shun Zhang et al. found that PINK1-Parkin-mediated mitophagy alleviates sorafenib and regorafenib antitumor effected in vitro and in vivo. [Read the Full Post]

In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells

423 | Apr 01 2022

Alessio Malacrida et al. thought that rigosertib could be a potential therapeutic option, alone or in combination with radiations, for nonresectable patients with cholangiocarcinoma. [Read the Full Post]

Rigosertib and Cholangiocarcinoma: A Cell Cycle Affair

355 | Mar 31 2022

Alessio Malacrida et al. hypothesized the mechanism of the action of Rigosertib against cholangiocarcinoma EGI-1 cells, highlighting the importance of proteins involved in the regulation of cell cycles. [Read the Full Post]

Response to netarsudil in goniotomy-treated eyes and goniotomy-naïve eyes: a pilot study

618 | Mar 29 2022

Haochen Xu et al.showed that netarsudil had a greater IOP-lowering effect in eyes treated with prior goniotomy and might serve as a promising adjunctive ocular hypotensive agent to further reduce IOP in eyes with prior goniotomy. [Read the Full Post]

CDK4/6 inhibition synergizes with inhibition of P21-Activated Kinases (PAKs) in lung cancer cell lines

185 | Mar 28 2022

Gabriela M Wright et al. suggested that a unique combination of PAKs played a crucial role in the synergy of PAK inhibitors with CDK4/6i. [Read the Full Post]

Modulation of KIF17/NR2B crosstalk by tozasertib attenuates inflammatory pain in rats

480 | Mar 27 2022

Ankit Uniyal et al. suggested that tozasertib mediates anti-nociceptive activity by inhibiting aurora kinase-mediated KIF17/mLin10/NR2B signaling. [Read the Full Post]

Aurora kinase A induces migration and invasion by inducing epithelial-to-mesenchymal transition in colon cancer cells

435 | Mar 27 2022

On-Yu Hong 1 et al. showed aurora kinase A is a key molecule in PKC-induced metastasis in colon cancer cells. [Read the Full Post]

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

627 | 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 effect of danusertib, an Aurora kinase inhibitor, onto the cytotoxicity, cell cycle and apoptosis in pancreatic ductal adenocarcinoma cells

667 | Mar 11 2022

Ismail Ayberk Kirbiyik et al. thought that Aurora kinase inhibitor danusertib might be a potential alternative to the treatment of pancreatic cancers. [Read the Full Post]

Combined Inhibition of Polo-Like Kinase-1 and Wee1 as a New Therapeutic Strategy to Induce Apoptotic Cell Death in Neoplastic Mast Cells

672 | Mar 10 2022

Manuela Mancini et al. showed that repurposing Plk1 or AKA ± Wee1 inhibitors in advanced clinical development for other indications was a therapeutic strategy worthy of being explored, in order to improve the outcome of patients with advanced SM. [Read the Full Post]

Unfolded protein response-induced expression of long noncoding RNA Ngrl1 supports peripheral axon regeneration by activating the PI3K-Akt pathway

166 | Mar 06 2022

Dong Wang found that unfolded protein response-induced Ngrl1 expression supports the intrinsic control of peripheral axon regeneration by modulating the activation of the PI3K-Akt pathway following SNC. [Read the Full Post]

A FAK Inhibitor Boosts Anti-PD1 Immunotherapy in a Hepatocellular Carcinoma Mouse Model

386 | Mar 05 2022

Yuhua Wei et al. suggested that combination of the FAK inhibitor VS4718 and anti-PD1 could be a potential therapy for HCC by improving the immune environment, reducing liver fibrosis and simultaneously preventing PD1 from binding to the increased PD-L1 induced by FAK inhibitor VS4718. [Read the Full Post]

The Role of E-Cadherin and microRNA on FAK Inhibitor Response in Malignant Pleural Mesothelioma (MPM)

276 | Mar 04 2022

Man Lee Yuen et al. showed that MPM cells with high CDH1 mRNA levels exhibited resistance to the FAK inhibitor PND-1186. [Read the Full Post]

Functional Assessment of Kinesin-7 CENP-E in Spermatocytes using In Vivo Inhibition, Immunofluorescence and Flow Cytometry

294 | Feb 24 2022

Meng-Fei Xu et al. found that CENP-E inhibition resulted in chromosome misalignment and metaphase arrest in primary spermatocytes during meiosis I. [Read the Full Post]

Pro-Inflammatory and Pro-Oxidative Changes During Nilotinib Treatment in CML Patients: Results of a Prospective Multicenter Front-Line TKIs Study (KIARO Study)

408 | Feb 20 2022

Anna Sicuranza et al. showed a pro-inflammatory/pro-oxidative milieu increasing along treatment with nilotinib compared with imatinib or dasatinib. [Read the Full Post]

The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction

408 | Feb 14 2022

Casandra Gomez-Paredes et al. found that following pharmacological activation in vivo,the heat shock response impairment in tibialis anterior, brain hemispheres and striatum was comparable between zQ175 and R6/2 mice. [Read the Full Post]

Drug-repurposing against COVID-19 by targeting a key signaling pathway: An in silico study

398 | Feb 13 2022

Ki Kwang Oh et al. provided three key elements to alleviate COVID-19 symptoms might be anti-inflammatory effects on SARs-CoV-2-infected lung cells. [Read the Full Post]

Phorbol-12-myristate 13-acetate inhibits Nephronectin gene expression via Protein kinase C alpha and c-Jun/c-Fos transcription factors

247 | Feb 07 2022

Mitsuhiro Kinoshita et al. suggested regulation of Npnt gene expression via the PKCα and c-Jun/c-Fos pathway. [Read the Full Post]

Role of KSP inhibitors as anti-cancer therapeutics: an update

359 | Feb 06 2022

Rinkal Chamariya et al. thought that KSP inhibitors had exhibited promising results and continued exploration was greatly required to establish the clinical potential of KSP inhibitors. [Read the Full Post]

Efficacy and Synergy of Small Molecule Inhibitors Targeting FLT3-ITD + Acute Myeloid Leukemia

346 | Feb 06 2022

Javier Bregante et al. suggested WS6, ispinesib, ponatinib and cabozantinib as novel options for targeting FLT3-ITD+ AML. [Read the Full Post]

A Novel Role for the Regulatory Nod-Like Receptor NLRP12 in Anti-Dengue Virus Response

377 | Jan 28 2022

Xingyu Li et al. demonstrated a novel mechanism that NLRP12 exerted anti-viral properties in DENV and other flaviviruses (JEV, YFV, ZIKV) infection. [Read the Full Post]

Inhibitor GSK690693 extends Drosophila lifespan via reduce AKT signaling pathway

943 | Jan 27 2022

Xingyi Cheng et al. indicated that GSK690693 might become an effective compound for anti-aging intervention. [Read the Full Post]

The main difference between Alvespimycin vs. 17-DMAG. Biomimetic Platform Based on Mesoporous Platinum for Multisynergistic Cancer Therapy

393 | Jan 27 2022

Gaoqian Zhao et al. showed that 17-DMAG/MPNPs@PM could accumulate in the tumor and effectively inhibit the growth of tumor cells. [Read the Full Post]

Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics

352 | Jan 19 2022

Matthew Z Guo et al.discussed limitations of capmatinib, and highlighted ongoing trials of capmatinib in combinatorial approaches. [Read the Full Post]

Novel function of THEMIS2 in the enhancement of cancer stemness and chemoresistance by releasing PTP1B from MET

342 | Jan 18 2022

Wei-Chieh Huang et al. found that non-cytotoxic dosages of cryptotanshinone (CPT) could potently inhibit cancer stemness, chemoresistance and tumorigenicity by suppressing expression of THEMIS2. [Read the Full Post]

Single cell transcriptomic profiling of neurodegeneration mediated by tau in a novel 3D neuron-astrocyte coculture model

390 | Jan 14 2022

Hannah Rickner et al. demonstrated the power to model the reduction of tau pathology by drug treatment. [Read the Full Post]

The α1-adrenergic receptors in the amygdala regulate the induction of learned despair through protein kinase C-beta signaling

0 | Jan 12 2022

Shisui Fujita et al. suggested that the α1-adrenoreceptor in amygdala regulated the induction of learned despair via PKCβ. [Read the Full Post]

Signaling Pathway of Histamine H 1 Receptor-Mediated Histamine H 1 Receptor Gene Upregulation Induced by Histamine in U-373 MG Cells

262 | Jan 12 2022

Hiroyuki Mizuguchi et al. thought that the H1R-activated H1R gene expression signaling pathway in U-373 MG cells was different from that in HeLa cells, possibly by using different promoters. [Read the Full Post]

Collagen XV Promotes ER Stress-Induced Inflammation through Activating Integrin β1/FAK Signaling Pathway and M1 Macrophage Polarization in Adipose Tissue

354 | Jan 02 2022

Changxing Li et al. provided new ideas for solving the problems of adipose tissue metabolism disorders caused by abnormal accumulation of ECM. [Read the Full Post]

Cilengitide Inhibits Neovascularization in a Rabbit Abdominal Aortic Plaque Model by Impairing the VEGF Signaling

153 | Dec 27 2021

Fawang Zhu et al. found that cilengitide effectively inhibited the growth of plaque size by inhibiting the angiogenesis of the abdominal aortic plaques and blocking the VEGF-mediated angiogenic effect on HUVECs. [Read the Full Post]

Phase 1 multicenter study of the HSP90 inhibitor SNX-5422 plus carboplatin and paclitaxel in patients with lung cancers

526 | Dec 17 2021

Martin Gutierrez et al. found that the triplet combination of SNX-5422, carboplatin and paclitaxel followed by maintenance SNX-5422 therapy was well-tolerated and showed anti-tumor activity. [Read the Full Post]

Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells

481 | Dec 16 2021

Ria Goswami et al. found that SNX-5422 interrupted expression of host factors demonstrated to be crucial for SARS-CoV-2 replication. [Read the Full Post]

HSP90 inhibition downregulates DNA replication and repair genes via E2F1 repression

631 | Dec 05 2021

Hanqing Liu et al. found that HSP90 inhibitors might be useful in combination therapies for MCL. [Read the Full Post]

Investigation of anticancer activities of STA-9090 (ganetespib) as a second generation HSP90 inhibitor in Saos-2 osteosarcoma cells

604 | Dec 05 2021

Aykut Özgür found the down-regulation of the expression levels of oncogenic genes. [Read the Full Post]

The Role of Syk in Inflammatory Response of Human Abdominal Aortic Aneurysm Tissue

0 | Dec 01 2021

Ryo Kanamoto et al. found an important role of Syk for IgG-dependent inflammatory response in human AAA. [Read the Full Post]

Spleen tyrosine kinase (SYK) inhibitor PRT062607 protects against ovariectomy-induced bone loss and breast cancer-induced bone destruction

809 | Nov 30 2021

Gang Xie et al. suggested the potential value of PRT in managing osteolytic diseases mediated by osteoclasts. [Read the Full Post]

MLK3 mediates impact of PKG1α on cardiac function and controls blood pressure through separate mechanisms

764 | Nov 25 2021

Timothy D Calamaras et al. suggested augmenting MLK3 kinase activity could preserve LV function in HF but avoid hypotension from PKG1α activation. [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]

Multimodal obstruction of tumorigenic energy supply via bionic nanocarriers for effective tumor therapy

383 | Nov 19 2021

Xiaoqian Yu et al. found that the CA4P/VK2-MSNs-TBAM/TSAG-HA (CVMMGH for short) nanocarrier combined well-controllable manipulation of tumor vasculature and tumor mitochondria to effectivly cut off the tumorigenic energy supply. [Read the Full Post]

A high-throughput and simultaneous determination of combretastatin A-4 phosphate and its metabolites in human plasma using HPLC-MS/MS: Application to a clinical pharmacokinetic study

355 | Nov 18 2021

Qizhen Wu et al. thought that an abundant ammonium adduct ion of CA4G in ESI+ was observed as an ideal precursor ion. [Read the Full Post]

Sequential drug delivery by injectable macroporous hydrogels for combined photodynamic-chemotherapy

363 | Nov 18 2021

Yuanyuan Zhong et al. found that dual drugs treated groups had better tumor inhibition than solo drug under near infrared laser irradiation [Read the Full Post]

Phase Ib Dose Expansion and Translational Analyses of Olaparib in Combination with Capivasertib in Recurrent Endometrial, Triple-Negative Breast, and Ovarian Cancer

343 | Nov 08 2021

Shannon N Westin et al. found that the combination of olaparib and capivasertib was associated to no serious adverse events and demonstrated durable activity in ovarian, endometrial, and breast cancers, with promising responses in endometrial cancer. [Read the Full Post]

FAK-targeting PROTAC demonstrates enhanced antitumor activity against KRAS mutant non-small cell lung cancer

505 | Nov 03 2021

Jinyuan Liu et al. thought that PROTACs might serve as promising therapeutic agents for the intractable NSCLC harboring KRAS mutations. [Read the Full Post]

Chemical Genetics Screen Identifies COPB2 Tool Compounds That Alters ER Stress Response and Induces RTK Dysregulation in Lung Cancer Cells

431 | Nov 01 2021

Punit Saraon et al. found that targeting of COPB2 with EMI66 presented a viable approach to attenuate mutant EGFR signalling and growth in NSCLC. [Read the Full Post]

Co-Expression of CD34, CD90, OV-6 and Cell-Surface Vimentin Defines Cancer Stem Cells of Hepatoblastoma, Which Are Affected by Hsp90 Inhibitor 17-AAG

707 | Oct 26 2021

Mieun Lee-Theilen et al. identified CSCs of hepatoblastoma using CD34, CD90, OV-6 and csVimentin. [Read the Full Post]

Identification of a circRNA-miRNA-mRNA regulatory network for exploring novel therapeutic options for glioma

775 | Oct 25 2021

Yi He et al. highlighted the potential pathogenesis of the circRNA-miRNA-mRNA regulatory network and identified novel therapeutic options for glioma. [Read the Full Post]

Chemical Reprogramming of Somatic Cells in Neural Direction: Myth or Reality?

0 | Oct 22 2021

E M Samoilova et al. thought that reprogramming with small molecules without additional factors modifying gene expression did not allow reproducible production of human neural stem cell-like progenitors that could be used as the source of neural tissue for the regenerative therapy. [Read the Full Post]

HSP90 inhibition acts synergistically with heat to induce a pro-immunogenic form of cell death in colon cancer cells

1005 | Oct 14 2021

Petros X E Mouratidis et al. found that sub-ablative heating could act synergistically with the clinically relevant HSP90 inhibitor NVP-AUY922 to induce a pro-immunogenic form of cell death in colon cancer cells. [Read the Full Post]

Evolution of kinase polypharmacology across HSP90 drug discovery

981 | Oct 13 2021

Albert A Antolin et al. found that the resorcinol clinical candidates ganetespib and, to a lesser extent, luminespib, displayed unique off-target kinase pharmacology as compared with other HSP90 inhibitors. [Read the Full Post]

Synthesis and evaluation of FAK inhibitors with a 5-fluoro-7H-pyrrolo[2,3-d]pyrimidine scaffold as anti-hepatocellular carcinoma agents

751 | Oct 12 2021

Hanyi Tan et al. suggested that 16c inhibited the malignant proliferation of hepatocellular carcinoma (HCC) cells through decreasing the phosphorylation in the FAK cascade. [Read the Full Post]

FSH stimulated bovine granulosa cell steroidogenesis involves both canonical and noncanonical WNT signaling

336 | Oct 08 2021

M Ashry et al. found that both canonical and noncanonical WNT pathways activation was linked to FSH stimulation of E2 production by bovine granulosa cells. [Read the Full Post]

Aspiration Is Associated with Poor Treatment Response in Pediatric Pulmonary Vein Stenosis

980 | Oct 06 2021

Maria Niccum et al. found that potentially modifiable risk factor for poor treatment response in pediatric multi-vessel intraluminal pulmonary vein stenosis in patients with 2-ventricle physiology. [Read the Full Post]

Proteomics of resistance to Notch1 inhibition in acute lymphoblastic leukemia reveals targetable kinase signatures

567 | Sep 17 2021

Giulia Franciosa et al. highlighted the potential of proteomics to dissect alterations in cellular signaling and identified druggable pathways in cancer. [Read the Full Post]

Cannabinoid receptor 2 plays a central role in renal tubular mitochondrial dysfunction and kidney ageing

609 | Sep 16 2021

Shan Zhou et al. showed CB2 played a central role in renal tubular mitochondrial dysfunction and kidney ageing. [Read the Full Post]

Tumor-promoting function of PIMREG in glioma by activating the β-catenin pathway

554 | Sep 12 2021

Dekang Wang et al. provided new insights into the molecular mechanism for glioma pathogenesis and treatment. [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]

ER+ Breast Cancer Strongly Depends on MCL-1 and BCL-xL Anti-Apoptotic Proteins

422 | Aug 19 2021

Clara Alcon et al. found that the anti-apoptotic proteins BCL-xL and MCL-1 were crucial for ER+ breast cancer cells resistance to therapy. [Read the Full Post]

Pharmacokinetics of Ipatasertib in Subjects With Hepatic Impairment Using Two Methods of Classification of Hepatic Function

453 | Aug 18 2021

Rucha Sane et al. showed that no dosage adjustment was required for ipatasertib when treating patients with mild hepatic impairment, whereas a dose reduction would be recommended for subjects with moderate or severe hepatic impairment. [Read the Full Post]

Wnt-C59 inhibits proinflammatory cytokine expression by reducing the interaction between β-catenin and NF-κB in LPS-stimulated epithelial and macrophage cells

794 | Aug 17 2021

Jaewoong Jang et al. suggested that the anti-inflammatory effect of Wnt-C59 was mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB. [Read the Full Post]

Wnt-Signaling Inhibitor Wnt-C59 Suppresses the Cytokine Upregulation in Multiple Organs of Lipopolysaccharide-Induced Endotoxemic Mice via Reducing the Interaction between β-Catenin and NF-κB

379 | Aug 16 2021

Jaewoong Jang et al. thought that Wnt-C59 might be useful for the suppression of the multiple-organ dysfunction during sepsis. [Read the Full Post]

Inhibition of AKR1B10-mediated metabolism of daunorubicin as a novel off-target effect for the Bcr-Abl tyrosine kinase inhibitor dasatinib

1187 | Aug 09 2021

Neslihan Büküm et al. demonstrated that dasatinib could synergize with Daun in human cancer cells and enhance its therapeutic effectiveness. [Read the Full Post]

Angiokinase inhibition of VEGFR-2, PDGFR and FGFR and cell growth inhibition in lung cancer: Design, synthesis, biological evaluation and molecular docking of novel azaheterocyclic coumarin derivatives

1237 | Jul 21 2021

Eman Y Ahmed et al. found that 4a was capable of arresting the cell cycle at pre-G1 phase and S phase and inducing apoptosis. [Read the Full Post]

Diffuse optical tomography breast imaging measurements are modifiable with pre-surgical targeted and endocrine therapies among women with early stage breast cancer

513 | Jul 06 2021

Julia E McGuinness et al. demonstrated that DOTBIS-derived measurements are modifiable with pre-surgical AKT inhibition and endocrine therapy. [Read the Full Post]

GSK3ß inhibitor CHIR 99021 modulates cerebral organoid development through dose-dependent regulation of apoptosis, proliferation, differentiation and migration

667 | Jun 29 2021

Chloe Delepine et al. revealed new mechanisms of the pleiotropic effects of GSK3β during organoid development, providing essential information for the improvement of organoid production and ultimately shedding light on the mechanisms of embryonic brain development. [Read the Full Post]

A Rho Kinase (ROCK) Inhibitor, Y-27632, Inhibits the Dissociation-Induced Cell Death of Salivary Gland Stem Cells

863 | Jun 23 2021

Kichul Kim et al. demonstrated the protective effects of Y-27632 against dissociation-induced apoptosis of SGSCs during their culture in vitro. [Read the Full Post]

Efficacy and safety of 177 Lu-DOTATATE in lung neuroendocrine tumors: a bi-center study

686 | May 31 2021

Lamiaa Zidan et al. found that in patients with advanced progressive lung NET and satisfactory SSR expression, 177Lu-DOTATATE was effective and safe with a high disease control rate and encouraging PFS and OS. [Read the Full Post]

The efficacy and safety of niraparib for ovarian cancer: a single-center observational study from China

954 | May 28 2021

Jing Ni et al. found that it was feasible that patients receiving a bolus of 200 mg/d in patients from Chinese population could acquire promising efficacy and tolerance. [Read the Full Post]

Development and validation of an MRI-based radiomics nomogram for distinguishing Warthin's tumour from pleomorphic adenomas of the parotid gland

693 | May 07 2021

Ying-Mei Zheng et al. found that the MRI-based radiomics nomogram had good performance in distinguishing parotid WT from PMA, which could optimize clinical decision-making. [Read the Full Post]

A fluorometric erythrophagocytosis assay using differentiated monocytic THP-1 cells to assess the clinical significance of antibodies to red blood cells

601 | May 06 2021

Abdelwahab Hassan Ahmed Balola et al. thought that the flow cytometry-based erythrophagocytosis test described here was quantitative, highly reliable, and might be helpful for the assessment of the clinical significance of antibodies to RBCs. [Read the Full Post]

Glutamine deficiency promotes stemness and chemoresistance in tumor cells through DRP1-induced mitochondrial fragmentation

422 | Apr 27 2021

Parash Prasad et al. suggested that glutamine deficiency in the core of tumors could increase the cancer stem cell population and the combination therapy with MDiVi-1 and L-DON was a useful approach to reduce CSCs population in tumor. [Read the Full Post]

Therapeutic targeting PLK1 by ON-01910.Na is effective in local treatment of retinoblastoma

668 | Apr 21 2021

Huan Ma et al. demonstrated targetability of PLK1 in retinoblastoma by efficiently causing cell cycle arrest and apoptosis. [Read the Full Post]

A Contaminant Impurity, Not Rigosertib, Is a Tubulin Binding Agent

704 | Apr 21 2021

Stacey J Baker et al. found that these cells failed to proliferate in the presence of rigosertib at concentrations that are lethal to wild-type cells. [Read the Full Post]

Water Mapping and Scoring approaches to predict the role of Hydration sites in Binding Affinity of PAK1 inhibitors

400 | Apr 18 2021

Jayashree Biswal et al. determined the best scoring function, established SARs and predicted active molecules through a computational model. [Read the Full Post]

Netarsudil: A new ophthalmic drug in the treatment of chronic primary open angle glaucoma and ocular hypertension

748 | Apr 18 2021

Mansi Batra et al. showed that the discovery of netarsudil was a breakthrough in the therapy of glaucoma with proven efficacy in a wide range of eye pressures and was well tolerated in cases with ocular hypertension and chronic glaucoma. [Read the Full Post]

The anti-apoptotic proteins Bcl-2 and Bcl-xL suppress Beclin 1/Atg6-mediated lethal autophagy in polyploid cells

1070 | Apr 16 2021

Jing Zhang et al. found that Bcl-2 and Bcl-xL negatively modulated MYC-VX-680 synthetic lethality. [Read the Full Post]

Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC)

1460 | Apr 15 2021

Christine Song et al. suggested an essential role of Cdc20 in tumor formation and metastasis of TNBC, which might be a potential target therapy for TNBC treatment. [Read the Full Post]

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

1062 | 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]

FARP1 boosts CDC42 activity from integrin αvβ5 signaling and correlates with poor prognosis of advanced gastric cancer

299 | Mar 24 2021

Takuro Hirano et al. suggested that the integrin αvβ5-FARP1-CDC42 axis played a crucial role in gastric cancer cell migration and invasion. [Read the Full Post]

Curcumin promotes cell cycle arrest and apoptosis of acute myeloid leukemia cells by inactivating AKT

374 | Mar 18 2021

Hao Zhou et al. demonstrated that curcumin exerted anti‑AML roles by inactivating AKT. [Read the Full Post]

Cardioautonomic control in healthy singleton and twin pregnancies

624 | Mar 16 2021

Victoria L Meah wt al. suggested that individuals with twin pregnancies had greater sympathetic and lower parasympathetic contributions to heart rate and that cardiac, but not vascular, autonomic control was impacted during twin compared to singleton pregnancy. [Read the Full Post]

Kinesin-7 CENP-E regulates the formation and structural maintenance of the acrosome

499 | Mar 06 2021

Zhen-Yu She et al. found that light on the molecular mechanisms involved in vesicle trafficking and architecture maintenance of the acrosome. [Read the Full Post]

Discovery of repurposing drug candidates for the treatment of diseases caused by pathogenic free-living amoebae

763 | Feb 25 2021

Christopher A Rice et al. demonstrated the utility of phenotypic screens for discovery of new drugs for pathogenic free-living amoebae, including Acanthamoeba for the first time. [Read the Full Post]

Priming with HDAC Inhibitors Sensitizes Ovarian Cancer Cells to Treatment with Cisplatin and HSP90 Inhibitors

695 | Feb 24 2021

Ana J Rodrigues Moita et al. found that priming with HDACi sensitized ovarian cancer cells to treatment with HSP90i or cisplatin and had an influence on the development of cisplatin resistance, both of which might contribute to an improved ovarian cancer treatment. [Read the Full Post]

Multi-functionalised graphene nanoflakes as tumour-targeting theranostic drug-delivery vehicles

505 | Feb 16 2021

Jennifer Lamb et al. showed that GNFs were suitable candidates for use in theranostic drug design. [Read the Full Post]

Pharmacological Protein Kinase C Modulators Reveal a Pro-hypertrophic Role for Novel Protein Kinase C Isoforms in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

454 | Feb 16 2021

Lotta Pohjolainen et al. showed similar hypertrophic responses to PKC modulators in NRVMs and hiPSC-CMs. [Read the Full Post]

enAsCas12a Enables CRISPR-Directed Evolution to Screen for Functional Drug Resistance Mutations in Sequences Inaccessible to SpCas9

439 | Feb 14 2021

Jasper Edgar Neggers et al. demonstrated that enAsCas12a is a promising new addition to the CRISPR screening toolbox and allows targeting sites not readily accessible to SpCas9. [Read the Full Post]

Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer

548 | Feb 03 2021

Chih-Yang Wang et al. found that upregulation of PPARA and lipid metabolism-related genes were potential pathways in the carcinogenesis and development of ampullary cancer. [Read the Full Post]

17-DMAG dually inhibits Hsp90 and histone lysine demethylases in alveolar rhabdomyosarcoma

652 | Feb 03 2021

Shivendra Singh et al. indicated that targeting KDM in combination with chemotherapy might serve as a therapeutic approach to PAX3-FOXO1-positive aRMS. [Read the Full Post]

Augmenter of Liver Regeneration (ALR) regulates bile acid synthesis and attenuates bile acid-induced apoptosis via glycogen synthase kinase-3β (GSK-3β) inhibition

1343 | Feb 02 2021

Sara Ibrahim et al. thought that rALR might contribute to protecting hepatocytes from toxic concentrations of bile acids by down-regulating their denovo synthesis, attenuating apoptosis by activation of PI3K/Akt - GSK3β pathway and inhibition of JNK signaling. [Read the Full Post]

Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro

642 | Jan 27 2021

Natalia Kosyakova et al. described the differential effects that two widely used stromal cell populations, fibroblasts (FBs) and pericytes (PCs), had on μVN formation. [Read the Full Post]

Suppression of MET signaling mediated by pitavastatin and capmatinib inhibits oral and esophageal cancer cell growth

697 | Jan 26 2021

Bo Xu et al. suggested that the combination of pitavastatin with capmatinib was a useful therapeutic strategy in OSCC and ESCC. [Read the Full Post]

The α1-adrenergic receptors in the amygdala regulate the induction of learned despair through protein kinase C-beta signaling

571 | Jan 22 2021

Shisui Fujita et al. suggested that the α1-adrenoreceptor in amygdala regulated the induction of learned despair via PKCβ. [Read the Full Post]

Effect of leech-centipede medicine on improving erectile function in DIED rats via PKC signalling pathway-related molecules

510 | Jan 22 2021

Ji-Sheng Wang et al. found that "leech-centipede" medicine could improve erectile dysfunction by inhibiting the expression of PKC pathway-related molecules in DIED rats and protected endothelial function and anti-platelet activation. [Read the Full Post]

CB 1 Cannabinoid Receptors Stimulate Gβγ-GRK2-Mediated FAK Phosphorylation at Tyrosine 925 to Regulate ERK Activation Involving Neuronal Focal Adhesions

611 | Jan 12 2021

George D Dalton et al. found that FAK 925 Tyr-P occured concurrently with CB1-stimulated ERK2 activation and required the actin cytoskeleton and Gi/oβγ-GRK2-mediated cross-talk between CB1, integrins, and receptor tyrosine kinases (RTKs). [Read the Full Post]

Mechanotransduction-targeting Drugs Attenuate Stiffness-induced Hepatic Stellate Cell Activation in vitro

583 | Jan 10 2021

Mutsuko Sakai et al. showed that an integrin antagonist and mechanotransduction-targeting drugs reduced stiffness-induced HSC activation in a dose-dependent fashion. [Read the Full Post]

The Integrin Inhibitor Cilengitide and Bleomycin-Induced Pulmonary Fibrosis : Cilengitide and Bleomycin-Induced Pulmonary Fibrosis

249 | Jan 05 2021

Jeffrey D Ritzenthaler et al. suggested that, despite its in vitro activity in fibroblasts, daily injections of cilengitide (20 mg/kg) did not inhibit the development of or ameliorate bleomycin-induced pulmonary fibrosis in mice. [Read the Full Post]

Deciphering the Inhibition Mechanism of under Trial Hsp90 Inhibitors and Their Analogues: A Comparative Molecular Dynamics Simulation

555 | Dec 28 2020

Asma Nazar et al. suggested that under trial Hsp90 inhibitors MPC-3100 could be a potential starting point into the development of potential anticancer agents with the possibility of future directions for the improvement of early existing Hsp90 inhibitors CNF-2024 and SNX-5422 as an anticancer agent. [Read the Full Post]

Heat Shock Protein 90 Inhibitors AUY922, BIIB021 and SNX5422 Induce Bim-mediated Death of Thyroid Carcinoma Cells

587 | Dec 27 2020

Si Hyoung Kim et al. found that AUY922, BIIB021 and SNX5422 induced cytotoxicity by modulating Bim and ERK1/2, AKT and AMPK signaling in thyroid carcinoma cells. [Read the Full Post]

HSP90 Inhibitor Ganetespib (STA-9090) Inhibits Tumor Growth in c-Myc-Dependent Esophageal Squamous Cell Carcinoma

648 | Dec 17 2020

Liuliu Guan et al. supported that the HSP90 inhibitor, STA-9090, suppressed the expression of the MYC protein and interferes with HSP90-MYC protein-protein interaction. [Read the Full Post]

Ganetespib in Combination with Pemetrexed-Platinum Chemotherapy in Patients with Pleural Mesothelioma (MESO-02): A Phase Ib Trial

734 | Dec 16 2020

Dean A Fennell et al. found that ganetespib could be combined safely with pemetrexed and platinum chemotherapy to treat patients with MPM. [Read the Full Post]

The Role of Syk in Inflammatory Response of Human Abdominal Aortic Aneurysm Tissue

1421 | Dec 13 2020

Ryo Kanamoto et al. demonstrated an important role of Syk for IgG-dependent inflammatory response in human AAA. [Read the Full Post]

Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis

0 | Dec 12 2020

Alejandro Torres-Hernandez et al. found that SYK is an attractive target for experimental therapeutics in treating hepatic fibrosis and oncogenesis. [Read the Full Post]

Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity

947 | Dec 07 2020

Sandeep Kumar et al. demonstrated that MLK3 played an important role in T cell biology, and targeting MLK3 could serve as a potential therapeutic intervention via increasing T cell cytotoxicity in cancer. [Read the Full Post]

LGR5 induces β activation and augments tumor progression by activating STAT3 in human intrahepatic cholangiocarcinoma

1015 | 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]

FXIIIa substrate peptide decorated BLZ945 nanoparticles for specifically remodeling tumor immunity

513 | Nov 30 2020

Qi Wei et al. established a novel combination strategy for anti-tumor therapy. [Read the Full Post]

Design and Evaluation of Rhein-Based MRI Contrast Agents for Visualization of Tumor Necrosis Induced by Combretastatin A-4 Disodium Phosphate

433 | Nov 30 2020

Libang Zhang et al. found that GdP1 might serve as a potential candidate for early evaluation of tumor response to CA4P treatment. [Read the Full Post]

Bevacizumab plus fosbretabulin in recurrent ovarian cancer: Overall survival and exploratory analyses of a randomized phase II NRG oncology/gynecologic oncology group study

395 | Nov 29 2020

Krishnansu S Tewari et al. found that although no significant survival benefit was observed, the trend showing a reduced HR for progression or death with increasing tumor size when fosbretabulin was added to bevacizumab compared to bevacizumab alone warrants further study. [Read the Full Post]

CXCL14 inhibits the growth and promotes apoptosis of hepatocellular carcinoma cells via suppressing Akt/mTOR pathway

406 | Nov 17 2020

Jianqiang Bi et al. thought that CXCL14 inhibited growth but promoted apoptosis of HCC cells via suppressing Akt/mTOR pathway and CXCL14 might be a potential target for HCC treatment in clinical practice. [Read the Full Post]

Defactinib attenuates osteoarthritis by inhibiting positive feedback loop between H-type vessels and MSCs in subchondral bone

571 | Nov 13 2020

Yanjun Hu et al. demonstrated that defactinib inhibited OA by suppressing the positive feedback loop between H-type vessels and MSCs in subchondral bone. [Read the Full Post]

Activating JAK-mutations confer resistance to FLT3 kinase inhibitors in FLT3-ITD positive AML in vitro and in vivo

472 | Nov 10 2020

Christoph Rummelt et al. characterized a novel mechanism of resistance to FLT3-ITD inhibition and might offer a potential therapy, using dual JAK and FLT3 inhibition. [Read the Full Post]

VDAC upregulation and αTAT1‑mediated α‑tubulin acetylation contribute to tanespimycin‑induced apoptosis in Calu‑1 cells

2056 | Nov 02 2020

Qilin Wang et al. provided evidence for the use of a combination of drugs that target VDAC1 and tubulin to induce tumour cell apoptosis. [Read the Full Post]

Identification of Subtype-Specific Metastasis-Related Genetic Signatures in Sarcoma

734 | Nov 02 2020

Ya-Ling Li et al. provided new insights into the pathogenesis, diagnosis, treatment, and prognosis of sarcomas and provided new directions for further study of sarcoma. [Read the Full Post]

Chemical Reprogramming of Somatic Cells in Neural Direction: Myth or Reality?

802 | Oct 27 2020

E M Samoilova et al. found that reprogramming with small molecules without additional factors modifying gene expression did not allow reproducible production of human neural stem cell-like progenitors that could be used as the source of neural tissue for the regenerative therapy. [Read the Full Post]

Hsp90 Inhibitor; NVP-AUY922 in Combination with Doxorubicin Induces Apoptosis and Downregulates VEGF in MCF-7 Breast Cancer Cell Line

733 | Oct 16 2020

Mahshid Mohammadian et al. indicated an effective action of NVP-AUY922 in combined with DOX in this cell line. [Read the Full Post]

Heat Shock Protein 90 (Hsp90)-Inhibitor-Luminespib-Loaded-Protein-Based Nanoformulation for Cancer Therapy

788 | Oct 15 2020

Ankit K Rochani et al.suggested that DNP-based aqueous nanoformulations could be used in both pancreatic (MIA PaCa-2) and breast (MCF-7) cancer therapy. [Read the Full Post]

An exon skipping screen identifies antitumor drugs that are potent modulators of pre-mRNA splicing, suggesting new therapeutic applications

628 | Oct 14 2020

Yihui Shi et al.supported the broad potential for the development of agents that targeted the spliceosome for the treatment of cancer and other diseases, as well as new avenues for the discovery of new chemotherapeutic agents for a range of diseases. [Read the Full Post]

A rare maternal gastrointestinal stromal tumor found in the second trimester of pregnancy: A case report

838 | Oct 03 2020

Naoko Tanaka et al. believed that pregnant patients should be managed by a multidisciplinary team with expertise in gastrointestinal tumors and fetal-maternal medicine. [Read the Full Post]

A Slug-dependent mechanism is responsible for tumor suppression of p53-stabilizing compound CP-31398 in p53-mutated endometrial carcinoma

354 | Oct 03 2020

Ling Liu et al. showed that CP-31398-regulated Slug downregulation repressed the p53-mutated EC via the p53/Wnt/Puma pathway. [Read the Full Post]

Effective Reconstruction of Functional Urethra Promoted With ICG-001 Delivery Using Core-Shell Collagen/Poly(Llactide-co-caprolactone) [P(LLA-CL)] Nanoyarn-Based Scaffold: A Study in Dog Model

405 | Sep 08 2020

Kaile Zhang et al. applied a novel drug-delivering nanoyarn scaffold in urethroplasty in dog model, which continuously delivered ICG-001 during tissue reconstruction, and could effectively promote urethral recovery and resume fully functional urethra within 12 weeks. [Read the Full Post]

Sotrastaurin, a PKC inhibitor, attenuates RANKL-induced bone resorption and attenuates osteochondral pathologies associated with the development of OA

475 | Sep 08 2020

Cong Pang et al. provided evidence for the protective effects of SO against OA by preventing aberrant subchondral bone and articular cartilage changes. [Read the Full Post]

Combined treatment with CBP and BET inhibitors reverses inadvertent activation of detrimental super enhancer programs in DIPG cells

451 | Aug 30 2020

Maria Wiese et al. found that combinatorial treatment with CBP and BET inhibitors was highly efficient in H3K27M-mutant DIPG due to reversal of inadvertent activation of detrimental SE programs in comparison with monotherapy. [Read the Full Post]

Quercetin promotes human epidermal stem cell proliferation through the estrogen receptor/β-catenin/c-Myc/cyclin A2 signaling pathway

488 | 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]

Pharmacokinetics and bioavailability of ipatasertib in dog plasma using LC/MS/MS

440 | Jul 27 2020

Ying Liu et al. showed that the bioavailability of ipatasertib was determined to be 19.3%. [Read the Full Post]

Combined inhibition of ACK1 and AKT shows potential toward targeted therapy against KRAS-mutant non-small-cell lung cancer

448 | Jul 27 2020

Xiangjing Yu et al. demonstrated the promising therapeutic potential of combined ACK1/AKT inhibition as a strategy against KRAS-mutant NSCLC. [Read the Full Post]

Exosomal release of microRNA-454 by breast cancer cells sustains biological properties of cancer stem cells via the PRRT2/Wnt axis in ovarian cancer

345 | Jul 23 2020

Ling Wang et al. discovered that C59 reversed the repressive role of exosomes in stemness of CSCs. When being evaluated in a mouse model, exosomal miR-454 led to an efficacious effect in suppressing the tumor weight and volume in vivo. [Read the Full Post]

Differentiation of Human Cardiac Atrial Appendage Stem Cells into Adult Cardiomyocytes: A Role for the Wnt Pathway?

388 | Jul 23 2020

Leen Willems et al. indicated that Wnt signaling had limited effects on CASC clonogenicity, proliferation, and differentiation. [Read the Full Post]

A Global PROTAC Toolbox for Degrading BCR-ABL Overcomes Drug-Resistant Mutants and Adverse Effects

1167 | Jul 15 2020

Yiqing Yang et al. found that PROTACs showed better selectivity and less adverse effects than inhibitors, indicating that PROTACs had a great potential for overcoming clinical drug resistance and safety issues. [Read the Full Post]

Overexpression of Fibroblast Growth factor-21 (FGF-21) Protects Mesenchymal Stem Cells Against Caspase-Dependent Apoptosis Induced by Oxidative Stress and Inflammation

1230 | Jun 22 2020

Gabriel R Linares et al. provided compelling evidence that FGF-21 played a crucial role in protecting MSCs from apoptosis induced by oxidative stress and inflammation, and merited further investigation as a strategy for enhancing the therapeutic efficacy of stem cell-based therapies. [Read the Full Post]

Staurosporine and NEM Mainly Impair WNK-SPAK/OSR1 Mediated Phosphorylation of KCC2 and NKCC1

1227 | Jun 18 2020

Jinwei Zhang et al. identified phospho-sites that are responsive to staurosporine or NEM application. [Read the Full Post]

LGR5 Controls Extracellular Matrix Production by Stem Cells in the Developing Intestine

427 | Jun 14 2020

Valeria Fernandez Vallone et al. provided that Lgr5 antagonizes the Rspondin 2-Wnt-mediated response in ISCs in organoids, revealing a sophisticated regulatory process for Wnt signaling in ISCs. [Read the Full Post]

Generation of Liver Bipotential Organoids With a Small-Molecule Cocktail

815 | Jun 05 2020

Xin Wang et al. demonstrated that Wnt/β-catenin, NMII-Rac, and PKA-ERK are core signaling pathways essential and sufficient for mouse liver progenitor expansion. [Read the Full Post]

Phase II Trial of AKT Inhibitor MK-2206 in Patients With Advanced Breast Cancer Who Have Tumors With PIK3CA or AKT Mutations, and/or PTEN loss/PTEN Mutation

590 | May 31 2020

Yan Xing et al. found that MK-2206 monotherapy had limited clinical activity in advanced breast cancer patients selected for PIK3CA/AKT1 or PTEN mutations or PTEN loss. This may, in part, be due to inadequate target inhibition at tolerable doses in heavily pre-treated patients with pathway activation, as well as tumor heterogeneity and evolution in markers such as PTEN conferring challenges in patient selection. [Read the Full Post]

CHIR-99021 Regulates Mitochondrial Remodelling via β-Catenin Signalling and miRNA Expression During Endodermal Differentiation

0 | May 22 2020

Yuejiao Ma et al. demonstrated that CHIR-99021 played a role in mitochondrial structure and function remodelling via activation of the β-catenin signalling pathway and inhibited the expression of miRNAs during definitive endodermal differentiation. [Read the Full Post]

Glucagon-like peptide 1 reverses myocardial hypertrophy through cAMP/PKA/RhoA/ROCK2 signaling.

955 | May 14 2020

Fan S et al. suggested that GLP-1 might reverse myocardial hypertrophy through the PKA/RhoA/ROCK2 signaling pathway. [Read the Full Post]

The Rho-associated kinase inhibitor fasudil can replace Y-27632 for use in human pluripotent stem cell research

1318 | May 12 2020

So S et al. suggested that fasudil can replace Y-27632 for use in stem research. [Read the Full Post]

FOXK1 Promotes Proliferation and Metastasis of Gallbladder Cancer by Activating AKT/mTOR Signaling Pathway

418 | May 07 2020

Wencong M et al. suggested that FOXK1 promotes GBC cells progression and represent a novel prognostic biomarker and potential therapeutic target in GBC. [Read the Full Post]

A Phase I Study of PF-04929113 (SNX-5422), an Orally Bioavailable Heat Shock Protein 90 Inhibitor, in Patients With Refractory Solid Tumor Malignancies and Lymphomas

571 | Apr 19 2020

Arun Rajan et al. showed that PF-04929113 administered orally twice a week is well tolerated and inhibits its intended target Hsp90. No objective responses were seen, but long-lasting stabilizations were obtained. Although no clinically significant drug-related ocular toxicity was seen in this study, the development of PF-04929113 has been discontinued because of ocular toxicity seen in animal models and in a separate phase I study. [Read the Full Post]

SNX-2112, a Selective Hsp90 Inhibitor, Potently Inhibits Tumor Cell Growth, Angiogenesis, and Osteoclastogenesis in Multiple Myeloma and Other Hematologic Tumors by Abrogating Signaling via Akt and ERK

530 | Apr 19 2020

Yutaka Okawa et al. provided the framework for clinical studies of SNX-2112 to improve patient outcome in MM and other hematologic malignancies. [Read the Full Post]

Development Of Novel Liposome-Encapsulated Combretastatin A4 Acylated Derivatives: Prodrug Approach For Improving Antitumor Efficacy

505 | Apr 08 2020

Gu Y et al. suggested that the release or hydrolysis of the parent drug from the prodrug was closely related with the in vitro and in vivo properties. The slow drug release of CA4 modified with longer acyl chain could prolong the circulation time and increase the concentration of the drug in the tumor tissue. These effects play a critical role in increasing the antitumor efficacy. [Read the Full Post]

Covalent functionalization of SWCNT with combretastatin A4 for cancer therapy

501 | Apr 08 2020

Assali M et al. suggested that the novel SWCNT-CA4 has a significant anticancer activity that might be superior to that of free CA4. [Read the Full Post]

Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD)

710 | Mar 15 2020

Nikonova AS et al. identified a new biologic activity for HSP90 and support a cilia-based mechanism for cyst repression.-Nikonova, A. S., Deneka, A. Y., Kiseleva, A. A., Korobeynikov, V., Gaponova, A., Serebriiskii, I. G., Kopp, M. C., Hensley, H. H., Seeger-Nukpezah, T. N., Somlo, S., Proia, D. A., Golemis, E. A. Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD). [Read the Full Post]

The novel HSP90 inhibitor STA-9090 exhibits activity against Kit-dependent and -independent malignant mast cell tumors

638 | Mar 15 2020

Lin TY et al. showed that STA-9090 exhibits broad activity against mast cells expressing WT or mutant Kit, suggesting it may be an effective agent in the clinical setting against mast cell malignancies. [Read the Full Post]

Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation of RAS/MAPK Signaling

1040 | Mar 14 2020

Nelson-Taylor SK et al. demonstrated that resistance to ponatinib in RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms that result in restored RAS/MAPK activation. [Read the Full Post]

AKT Antagonist AZD5363 Influences Estrogen Receptor Function in Endocrine-Resistant Breast Cancer and Synergizes with Fulvestrant (ICI182780) In Vivo

422 | Feb 12 2020

Ribas R et al. supported the combination of AZD5363 with fulvestrant as a potential therapy for breast cancer that is sensitive or resistant to E-deprivation or tamoxifen and that activated AKT is a determinant of response, supporting the need for clinical evaluation. [Read the Full Post]

Rho-kinase ROCK inhibitors reduce oligomeric tau protein

1041 | Feb 10 2020

Hamano T et al. suggested that ROCK inhibitors represent a viable therapeutic route to reduce the pathogenic forms of tau protein in tauopathies, including Alzheimer's disease. [Read the Full Post]

Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib

877 | Feb 07 2020

Casavecchia G et al. reported and discussed most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. [Read the Full Post]

Protein tyrosine kinase 2: a novel therapeutic target to overcome acquired EGFR-TKI resistance in non-small cell lung cancer

582 | Feb 03 2020

Tong X et al. suggested that this combination therapy may be a viable option to overcome EGFR-TKI resistance in NSCLC. [Read the Full Post]

Cost-effectiveness of midostaurin in the treatment of newly diagnosed FLT3-mutated acute myeloid leukemia in France

547 | Jan 25 2020

Tremblay G et al. indicated that MIDO represents a clinically significant advancement in the management of newly diagnosed FLT3-mutated AML. In this analysis, MIDO add-on therapy showed gains in LYs and QALYs versus SOC alone and was found to be a cost-effective option at a €100,000 per QALY threshold for end-of-life treatment. [Read the Full Post]

17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model

744 | Jan 08 2020

Joshi SS et al. indicated their sdudies support a role for 17-AAG and HSP90 inhibition in enhancing cellular immunotherapy for melanoma. [Read the Full Post]

Tanespimycin as antitumor therapy

0 | Jan 07 2020

Dimopoulos MA et al. indiacated that tanespimycin represents a promising new agent for the treatment of relapsed/refractory MM. Results of ongoing and future trials will determine the role of tanespimycin both in MM and other malignancies, including breast cancer. [Read the Full Post]

Generation of Urine Cell-Derived Non-integrative Human iPSCs and iNSCs: A Step-by-Step Optimized Protocol

0 | Jan 03 2020

Cheng L et al. showed the optimized protocol is an easy and fast procedure to yield both iPSC and iNSC lines from a convenient source of human urine in a single experiment. [Read the Full Post]

Hsp90 inhibitors induce the unfolded protein response in bovine and mice lung cells

682 | Dec 19 2019

Kubra KT et al. demonstrated that Hsp90 inhibition triggers the activities of the unfolded protein response, and suggests that this molecular machinery contributes in the protective action of Hsp90 inhibitors in the lung microvasculature. [Read the Full Post]

NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo

0 | Dec 19 2019

Lian J et al. indicated that NVP-AUY922 exhibits potent anti-PCC activities in vitro and in vivo and represents a promising therapeutic small molecule for treating malignant PCC. [Read the Full Post]

Activity of the Hsp90 inhibitor luminespib among non-small-cell lung cancers harboring EGFR exon 20 insertions

683 | Dec 18 2019

Piotrowska Z et al.showed that this study met its primary end point, suggesting that luminespib may be an active therapy for advanced NSCLC patients with EGFR ins20. Luminespib is generally well-tolerated, though reversible low-grade ocular toxicity is common. Further study of luminespib and other hsp90 inhibitors in this population is warranted. [Read the Full Post]

miR-193b-Regulated Signaling Networks Serve as Tumor Suppressors in Liposarcoma and Promote Adipogenesis in Adipose-Derived Stem Cells

562 | Dec 16 2019

Mazzu YZ et al. indicated that miR-193b not only functions as a tumor suppressor in liposarcoma but also promotes adipogenesis in ASC. Furthermore, this study reveals key tyrosine kinase and DNA methylation pathways in liposarcoma, some with immediate implications for therapeutic exploration. [Read the Full Post]

Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells

948 | Dec 10 2019

Kuntz EM et al. provided a strong rationale for investigation of the use of TKIs in combination with tigecycline to treat patients with CML with minimal residual disease. [Read the Full Post]

Raloxifene inhibits adipose tissue inflammation and adipogenesis through Wnt regulation in ovariectomized rats and 3 T3-L1 cells

490 | Dec 10 2019

Shen HH et al. showed that distinct activation of canonical β-catenin on inhibition of adipogenesis and non-canonical SFRP5 on suppression of WAT inflammation may contribute to the beneficial effects of RAL. Therefore, this study provides a rationale for the therapeutic potential of RAL for postmenopausal obesity. [Read the Full Post]

Y-27632 preserves epidermal integrity in a human skin organ-culture (hSOC) system by regulating AKT and ERK signaling pathways

471 | Nov 23 2019

Zhang X et al. found that Y-227632 can maintain skin epidermal integrity through regulation of AKT and ERK activity in the hSOC. [Read the Full Post]

ICG-001 suppresses growth of gastric cancer cells and reduces chemoresistance of cancer stem cell-like population

0 | Nov 17 2019

Liu Y et al. suggested that ICG-001 suppresses GC cell line growth, metastasis and reduces its stem cell-like properties and chemoresistance, indicating that ICG-001 is a potentially useful small molecule therapeutic for GC. [Read the Full Post]

Effects of pentoxifylline and H-89 on epileptogenic activity of bucladesine in pentylenetetrazol-treated mice

516 | Nov 11 2019

Hosseini-Zare MS et al. showed that seizure activities were affected by pentoxifylline, H-89 and bucladesine via interactions with intracellular cAMP and cGMP signaling pathways, cyclic nucleotide-dependent protein kinases, and related neurotransmitters. [Read the Full Post]

Treatment with XAV-939 prevents in vitro calcification of human valvular interstitial cells

504 | Nov 10 2019

Dittfeld C et al. indicated that XAV-939 was therefore able to prevent calcification of human VIC cultures, and XAV-939 treatment was accompanied by upregulation of active non-phospho-β-catenin. Although XAV-939 does not downregulate active β-catenin, treatment with XAV-939 results in Sox9 upregulation that may prevent the calcification process. [Read the Full Post]

The novel inhibitor PRI-724 for Wnt/β-catenin/CBP signaling ameliorates bleomycin-induced pulmonary fibrosis in mice

1387 | Nov 10 2019

Okazaki H et al. suggested that the β-catenin/CBP inhibitor PRI-724 is a potent antifibrotic agent that acts by modulating the activity of macrophages in the lungs. [Read the Full Post]

Nuclear localization of β-catenin and expression of target genes are associated with increased Wnt secretion in oral dysplasia

1326 | Oct 27 2019

Reyes M et al. indicated that secretion of Wnt ligands is critical for β-catenin nuclear localization and expression of target genes in oral dysplasia. [Read the Full Post]

Targeting the PI3K/Akt/mTOR-pathway with the pan-Akt inhibitor GDC-0068 in PIK3CA-mutant breast cancer brain metastases

505 | Oct 08 2019

Ippen FM et al. suggested that the Akt-inhibitor GDC-0068 may be an encouraging targeted treatment strategy for breast cancer brain metastasis patients with activating mutations in the PI3K pathway. These data provide a rationale to further evaluate the efficacy of GDC-0068 in patients with brain metastases. [Read the Full Post]

Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial

673 | Oct 03 2019

Kim SB et al. supported AKT-targeted therapy for triple-negative breast cancer. Ipatasertib warrants further investigation for the treatment of triple-negative breast cancer. [Read the Full Post]

Influence of Wilms' tumor suppressor gene WT1 on bovine Sertoli cells polarity and tight junctions via non-canonical WNT signaling pathway

487 | Oct 01 2019

Wang X et al. indicated that WT1 mediates the regulation of several proteins involved in bovine SCs polarity maintenance and intercellular tight junctions (TJ) by non-canonical WNT signaling pathway. [Read the Full Post]

Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models

1078 | Sep 23 2019

Gozgit JM et al. showed that ponatinib is a potent pan-FGFR inhibitor and provide strong rationale for its evaluation in patients with FGFR-driven cancers. [Read the Full Post]

NK2 receptor mediated detrusor muscle contraction involves Gq/11-dependent activation of voltage-dependent calcium channels and the RhoA-Rho kinase pathway

1077 | Aug 30 2019

Dér B et al. identified potential therapeutic targets of bladder dysfunctions related to upregulation of TKs. [Read the Full Post]

Alkylation of Staurosporine to Derive a Kinase Probe for Fluorescence Applications

686 | Aug 18 2019

Disney AJ et al. reported that this fluorescein-staurosporine conjugate binds to cAMP-dependent protein kinase in the nanomolar range. Furthermore, its binding can be antagonised with unmodified staurosporine as well as ATP, indicating it targets the ATP binding site in a similar fashion to native staurosporine. This reagent has potential application as a screening tool for protein kinases of interest. [Read the Full Post]

The Wnt inhibitor LGK-974 enhances radiosensitivity of HepG2 cells by modulating Nrf2 signaling

529 | Aug 11 2019

Tian D et al. found that HepG2 cells became more sensitive to radiation with increasing LGK-974 concentrations. Upon 2 Gy or 4 Gy irradiation, the cells treated with LGK-974 more frequently underwent apoptosis and grew less rapidly. PCR and western blot results showed that inhibiting the secretion of Wnt3A blocked the Wnt signaling pathway and prevented Nrf2 signaling. Notably, the Wnt inhibitor may serve as a radiosensitizing drug. [Read the Full Post]

Treatment Patterns in Patients with Chronic-Phase Chronic Myeloid Leukaemia in Routine Clinical Practice: the SIMPLICITY Italian Population

1403 | Aug 10 2019

Abruzzese E et al. provided valuable insights into management and treatment patterns in Italian patients with CML within routine clinical practice. [Read the Full Post]

A Phase II Trial of Neoadjuvant MK-2206, an AKT Inhibitor, with Anastrozole in Clinical Stage II or III PIK3CA-Mutant ER-Positive and HER2-Negative Breast Cancer

552 | Jul 24 2019

Ma CX et al. indicated that MK-2206 is unlikely to add to the efficacy of anastrozole alone in PIK3CA-mutant ER+ breast cancer and should not be studied further in the target patient population. [Read the Full Post]

Airway Progenitor Clone Formation Is Enhanced by Y-27632-Dependent Changes in the Transcriptome

1222 | Jul 10 2019

Reynolds SD et al. concluded that Y-27632 fundamentally alters cell-cell and cell-ECM interactions, which preserves basal progenitor cells and allows greater cell amplification. [Read the Full Post]

Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND-A Double-Blind, Randomized, Phase II Study

666 | Jul 07 2019

Fennell DA et al. indicated that neither PFS nor OS was improved by defactinib after first-line chemotherapy in patients with merlin-low MPM. Defactinibcannot be recommended as maintenance therapy for advanced MPM. [Read the Full Post]

Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects

818 | Jun 30 2019

Tran P et al. presented the results of human oral absorption, distribution, metabolism, excretion (ADME) and in vitro studies that together provide an overall understanding of the metabolism, distribution and clearance of asciminib in humans. [Read the Full Post]

TKI-Related Platelet Dysfunction Does Not Correlate With Bleeding in Patients With Chronic Phase-Chronic Myeloid Leukemia With Complete Hematological Response

901 | Jun 21 2019

Sener Y et al. concluded that TKIs may impair in vitro platelet aggregation but this impairment is not associated with bleeding diathesis. [Read the Full Post]

Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/β-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial

676 | Jun 19 2019

Kimura K et al. showed that administration of 10 or 40mg/m2/day intravenous PRI-724 over 12weeks was well-tolerated by patients with HCV cirrhosis; however, liver injury as a possible related serious adverse event was observed in the 160mg/m2/day cohort. [Read the Full Post]

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

719 | Jun 07 2019

Stone RM et al. indicated the addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy significantly prolonged overall and event-free survival among patients with AML and a FLT3 mutation. [Read the Full Post]

NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo

929 | May 31 2019

Lian J et al. showed that NVP-AUY922 exhibits potent anti-PCC activities in vitro and in vivo and represents a promising therapeutic small molecule for treating malignant PCC. [Read the Full Post]

KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells

992 | May 31 2019

Diep DTV et al. indicated that KD025suppresses adipocyte differentiation by modulation of key factors activated at the intermediate stage of differentiation, and not by inhibition of ROCK2. [Read the Full Post]

Quantitative phosphoproteomic analysis of acquired cancer drug resistance to pazopanib and dasatinib

851 | May 26 2019

Vyse S et al. provided a useful resource detailing the candidate signalling determinants of acquired TKI resistance; and reveals a therapeutic approach of inhibiting HSP90 function as a means of salvage therapy to overcome pazopanib and dasatinib resistance. [Read the Full Post]

Midostaurin/PKC412 for the treatment of newly diagnosed FLT3 mutation-positive acute myeloid leukemia

811 | May 25 2019

Luskin MR et al. indicated that expert commentary: The approval of midostaurin represents the first new therapy for AML in several decades. It is also the first targeted therapy approved for AML. Future studies will focus on defining mechanisms of resistance to midostaurin as well as establishing the role of midostaurin in combination with hypomethylating agents and as maintenance therapy. Second generation, more potent and selective FLT3 inhibitors are also in development; these agents need to be compared to midostaurin. [Read the Full Post]

Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling

918 | May 06 2019

Kuusanmäki H et al. showed alternative approaches to inhibit STAT3 activity and suggest Hsp90 as a therapeutic target in lymphoproliferative disorders with constitutively active STAT3. [Read the Full Post]

High-throughput Chemical Screening Identifies Focal Adhesion Kinase and Aurora Kinase B Inhibition as a Synergistic Treatment Combination in Ewing Sarcoma

701 | Apr 14 2019

Wang S et al. indicated that FAK and Aurora kinase B inhibitors synergistically impair Ewing sarcoma cell viability and significantly inhibit tumor progression. This study provides preclinical support for the consideration of a clinical trial testing the safety and efficacy of this combination for patients with Ewing sarcoma. [Read the Full Post]

ICG-001 suppresses growth of gastric cancer cells and reduces chemoresistance of cancer stem cell-like population

677 | Apr 10 2019

Liu Y et al. suggested that ICG-001 suppresses GC cell line growth, metastasis and reduces its stem cell-like properties and chemoresistance, indicating that ICG-001 is a potentially useful small molecule therapeutic for GC. [Read the Full Post]

Oncogenic role of ABHD5 in endometrial cancer

719 | Apr 04 2019

Zhou Q suggested that ABHD5 may play an oncogenic role in endometrial cancer via the AKT pathway. [Read the Full Post]

Mechanisms of U46619-induced contraction in mice intrarenal arteries

1253 | Mar 27 2019

Yan H et al. suggested that the U46619-induced contraction of mouse intrarenal arteries is mediated by Cav1.2 and SOC channel, through the activation of thromboxane-prostanoid receptors and its downstream signaling pathway. [Read the Full Post]

Generation of Urine Cell-Derived Non-integrative Human iPSCs and iNSCs: A Step-by-Step Optimized Protocol

1256 | Mar 24 2019

Cheng L et al. showed the optimized protocol is an easy and fast procedure to yield both iPSC and iNSC lines from a convenient source of human urine in a single experiment. [Read the Full Post]

IWR-1 Inhibits Collagen-Induced Platelet Activation and Protects against Thrombogenesis

719 | Mar 12 2019

Wang W et al. demonstrated that IWR-1 could effectively block collagen-induced platelet activity in vitro and in vivo, and suggest its candidacy as a new antiplatelet agent. [Read the Full Post]

Combination AZD5363 with Enzalutamide Significantly Delays Enzalutamide-resistant Prostate Cancer in Preclinical Models

759 | Mar 11 2019

Toren P et al. provided preclinical data to support evaluation of combination targeting of the PI3K/Akt pathway and the androgen-receptor axis in the clinic using AZD5363 and ENZ, respectively. [Read the Full Post]

Combination treatment with docetaxel and histone deacetylase inhibitors downregulates androgen receptor signaling in castration-resistant prostate cancer

707 | Mar 06 2019

Park SE et al. suggested that docetaxel, in combination with HDACIs, suppressed the expression and nuclear translocation of AR-FL and AR-Vs and showed synergistic anti-proliferative effect in CRPC cells. This combination therapy may be useful for the treatment of patients with CRPC. [Read the Full Post]

Sotrastaurin in calcineurin inhibitor-free regimen using everolimus in de novo kidney transplant recipients

757 | Mar 03 2019

Tedesco-Silva H et al. indicated that sotrastaurin combined with EVR showed higher efficacy failure rates and some improvement in renal allograft function compared to a CsA-based therapy. [Read the Full Post]

UBE2S mediates tumor progression via SOX6/β-Catenin signaling in endometrial cancer

1661 | Mar 03 2019

Lin M et al. suggested UBE2S may serve as a promising prognostic factor and function as an oncogene in EMC. The newly identified UBE2S/SOX6/β-Catenin axis represents a new potential therapeutic target for EMC intervention. [Read the Full Post]

Tanespimycin as antitumor therapy

1114 | Feb 24 2019

Dimopoulos MA et al. showed that tanespimycin represents a promising new agent for the treatment of relapsed/refractory MM. Results of ongoing and future trials will determine the role of tanespimycin both in MM and other malignancies, including breast cancer. [Read the Full Post]

Effects of cancer-associated point mutations on the structure, function, and stability of succinate dehydrogenase A

1061 | Feb 22 2019

Cao ZF et al. provided information important for understanding the molecular mechanisms of SDHA mutations in tumors. [Read the Full Post]

Potent in vivo lung cancer Wnt signaling inhibition via cyclodextrin-LGK974 inclusion complexes

672 | Feb 21 2019

Guimaraes PPG et al. indicated the development of these complexes enables safer and repeated oral or parenteral administration of Wnt signaling inhibitors, which hold promise for the treatment of multiple types of malignancies. [Read the Full Post]

ABCB1 Mediates Cabazitaxel-Docetaxel Cross-Resistance in Advanced Prostate Cancer

673 | Feb 16 2019

Lombard AP et al. suggested the potential in using combinations of antiandrogens with cabazitaxel for increased effect in treating advanced CRPC. [Read the Full Post]

27 T ultra-high static magnetic field changes orientation and morphology of mitotic spindles in human cells

742 | Jan 25 2019

Zhang L et al. not only found that ultra-high magnetic field can change the orientation and morphology of mitotic spindles, but also provided a tool to probe the role of spindle orientation and perturbation in developmental and cancer biology. [Read the Full Post]

Pharmacology and pharmacokinetics of imatinib in pediatric patients

1447 | Jan 22 2019

Suttorp M et al. indicated that adherence to imatinib intake may be the most prominent factor influencing treatment outcome in teenagers thus pointing towards the potential benefits of regular drug monitoring. [Read the Full Post]

Pharmacology and pharmacokinetics of imatinib in pediatric patients

0 | Jan 22 2019

Suttorp M et al. indicated taht pharmacokinetic variables (e.g. alpha 1-acid glycoprotein binding, drug-drug/food-drug interactions via cytochrome P450 3A4/5, cellular uptake mediated via OCT-1-influx variations and P-glycoprotein-mediated drug efflux) still await to be addressed in pediatric patients systematically. [Read the Full Post]

Ex vivo AKT-inhibition facilitates generation of polyfunctional stem cell memory-like CD8+ T cells for adoptive immunotherapy

0 | Jan 21 2019

Mousset CM et al. demonstrated that AKT-inhibitors with different modality of action promote the ex vivo generation of stem cell memory-like CD8+ T cells with a unique metabolic profile and retained polyfunctionality. Akt-inhibitor VIII and GDC-0068 outperformed other inhibitors, and are therefore promising candidates for ex vivo generation of superior tumor-reactive T cells for adoptive immunotherapy in cancer patients. [Read the Full Post]

A phase II, randomised study of mFOLFOX6 with or without the Akt inhibitor ipatasertib in patients with locally advanced or metastatic gastric or gastroesophageal junction cancer

878 | Jan 18 2019

Bang YJ et al. showed that Ipatasertib/mFOLFOX6 compared with placebo/mFOLFOX6 did not improve PFS in unselected or biomarker-selected patients. No unexpected safety concerns were observed. [Read the Full Post]

Inhibition of related JAK/STAT pathways with molecular targeted drugs shows strong synergy with ruxolitinib in chronic myeloproliferative neoplasm

1027 | Jan 08 2019

Barrio S et al. showed the combination of ruxolitinib with inhibitors that target these pathways has a strong synergistic effect, which may be due to decreased activation of the common effector, STAT5. [Read the Full Post]

Selective HDAC inhibition by ACY-241 enhances the activity of paclitaxel in solid tumor models

745 | Jan 04 2019

Huang P et al. provided a strong rationale for clinical development of this combination in patients with advanced solid tumors. [Read the Full Post]

WNT5A: a motility-promoting factor in Hodgkin lymphoma

835 | Dec 22 2018

Linke F et al. proposed a model where WNT signaling has an important role in regulating tumor-promoting processes. [Read the Full Post]

PI3K Catalytic Isoform Alteration Promotes the LIMK1-related Metastasis Through the PAK1 or ROCK1/2 Activation in Cigarette Smoke-exposed Ovarian Cancer Cells

0 | Dec 18 2018

Park GB et al. showed that characterization of the p110 isotypes of PI3K is critical for regulating cancer metastasis; LIMK1 could be a common therapeutic target of ovarian cancer metastasis. [Read the Full Post]

FAM83A is amplified and promotes cancer stem cell-like traits and chemoresistance in pancreatic cancer

1171 | 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]

Identification of DNA-PKcs as a primary resistance factor of TIC10 in hepatocellular carcinoma cells

814 | Dec 14 2018

Cheng L et al. found that TIC10 showed promising anti-HCC activity, alone or together with DNA-PKcs inhibitors. [Read the Full Post]

Cancer stem cell marker phenotypes are reversible and functionally homogeneous in a preclinical model of pancreatic cancer

0 | Nov 27 2018

Dosch JS et al. showed that the hierarchical organization of CSCs in human disease is not recapitulated in a commonly used mouse model of pancreatic cancer and therefore provide a new view of the phenotypic and functional heterogeneity of tumor cells. [Read the Full Post]

PI3K Catalytic Isoform Alteration Promotes the LIMK1-related Metastasis Through the PAK1 or ROCK1/2 Activation in Cigarette Smoke-exposed Ovarian Cancer Cells.

1402 | Nov 23 2018

Park GB et al. found that LIMK1 could be a common therapeutic target of ovarian cancer metastasis. [Read the Full Post]

Host Serine/Threonine Kinases mTOR and Protein Kinase C-α Promote InlB-Mediated Entry of Listeria monocytogenes

5971 | Nov 21 2018

Bhalla M et al. identified mTOR and PKC-α to be host factors exploited by Listeria to promote infection. PKC-α controls Listeria entry, at least in part, by regulating the actin cytoskeleton downstream of the Met receptor. [Read the Full Post]

Identification of approved and investigational drugs that inhibit hypoxia-inducible factor-1 signaling

0 | Nov 17 2018

Hsu CW et al. underlined the importance of developing a battery of robust assay platforms and confirmation studies that focus on endogenous protein targets so that only relevant and reliable data will be taken into pre-clinical and clinical studies. [Read the Full Post]

Stathmin decreases cholangiocarcinoma cell line sensitivity to staurosporine-triggered apoptosis via the induction of ERK and Akt signaling

777 | Nov 04 2018

Wang Y et al. indicated that understanding the regulation of anti-apoptosis effect by Stathmin might provide new insight into how to overcome therapeutic resistance in cholangiocarcinoma. [Read the Full Post]

Curdione attenuates thrombin-induced human platelet activation: β1-tubulin as a potential therapeutic target

1624 | Oct 24 2018

Zhang D et al. indicated that β1-tubulin may be a potential target of curdione, which attenuates thrombin-induced human platelet activation. [Read the Full Post]

Reversible lysine-specific demethylase 1 antagonist HCI-2509 inhibits growth and decreases c-MYC in castration- and docetaxel-resistant prostate cancer cells

0 | Oct 18 2018

Gupta S et al. found that LSD1 inhibition with HCI-2509 decreases the c-MYC level in poorly differentiated prostate cancer cell lines and has a therapeutic potential in castration- and docetaxel-resistant prostate cancer. [Read the Full Post]

Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation of RAS/MAPK Signaling

1787 | Oct 12 2018

Nelson-Taylor SK et al. demonstrated that resistance to ponatinib in RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms that result in restored RAS/MAPK activation. [Read the Full Post]

Activation of Wnt/β-catenin signalling is required for TGF-β/Smad2/3 signalling during myofibroblast proliferation

853 | Oct 12 2018

Xu L et al. found that a major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFβ1-smad2/3 signalling through Wnt/β-catenin contribute to lung fibrosis. [Read the Full Post]

Synergistic cytotoxicity of BIIB021 with triptolide through suppression of PI3K/Akt/mTOR and NF-κB signal pathways in thyroid carcinoma cells

3329 | Oct 07 2018

Kim SH et al. suggested that BIIB021 has a cytotoxic activity accompanied by regulation of hsp90 client proteins in thyroid carcinoma cells. Moreover, the synergism between BIIB021 and triptolide in induction of cytotoxicity is associated with the inhibition of PI3K/Akt/mTOR and NF-κB signal pathways, the underexpression of survivin and the activation of DNA damage response in thyroid carcinoma cells. [Read the Full Post]

Efficacy of focal adhesion kinase inhibition in non-small cell lung cancer with oncogenically activated MAPK pathways

1014 | Sep 27 2018

Zhang H, et al. demonstrated efficacy both in vitro and in vivo in lung cancers with either oncogenic RAS or EGFR mutations. In addition, FAK inhibition in combination with inhibitors of Bcl-2 family of anti-apoptotic proteins has synergistic activity in these MAPK-activated non-small cell lung cancer cell line models. [Read the Full Post]

Inhibition of adhesion, migration and of α5β1 integrin in the HCT-116 colorectal cancer cells treated with the ruthenium drug NAMI-A

2626 | Sep 26 2018

Pelillo C et al. supported the new concept that metal-based drugs can inhibit tumour metastases through targeting of integrins and of other proteins which mediate tumour progression-related cell functions such as adhesion and migration. [Read the Full Post]

Novel Allosteric Pathway of Eg5 Regulation Identified through Multivariate Statistical Analysis of Hydrogen-Exchange Mass Spectrometry (HX-MS) Ligand Screening Data

0 | Sep 02 2018

Sheff JG et al. suggested that a different approach to inhibitor development may be fruitful. [Read the Full Post]

Upregulation of programmed cell death ligand 1 promotes resistance response in non-small-cell lung cancer patients treated with neo-adjuvant chemotherapy

2482 | Aug 26 2018

Zhang P et al. suggested that the upregulation of PD-L1 promotes a resistance response in lung cancer cells that might be through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway and suppression of tumor-infiltrating lymphocytes. The high expression of PD-L1 after NAC could be an indication of therapeutic resistance and poor prognosis in patients with non-small-cell lung cancer. [Read the Full Post]

Novel Allosteric Pathway of Eg5 Regulation Identified through Multivariate Statistical Analysis of Hydrogen-Exchange Mass Spectrometry (HX-MS) Ligand Screening Data

0 | Aug 24 2018

Sheff JG et al. suggested that a different approach to inhibitor development may be fruitful. [Read the Full Post]

Honokiol Induces Apoptosis, G1 Arrest, and Autophagy in KRAS Mutant Lung Cancer Cells

1454 | Aug 22 2018

Luo LX et al. indicated these results broaden our understanding of the mechanisms on honokiol effects in lung cancer, and reinforce the possibility of its potential anticancer benefit as a popular Chinese herbal medicine (CHM). [Read the Full Post]

Novel Allosteric Pathway of Eg5 Regulation Identified through Multivariate Statistical Analysis of Hydrogen-Exchange Mass Spectrometry (HX-MS) Ligand Screening Data

0 | Aug 15 2018

Sheff JG et al. suggested that a different approach to inhibitor development may be fruitful. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

0 | Aug 14 2018

Song M et al. indicated that small interfering RNA (siRNA)-based screening of ∼4800 druggable genes in 3-dimensional CSLC cultures in comparison to 2-dimensional bulk cultures of U87 glioma cells revealed 3 groups of genes essential for the following: survival of the CSLC population only, bulk-cultured population only, or both populations. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

0 | Aug 13 2018

Song M et al. provided a useful resource that can be exploited for the selective elimination of CSLCs.-Song, M., Lee, H., Nam, M.-H., Jeong, E., Kim, S., Hong, Y., Kim, N., Yim, H. Y., Yoo, Y.-J., Kim, J. S., Kim, J.-S., Cho, Y.-Y., Mills, G. B., Kim, W.-Y., Yoon, S. Loss-of-function screens of druggable targetome against cancer stem-like cells. [Read the Full Post]

MKP1 mediates chemosensitizer effects of E1a in response to cisplatin in non-small cell lung carcinoma cells

1115 | Aug 05 2018

Cimas FJ et al. indicated that the present work reinforce the critical role of MKP1 in the cellular response to cisplatin highlighting the importance of this phosphatase in future gene therapy approach based on E1a gene. [Read the Full Post]

Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study

1152 | Jul 17 2018

Feng Y et al. demonstrated the potent anti-lung cancer activity by ONC201. [Read the Full Post]

PI3Kα isoform-dependent activation of RhoA regulates Wnt5a-induced osteosarcoma cell migration

0 | Jul 15 2018

Zhang A et al. demonstrated that RhoA acts as the downstream of PI3K/Akt signaling (specific PI3Kα, Akt1 and Akt2 isoforms) and mediated Wnt5a-induced the migration of osteosarcoma cells. [Read the Full Post]

AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo

3452 | Jun 20 2018

Xi Y et al. supported the progression of this molecule into future evaluation as a valuable anti-gastric cancer candidate. [Read the Full Post]

Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo

1847 | Jun 18 2018

Karpel-Massler G et al. suggested that targeting deubiquitinases for glioma therapy is feasible and effective. [Read the Full Post]

The Deubiquitinase USP9X Maintains DNA Replication Fork Stability and DNA Damage Checkpoint Responses by Regulating CLASPIN during S-Phase

2069 | Jun 18 2018

McGarry E et al. revealed a novel role for USP9X in the maintenance of genomic stability during DNA replication and provide potential mechanistic insights into its tumor suppressor role in certain malignancies. [Read the Full Post]

The non-Geldanamycin Hsp90 inhibitors enhanced the antifungal activity of fluconazole

1469 | Jun 09 2018

Li L et al. showed that the activity of FLC against C. albicans biofilm formation in vitro is significantly enhanced when used in combination with HSP990. [Read the Full Post]

Aurora kinase A revives dormant laryngeal squamous cell carcinoma cells via FAK/PI3K/Akt pathway activation

1097 | May 29 2018

Yang LY et al. concluded that AURKA may revive dormant tumor cells via FAK/PI3K/Akt pathway activation, thereby promoting migration and invasion in laryngeal cancer. AURKA/FAK/PI3K/Akt inhibitors may thus represent potential targets for clinical LSCC treatment. [Read the Full Post]

Novel Akt activator SC-79 is a potential treatment for alcohol-induced osteonecrosis of the femoral head

0 | May 27 2018

Chen YX et al. proposed that SC-79 treatment to rescue Akt activation could be tested in the clinic as a potential therapeutic approach to preventing the development of alcohol-induced ONFH. [Read the Full Post]

SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling

1000 | May 27 2018

Gong YQ et al. suggest that SC79 protects RPE cells from UV damages possibly via activating Akt-Nrf2 signaling axis. [Read the Full Post]

Unique roles of Akt1 and Akt2 in IGF-IR mediated lung tumorigenesis

1815 | May 21 2018

Franks SE et al. suggested that compounds selectively targeting AKT1 may prove more effective than compounds that inhibit all three AKT isoforms at least in the treatment of lung adenocarcinoma. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | May 21 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

PI3Kα isoform-dependent activation of RhoA regulates Wnt5a-induced osteosarcoma cell migration

6160 | May 20 2018

Zhang A et al. demonstrated that RhoA acts as the downstream of PI3K/Akt signaling (specific PI3Kα, Akt1 and Akt2 isoforms) and mediated Wnt5a-induced the migration of osteosarcoma cells. [Read the Full Post]

Oncogenic epithelial cell-derived exosomes containing Rac1 and PAK2 induce angiogenesis in recipient endothelial cells

0 | May 07 2018

Gopal SK et al. demonstrated for the first time that oncogenic cells undergoing EMT can communicate with endothelial cells via exosomes, and establish exosomal Rac1/PAK2 as angiogenic promoters that may function from early stages of the metastatic cascade. [Read the Full Post]

Phosphoproteome Profiling of SH-SY5y Neuroblastoma Cells Treated with Anesthetics: Sevoflurane and Isoflurane Affect the Phosphorylation of Proteins Involved in Cytoskeletal Regulation

860 | May 07 2018

Lee J et al. showed that anesthetics affect the phosphorylation of proteins involved in cytoskeletal remodeling pathways. [Read the Full Post]

Co-occurring Mutations of Tumor Suppressor Genes, LATS2 and NF2, in Malignant Pleural Mesothelioma

1183 | May 05 2018

Tranchant R et al. identified a new MPM molecular subgroup that shares common genetic and transcriptomic characteristics. Our results made it possible to highlight a greater sensitivity to an anticancer compound for this MPM subgroup and to identify a specific potential biomarker. [Read the Full Post]

Uterine RAC1 via Pak1-ERM signaling directs normal luminal epithelial integrity conducive to on-time embryo implantation in mice

840 | May 03 2018

Tu Z et al. demonstrated that Rac1 via P38 MAPK signaling ensures timely epithelial apoptotic death at postimplantation. Besides uncovering a potentially important molecule machinery governing uterine luminal integrity for embryo implantation, our finding has high clinical relevance, because Rac1 is essential for normal endometrial functions in women. [Read the Full Post]

Lipopolysaccharide and heat stress impair the estradiol biosynthesis in granulosa cells via increase of HSP70 and inhibition of smad3 phosphorylation and nuclear translocation

1535 | May 01 2018

Li H et al. suggested that LPS and heat stress could impair estradiol biosynthesis in GCs via increased HSP70 and indirect inhibition of Smad3 phosphorylation and nuclear translocation. [Read the Full Post]

Focal adhesion kinase depletion reduces human hepatocellular carcinoma growth by repressing enhancer of zeste homolog 2

1142 | May 01 2018

Gnani D et al. demonstrated that FAK depletion reduces HCC cell growth by affecting cancer-promoting genes including the pro-oncogene EZH2. Furthermore, we unveil a novel unprecedented FAK/EZH2 crosstalk in HCC cells, thus identifying a targetable network paving the way for new anticancer therapies. [Read the Full Post]

Mdivi-1 Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats, Possibly via Inhibition of Drp1-Activated Mitochondrial Fission and Oxidative Stress

817 | Apr 16 2018

Wu P et al. suggested that Mdivi-1 exerts neuroprotective effects against cell death induced by SAH and the underlying mechanism may be inhibition of Drp1-activated mitochondrial fission and oxidative stress. [Read the Full Post]

Polyphyllin I induces mitophagic and apoptotic cell death in human breast cancer cells by increasing mitochondrial PINK1 levels

785 | Apr 15 2018

Li GB, et al. describe the mechanism by which PINK1 contributes to polyphyllin I-induced mitophagy and apoptosis and suggest that polyphyllin I may be an effective drug for breast cancer treatment. [Read the Full Post]

Inhibition of autophagy enhances effects of PF-04691502 on apoptosis and DNA damage of lung cancer cells

2106 | Apr 14 2018

Fei HR et al. suggested that a strategy of blocking autophagy to enhance the activity of PI3K/mTOR inhibitors warrants further attention in treatment of NSCLC cells. [Read the Full Post]

In situ electrochemical evaluation of dsDNA interaction with the anticancer drug danusertib nitrenium radical product using the DNA-electrochemical biosensor

3302 | Apr 05 2018

Diculescu VC et al. indicated the danusertib nitrenium cation radical redox metabolite was covalently attached to the C8 of guanine residues preventing their oxidation. An interaction mechanism of dsDNA-danusertib is proposed and the formation of the danusertib redox nitrenium radical metabolite-guanine adduct explained. [Read the Full Post]

Regulation of glutamate transporter trafficking by Nedd4-2 in a Parkinson's disease model

0 | Mar 23 2018

Zhang Y et al. indicated that Nedd4-2 may serve as a potential therapeutic target for the treatment of PD. [Read the Full Post]

Oncogenic epithelial cell-derived exosomes containing Rac1 and PAK2 induce angiogenesis in recipient endothelial cells

1020 | Mar 19 2018

Gopal SK et al. demonstrated for the first time that oncogenic cells undergoing EMT can communicate with endothelial cells via exosomes, and establish exosomal Rac1/PAK2 as angiogenic promoters that may function from early stages of the metastatic cascade. [Read the Full Post]

Prolactin signaling through focal adhesion complexes is amplified by stiff extracellular matrices in breast cancer cells

1268 | Mar 18 2018

Barcus CE et al. suggested that PRL signaling to FAK and SFKs may be useful targets in clinical aggressive ERα+ breast carcinomas. [Read the Full Post]

METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion

0 | Mar 18 2018

Zhang Z et al. identified METTL13 as a tumor suppressor and might provide promising approaches for bladder cancer treatment and prevention. [Read the Full Post]

Hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) mediates radiation-induced invasiveness through the SDF-1α/CXCR4 pathway in non-small cell lung carcinoma cells

815 | Mar 17 2018

Gu Q et al. found the underlying mechanisms of the irradiation-enhanced invasiveness of NSCLC cells. [Read the Full Post]

Epothilone B induces apoptosis and enhances apoptotic effects of ABT-737 on human cancer cells via PI3K/AKT/mTOR pathway

0 | Mar 16 2018

Li YL et al. indicated that ABT-737 may be a pertinent sensitizer to epothilone B, and the strategy of combining epothilone B with ABT-737 appears to be an attractive option for overcoming the resistance and neurotoxicity of epothilone B. [Read the Full Post]

AURKA promotes cell migration and invasion of head and neck squamous cell carcinoma through regulation of the AURKA/Akt/FAK signaling pathway

0 | Mar 04 2018

Wu J, et al. indicated AURKA activates FAK through the AURKA/Akt/FAK signaling pathway, promoting the migration and invasion of HNSCC cells, which may subsequently provide a novel approach for the treatment of HNSCC. [Read the Full Post]

AURKA promotes cell migration and invasion of head and neck squamous cell carcinoma through regulation of the AURKA/Akt/FAK signaling pathway

1196 | Mar 02 2018

Wu J et al. found that AURKA activates FAK through the AURKA/Akt/FAK signaling pathway, promoting the migration and invasion of HNSCC cells, which may subsequently provide a novel approach for the treatment of HNSCC. [Read the Full Post]

Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency

1171 | Feb 24 2018

Yang Y et al. found a first step toward capturing pluripotent stem cells with extraembryonic developmental potentials in culture and open new avenues for basic and translational research. VIDEO ABSTRACT. [Read the Full Post]

Principles of early human development and germ cell program from conserved model systems

1212 | Feb 22 2018

Kobayashi T et al. used human, porcine and monkey in vivo and in vitro models provides synthetic insights into early human development. [Read the Full Post]

The effect of increased lipoproteins levels on the disposition of vincristine in rat

1345 | Feb 20 2018

Khalil HA et al. found that HL can potentiate another drug-drug or drug-disease interaction involving VCR warrants further studying and monitoring to ensure therapeutic safety and efficiency. [Read the Full Post]

E-cadherin expression is correlated with focal adhesion kinase inhibitor resistance in Merlin-negative malignant mesothelioma cells

1295 | Feb 19 2018

Kato T et al. suggested that E-cadherin serves as a predictive biomarker for molecular target therapy with FAK inhibitors for patients with mesothelioma and that its expression endows MM cells with resistance to FAK inhibitors. [Read the Full Post]

Survivin inhibitor YM155 induces mitochondrial dysfunction, autophagy, DNA damage and apoptosis in Bcl-xL silenced glioma cell lines

1485 | Feb 14 2018

Jane EP et al. provided a new insight into the link between Bcl-xL and survivin inhibition for the development of novel therapies for glioma. [Read the Full Post]

Ligation of CD180 inhibits IFN-α signaling in a Lyn-PI3K-BTK-dependent manner in B cells

3539 | Feb 14 2018

You M et al. provided molecular insight into the mechanism of IFN-α signaling activation in SLE B cells and a potential therapeutic approach for SLE treatment. [Read the Full Post]

Three-dimensional matrix stiffness and adhesive ligands affect cancer cell response to toxins

971 | Feb 11 2018

Zustiak SP et al. indicated that both 3D matrix stiffness and cell-matrix adhesions are important parameters in the design of more predictive in vitro platforms for drug development and toxicity screening. [Read the Full Post]

ART3 regulates triple-negative breast cancer cell function via activation of Akt and ERK pathways

1475 | Jan 30 2018

Tan L et al. showed that ART 3 overexpression activated AKT and ERK in vitro and in xenograft tumors. Together, our findings demonstrate that ART3 is a critical TNBC marker with functional significance. [Read the Full Post]

Targeting MUC1-C inhibits the AKT-S6K1-elF4A pathway regulating TIGAR translation in colorectal cancer

1285 | Jan 29 2018

Ahmad R et al. indicated that MUC1-C is a potential target for the treatment of colorectal cancer. Colorectal cancer patients who overexpress MUC1-C may be candidates for treatment with the MUC1-C inhibitor alone or in combination therapy with other agents. [Read the Full Post]

Differentiation of induced pluripotent stem cell-derived neutrophil granulocytes from common marmoset monkey (Callithrix jacchus).

1928 | Jan 27 2018

Schrimpf C et al. indicated cj-iPSC-derived neutrophils bare high hopes in hematologic cell replacement therapy. They exhibit high morphologic similarity to native neutrophils and present neutrophil-specific surface antigens, antimicrobial proteins, and gene products yielding an auspicious approach for continuative experiments including tests in living animals. [Read the Full Post]

Targeted inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis and Preserves Heart Function in Adverse Cardiac Remodeling

1085 | Jan 21 2018

Zhang J et al. suggested that pharmacological inhibition of FAK may become an effective therapeutic strategy against adverse fibrosis. [Read the Full Post]

CK1δ kinase activity is modulated by protein kinase C α (PKCα)-mediated site-specific phosphorylation

3799 | Jan 14 2018

Meng Z et al. contributed to a deeper understanding of cellular signal transduction networks thereby helping to form a basis for the development of future therapeutic concepts. [Read the Full Post]

Extracellular heat shock protein 90α mediates HDM-induced bronchial epithelial barrier dysfunction by activating RhoA/MLC signaling

1694 | Jan 04 2018

Dong HM et al. suggested that eHsp90α is a potential therapeutic target for treatment of asthma. [Read the Full Post]

Noninvasive Bioluminescence Imaging of AKT Kinase Activity in Subcutaneous and Orthotopic NSCLC Xenografts: Correlation of AKT Activity with Tumor Growth Kinetics

1121 | Jan 01 2018

Suchowski K et al. demonstrated that BAR can be applied to study drug dosing, drug combinations, and treatment efficacy in orthotopic mouse lung tumor models. [Read the Full Post]

Lenvatinib enhances the antitumor effects of paclitaxel in anaplastic thyroid cancer

1396 | Dec 22 2017

Jing C et al. suggested that lenvatinib/paclitaxel combination may be a promising candidate therapeutic strategy for ATC. [Read the Full Post]

Dasatinib inhibits actin fiber reorganization and promotes endothelial cell permeability through RhoA-ROCK pathway

2571 | Dec 21 2017

Dasgupta SK et al. suggested that ROCK inhibitors could serve as therapeutic modalities to ameliorate the dasatinib-induced pulmonary changes. [Read the Full Post]

Perifosine and ABT-737 synergistically inhibit lung cancer cells in vitro and in vivo

1263 | Dec 18 2017

Shen J et al. supported the feasibility of further investigation of the perifosine plus ABT-737 regimen in future lung cancer clinical tests. [Read the Full Post]

Proteome and Acetylome Analysis Identifies Novel Pathways and Targets Regulated by Perifosine in Neuroblastoma

1237 | Dec 17 2017

Gu X et al. details the impact of perifosine on proteome and lysine acetylome in SK-N-AS cells and expands our understanding of the mechanisms of perifosine action in neuroblastoma. [Read the Full Post]

MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity

1285 | Dec 14 2017

Chen X et al. showed that mitotic phosphorylation-deficient mutant MST2-S385A possesses higher activity in suppressing cell proliferation and anchorage-independent growth in vitro and tumorigenesis in vivo. Together, our findings reveal a novel layer of regulation for MST2 in mitosis and its role in tumorigenesis. [Read the Full Post]

Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells

4048 | Dec 10 2017

Abraham SA et al. found that LSCs can be eradicated. [Read the Full Post]

Differential regulation of mTOR signaling determines sensitivity to AKT inhibition in diffuse large B cell lymphoma

1678 | Dec 08 2017

Combined inhibition of AKT and BTK, PIM2, or S6K1 proved to be an effective strategy to overcome resistance to AKT inhibition in DLBCL. [Read the Full Post]

Optogenetic clustering of CNK1 reveals mechanistic insights in RAF and AKT signalling controlling cell fate decisions

1507 | Dec 08 2017

Fischer A et al. found that CNK1 expression, CNK1 clustering and the thereto related differential signalling processes decide on proliferation and differentiation in a cell type- and cell stage-dependent manner by orchestrating AKT and RAF signalling. [Read the Full Post]

Autophagy prevention sensitizes AKTi-1/2-induced anti-hepatocellular carcinoma cell activity in vitro and in vivo

0 | Nov 30 2017

Zhang Q et al. demonstrated that autophagy activation serves as a main resistance factor of AKTi-1/2 in HCC cells. Autophagy prevention therefore sensitizes AKTi-1/2-induced anti-HCC activity in vitro and in vivo. [Read the Full Post]

HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death

1820 | Nov 29 2017

Jacobsen AV et al. implicated HSP90 as a modulator of necroptosis at the level of MLKL, a function that complements HSP90's previously demonstrated modulation of the upstream necroptosis effector kinases, RIPK1 and RIPK3. [Read the Full Post]

Autophagy prevention sensitizes AKTi-1/2-induced anti-hepatocellular carcinoma cell activity in vitro and in vivo

1182 | Nov 29 2017

Zhang Q et al. demonstrate that autophagy activation serves as a main resistance factor of AKTi-1/2 in HCC cells. [Read the Full Post]

MicroRNA-520e suppresses non-small-cell lung cancer cell growth by targeting Zbtb7a-mediated Wnt signaling pathway

1450 | Nov 26 2017

Zhijun Z et al. indicated that overexpressing miR-520e is involved in regulating the NSCLC cell growth, invasion and migration by targeting Zbtb7a partly depending on Wnt signaling. [Read the Full Post]

The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms

2016 | Nov 25 2017

Paraiso KH et al.showed that HSP90 inhibition may be a highly effective strategy at managing the diverse array of resistance mechanisms being reported to BRAF inhibitors and appears to be more effective at restoring BIM expression and downregulating Mcl-1 expression than combined MEK/PI3K inhibitor therapy. [Read the Full Post]

Hsp90β promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma

1808 | Nov 24 2017

Meng J et al. investigated the correlation between Hsp90β expression and CD31+ endothelial cell-dependent vessel density. [Read the Full Post]

Hyperinsulinemia enhances interleukin-17-induced inflammation to promote prostate cancer development in obese mice through inhibiting glycogen synthase kinase 3-mediated phosphorylation and degradation of interleukin-17 receptor

1070 | Nov 23 2017

Liu S et al.revealed a mechanism underlying the intensified inflammation in obesity and obesity-associated development of aggressive prostate cancer, suggesting that targeting GSK3 may be a potential therapeutic approach to suppress IL-17-mediated inflammation in the prevention and treatment of prostate cancer, particularly in obese men. [Read the Full Post]

Targeting protein kinase C in mantle cell lymphoma

1565 | Nov 16 2017

Rauert-Wunderlich H et al. showed that MCL cells are heterogeneous in their response to BTK or PKC inhibition, indicating the need for even more individualized targeted treatment approaches in subsets of MCL patients. [Read the Full Post]

HSP90 Shapes the Consequences of Human Genetic Variation

0 | Nov 14 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

Novel Allosteric Pathway of Eg5 Regulation Identified through Multivariate Statistical Analysis of Hydrogen-Exchange Mass Spectrometry (HX-MS) Ligand Screening Data

1149 | Nov 11 2017

Sheff JG et al. suggested that a different approach to inhibitor development may be fruitful. [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 | Nov 08 2017

Simioni C et al. indicated that 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]

Inhibition of β-Catenin to Overcome Endocrine Resistance in Tamoxifen-Resistant Breast Cancer Cell Line

0 | Oct 31 2017

Won HS et al. suggested that beta-catenin plays a role in tamoxifen-resistant breast cancer, and the inhibition of beta-catenin may be a potential target in tamoxifen-resistant breast cancer. [Read the Full Post]

Coordinate involvement of Nodal-dependent inhibition and Wnt-dependent activation in the maintenance of organizer-specific bmp2b in zebrafish

1468 | Oct 30 2017

Xue Y et al. suggested that maintenance of organizer-specific bmp2b expression involves opposite and concerted regulation by Nodal and Wnt signaling. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

0 | Oct 19 2017

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy. [Read the Full Post]

Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis

2451 | Oct 16 2017

Zhang F et al. provided evidence that the canonical hedgehog pathway controlled HSC-mediated liver angiogenesis. Selective inhibition of HSC hedgehog signalling could be a promising therapeutic approach for hepatic fibrosis. [Read the Full Post]

Antagonizing Integrin β3 Increases Immunosuppression in Cancer

1058 | Oct 13 2017

Su X et al. suggest that effects of integrin β3 therapies on immune cells should be considered to improve outcomes. [Read the Full Post]

Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma

0 | Oct 12 2017

Saha SK et al. provided a systematic and broadly applicable approach to define targets of kinase inhibitors underlying drug responsiveness. [Read the Full Post]

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

2994 | Sep 30 2017

Here Han T et al. showed that indisulam promotes the recruitment of RBM39 (RNA binding motif protein 39) to the CUL4-DCAF15 E3 ubiquitin ligase, leading to RBM39 polyubiquitination and proteasomal degradation. [Read the Full Post]

Malignant gliomas induce and exploit astrocytic mesenchymal-like transition by activating canonical Wnt/β-catenin signaling

1673 | Sep 29 2017

Lu P et al. established that glioma cells remarkably activated astrocytes via upregulating Wnt/β-catenin signaling, with obviously mesenchymal-like transition and increased migration and invasion ability, indicating that glioma cells may stimulate adjacent astrocytes to degrade extracellular matrix and thereby promoting tumor invasiveness. [Read the Full Post]

HSP90 Shapes the Consequences of Human Genetic Variation

0 | Sep 26 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

HSP90 Shapes the Consequences of Human Genetic Variation

2023 | Sep 25 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

Hyperthermia reduces migration of osteosarcoma by suppression of autocrine motility factor

2025 | Sep 09 2017

Nakajima K et al. indicated hyperthermia reduced AMF expression and tumor cell motility via HSP27 and may therefore be applied as osteosarcoma treatment. [Read the Full Post]

Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma

2301 | Sep 09 2017

Thompson JM et al. suggested that synthetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC. [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

3208 | Sep 01 2017

Simioni C et al. showed that dephosphorylation of pAkt and pS6 showed the cytotoxicity of these compounds. 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]

miR-18a promotes cell proliferation of esophageal squamous cell carcinoma cells by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis

0 | Aug 25 2017

Zhang W et al. demonstrated the upregulation of miR-18a promoted cell proliferation by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis, suggesting that small molecule inhibitors of AKT-mTOR signaling are potential agents for the treatment of ESCC patients with upregulation of miR-17-92 cluster. [Read the Full Post]

Downregulation of GLUT4 contributes to effective intervention of estrogen receptor-negative/HER2-overexpressing early stage breast disease progression by lapatinib

0 | Aug 19 2017

Acharya S et al. indicated that lapatinib, through its inhibition of key signaling pathways and tumor-promoting metabolic events, is a promising agent for the prevention/early intervention of ER-/HER2+ breast cancer progression. [Read the Full Post]

Cell Death Induction by the Indirubin Derivative 7BIO and the BH3 Mimetic Drugs ABT-737 and GX15-070 in Medullary Thyroid Carcinoma Cells

2434 | Aug 15 2017

Broecker-Preuss M et al. showed that although the exact kind of cell death and target molecules of 7BIO and GX15-070 are not yet defined, direct induction of cell death may be a new therapeutic option in medullary thyroid carcinoma cells. [Read the Full Post]

A novel sgRNA selection system for CRISPR-Cas9 in mammalian cells

2685 | Aug 14 2017

Zhang H et al. provided a potential application to optimize the sgRNAs in different species and to generate a powerful CRISPR-Cas9 genome-wide screening system with minimum amounts of sgRNAs. [Read the Full Post]

Image-Guided Radiotherapy Targets Macromolecules through Altering the Tumor Microenvironment

2913 | Aug 01 2017

Appelbe OK et al. suggest repurposing image-guided radiotherapy as a tool to guide cancer nanomedicine delivery, enhancing local control for primary tumors and metastatic disease while limiting systemic toxicity. [Read the Full Post]

Y-632 inhibits heat shock protein 90 (Hsp90) function by disrupting the interaction between Hsp90 and Hsp70/Hsp90 organizing protein, and exerts antitumor activity in vitro and in vivo

2804 | Aug 01 2017

Wang W et al. believe that Y-632, acting as a novel small-molecule inhibitor of the Hsp90-Hsp70/Hsp90 organizing protein complex, has great potential to be a promising Hsp90 inhibitor for cancer therapy, such as for imatinib-resistant leukemia. [Read the Full Post]

Xanthatin anti-tumor cytotoxicity is mediated via glycogen synthase kinase-3β and β-catenin.

0 | Jul 22 2017

Tao L et al. provided insight into how xanthatin and related molecules could be effectively targeted toward certain tumors. [Read the Full Post]

A PGC1α-mediated transcriptional axis suppresses melanoma metastasis

2955 | Jun 23 2017

Luo C et al. revealed that PGC1α maintains mitochondrial energetic metabolism and suppresses metastasis through direct regulation of parallel acting transcriptional programs. [Read the Full Post]

Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling

5872 | Jun 14 2017

Tsioumpekou M et al. found that PDGF-BB-induced Erk5 activation involves parallel stimulatory and inhibitory pathways and promotes Smad1/5/8 signaling. [Read the Full Post]

Transmembrane protein 88 attenuates liver fibrosis by promoting apoptosis and reversion of activated hepatic stellate cells

2008 | Jun 13 2017

Cai SP et al. found that Tmem88 played an important role in HSCs activation, proliferation and apoptosis, and Tmem88 expression might be modulated by Dnmt3a. [Read the Full Post]

DDX17 nucleocytoplasmic shuttling promotes acquired gefitinib resistance in non-small cell lung cancer cells via activation of β-catenin

4301 | Jun 12 2017

Li K et al. revealed a novel and important mechanism by which DDX17 contributes to acquired gefitinib resistance through exportin/importin-dependent cytoplasmic shuttling and followed by activation of β-catenin, and DDX17 inhibition may be a promising strategy to overcome acquired resistance of gefitinib in NSCLC patients. [Read the Full Post]

Inhibition of green tea polyphenol EGCG((-)-epigallocatechin-3-gallate) on the proliferation of gastric cancer cells by suppressing canonical wnt/β-catenin signalling pathway

1925 | Jun 08 2017

Yang C et al. established that EGCG suppressed gastric cancer cell proliferation and demonstrate that this inhibitory effect is related to canonical Wnt/β-catenin signalling. [Read the Full Post]

Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model

3246 | Jun 06 2017

Guo SC et al. provided evidence of the probable molecular mechanisms underlying the PRP effect on healing of chronic ulcers and describe a promising resource of growth factors from exosomes without species restriction. [Read the Full Post]

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

0 | Jun 05 2017

Gillan V et al. provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

The antitumor toxin CD437 is a direct inhibitor of DNA polymerase α

4591 | Jun 04 2017

Han T et al. found that CD437 is a retinoid-like small molecule that selectively induces apoptosis in cancer cells, but not in normal cells, through an unknown mechanism. [Read the Full Post]

Reversible lysine-specific demethylase 1 antagonist HCI-2509 inhibits growth and decreases c-MYC in castration- and docetaxel-resistant prostate cancer cells

1322 | May 30 2017

Gupta S et al. found that LSD1 inhibition with HCI-2509 decreases the c-MYC level in poorly differentiated prostate cancer cell lines and has a therapeutic potential in castration- and docetaxel-resistant prostate cancer. [Read the Full Post]

Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

0 | May 22 2017

Massa MG et al. provided an avenue for studies with a greater cell- and human-specific focus, specifically in the context of genetic contributions to neurodegeneration and drug discovery. [Read the Full Post]

Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters

2393 | May 22 2017

Zhang YK et al. found that bafetinib reversed ABCB1- and ABCG2-mediated MDR by blocking the drug efflux function of these transporters [Read the Full Post]

Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers

1876 | May 18 2017

Morrison-Joly M et al. found that Rictor/mTORC2 signaling drives Akt-dependent tumor progression in HER2-amplified breast cancers, rationalizing clinical investigation of dual mTORC1/2 kinase inhibitors and developing mTORC2-specific inhibitors for use in this setting. [Read the Full Post]

Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib

3720 | May 17 2017

Miller RE et al. suggested that dasatinib merits investigation for the treatment of patients with ARID1A-mutant OCCC. [Read the Full Post]

Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells

3379 | May 15 2017

Shi H et al. demonstrated for the first time that c-kit is not only expressed in CDCs but may also directly participate in CDC differentiation into an endothelial lineage. [Read the Full Post]

Transforming growth factor-β-dependent Wnt secretion controls myofibroblast formation and myocardial fibrosis progression in experimental autoimmune myocarditis

0 | May 08 2017

Blyszczuk P et al. identified TAK1-mediated rapid Wnt protein secretion as a novel downstream key mechanism of TGF-β-mediated myofibroblast differentiation and myocardial fibrosis progression in human and mouse myocarditis. [Read the Full Post]

Epidermal Growth Factor Receptor Mutation Enhances Expression of Cadherin-5 in Lung Cancer Cells

0 | May 06 2017

Hung MS et al. provided an insight into the association of mutant EGFR and CDH5 expression in lung cancer and aid further development of target therapy for NSCLC in the future. [Read the Full Post]

Uroguanylin modulates (Na(+)+K(+))ATPase in a proximal tubule cell line: Interactions among the cGMP/protein kinase G, cAMP/protein kinase A, and mTOR pathways.

1597 | May 01 2017

Arnaud-Batista FJ et al suggested that the molecular mechanism of action of UGN on sodium reabsorption in PT cells is more complex than previously thought. We propose that PKG-dependent activation of PKA leads to the inhibition of the mTORC2/PKB/mTORC1/S6K pathway, an important signaling pathway involved in the maintenance of the PT sodium pump expression and activity. [Read the Full Post]

Epidermal Growth Factor Receptor Mutation Enhances Expression of Cadherin-5 in Lung Cancer Cells

1692 | Apr 29 2017

Hung MS et al. provided an insight into the association of mutant EGFR and CDH5 expression in lung cancer and aid further development of target therapy for NSCLC in the future. [Read the Full Post]

Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation

0 | Apr 28 2017

Han J et al suggested that electrospun anisotropic fibrous scaffolds, as a single method, have limited effect on improving the maturation of hPSC-CMs. [Read the Full Post]

Electrochemical biosensor for protein kinase A activity assay based on gold nanoparticles-carbon nanospheres, phos-tag-biotin and β-galactosidase

3028 | Apr 21 2017

Zhou Y et al. found the fabricated biosensor can be applied to detect PKA in human normal gastricepithelial cell line and human gastric carcinoma cell line with satisfactory results. [Read the Full Post]

Activation of G protein-coupled receptor 30 by thiodiphenol promotes proliferation of estrogen receptor α-positive breast cancer cells

4403 | Apr 20 2017

Lei B et al. indicated a novel mechanism through which TDP may exert relevant estrogenic action in ERα positive cancer cells. [Read the Full Post]

Dual Targeting of Akt and mTORC1 Impairs Repair of DNA Double-Strand Breaks and Increases Radiation Sensitivity of Human Tumor Cells

0 | Apr 19 2017

Holler M et al suggested that dual targeting of mTORC1 and Akt1 inhibits repair of DNA-DSB leading to radiosensitization of solid tumor cells. [Read the Full Post]

Inhibition of Phospho-S6 Kinase, a Protein Involved in the Compensatory Adaptive Response, Increases the Efficacy of Paclitaxel in Reducing the Viability of Matrix-Attached Ovarian Cancer Cells.

3487 | Apr 17 2017

Choi JI et al found that addition of BX795 or CCT128930 to inhibit pS6 (S240/S244) or pS6 (S235/S236) restricted the compensatory adaptive response to paclitaxel in HeyA8 and SKOV3 cells. These inhibitors increased the efficacy of paclitaxel in reducing cancer cell viability. [Read the Full Post]

A causal link from ALK to hexokinase II overexpression and hyperactive glycolysis in EML4-ALK-positive lung cancer.

0 | Apr 16 2017

Ma Y et al revealed a novel EML4-ALK-HIF1α-HK2 cascade to enhance glucose metabolism in EML4-ALK-positive NSCLC. [Read the Full Post]

Phosphatidylinositol 3-Kinase/Akt Mediates Integrin Signaling To Control RNA Polymerase I Transcriptional Activity

7239 | 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]

Centrosomal Protein of 55 Regulates Glucose Metabolism, Proliferation and Apoptosis of Glioma Cells via the Akt/mTOR Signaling Pathway

1464 | Apr 08 2017

Wang G et al. found that CEP55 regulates glucose metabolism, proliferation and apoptosis of glioma cells via the Akt/mTOR signaling pathway, and its promotive effect on glioma tumorigenesis can be a potential target for glioma therapy in the future. [Read the Full Post]

A Repurposing Strategy for Hsp90 Inhibitors Demonstrates Their Potency against Filarial Nematodes

1 | Mar 27 2017

Gillan V et al provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner

2135 | Mar 14 2017

Huyan T et al. suggested that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy. [Read the Full Post]

Nicotine-Mediated Ca2+ -Influx Induces IL-8 Secretion in Oral Squamous Cell Carcinoma Cell

2650 | Mar 14 2017

Tsunoda K et al. suggested that the binding of nicotine to nAChR induces Ca(2+) influx, which results in the activation and phosphorylation of CaMK II and NF-κB p65, respectively. Nicotine-mediated IL-8 induction should be a trigger for the initiation of various diseases. [Read the Full Post]

AURKA promotes cell migration and invasion of head and neck squamous cell carcinoma through regulation of the AURKA/Akt/FAK signaling pathway

1993 | Mar 07 2017

Wu J et al. found that AURKA activates FAK through the AURKA/Akt/FAK signaling pathway, promoting the migration and invasion of HNSCC cells, which may subsequently provide a novel approach for the treatment of HNSCC. [Read the Full Post]

Structural Insights into the Pharmacophore of Vinca Domain Inhibitors of Microtubules

1425 | Mar 03 2017

Wang Y et al. found that the rational design of novel vinca domain ligands and may facilitate the development of microtubule inhibitors with high specificity, affinity, and efficiency as payloads for ADCs in cancer therapy. [Read the Full Post]

Novel pyrimidine-2,4-diamine derivative suppresses the cell viability and spindle assembly checkpoint activity by targeting Aurora kinases

1159 | Mar 02 2017

Salmela AL et al. suggested that this new pharmacophore possesses interesting anticancer properties that could be exploited in development of mitosis-targeting therapies. [Read the Full Post]

Suppressing Cyclooxygenase-2 prevents nonalcoholic steatohepatitis and inhibits apoptosis of hepatocytes that are involved in the Akt/p53 signal pathway

1461 | Feb 27 2017

Wu J, et al.'s findings suggested that suppressing COX-2 can improve steatohepatitis by inhibiting hepatocyte apoptosis in mice via regulating the Akt/p53 pathway. Celecoxib treatment may be a favorable treatment option for NASH. [Read the Full Post]

Epothilone B induces apoptosis and enhances apoptotic effects of ABT-737 on human cancer cells via PI3K/AKT/mTOR pathway

1447 | Feb 25 2017

These data indicate that ABT-737 may be a pertinent sensitizer to epothilone B, and the strategy of combining epothilone B with ABT-737 appears to be an attractive option for overcoming the resistance and neurotoxicity of epothilone B. [Read the Full Post]

Hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) mediates radiation-induced invasiveness through the SDF-1α/CXCR4 pathway in non-small cell lung carcinoma cells

3041 | Feb 24 2017

Gu Q et al.'s findings have elucidated the underlying mechanisms of the irradiation-enhanced invasiveness of NSCLC cells. [Read the Full Post]

Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer

0 | Feb 17 2017

Manteghi S et al. establish HD-PTP/PTPN23 as a prominent haploinsufficient tumor suppressor gene preventing tumor progression through control of integrin trafficking. [Read the Full Post]

The PI3K/Akt Pathway Regulates Oxygen Metabolism via Pyruvate Dehydrogenase (PDH)-E1α Phosphorylation

5216 | Feb 12 2017

Cerniglia GJ, et al.‘s’ findings highlight an association between the PI3K/mTOR pathway and tumor cell oxygen consumption that is regulated in part by PDH phosphorylation. These results have important implications for understanding the effects of PI3K pathway activation in tumor metabolism and also in designing cancer therapy trials that use inhibitors of this pathway. [Read the Full Post]

Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells

0 | Feb 12 2017

Jian Y, et al.'s study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells. [Read the Full Post]

Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection

1353 | Feb 09 2017

Yun B, et al. suggested that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV. [Read the Full Post]

Ph-like ALL-related novel fusion kinase ATF7IP-PDGFRB exhibits high sensitivity to tyrosine kinase inhibitors in murine cells.

0 | Feb 05 2017

Ishibashi T, et al.'s observations suggest the therapeutic importance of tyrosine kinase inhibitors and possibly MEK inhibitor for a subset of BCP-ALL harboring PDGFRB-related fusion kinases. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

0 | Feb 04 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

4755 | Jan 29 2017

Gillan V et al. provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

0 | Jan 26 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner

2219 | Jan 22 2017

Huyan T, et al.'s findings suggest that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy. [Read the Full Post]

Nicotine-Mediated Ca2+ -Influx Induces IL-8 Secretion in Oral Squamous Cell Carcinoma Cell

2850 | Jan 22 2017

The results fromTsunoda K, et al.'s study indicate that the binding of nicotine to nAChR induces Ca(2+) influx, which results in the activation and phosphorylation of CaMK II and NF-κB p65, respectively. Nicotine-mediated IL-8 induction should be a trigger for the initiation of various diseases. [Read the Full Post]

Suppressing Cyclooxygenase-2 prevents nonalcoholic steatohepatitis and inhibits apoptosis of hepatocytes that are involved in the Akt/p53 signal pathway

0 | Jan 14 2017

Wu J, et al.'s findings suggested that suppressing COX-2 can improve steatohepatitis by inhibiting hepatocyte apoptosis in mice via regulating the Akt/p53 pathway. Celecoxib treatment may be a favorable treatment option for NASH. [Read the Full Post]

Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells

2891 | Jan 05 2017

Jian Y, et al.'s our study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells. [Read the Full Post]

The PI3K/Akt Pathway Regulates Oxygen Metabolism via Pyruvate Dehydrogenase (PDH)-E1α Phosphorylation

0 | Jan 04 2017

Cerniglia GJ, et al. 's results have important implications for understanding the effects of PI3K pathway activation in tumor metabolism and also in designing cancer therapy trials that use inhibitors of this pathway. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

2574 | Jan 01 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

Ph-like ALL-related novel fusion kinase ATF7IP-PDGFRB exhibits high sensitivity to tyrosine kinase inhibitors in murine cells

2819 | Dec 29 2016

Ishibashi T, et al.‘’s observations suggest the therapeutic importance of tyrosine kinase inhibitors and possibly MEK inhibitor for a subset of BCP-ALL harboring PDGFRB-related fusion kinases. [Read the Full Post]

WISP1 overexpression promotes proliferation and migration of human vascular smooth muscle cells via AKT signaling pathway

2907 | Dec 18 2016

Lu S et al. demonstrated that Akt signaling pathway mediates WISP1-induced migration and proliferation of human VSMCs, suggesting that WISP1 may act as a novel potential therapeutic target for vascular restenosis. [Read the Full Post]

Xanthatin anti-tumor cytotoxicity is mediated via glycogen synthase kinase-3β and β-catenin

2730 | Dec 15 2016

Tao L, et al. provided insight into how xanthatin and related molecules could be effectively targeted toward certain tumors. [Read the Full Post]

Upregulation of AKT3 Confers Resistance to the AKT Inhibitor MK2206 in Breast Cancer.

1968 | Dec 08 2016

Stottrup C et al. provided a rationale for developing therapeutics targeting AKT3 to circumvent acquired resistance in breast cancer. [Read the Full Post]

Downregulation of GLUT4 contributes to effective intervention of estrogen receptor-negative/HER2-overexpressing early stage breast disease progression by lapatinib

2270 | Dec 05 2016

Acharya S et al.’s results indicated that lapatinib, through its inhibition of key signaling pathways and tumor-promoting metabolic events, is a promising agent for the prevention/early intervention of ER-/HER2+ breast cancer progression. [Read the Full Post]

miR-18a promotes cell proliferation of esophageal squamous cell carcinoma cells by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis

2141 | Dec 04 2016

Zhang W et al.’s results demonstrated the upregulation of miR-18a promoted cell proliferation by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis, suggesting that small molecule inhibitors of AKT-mTOR signaling are potential agents for the treatment of ESCC patients with upregulation of miR-17-92 cluster. [Read the Full Post]

Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts

5622 | Nov 26 2016

Multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO. [Read the Full Post]

In Silico Analysis Guides Selection of BET Inhibitors for Triple-Negative Breast Cancer Treatment

1970 | Nov 26 2016

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]

Ultrasound Enhances the Expression of Brain-Derived Neurotrophic Factor in Astrocyte Through Activation of TrkB-Akt and Calcium-CaMK Signaling Pathways

3108 | Nov 24 2016

Liu SH et al. found that LIPUS stimulation might play a crucial and beneficial role in neurodegenerative diseases. [Read the Full Post]

Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma

4489 | Nov 16 2016

Saha SK et al. showed that IDHm ICC cells have a unique dependency on SRC and suggested that dasatinib may have therapeutic benefit against IDHm ICC. [Read the Full Post]

Antagonizing Integrin β3 Increases Immunosuppression in Cancer

1645 | Nov 15 2016

Su X et al. suggested that effects of integrin β3 therapies on immune cells should be considered to improve outcomes. [Read the Full Post]

Inhibition of β-Catenin to Overcome Endocrine Resistance in Tamoxifen-Resistant Breast Cancer Cell Line

2488 | Nov 11 2016

Won HS et al. suggested that β-catenin plays a role in tamoxifen-resistant breast cancer, and the inhibition of β-catenin may be a potential target in tamoxifen-resistant breast cancer. [Read the Full Post]

Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer.

3131 | Nov 08 2016

Manteghi S, et al.found that we establish HD-PTP/PTPN23 as a prominent haploinsufficient tumor suppressor gene preventing tumor progression through control of integrin trafficking. [Read the Full Post]

Ajuba Phosphorylation by CDK1 Promotes Cell Proliferation and Tumorigenesis

2455 | Nov 04 2016

Chen X et al. revealed a previously unrecognized mechanism for Ajuba regulation in mitosis and its role in tumorigenesis. [Read the Full Post]

Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection

1559 | Nov 02 2016

Yun B et al. suggested that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV. [Read the Full Post]

The antitumor toxin CD437 is a direct inhibitor of DNA polymerase α

2204 | Nov 01 2016

The discovery of POLA1 as the direct anticancer target for CD437 has the potential to catalyze the development of CD437 into an anticancer therapeutic. [Read the Full Post]

SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A

2933 | Oct 28 2016

[Read the Full Post]

Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

4308 | Oct 19 2016

[Read the Full Post]

Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters

3133 | Oct 19 2016

Zhang YK et al. found that bafetinib reversed ABCB1- and ABCG2-mediated MDR by blocking the drug efflux function of these transporters. [Read the Full Post]

Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells

4269 | Oct 13 2016

Shi H et al. demonstrated for the first time that c-kit is not only expressed in CDCs but may also directly participate in CDC differentiation into an endothelial lineage. [Read the Full Post]

Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers

2173 | Oct 12 2016

Morrison-Joly M et al. that Rictor/mTORC2 signaling drives Akt-dependent tumor progression in HER2-amplified breast cancers, rationalizing clinical investigation of dual mTORC1/2 kinase inhibitors and developing mTORC2-specific inhibitors for use in this setting. [Read the Full Post]

Transforming growth factor-β-dependent Wnt secretion controls myofibroblast formation and myocardial fibrosis progression in experimental autoimmune myocarditis

2529 | Oct 08 2016

Blyszczuk P et al. identified TAK1-mediated rapid Wnt protein secretion as a novel downstream key mechanism of TGF-β-mediated myofibroblast differentiation and myocardial fibrosis progression in human and mouse myocarditis. [Read the Full Post]

Uroguanylin modulates (Na++K+)ATPase in a proximal tubule cell line: Interactions among the cGMP/protein kinase G, cAMP/protein kinase A, and mTOR pathways

2149 | Sep 27 2016

Arnaud-Batista FJ et al. suggested that the molecular mechanism of action of UGN on sodium reabsorption in PT cells is more complex than previously thought. [Read the Full Post]

Dual Targeting of Akt and mTORC1 Impairs Repair of DNA Double-Strand Breaks and Increases Radiation Sensitivity of Human Tumor Cells

2318 | Sep 21 2016

Holler M et al. dual targeting of mTORC1 and Akt1 inhibits repair of DNA-DSB leading to radiosensitization of solid tumor cells. [Read the Full Post]

A causal link from ALK to hexokinase II overexpression and hyperactive glycolysis in EML4-ALK-positive lung cancer

2196 | Sep 19 2016

Ma Y et al. revealed a novel EML4-ALK-HIF1α-HK2 cascade to enhance glucose metabolism in EML4-ALK-positive NSCLC. [Read the Full Post]

Inhibition of Phospho-S6 Kinase, a Protein Involved in the Compensatory Adaptive Response, Increases the Efficacy of Paclitaxel in Reducing the Viability of Matrix-Attached Ovarian Cancer Cells

2157 | Sep 19 2016

[Read the Full Post]

Phosphatidylinositol 3-Kinase/Akt Mediates Integrin Signaling To Control RNA Polymerase I Transcriptional Activity

3414 | Sep 12 2016

Wu C et al. revealed that 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]

The role of DNA-dependent protein kinase in dendritic cells in house dust mite-induced asthma

4339 | Mar 03 2015

Mishra et al. demonstrated the immune role of DNA-PK in response to house dust mite (HDM) antigen in dendritic cells (DCs). [Read the Full Post]

The small GTPase Rap1b acts as a negative regulator of neutrophil recruitment to inflamed lung with acute lung injury

3487 | Feb 11 2015

Kumar et al. found small GTPase Rap1b acts as a critical suppressor of neutrophil accumulation to inflamed lungs. [Read the Full Post]

Inhibition of proteasome restores bortesomib-induced thrombocytopenia

10503 | Feb 10 2015

Shi et al. reported clinical proteasome inhibitor enable to block proplatelet formation by megakaryocytes in human and mouse model. [Read the Full Post]

Star27 overcomes synthetic lethal toxicity for FLT3-targeted therapy against acute myeloid leukemia

4909 | Feb 06 2015

For overcoming myelosuppression, Warkentin et al. reported a staurosporine analog, Star27, that enable to inhibit FLT3 while avoiding KIT inhibition. [Read the Full Post]

A protocol for human pluripotent stem cell differentiation into endoderm related cells

7504 | Feb 02 2015

Diekmann et al. showed a detailed protocol started from a defined cell number of dispersed single cells of three different human ESC lines, and one human iPSC line. [Read the Full Post]

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

15344 | Jan 23 2015

Dubrovsky et al. developed an antibody, ESKM, which is therapeutically effective on acute and chronic leukemias in murine models. [Read the Full Post]

MAPK cascade promotes early axonal degeneration in response to injury

6122 | Jan 21 2015

By using traumatic injury as a model, Yang et al. demonstrated a critical role of mitogen-activated protein kinase (MAPK) cascade in early axonal degeneration in response to injury. [Read the Full Post]

The new finding of PI3K signaling regulation provides a novel therapeutic strategy for luminal breast cancer

8452 | Jan 15 2015

Costa et al. found the high efficiency of p110α inhibition by BYL719 is attenuated due to p110β accumulation. [Read the Full Post]

The mechanism of kinase independent AKT in promoting cancer development

6064 | Jan 12 2015

Vivanco et al. revealed the mechanism and emphasized a kinase-independent function of AKT in regulating cancer cell survival. [Read the Full Post]

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

12579 | 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]

The mechanism of GSI resistance in T cell acute lymphoblastic leukemia

5881 | Dec 30 2014

Knoechel et al. identified BRD4 is an important regulator of GSI resistance in T-ALL cells, and the combination of GSI and JQ1, the BRD4 inhibitor, is effective against T-ALL in vivo. [Read the Full Post]

CCR4 mutations act as key factors in adult T-cell leukemia/lymphoma pathogenesis

4520 | Dec 22 2014

Nakagawa et al. reported the dysregulation of CCR4 is critical in ATLL pathogenesis, and the inhibition of CCR4 signaling may have clinical value for curative treatment of ATLL. [Read the Full Post]

Retinoic acid and Wnt signaling are key regulators in development of hematopoietic stem cells

6577 | Dec 02 2014

Chanda et al. identified retinoic acid (RA) and Wnt signaling pathways as key mediators of HSC development. [Read the Full Post]

Mechanism of Cdo-induced Wnt suppression during neuronal differentication

4580 | Nov 28 2014

Jeong et al. found that Wnt signaling is negatively regulated by Cdo, a Shh multifunctional co-receptor which is highly expressed in the central nervous system, in order to promote neuronal differentiation. [Read the Full Post]

SGK3 and INPP4B mediate PI3K signaling pathway in breast cancer

5444 | Nov 18 2014

Gasser et al. found a new PI3K signaling axis, with SGK3 and INPP4B as key factors and in the absence of Akt activity, for regulation of tumorigenesis, tumor cell proliferation and invasive migration. [Read the Full Post]

The activation of BMP and WNT signals specifies epicardial lineage from hESCs

7027 | Nov 12 2014

Witty et al. describe a new strategy of using human pluripotent stem cells (hESCs) to generate epicardial lineage cells by activation the BMP and WNT signaling pathways in a stage-specific way. [Read the Full Post]

The inhibition of AKT pathway by truncated CNT-1 enhances cell apoptosis

4620 | Nov 11 2014

Nakagawa et al. demonstrated a new negative regulator of AKT signaling, tCNT-1, can promote cell apoptosis and suppress cell growth and proliferation. [Read the Full Post]

New platform of high efficiency iPSC reprogramming

8771 | Nov 05 2014

Vidal et al. found the inhibition of transforming growth factor β (TGF-β) or activation of Wnt signaling, or both, can provide a high efficient iPSC reprogramming in a cell-type-specific manner. [Read the Full Post]

Y27632 is a biochemical tool used in the study of the ROCK

5829 | Mar 05 2014

Y-27632 2HCl inhibits ROCK-II while displaying little activity against PKC. [Read the Full Post]

Perifosine is a drug candidate being developed for a variety of cancer indication

3364 | Mar 05 2014

Perifosine combining with temozolomide reduces tumor proliferation in vivo. [Read the Full Post]

GDC 0068 is a highly selective small molecule inhibitor of Akt

3417 | Feb 07 2014

GDC-0068 is a highly selective pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 5 nM/18 nM/8 nM, 620-fold selectivity over PKA. [Read the Full Post]

Y 27632 is available in a 5 mg format and has been optimized

5520 | Jan 17 2014

Y-27632 2HCl is a selective ROCK1 (p160ROCK) inhibitor with Ki of 140 nM, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK. [Read the Full Post]

Y 27632 is a biochemical tool used in the study of the rho associated protein kinase

5607 | Jan 10 2014

Y-27632 2HCl is a selective ROCK1 inhibitor with Ki of 140 nM, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK. [Read the Full Post]

Perifosine is structurally related to miltefosine

3513 | Dec 26 2013

Perifosine develops anti-proliferative properties with IC50 of 0.6-8.9 μM in immortalized keratinocytes (HaCaT), and head and neck squamous carcinoma cells. [Read the Full Post]

Wnt C59 was first disclosed in patent WO2010101849 as a potent

4097 | Dec 19 2013

Wnt-C59 is claimed to inhibit PORCN enzyme activity at nanomolar concentrations. [Read the Full Post]

XAV 939 is a small molecule and selective Wnt pathway

4411 | Dec 11 2013

XAV-939 specifically inhibits tankyrase PARP activity. [Read the Full Post]

Triciribine is a synthetic tricyclic nucleoside which acts as a specific inhibitor of the Akt

3643 | Dec 04 2013

Triciribine is a DNA synthesis inhibitor, also inhibits Akt and HIV-1 with IC50 of 130 nM and 20 nM, respectively; does not inhibit PI3K/PDK1; 5000-fold less active in cells lacking adenosine kinase. [Read the Full Post]

Thiazovivin helps in promoting human embryonic stem cell

5323 | Nov 22 2013

Thiazovivin (Tzv) is a novel ROCK inhibitor with IC50 of 0.5 μM, promotes hESC survival after single-cell dissociation. [Read the Full Post]

Thiazovivin is a drug which dramatically improves the survival of hES

5678 | Nov 05 2013

Thiazovivin (Tzv) is a novel ROCK inhibitor with IC50 of 0.5 μM, promotes hESC survival after single-cell dissociation. [Read the Full Post]

Staurosporine is a potent PKC inhibitor with IC50

5908 | Sep 24 2013

Staurosporine, a microbial alkaloid, significantly inhibits protein kinase C from rat brain with IC50 of 2.7 nM. [Read the Full Post]

Y27632 is a selective inhibitor of the Rhoassociated kinase p160ROCK

5524 | Sep 12 2013

Y27632 2HCl inhibits ROCK-II while displaying little activity against PKC, cAMP-dependent protein kinase and myosin light-chain kinase (MLCK) with Ki of 26 μM, 25 μM and > 250 μM, respectively, as well as PKA activated by another Rho-family GTPase member, Cdc42. [Read the Full Post]

Triciribine was initially described as a DNA synthesis inhibitor

3523 | Aug 21 2013

Triciribine is a DNA synthesis inhibitor, also inhibits Akt and HIV-1 with IC50 of 130 nM and 20 nM [Read the Full Post]

Perifosine is a drug candidate being developed for a variety of cancer indications

3431 | Jul 09 2013

Perifosine develops anti-proliferative properties with IC50 of 0.6-8.9 μM in immortalized keratinocytes (HaCaT), and head and neck squamous carcinoma cells. [Read the Full Post]

y27632 is a biochemical tool used in the study of the rho associated protein kinase signaling pathways

5872 | Jun 07 2013

Oral administration of Y-27632 2HCl at 30 mg/kg significantly decreases the blood pressure in a dose-dependent manner in spontaneous hypertensive rats, renal hypertensive rats, as well as deoxycorticosterone acetate (DOCA)-salt hypertensive rats. [Read the Full Post]

Taxol is a mitotic inhibitor used in cancer chemotherapy

2828 | May 06 2013

Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a US National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol. Later it was discovered that endophytic fungi in the bark synthesize paclitaxel. [Read the Full Post]

AEB071 is a potent selective pan PKC inhibitor

4575 | Jan 16 2013

Multiple sclerosis is a chronic and debilitating immune-mediated disease of the central nervous system . Recent epidemiological data supports the established view that the incidence of AEB071 MS peaks at about 30 years of age and that it is a disease with a positive female-to-male ratio. [Read the Full Post]

PKC Inhibitors is associated with endothelial dysfunction

4691 | Dec 06 2012

Atherosclerosis is initiated by the deposition, retention and oxidative modification of apolipoprotein (apo)B-containing lipoproteins, notably low-density lipoprotein cholesterol (LDL-C) in the vessel wall. This is associated with endothelial PKC Inhibitors dysfunction and recruitment of monocytes that take up oxidised LDL to become macrophage-derived foam cells, collectively apparent macroscopically as "fatty streaks". [Read the Full Post]

ROCK Kinase is involved in cytokinesis

5873 | Dec 03 2012

The first evidence that the JNK pathway, the low level of expression in SMC Lon RGS4 ch Lt, then led end F F promotion from SMC contraction. Inhibition of tonic RGS4 expression by JNK pathway represents a novel mechanism for the contribution of the JNK pathway in the regulation of smooth muscle contraction. crosstalk between MAPK and JNK by other means NFkB not well ROCK Kinase understood. [Read the Full Post]

MK-2206, a potent Akt inhibitor

6696 | Oct 16 2012

Characterization of MK-2206 Akt is identified as a serine-threonine kinase on the basis of its homology to protein kinase A (PKA), protein kinase C (PKC) and the retroviral oncogene, viral Akt. The known three human AKT isozymes (Akt1, Akt2 and Akt3) are highly homologous multi-domain proteins with both overlapping and distinct cellular functions. So far, there are a lot of AKT isozyme-selective allosteric inhibitors that have been reported, and MK-2206 is one member of them. MK-2206 is a potent, oral allosteric inhibitor of all AKT isoforms, which binds to a site outside the PH domain and binds very weakly to the PH domain of Akt. MK-2206 has the solubility around 96 mg/mL in both dimethyl sulfoxide (DMSO) and water, however it is scarcely soluble in ethanol with solubility of 2 mg/mL. And the approximate price of MK-2206 is $214 per 10 mg and $718 per 50 mg in selleckchem.com, and MK-2206 price may vary according to the proportion purity of the preparation and/or from one MK-2206 supplier to different ones. [Read the Full Post]

Perifosine as a potent Akt inhibitor

4965 | Oct 15 2012

FEATURES OF PERIFOSINE Perifosine, also known as KRX-0401, is a synthetic novel alkylphospholipid (ALP) and a potent antitumor agents which inhibits PH domain mediated AKT membrane recruitment and activation. Perifosine structure has been elucidated through X-ray crystallography and it shows the similar structure with phospholipids that are the main constituents of cellular membranes. Perifosine is soluble in water and ethanol with solubility of 14 mg/mL and 92 mg/mL, respectively. But Perifosine solubility in DMSO is poor. Commercially researchers can obtain Perifosine with the price of about $210/mg from suppliers selleck chemicals. Perifosine stability keeps good for at least 2 years for the dry solid when stored at -20°C and for 6 months at -80°C in DMSO. [Read the Full Post]

MK-2206, as a pan Akt inhibitor

7921 | Oct 09 2012

MK-2206 AKT/Protein Kinase B is a serine/threonine-specific protein kinase that constitutes an important pathway that regulates the signaling of multiple essential biological processes such as glucose metabolism, apoptosis, cell proliferation, and cell migration. AKT can be recruited to the membrane and activated with increases in PIP3 induced by PI3K. Since activating mutations of PI3K occur in human tumors, the AKT pathway is a promising potential target for cancer chemotherapy. MK-2206, is identified as an orally bioavailable allosteric inhibitor of Akt with potential antineoplastic activity. MK-2206 has shown cytotoxic activity in vitro cell line, such as T-cell acute lymphoblastic leukemia (T-ALL), and the efficacy of MK-2206 also has been proven in preclinical models of human cancers. [Read the Full Post]

DASATINIB; An Inhibitor of Receptor Tyrosine Kinase

0 | Sep 06 2012

CHARACTERISTICS OF DASATINIB Experts and also scientists are trying hard to find improve drug that will be able to possess efficiency as against cancer which has become responsible of heavy death all over the world and also resistance towards the available drugs in cancer cells is also motivating scientists. Cancer cells avoid both the action of particular medicine by mutating themselves in a number of steps. Metastasis is actually also other problem related to disease. For chemotherapy of disease cell toxicity increases the problem. To attack these afore mentioned errors the only key to combat it to be able to devise new medication. Imatinib was used for many years but toxicity and other consequences mentioned above it obligate scientists to develop one less harmful and more efficient prescription. So in this respect Jagabandhu Das developed one medicine known as Dasatinib. Dasatinib BMS 354825 got very popular compared to Imatinib because of its less toxicity and more performance. It's developed through a pharmaceutical business Squibb and offered under the trade name on Sprycel. [Read the Full Post]

ONCOGENES AND HSP90 INHIBITORS

5201 | Aug 24 2012

PATHWAY OF HSP90 AND CANCER CELL LINES: Heat shock protein 90 or Hsp90 is actually a non-fibrous protein which gained its name from its molecular weight that is 90kDa. Hsp90 is most abundant cytoplasmic protein which plays a significant role in cells by acting like a molecular chaperone for many proteins related to some important signaling cascades of the cell. Different proteins chaperones that are existing in the cell, involve serine/theronine kinases and tyrosine kinases as well hence they are very much important for the proper regulation of cell growth and cell cycle. A detailed research is carried out to describe the relation between Hsp90 and cancers. To inhibit this chaperone i.e. Hsp90, the simple strategy of designing Hsp protein inhibitor was developed when Hsp90 was found to be existing in different cancerous cell lines activated through the activation of oncogenes. It has been proved a very fruitful therapy for cancer. [Read the Full Post]

HSP90 INHIBITORS AND ONCOGENES

5495 | Aug 16 2012

HSP90 CASCADE AND CANCER CELLS: Hsp90 or the Heat shock protein 90 is a non fibrous protein that gained its name on the basis of its molecular weight i.e., 90kDa. Heat shock protein 90 is the most abundant protein present in cytoplasm that plays a significant role in the cells by acting as molecular chaperones for different proteins associated with some important signaling pathways in the cells. Various molecular chaperones existing in the cells, involves in the tyrosine kinases and serine/theronine kinases as well, so they are very important for proper regulation of cell cycle and cell growth. A complete research has been done to describe the relation between cancer and Hsp90. For the inhibition of Hsp90 chaperone a simple strategy is designed i.e., development of Hsp-60 inhibitor in case of presence of Hsp90 in the cancerous cells and activated by the activation of various oncogenes. It was proved to be an efficient therapy for the treatment of cancer. [Read the Full Post]

INHIBITON OF AKT FOR THE TREATMENT OF CANCER

4009 | Aug 10 2012

CELL PROLIFERATION AND AKT PATHWAY Signal transduction pathways involve various types of kinase enzymes. AKT kinase is such an enzyme that is responsible of phosphorylating the proteins on their specifically serine/threonine sites specifically. It is also named as PKB which means Protein kinase B. It is involved in different kinds of cellular processes like apoptosis, transcription, translation, metabolism and the most important of above all is the cell proliferation and cell migration. Many cancerous cells have been found to exhibit AKT dysfunction therefore it is thought to have an important role in the regulation of cell cycle. AKT pathway gets active by stimulation from PI3K and it also activates by itself mTOR protein to initiate the further process. When PI3K gets hyperactivated, there is an increase in rate of cell division process etc. hence caused tumorigenesis. As compared to any other pathway of signal transduction, this AKT pathway exists more frequently in the cancer cells due to event of amplification, mutation and translocation in its kinase proteins. To fight against various types of cancers and tumors the strategy applied is to target any one of these kinase proteins of this pathway and the AKT inhibitors were found quite good to be used for the treatment of cancer. [Read the Full Post]

INHIBITON OF AKT TO FIGHT CANCER

4029 | Aug 06 2012

AKT PATHWAY AND CELL PROLIFERATION Different types of kinases are involved in the signal transduction pathways. AKT kinase is one such kinase that specifically phosphorylates proteins at their serine/threonine amino acids site. It is also called as PKB i.e., Protein kinase B and is involved multiple types of cellular processes e.g., glucose metabolism, transcription, translation, apoptosis and important of all cell proliferation and its migration. Many of the cancer cells have been found to have AKT dysfunction in them therefore it is considered to have a very important role in cell cycle regulation. AKT gets activated by PI3K and activates itself mTOR protein and further process in the cell gets initiated. Hyperactivation of PI3K increases the rate of cellular process of division etc. and hence takes part in tumorigenesis. This pathway is more frequently found in cancer than any other signal transduction pathway due to the occurrence of mutation, translocation and amplification in its protein kinases. Targeting one of the kinases of this pathway is the strategy to fight against many types of cancers and PKB inhibitors have been found to be quite feasible to be used against cancer. [Read the Full Post]

HSP90 INHIBITORS AND ONCOGENES

5301 | Aug 02 2012

HSP90 PATHWAY AND CANCER CELLS: Heat shock protein 90 or Hsp90 is a non-fibrous protein that has gained its name from its 90kDa molecular weight. This is the most abundant protein present in cytoplasm and plays an important role in the cell by acting as a chaperone for many of the proteins involved in important signaling pathways of the cell. There are various proteins chaperones which are present in the cell, includes TKs or tyrosine kinases and theronine/serine kinases as well and these are very important for the regulation of cell cycle and growth. Detailed research has been conducted to connect cancers and Hsp90. As Hsp90 has shown by different cancerous cells which are activated via activating oncogenes a simple strategy for the inhibition of this chaperone has developed by designing Hsp90 inhibitors. This approach has been fruitful for cancer therapy. [Read the Full Post]

NILOTINIB AND PHILADELPHIA

6297 | Jul 25 2012

CML AND PHILADELPHIA CHROMOSOME During meiosis the fusion of two genes including BCR a breakpoint cluster and ABL tyrosine kinase results in the formation of Philadelphia chromosome. The resultant fusion protein expressed due to Philadelphia chromosome is not controlled and function abnormally leading to an oncoprotein. Chronic myelogenous leukemia or CML is caused by this fusion oncoprotein in 90% of the patients of CML. Due to huge part of this protein in CML, in drug development for cancer treatment this protein is being targeted by researchers by the help of small molecule screening. Nilotinib AMN-107 is one of the inhibitor used for this purpose to cure CML. [Read the Full Post]

AKT INHIBITORS AS ANTI TUMOR AGENTS

4367 | Jul 24 2012

AKT PATHWAY AND CANCERS: AKT is a kinase specific for threonine/serine amino acids which is also known as Protein kinase kinase B (PKB). This kinase is involved in various cellular pathways such as glucose metabolism, apoptosis, transcription and the most important functions are cell migration and proliferation. In cancer cells many of the crucial functions are controlled by AKT which depicts its importance. AKT is downstream to PI3K and mostly it is hyper activated during formations of cancers therefore taking a part in tumorigenesis through a hyperactive PI3K/AKT/mTOR pathway. As mutations, translocations and amplifications in PI3K/AKT/mTOR pathway result into hyperactivation of this pathway are more frequent than other signaling pathways. AKT inhibitors are one of the most feasible approaches to fight against cancer. [Read the Full Post]

NILOTINIB 

6962 | Jul 12 2012

ASSOCIATION OF PHILADELPHIA CHROMOSOME WITH CHRONIC MYELOGENOUS LEUKEMIA Philadelphia chromosome is composed by fusion of a tyrosine kinase ABL (Abelson) and BCR (break point cluster) gene during the cross linking of chromosomes in meiosis. This Philadelphia chromosome promotes fusion protein that functions in an uncontrolled manner as a tyrosine kinase making it an oncoprotein. This fusion oncoprotein is involved in causing CML i.e., chronic myelogenous leukemia in 90 % of patients of this disease. Due to the involvement of this fusion protein in CML, it is being targeted in lots of research going on for cancer therapeutics. Nilotinib bcr-abl inhibitor is one these inhibitors being used against CML. [Read the Full Post]

NILOTINIB

5844 | Jul 05 2012

CHRONIC MYELOGENOUS LEUKEMIA AND PHILADELPHIA CHROMOSOME During meiosis if BCR and tyrosine kinase ABL are unable to separate and fuse together it leads to condition called Philadelphia chromosome. Due to the fusion of these genes it leads to translation of abnormal protein which acts as malfunctioned tyrosine kinase that makes it oncoprotein. Around 90% of patients suffering from Ph+ also suffer from chronic myelogenous leukemia or CML. This fusion protein is being targeted for therapy of cancer since it is involved in CML and various researches are being carried out in this regard. An inhibitor of this protein is Nilotinib bcr-abl inhibitor which is used to treat CML. [Read the Full Post]

NILOTINIB

6702 | Jun 28 2012

CHRONIC MYELOGENOUS LEUKEMIA AND PHILADELPHIA CHROMOSOME During meiosis if BCR and tyrosine kinase ABL are unable to separate and fuse together it leads to condition called Philadelphia chromosome. Due to the fusion of these genes it leads to translation of abnormal protein which acts as malfunctioned tyrosine kinase that makes it oncoprotein. Around 90% of patients suffering from Ph+ also suffer from chronic myelogenous leukemia or CML. This fusion protein is being targeted for therapy of cancer since it is involved in CML and various researches are being carried out in this regard. An inhibitor of this protein is Nilotinib bcr-abl inhibitor which is used to treat CML. [Read the Full Post]

NILOTINIB AND PH+

6511 | Jun 10 2012

PHILADELPHIA CHROMOSOME AND CML Philadelphia chromosome is formed by fusion of a tyrosine kinase ABL (Abelson) and BCR (break point cluster) gene during the cross linking of chromosomes in meiosis. This Philadelphia chromosome gives rise to a fusion protein that is functions in an uncontrolled manner as a tyrosine kinase making it an oncoprotein. This fusion oncoprotein is involved in causing CML i.e., chronic myelogenous leukemia in 90 % of patients of this disease. Due to the involvement of this fusion protein in CML, it is being targeted in lots of research going on for cancer therapeutics. Nilotinib bcr-abl inhibitor is one these inhibitors being used against CML. [Read the Full Post]

DASATINIB- A DRUG OF CHOICE

7021 | Jun 04 2012

INTRODUCTION Diverse types of cellular systems are there in human bodies that differ structurally and functionally from one another. Each cellular system is controlled by a variety of controllers called cell cycle regulatory proteins. Defective controllers may lead to abnormal cellular systems and the condition known as cancer may develop. Cancer may be of different types depending upon the defect in the cell cycle regulatory proteins. Cancer may also vary on the basis of stage of the defective condition. Many therapies have been devised in order to treat cancerous cells. Further research is also being done for developing better, more specific and less toxic therapies and to cope with the development of resistance in the defective cells against existing therapies. Besides resistance, metastasis is also another issue to be resolved in case of cancerous cells. Imatinib has been used against leukemia for several years but due to high levels of toxicity scientists discovered a new drug, called Dasatinib, for the same therapy. Dasatinib BMS-354825 is more efficient and less toxic as compared to Imatinib. The drug is being marketed by the name of Sprycel. As Dasatinib was discovered by Jagabandhu Das, it was named Dasatinib. Development of the drug was done by Squibb Company. [Read the Full Post]

NILOTINIB

6866 | May 30 2012

ROLE OF BCR-ABL TYROSINE KINASES IN CML: A chimeric BCR-ABL oncogene is obtained by the fusion of Abelson (ABL) tyrosine kinase (TK) gene and break-point cluster (BCR) gene, and here TK has been related to pathogenesis of CML (Chronic Myelogenous Leukemia), 90% of this debilitating disease involves chromosomal abnormalities leading to formation of so-called Philadelphia chromosome. As there is a confirmed participation of BCR-ABL TK in PH+ CML, different inhibitors that target this TK have registered remarkable success in treatment of CML and among them Nilotinib bcr-abl inhibitor is the most valuable one. It is a form of tyrosine kinase inhibitor and is a hydrochloride monohydrate salt. [Read the Full Post]

IMATINIB – INHIBITS MULTIPLE KINASES

6005 | May 07 2012

INTRODUCTION: SRC inhibitors are the molecules specific for targeting the non rector tyrosine kinase enzymes of SRC family and have the potential of inhibiting the 2 or more members of two SRC subfamilies, Fyn, Src. Fgr, Yes, Lck, Blk, Frk and Hck SRC kinases. These kinase enzymes take part in various pathways, so targeting them has became an attractive and valuable approach in the field of chemotherapy. Imatinib is commonly known as STI-571. Imatinib SRC inhibitor is a molecule originally named as STI571 and marketed by the company Novartis in the form of its mesylate salt hence known as STI-571 Imatinib Mesylate. This salt form is especially developed for targeting the cancer cells sparing the normal cells from them hence developed as personalized drug. [Read the Full Post]

NILOTINIB

4419 | Apr 08 2012

ROLE OF BCR-ABL IN CML BCR (break-point cluster) and (ABL) Abelson genes code for the protein tyrosine kinases that are involved in signal transduction fusion of these two genes occur when a philadalphia chromosome is formed after some mistake in the process of crossing over. This chimeric oncogene is known as BCR-ABL and is known to be involved in the development of leukemia especially (CML) Chronic Myelogenous Leukemia. This type of fusion is known to be responsible for almost 90% CML cases and is known as PH+ CML. The participation of BCR-ABL in PH+ CML has urged the scientists to inhibit this fusion protein. Different types of inhibitors targeting this oncogenic fusion protein have been registered. Nilotinib Src-bcr-Abl inhibitor is one of such inhibitors against CML. [Read the Full Post]

PACLITAXEL – A MICROTUBULE INHIBITOR WITH MULTIPLE ROLES

3144 | Apr 04 2012

PACLITAXEL: Paclitaxel is an inhibitor of mitosis and it was discovered in the bark of a tree called Taxus brevifolia and later on its presence was also reported in hazel cells. Many of the cancer drugs target microtubules in the cancer cells, Paclitaxel microtubules inhibitor is a new hope for cancer treatment. The structure of this compound is complex as it contains diterpene along with an oxatane ring and taxane. The generic name has been changed by the manufacturers of Paclitaxel that was Taxol the brand name of this inhibitor is Abraxane and any one can buy Paclitaxel for medicinal usage. Paclitaxel is soluble in methanol and DMSO and in order to gain long term stability for this compound one should keep it away from any strong acidic or alkaline solution. The Paclitxel price is variable as it depends on its purity and Paclitaxel supplier. Its cost is reasonable and one can purchase Paclitaxel for research purposes as well. [Read the Full Post]

STAUROSPORINE: A PKC INHIBITOR

6257 | Mar 25 2012

STAUROSPORINE PROPERTIES AND ORIGIN: The discovery of Staurosporine was done during the research on a bacterium Streptomyces staurosporeus in 1977, this compound was identified as an antibiotic and now this molecules has been studied thoroughly. Another alternate name of this molecule is STS or Staurosporine AM-2282, its configuration and structure was identified by certain physical techniques such as analysis of X-ray. Staurosporine PKC inhibitor is also found as active against a good number of protein kinases (PKs), Staurosporine IC50 for PKA, PKC and PKG is 7.0 nM, 0.7 nM and 8.5 nM respectively. When Staurosporine is stored at -20 oC it’s stability remains un-affected for two years. This compound is soluble in DMSO. Molecular weight of Staurosporine is 466.53 and it is expensive as Staurosporine price for 1 mg is more than $500, however the price is variable from one Staurosporine supplierto other. Staurosporine PKC inhibitor is available easily and if someone wants to purchase Staurosporine for laboratory and research use one can buy Staurosporine easily. [Read the Full Post]

PACLITAXEL – MULTIPLE ROLES AS MICROTUBULE STABILIZER

3462 | Mar 19 2012

Introduction: Mitosis and Cytokinesis An essential part of the cell cycle is the M phase where the cell physically divides into two unique cells. This process is consists of two different phases mitosis and cytokinesis. Cytokinesis is the phase where the contents of the cell are divided into two equal portions along with the duplicate chromosomes and nuclei. The cell membrane then pinches together and eventually splits into two segments. Mitosis, on the other hand is the division of the duplicate chromosomes and nuclei into opposite ends of the cell. To do this; microtubule form from one end of the elongated cell to the newly formed chromosomes, these tubules then decrease in length pulling the chromosomes pairs apart. The same happens for the nuclei. This process is complex and involved but it is sufficient to indicate that action of inhibitors against the dismantling of the microtubules would halt the cell separation causing apoptosis to initiate. A small molecule that can induce such a reaction is Paclitaxel microtubule stabilization has been used as the standard treatment for a variety of cancer types for many years. [Read the Full Post]

HSP INHIBITORS AGAINST PROTEIN FOLDING

4471 | Mar 19 2012

Introduction: Cellular Quality Assurance The network of chemical reactions linked to the mechanisms behind cellular growth, proliferation and differentiation are complex. Referred to as biochemical pathways these mechanisms operate on some simple principles starting with the receipt of a message from the host system to the cell itself. The pathway system can be likened to a production line facility with the product being a normal health cell. So mechanisms exists for stock piling of raw materials, for the synthesis of component parts, for the recycling of waste materials, for the removal of unwelcome molecules, quality assurance and final product viability. One the key aspects of cellular growth is the delicacy of the whole process, it does not take much to drive a mechanism off balance and produce a faulty product, to ensure quality under stress induced conditions a series of proteins exist referred to as Heat Shock Proteins that assess the quality of proteins being constructed for cell growth purposes. [Read the Full Post]

ENZASTAURIN AGAINST MALIGNANCIES

4111 | Mar 20 2012

Introduction: The Protein Kinase C family A cytosolic protein kinase isolated in the late 1970’s by the Nishizuka group of Kobe University, Japan has been found to be a key factor in the regulation of the cell cycle. Established as the protein kinase C family several isoforms have subsequently be isolated. These serine / threonine kinases are activated by the diacylglycerol (DAG) which is generated by the agonist induced hydrolysis of Trans-membrane G-protein kinases or tyrosine kinases. Activation of protein kinase C leads to a movement of the protein to the either the cytosolic skeleton or to the cellular membrane triggering a cascade of downstream signals which induce cell growth, differentiation or proliferation activities, this process appears to be mediated by the release of Ca2+. One of the key elements to be discovered concerning this protein was the discovery that phorbol esters were also a ligand for activating this protein; this created a direct link between PKC and the formation of various tumors. [Read the Full Post]

THIAZOVIVIN: THE PLURIPOTENCY INDUCER

4801 | Mar 20 2012

POTENTIAL OF EMBRYONIC STEM CELLS OF HUMAN (hESCs): The stem cells are not only known for their property of pluripotency in nature which means they have the potency to replicate in an indefinite manner but also famous for their capability of getting differentiate into all other kinds of cells and organelles from the three basic germinal layers named as ectoderm, mesoderm and endoderm. Embryonic stem cells of human (hESCs) have the ability of producing various numbers of types of cells in contrast to adult stem cells having the capability of producing only a limited cell types. Due to their pluripotency hESCs or human embryonic stem cells are of great interest and importance for the scientists and researchers as they are being used for detection and analysis of different genetic disorders of human in their research. The successful models of Human Embryonic Stem Cells are made for Fragile-X syndrome and Cystic fibrosis (CF) etc like genetic maladies and their will be many more in upcoming years. In olden years the usual practice was to use embryo to generate pluripotent stem cells which is brought down very significantly due to the process of insertion of various genes like Sox2, Oct4 and Klf4 etc into differentiated cells. These genes can enhance the pluripotency in differentiated cells and make them exactly like embryonic stem cells. A recent more advanced approach is to use molecules like Thiazovivin. [Read the Full Post]

TAXOL: BEFORE AND NOW

2846 | Mar 18 2012

Inhibition of cell division A well know cellular function is that of mitosis; which is the biological function whereby a cells nucleus splits into two identical units. The process is accompanied by cytokinesis where the cell membrane, cytosole and separate nuclei divide into to cells. This complete process is referred to as the”M” phase in the cell cycle theory. The complete process is supported by a scaffolding type structure called microtubules which provide the framework for cytokinesis and mitosi. A mitotic inhibitor is one which interferes with the stability of the microtubules which is of relevance in chemotherapy since unregulated cell division is one the strongest difference between tumor and normal cells. This difference can be exploited by a specifically designed inhibitor. Taxol, more commonly called Paclitaxel, is an inhibitor which disrupts the dismantling of the microtubules during cell division, hence cell mitosis cannot occur. Taxol is standard therapy in many forms of cancer including sarcoma, breast cancer, NSCLC, SCLC, ovarian cancer as well as head and neck cancer. [Read the Full Post]

FINGOLIMOD – THE IMMUNOMODULATOR

4625 | Mar 19 2012

Introduction: Fingolimod and Multiple Sclerosis One of the most widely used fungi in Chinese herbal medication is the ascomycete “Isaria sinclairii”. Known for its medical properties for centauries it was examined more closely after the immunosuppressant cyclosporin was discovered from a fungal source. From a screening of the extracts from this fungus came the molecule myriocin which demonstrated immunosuppressant properties as hope, however, it also killed the host in animal models. This molecule proved to be far too toxic for clinical use hence the molecule skeleton was used as a template to derive a series of derivatives in the effort to reduce the toxicity but preserve the immunosuppression potency. From this process came FTY720 which was researched pre-clinically in the area of transplant rejection, before being released in clinical trials as Fingolimod . [Read the Full Post]

IMATINIB – THE MULTI KINASE INHIBITOR

4009 | Mar 19 2012

Introduction: The kinase super family In recent years the broadening of technology has enabled researchers to investigate the role of ligands in relation to cellular responses. To achieve understanding the binding properties, conformation changes, receptor response and protein binding domains similarity have been extensively researched, most notably in the field of oncology. The protein kinases are not really a new discovery but the relationship between proteins is now beginning to be understood. Over 500 different distinct proteins exist under the super family heading of protein kinases. These proteins govern the growth, proliferation, differentiation and apoptosis of nearly all aspects of the mammalian system. The protein kinase family is subdivided into small related protein series that seem to work together to receive a signal from an extracellular source and translated this into cellular activity. [Read the Full Post]

FTY720 – THE IMMUNE CELLS’ TRAFFIC CONTROLLER

4146 | Mar 19 2012

Introduction: Multiple Sclerosis Multiple sclerosis is probably a condition that everybody has heard off but not many really understand the cause or nature of this destructive disease. Basically this disease is what is known as an inflammatory disease which affects area of the lining in the spinal cord or brain stem. The effect of this is the slow degradation of the functions of the spinal cord and brain stem. This means a loss of motor control, loss of communicative functions, loss of sight and digestive difficulties. Accompanying these debilitating symptoms are almost constant pain and fatigue, life quality of most suffers becomes very poor. There is currently no known cure for this disease, while treatment focuses on alleviating the symptoms or retarding the progression of the disease but always the end point is the same. Patients with this disease are known to try any form of treatment scientifically proven or not in the hope a remission can be triggered. Remission is the peculiar aspect of this disease in that it appears in phases with periods of relative peace in-between. However, relapses are usually progressively worse accumulating damage to essential functions that cannot be repaired. [Read the Full Post]

AKT INHIBITORS AGAINST TUMOR GROWTH

4702 | Mar 13 2012

AKT PATHWAY AND ITS LINK WITH CANCERS: With the emergence of the tyrosine kinase inhibitors attention was directed toward Akt, a serine/ threonine kinase of the protein kinase family. Akt is more formally known as protein kinase B and exists in three isoforms. Its role in the cellular signaling cascades has been well documented with downstream effects on mTOR, BAD and GSK3 The PI3K/Akt/mTOR pathway has been established as having an important role in apoptosis, cell migration and proliferation, transcription and glucose metabolism. In various known forms of malignancies Akt has been established as playing a crucial role, an elevated expression of phosphorylated Akt is a contraindication of survival. Hence focus was placed on the development of AKT inhibitor drugs. AKT inhibition has been achieved with Perifosine, MK-2206, RX-0201, Erucylphosphocholine (ErPC), PBI-05204, GSK690693, A-443654 and XL-418. [Read the Full Post]

DASATINIB – THE DOUBLE-EDGED SWORD

5314 | Mar 13 2012

Introduction: BCR-ABL and SCR targets Researchers are continuously searching for the magic compound which will cure all diseases but most know that this is a physical impossibility. Every disease is different and especially cancers where even tumors of the same site / type can be radically different. In CML, AML and ALL a mutation in two chromosomes has been linked to the onset of these diseases in a proportion of patients. The defect is referred to as the “Philadelphia chromosome”, here a section of chromosome 9 and chromosome 22 have swapped places (translocated). The end result is that chromosome 9 is longer than it should be while chromosome 22 is shorter than it should be. The significance of this change is that the coding for the BCR gene and the ABL gene become mixed up (fused). The protein from this genetic fusion is referred to as the BCR-ABL fusion protein. Studies have shown that this protein is related to the protein kinase super family and has serine / threonine kinase activity, it also has phosphorylation activity for the cytoskeletal enzyme p21 Rac (Cdc42). Imatinib is a small molecule inhibitor of the ABL in Chronic Myeloid Leukemia, Acute Myeloid Leukemia and Acute Lymphoblast Leukemia tumors that has been proven very successful in the clinic. However, patients with the translocated gene demonstrate resistance to Imatinib due in part to the nature of fused BCR-ABL gene. [Read the Full Post]

MK-2206, as an Akt Inhibitor, enhances antitumor efficacy by chemotherapeutic agents

3839 | Nov 17 2011

Development and maintenance of many tumors have been reported to be associated with abnormal activation of PI3K. Akt is a critical downstream factor of PI3K signaling pathway and is important in promoting cell survival and inhibiting apoptosis. Clinically, Akt activation and overexpression is often associated with resistance to chemotherapy or radiotherapy. Thus, clinically available small-molecule inhibitors of Akt have remarkable potential in cancer treatment. [Read the Full Post]

Roles of Hsp90 in wound healing and cancer

5736 | Oct 24 2011

Wound healing is an intricate process in which the skin (or another organ-tissue) repairs itself after injury. At present, local growth factors are considered to be the driving force for wound healing and only recombinant human platelet-derived growth factor-BB (PDGF-BB) has been approved by US FDA for topical treatment of diabetic ulcers. However, the use of PDGF-BB in clinical trials has been limited for its modest efficacy, high cost and risk of causing cancer. Thus, novel treatment for wound healing is needed to be explored. [Read the Full Post]

Enzastaurin, as the inhibitor of PKC, may be a novel PNC medical therapy

4899 | Sep 29 2011

Pancreatic cancer is the fourth most common cause of cancer death both in the United States. Regarding the pathology, pancreatic cancer mainly includes exocrine pancreas cancers, pancreatic cystic neoplasms and endocrine pancreatic cancers. Pancreatic neuroendocrine cancers (PNC) account for less than 3% of pancreatic tumors and the main treatments are surgery, hormone therapy, chemotherapy and so on at this stage. However, It is still needed to search for effective treatments for PNC, and understand the molecular pathways regulating neuroendocrine tumor cell proliferation. [Read the Full Post]

Rosse, C., M. Linch, et al. (2010). "PKC and the control of localized signal dynamics." Nat Rev Mol Cell Biol 11(2): 103-112.

5018 | Jul 19 2011

This review which was published in Nature review summary the role of PKC in different pathways and show the importance of PKCs in controlling spatial resolution in signaling processes using the MET and STAT3 example. [Read the Full Post]

Chin, Y. R. and A. Toker (2009). "Function of Akt/PKB signaling to cell motility, invasion and the tumor stroma in cancer." Cell Signal 21(4): 470-476.

3482 | Jun 23 2011

This article gives an introduction of akt signal pathway in cell motility, invasion and the tumor stroma in cancer. We can learn this overview of relationship between Akt and cancer. [Read the Full Post]

Narumiya, S., M. Tanji, et al. (2009). "Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion." Cancer Metastasis Rev 28(1-2): 65-76.

5675 | Jun 7 2011

This review summaries the Rho signaling in transformation, metastasis and invasion. It explains the relationship between Rho signaling and tumor cells, and it gives the perspectives in this review. [Read the Full Post]

Sarli, V. and A. Giannis (2008). "Targeting the kinesin spindle protein: basic principles and clinical implications." Clin Cancer Res 14(23): 7583-7587.

3967 | Jun 2 2011

This review describles the function of the kinesin spindle protein. This article also summary the inhibitors of the kinesin spindle protein. [Read the Full Post]

Mackay, H. J. and C. J. Twelves (2007). "Targeting the protein kinase C family: are we there yet?" Nat Rev Cancer 7(7): 554-562.

4608 | May 18 2011

This review summary the development of PKC inhibitors for cancer. It also explains the difficulties we meet. The author also give a prospect of PKC inhibitors. [Read the Full Post]

Chiosis, G., M. Vilenchik, et al. (2004). "Hsp90: the vulnerable chaperone." Drug Discov Today 9(20): 881-888.

4353 | Apr 19 2011

Agents that interact with its C-terminus or modify its post-translational status represent additional ways of interfering with chaperone activity. This review will discuss several emerging classes of Hsp90 inhibitors and their modes of action. [Read the Full Post]

Ren, R. (2005). "Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia." Nat Rev Cancer 5(3): 172-183.

4275 | Apr 15 2011

The review which was published in Nature Review Cancer introduces the relationships between CML and BCR-ABL. The researchers introduce not only the BCR–ABL and oncogenic activities of BCR–ABL, roles of BCR–ABL domains in leukaemogenesis, but pathways downstream of BCR–ABL as well. [Read the Full Post]

Yardy, G. W. and S. F. Brewster (2005). "Wnt signalling and prostate cancer." Prostate Cancer Prostatic Dis 8(2): 119-126.

4828 | Apr 8 2011

This article introduce the wnt pathway and the relationship between wnt and cancer. It really give athe detail information of wnt signal pathway. [Read the Full Post]

Yap, T. A., M. D. Garrett, et al. (2008). "Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises." Curr Opin Pharmacol 8(4): 393-412.

3406 | Apr 4 2011

This review is about the drug discovery of cancer which is targeting the PI3K-AKT-mTOR pathway. Basic knowledge of the PI3K-AKT-mTOR pathway and anticancer therapeutics are both in this article. Anyone who is interested in drug discovery can benefit after reading this article. [Read the Full Post]

Riento, K. and A. J. Ridley (2003). "Rocks: multifunctional kinases in cell behaviour." Nat Rev Mol Cell Biol 4(6): 446-456.

4905 | Mar 3 2011

This article introduces regulation of ROCK activity, ROCK function and ROCK inhibitors. This review concludes knowledge of ROCK in different ways. [Read the Full Post]