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Apoptosis

Targeting MCL-1 dysregulates cell metabolism and leukemia-stroma interactions and resensitizes acute myeloid leukemia to BCL-2 inhibition

1 | May 05 2021

Bing Z Carter et al. found that co-targeting MCL-1 and BCL-2 improved the efficacy of and overcame preexisting and acquired resistance to BCL-2 inhibition. [Read the Full Post]

Discovery of S64315, a Potent and Selective Mcl-1 Inhibitor

1 | May 04 2021

Zoltan Szlavik et al. reported the discovery of clinical candidate S64315, a selective small molecule inhibitor of Mcl-1. [Read the Full Post]

Simultaneously Inhibiting BCL2 and MCL1 Is a Therapeutic Option for Patients with Advanced Melanoma

1 | May 04 2021

Nabanita Mukherjee et al. suggested that several pro-apoptotic BCL2 family members, BCL2-like 11 (apoptosis facilitator) (BIM), phorbol-12-myristate-13-acetate-induced protein 1 (NOXA) or BID, played a role in the combination-induced effects. [Read the Full Post]

Direct Conjugation of NEDD8 to the N-Terminus of a Model Protein Can Induce Degradation

2 | May 03 2021

Kartikeya Vijayasimha et al. suggested that under certain conditions, such as the model system described here, the covalent linkage of NEDD8 to a protein substrate might result in the target proteins degradation. [Read the Full Post]

SLFN11 inactivation induces proteotoxic stress and sensitizes cancer cells to ubiquitin activating enzyme inhibitor TAK-243

1 | May 01 2021

Yasuhisa Murai et al. found that findings uncover a previously unknown function of SLFN11 as a regulator of protein quality control and attenuator of ER stress and UPR. Moreover, they suggest the potential value of TAK-243 in SLFN11-deficient tumors. [Read the Full Post]

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

1 | 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]

Loss of FADD and Caspases Affects the Response of T-Cell Leukemia Jurkat Cells to Anti-Cancer Drugs

3 | Apr 26 2021

Zuzana Mrkvová et al. thought that a combination of TNF-α and smac mimetic could be a suitable strategy for overcoming resistance to therapy in cells unable to trigger apoptosis. [Read the Full Post]

H3K36 methylation reprograms gene expression to drive early gametocyte development in Plasmodium falciparum

4 | Apr 25 2021

Jessica Connacher et al. found that H3K36me2&3-associated repression of genes was therefore involved in key transcriptional shifts that accompanied the transition from early gametocyte differentiation to intermediate development. [Read the Full Post]

Synthesis and Evaluation of Biphenyl-1,2,3-Triazol-Benzonitrile Derivatives as PD-1/PD-L1 Inhibitors

2 | Apr 23 2021

Suresh Narva et al. thought that compound 7 was thus a promising candidate for further optimization as an inhibitor of the PD-1/PD-L1 signaling pathway. [Read the Full Post]

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

4 | 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

3 | 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]

The molecular context of vulnerability for CDK9 suppression in triple wild-type melanoma

3 | Apr 19 2021

Samantha M Guhan et al. found that transcriptional blockade through selective targeting of CDK9 was an effective method of suppressing therapeutically-orphaned BRAF/NRAS/NF1 wild-type melanomas. [Read the Full Post]

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

3 | Apr 19 2021

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

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

3 | Apr 13 2021

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

Porcine Picornavirus 3C Protease Degrades PRDX6 to Impair PRDX6-mediated Antiviral Function

5 | Apr 12 2021

Congcong Wang et al. found that PRDX6 played an important antiviral role during porcine picornavirus infection, and the viral 3Cpro induced the degradation of PRDX6 to overcome PRDX6-mediated antiviral function. [Read the Full Post]

Emerging Effects of Sepantronium Bromide (YM155) on MOLT-4 Cell Line Apoptosis Induction and Expression of Critical Genes Involved in Apoptotic Pathways

4 | Apr 11 2021

Kobra Shojaei Moghadam found that use of YM155 could be a potential drug therapy in T-ALL patients with promising effects on apoptosis induction. [Read the Full Post]

A transposon screen identifies enhancement of NF-κB pathway as a mechanism of resistance to eribulin

3 | Apr 08 2021

Xiaozhong Teng et al. supported the use of a combination strategy of eribulin with NF-κB inhibitors, and provided evidence that transposon mutagenesis screens were capable of identifying drug-resistant genes. [Read the Full Post]

LncRNA XIST promotes inflammation by downregulating GRα expression in the adenoids of children with OSAHS

3 | Apr 08 2021

Zhen Zhou et al. demonstrated that the XIST-GRα-NF-κB signaling pathway contributed to inflammation in the adenoids of patients with OSAHS. [Read the Full Post]

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

5 | 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]

In vivo Pharmacokinetic Drug-Drug Interaction Studies Between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC/MS-MS Method

4 | Apr 04 2021

Congrong Tang et al. thought that the toxicity of fedratinib should be avoided when the concurrent use of fedratinib with CYP3A4 inhibitors might occur. [Read the Full Post]

Current Clinical Investigations in Myelofibrosis

3 | Apr 04 2021

Sangeetha Venugopal et al. provided insight into the novel therapies under clinical evaluation. [Read the Full Post]

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

5 | Apr 02 2021

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

Nucleotide variation in histone H2BL drives crossalk of histone modification and promotes tumour cell proliferation by upregulating c-Myc

4 | Mar 30 2021

Lei Zhang et al. revealed that an H2BK5ac-H2BK120ubi crosstalk which regulates gene transcription. [Read the Full Post]

Pharmacological inhibition of IKKβ dampens NLRP3 inflammasome activation after priming in the human myeloid cell line THP-1

5 | Mar 25 2021

Adeline Unterreiner et al. suggested that IκKβ might fulfill a dual role in coupling priming and activation of the NLRP3 inflammasome. [Read the Full Post]

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

9 | Mar 24 2021

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

Targeting phosphoinositide 3-kinases and histone deacetylases in multiple myeloma

7 | Mar 19 2021

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

Reversal of Cancer Multidrug Resistance (MDR) Mediated by ATP-Binding Cassette Transporter G2 (ABCG2) by AZ-628, a RAF Kinase Inhibitor

8 | Mar 16 2021

Jing-Quan Wang et al. indicated that AZ-628 could be used in combination chemotherapy against ABCG2-mediated MDR in cancers. [Read the Full Post]

Cardioautonomic control in healthy singleton and twin pregnancies

7 | 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]

Differential Outcomes in Codon 12/13 and Codon 61 NRAS-Mutated Cancers in the Phase 2 NCI-MATCH Trial of Binimetinib in Patients with NRAS-Mutated Tumors

12 | Mar 07 2021

James M Cleary et al. thought that the observation of increased OS and PFS in codon 61 NRAS-mutated colorectal cancer patients merited further investigation. [Read the Full Post]

Mnk inhibitors: a patent review

12 | Mar 07 2021

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

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

8 | 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]

Manipulating bovine granulosa cell energy metabolism limits inflammation

10 | Mar 03 2021

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

CD8 lymphocyte depletion enhances the latency reversal activity of the SMAC mimetic AZD5582 in ART-suppressed SIV-infected rhesus macaques

9 | Mar 01 2021

Maud Mavigner et al. suggested that the latency reversal induced by activation of the ncNF-κB signaling pathway with AZD5582 could be enhanced by CD8α+ cell depletion. [Read the Full Post]

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

13 | Feb 28 2021

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

Sensitization of head and neck squamous cell carcinoma to apoptosis by combinational SMAC mimetic and Fas ligand-Fc treatment in vitro

11 | Feb 26 2021

Roman C Brands et al. identified SMAC mimetics, particularly BV-6 as the compound with the highest pro-apoptotic potency, as promising antitumor agents. [Read the Full Post]

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

18 | 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]

Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity, and memory in mouse models of Alzheimer's disease

10 | Feb 24 2021

Mauricio M Oliveira et al. found that attenuating the ISR downstream of phosphorylated eIF2α might restore hippocampal protein synthesis and delay cognitive decline in AD patients. [Read the Full Post]

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

9 | 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]

Structure-based discovery of 1H-indole-2-carboxamide derivatives as potent ASK1 inhibitors for potential treatment of ulcerative colitis

9 | Feb 23 2021

Shaohua Hou et al. suggested that ASK1 inhibitors could potentially be used as a therapeutic strategy for UC. [Read the Full Post]

EGR1 knockdown alleviates the cerebral injury in rats with intracerebral hemorrhage (ICH) via STAT3/NF-κB pathway by reducing RXRα acetylation level

10 | Feb 23 2021

Lijuan Xie et al. found that EGR1 increased RXRα acetylation level by regulating p300, thereby aggravating brain damage in ICH rat model and dysfunction in BMECs, which might through the STAT3/NF-κB pathway. [Read the Full Post]

Selonsertib, a potential drug for liver failure therapy by rescuing the mitochondrial dysfunction of macrophage via ASK1-JNK-DRP1 pathway

12 | Feb 22 2021

Guohua Lou et al. thought that selonsertib protected against LPS/GalN-induced ALF by attenuating JNK-mediated DRP1 mitochondrial translocation and then rescuing mitochondrial damage in macrophages and might have therapeutic potential for early ALF patients. [Read the Full Post]

More Insights on the Use of γ-Secretase Inhibitors in Cancer Treatment

10 | Feb 21 2021

Pilar López-Nieva et al. suggested that selective targeting γ-secretase might offer an improved efficacy and toxicity profile over the effects caused by broad-spectrum GSIs. [Read the Full Post]

Active notch protects MAPK activated melanoma cell lines from MEK inhibitor cobimetinib

10 | Feb 19 2021

Letizia Porcelli et al. unveiled a coordinate action of MAPK and Notch signaling in promoting proliferation of BRAFV600E MM and GNAQQ209L UM cells. [Read the Full Post]

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

12 | Feb 16 2021

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

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

19 | 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]

The application of nanoparticles in cancer immunotherapy: Targeting tumor microenvironment

12 | Feb 13 2021

Muyue Yang et al. found that the changes of TME at various stages during tumor development are required to be further elucidated so that more individualized nanoplatforms could be designed. [Read the Full Post]

Selective reactivation of STING signaling to target Merkel cell carcinoma

10 | Feb 13 2021

Wei Liu et al. found that targeted delivery and activation of STINGS162A/G230I/Q266I in tumor cells held great therapeutic promise for the treatment of MCC and many other STING-deficient cancers. [Read the Full Post]

Hospitalization and Mortality in Patients With Heart Failure Treated With Sacubitril/Valsartan vs. Enalapril: A Real-World, Population-Based Study

11 | Feb 12 2021

Swathi Pathadka et al. found that in real-world settings, sacubitril/valsartan was associated with improved survival and reduced heart failure-related hospitalization compared to enalapril in Asian patients with heart failure. [Read the Full Post]

Albendazole-Induced SIRT3 Upregulation Protects Human Leukemia K562 Cells from the Cytotoxicity of MCL1 Suppression

12 | Feb 12 2021

Liang-Jun Wang et al. demonstrated that ABZ-induced SIRT3 upregulation delayed the apoptosis-inducing effect of MCL1 suppression on apoptosis induction in K562 cells. [Read the Full Post]

BMI1-Inhibitor PTC596 in Combination with MCL1 Inhibitor S63845 or MEK Inhibitor Trametinib in the Treatment of Acute Leukemia

13 | Feb 08 2021

Katja Seipel et al. thought that the combination of PTC596 and S63845 might be an effective treatment in CD34+ adverse risk AML with elevated MN1 gene expression and MCL1 protein levels. [Read the Full Post]

A thiol-bound drug reservoir enhances APR-246-induced mutant p53 tumor cell death

11 | Feb 08 2021

Sophia Ceder et al. found that redox homeostasis was a critical determinant of the response to mutant p53-targeted cancer therapy. [Read the Full Post]

Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Adults

14 | Feb 01 2021

D Gwyn Bebb et al. recommend considering a TRK inhibitor in all patients with TRK fusion cancer with no other effective treatment options. [Read the Full Post]

Neutrophil Extracellular Traps in Atherosclerosis and Thrombosis

17 | Jan 30 2021

Thomas M Hofbaue et al. found mechanisms of NET formation, evidence for their involvement in atherosclerosis and thrombosis, and potential therapeutic regimens specifically targeting NET components. [Read the Full Post]

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

15 | 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]

De novo protein synthesis is necessary for priming in preclinical models of migraine

16 | Jan 26 2021

Jacob Lackovic et al. suggested that targeting the regulation of protein synthesis might be a novel approach for new migraine treatment strategies. [Read the Full Post]

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

15 | 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]

Valve endothelial-interstitial interactions drive emergent complex calcific lesion formation in vitro

22 | Jan 24 2021

Terence W Gee et al. established that VEC actively induced VIC pathological remodeling and calcification via EndMT and paracrine signaling. [Read the Full Post]

Hypoxic modulation of fetal vascular MLCK abundance, localization, and function

12 | Jan 23 2021

Dane W Sorensen et al. found that changes in MLCK distribution are a significant component of fetal vascular responses to hypoxia. [Read the Full Post]

MDM2 inhibition: an important step forward in cancer therapy

19 | Jan 21 2021

Marina Konopleva et al. thought that targeting MDM2 was a promising treatment strategy. [Read the Full Post]

Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer

18 | Jan 17 2021

R Vatapalli et al. thought that DOT1L selectively regulated the tumorigenicity of AR-positive prostate cancer cells and was a promising therapeutic target for PCa. [Read the Full Post]

Salvianolate ameliorates oxidative stress and podocyte injury through modulation of NOX4 activity in db/db mice

18 | Jan 17 2021

Yiran Liang et al. identified that Salvianolate could prevent glucose-induced oxidative podocyte injury through modulation of NOX4 activity in DN and had a novel therapeutic potential for DN. [Read the Full Post]

Role of necroptosis in chronic hepatic inflammation and fibrosis in a mouse model of increased oxidative stress

13 | Jan 16 2021

Sabira Mohammed et al. found that necroptosis-mediated inflammation contributed to fibrosis in a mouse model of increased oxidative stress and accelerated aging, that also exhibited progressive HCC development. [Read the Full Post]

Kanglexin accelerates diabetic wound healing by promoting angiogenesis via FGFR1/ERK signaling

19 | Jan 15 2021

Yixiu Zhao et al. thought that KLX had the potential to be developed as a topical drug to promote diabetic wound healing. [Read the Full Post]

Nanog maintains stemness of Lkb1-deficient lung adenocarcinoma and prevents gastric differentiation

17 | Jan 15 2021

Xinyuan Tong et al. uncovered a previously unappreciated plasticity of LKB1-deficient tumors and identified the Nanog-Notch axis in regulating gastric differentiation, which hold important therapeutic implication for the treatment of mucinous lung cancer. [Read the Full Post]

MOMENTUM: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic

17 | Jan 13 2021

Srdan Verstovsek et al.showed that the MOMENTUM Phase III study was designed to confirm and extend observations of safety and clinical activity of MMB. [Read the Full Post]

CYT387, a Novel JAK2 Inhibitor, Suppresses IL-13-Induced Epidermal Barrier Dysfunction Via miR-143 Targeting IL-13Rα1 and STAT3

18 | Jan 13 2021

Yan Zu et al. revealed that the protective effects and the underlying mechanisms of CYT387 in AD, which provided evidence that miR-143 might be a novel therapeutic target for AD. [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

16 | 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]

Pergularia daemia alters epileptogenesis and attenuates cognitive impairment in kainate-treated mice: Insight into anti-inflammatory mechanisms

19 | Jan 12 2021

Antoine Kavaye Kandeda et al. suggested that anti-inflammatory mechanisms were involved in the antiepileptogenic effect of P. daemia extract. [Read the Full Post]

Effects and Mechanism of Action of PX-478 in Oxygen-Induced Retinopathy in Mice

19 | Jan 07 2021

Xiaoyan Pan et al. found that HIF-1α played a main role in OIR and could be considered a therapeutic target in OIR by suppressing downstream angiogenic factors, PX-478 decreasing the retinal avascular area and NV. [Read the Full Post]

Repurposing FDA Approved Drugs as JNK3 Inhibitor for Prevention of Neuroinflammation Induced by MCAO in Rats

16 | Jan 06 2021

Zikra Zulfiqar et al. demonstrated that the novel FDA-approved medications attenuate ischemic stroke-induced neuronal degeneration, possibly by inhibiting JNK3. [Read the Full Post]

Kinase activity-independent role of EphA2 in the regulation of M-phase progression

20 | Jan 04 2021

Yuichiro Kaibori et al. suggested that EphA2 regulated M-phase progression in a manner independent of its kinase activity. [Read the Full Post]

Synergistic Utilization of Necrostatin-1 and Z-VAD-FMK Efficiently Promotes the Survival of Compression-Induced Nucleus Pulposus Cells via Alleviating Mitochondrial Dysfunction

20 | Jan 03 2021

Songfeng Chen et al. found that the synergistic utilization of Necrostatin-1 and Z-VAD-FMK was a very worthwhile solution in preventing compression-mediated NP cells death, which might be largely attributed to restored mitochondrial function. [Read the Full Post]

Identification of SARS-CoV-2 3CL Protease Inhibitors by a Quantitative High-Throughput Screening

21 | Jan 02 2021

Wei Zhu et al. demonstrated a set of SARS-CoV-2 3CLpro inhibitors that might have potential for further clinical evaluation as part of drug combination therapies to treating COVID-19 patients and as starting points for chemistry optimization for new drug development. [Read the Full Post]

HDAC6 Degradation Inhibits the Growth of High-Grade Serous Ovarian Cancer Cells

19 | Jan 01 2021

Ahlam Ali et al. found that inhibition of HDAC6 catalytic activity with first generation HDAC6 inhibitors has limited efficacy as a monotherapy in HGSOC. [Read the Full Post]

A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury

26 | Dec 29 2020

Maria Kost-Alimova et al. suggested fostamatinib as a repurposing drug candidate for ALI. [Read the Full Post]

Gli affects the stemness and prognosis of epithelial ovarian cancer via homeobox protein NANOG

17 | Dec 28 2020

Huan Zhao et al. found that Gli and NANOG might be effective indicators of platinum resistance and prognosis in EOC. [Read the Full Post]

The phosphorylation of CHK1 at Ser345 regulates the phenotypic switching of vascular smooth muscle cells both in vitro and in vivo

15 | Dec 25 2020

Chen Xin et al. demonstrated that phosphorylation of CHK1 under DNA damage stress modulated VSMCs phenotypic switching. [Read the Full Post]

ScatLay: utilizing transcriptome-wide noise for identifying and visualizing differentially expressed genes

17 | Dec 24 2020

Thuy Tien Bui et al. provided a wider coverage of DE genes, and would likely pave way for finding more novel regulatory genes in future works. [Read the Full Post]

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

20 | 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

18 | 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]

Poziotinib suppresses ovarian cancer stem cell growth via inhibition of HER4-mediated STAT5 pathway

23 | Dec 15 2020

Heejin Lee et al. suggested that HER4 might be a promising therapeutic target for ovarian CSCs, and that poziotinib might be an effective therapeutic option for the prevention of ovarian cancer recurrence. [Read the Full Post]

Protein Kinase D1, Reduced in Human Pancreatic Tumors, Increases Secretion of Small Extracellular Vesicles From Cancer Cells That Promote Metastasis to Lung in Mice

19 | Dec 14 2020

Milena Armacki et al. found that human pancreatic ductal adenocarcinoma had reduced levels of PRKD1 compared with nontumor pancreatic tissues. [Read the Full Post]

Poziotinib Inhibits the Efflux Activity of the ABCB1 and ABCG2 Transporters and the Expression of the ABCG2 Transporter Protein in Multidrug Resistant Colon Cancer Cells

21 | Dec 14 2020

Yongchao Zhang et al. showed that poziotinib interacted with the ABCB1 and ABCG2 transporter, suggesting that poziotinib might increase the efficacy of certain chemotherapeutic drugs used in treating MDR CRC. [Read the Full Post]

Design, synthesis and evaluation of novel indirubin-based N-hydroxybenzamides, N-hydroxypropenamides and N-hydroxyheptanamides as histone deacetylase inhibitors and antitumor agents

22 | Dec 12 2020

Duong Tien Anh et.al found that the potential of the indirubin-hydroxamic acid hybrids and these compounds should be very promising for further development. [Read the Full Post]

Histone Deacetylase Inhibition Attenuates Aortic Remodeling in Rats under Pressure Overload

24 | Dec 12 2020

Hanna Jung et al. indicated that MGCD, an HDAC inhibitor, attenuated aortic remodeling in rats with TAC-induced pressure overload rats and might serve as a potential therapeutic target of antiaortic remodeling in pressure overload-induced hypertension-related diseases. [Read the Full Post]

Physical Nature of Substituent Effects in XH/π Interactions

19 | Dec 09 2020

Jacob W G Bloom et al. showed that the impact of substituents on XH/π interactions depended strongly on the identity of the XH group, and the strength of these effects increased with increasing polarization of the XH bond. [Read the Full Post]

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

20 | Dec 08 2020

Cristina Zahonero et al. confirmd that dacomitinib clearly affected receptor signaling in vivo and that its strong antitumoral effect was independent of the presence of mutant receptor isoforms although it could be affected by the PTEN status (as it was less effective in a PTEN-deleted GBM line). [Read the Full Post]

Novel miRNAs as Potential Regulators of PD-1/PD-L1 Immune Checkpoint, and Prognostic Value of MIR9-1 and MIR124-2 Methylation in Ovarian Cancer

26 | Dec 05 2020

N E Kushlinskii et al. suggested the role of inhibitors of the sPD-L1 immune checkpoint for five miRNAs (miR-124, miR-34b, miR-34c, miR-9, miR-339) and the possibility of using hypermethylated MIR9-1. [Read the Full Post]

NPM1 mutant maintains ULK1 protein stability via TRAF6-dependent ubiquitination to promote autophagic cell survival in leukemia

23 | Dec 04 2020

Yuting Tang et al. suggested that NPM1 mutant interacted with ULK1, and thus, maintained its protein stability, which was required for NPM1 mutant-mediated autophagic cell survival. [Read the Full Post]

Integrated pharmaco-proteogenomics defines two subgroups in isocitrate dehydrogenase wild-type glioblastoma with prognostic and therapeutic opportunities

24 | Dec 02 2020

Sejin Oh et al. guided GBM prognosis and precision treatment strategies. [Read the Full Post]

FXIIIa substrate peptide decorated BLZ945 nanoparticles for specifically remodeling tumor immunity

16 | 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

17 | 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

18 | 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]

Co-targeting PIM and PI3K/mTOR using multikinase inhibitor AUM302 and a combination of AZD-1208 and BEZ235 in prostate cancer

27 | Nov 22 2020

Sabina Luszczak et al. believed that a co-targeting approach was a viable therapeutic strategy that should be developed further in pre-clinical studies. [Read the Full Post]

An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development

23 | Nov 22 2020

Sunita Shankar et al. supported a biphasic model of pancreatic cancer development: an AGO2-independent early phase of PanIN formation reliant on EGFR-RAS signaling, and an AGO2-dependent phase wherein the mutant KRAS-AGO2 interaction was critical for PDAC progression. [Read the Full Post]

Discovery of a Potent and Selective BCL-XL Inhibitor with in Vivo Activity

20 | Nov 20 2020

Zhi-Fu Tao et al. found that A-1155463 represented an excellent tool molecule for studying BCL-XL biology as well as a productive lead structure for further optimization. [Read the Full Post]

Direct Activation of BAX by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia

0 | Nov 19 2020

Denis E Reyna et al. provided proof-of-concept for direct BAX activation as a treatment strategy in AML. [Read the Full Post]

RIP3 dependent NLRP3 inflammasome activation is implicated in acute lung injury in mice

23 | Nov 18 2020

Jingxian Chen et al. showed that RIP3 participated in the NLRP3 inflammasome activation in infiltrating macrophages in ALI induced by LPS. [Read the Full Post]

Rapalogues as hCES2A Inhibitors: In Vitro and In Silico Investigations

32 | Nov 17 2020

Cheng-Cheng Shi et al. demonstrated that several marketed rapalogues were potent and specific hCES2A inhibitors, and these agents could serve as leading compounds for the development of more efficacious hCES2A inhibitors to modulate the pharmacokinetic profiles and toxicity of hCES2A-substrate drugs (such as the anticancer agent irinotecan). [Read the Full Post]

Suppressor of Ty 16 promotes lung cancer malignancy and is negatively regulated by miR-1227-5p

27 | Nov 15 2020

Lu Yang et al. indicated that Spt16 was likely to be an essential regulator for lung cancer malignancy and was negatively regulated by miR-1227-5p. [Read the Full Post]

Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhage

40 | Nov 04 2020

Da-Qiang Ke et al. suggested that caspase-8 inhibition alleviated subarachnoid hemorrhage-induced brain injuries by suppressing inflammation. [Read the Full Post]

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

34 | 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

36 | 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]

Histone deacetylase 6 inhibition mitigates renal fibrosis by suppressing TGFß and EGFR signaling pathways in obstructive nephropathy

36 | Oct 28 2020

Xingying Chen et al. indicated that HDAC6 inhibition could attenuate development of renal fibrosis by suppression of TGFb1 and EGFR signaling, and suggested that HDAC6 would be a potential therapeutic target for the treatment of renal fibrosis. [Read the Full Post]

Cadmium induces apoptosis via generating reactive oxygen species to activate mitochondrial p53 pathway in primary rat osteoblasts

35 | Oct 27 2020

Jiaming Zheng et al. indicated that Cd could induce apoptosis in osteoblasts by increasing the generation of ROS and activating the mitochondrial p53 signaling pathway, and this mechanism required the transcriptional activation of p53. [Read the Full Post]

Antianemia Drug Roxadustat (FG-4592) Protects Against Doxorubicin-Induced Cardiotoxicity by Targeting Antiapoptotic and Antioxidative Pathways

38 | Oct 26 2020

Guangfeng Long et al.found that the protective effect of FG-4592 on DOX-induced cardiotoxicity possibly through upregulating HIF-1α and its target genes antagonizing apoptosis and oxidative stress. [Read the Full Post]

The therapeutic effect of the BRD4-degrading PROTAC A1874 in human colon cancer cells

30 | Oct 26 2020

An-Cheng Qin et al.thought that A1874-induced anti-colon cancer cell activity was more potent than the known BRD4 inhibitors (JQ1, CPI203, and I-BET151). [Read the Full Post]

mTOR Inhibition Ablates Cisplatin-Resistant Salivary Gland Cancer Stem Cells

31 | Oct 25 2020

T Nakano et al.suggested that a combination of an mTOR inhibitor and platinum-based chemotherapy might be beneficial to patients with salivary gland mucoepidermoid carcinoma. [Read the Full Post]

Piceatannol reduces resistance to statins in hypercholesterolemia by reducing PCSK9 expression through p300 acetyltransferase inhibition

35 | Oct 25 2020

Hyo-Jin Kim et al. indicated that PT was a new nutraceutical candidate to reduce the statin resistance and tolerance that occured in patients with hypercholesterolemia. [Read the Full Post]

Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4

25 | Oct 19 2020

Bao-You Fan et al.suggested that GPX4 inhibition induceed ferroptosis in oligodendrocytes, and that liproxstatin-1 was a potent inhibitor of ferroptosis. [Read the Full Post]

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

35 | 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]

Radiosensitization by Kinase Inhibition Revealed by Phosphoproteomic Analysis of Pancreatic Cancer Cells

29 | Oct 16 2020

Svenja Wiechmann et al.improved the understanding of radioresistance and provided avenues for developing radiotherapeutic strategies. [Read the Full Post]

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

38 | 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]

A study of human leukocyte antigen-haploidentical hematopoietic stem cells transplantation combined with allogenic mesenchymal stem cell infusion for treatment of severe aplastic anemia in pediatric and adolescent patients

56 | Sep 29 2020

Li Ding et al. suggested that cotransplantation of HLA-haploidentical HSC and allogenic mesenchymal stem cell might provide an effective and safe treatment for children and adolescents with SAA who lacked matched donors. [Read the Full Post]

Transient Receptor Potential Ankyrin 1 (TRPA1) is Up-Regulated in Response to Lipopolysaccharide via P38/ Mitogen-Activated Protein Kinase (MAPK) in Dental Pulp Cells and Promotes Mineralization

54 | Sep 22 2020

Kento Tazawa et al. demonstrated that LPS stimulation induced TRPA1 via the NO-p38 MAPK signaling pathway and TRPA1 agonists promoted differentiation or mineralization of dental pulp cells. [Read the Full Post]

Mcl-1 targeting strategies unlock the proapoptotic potential of TRAIL in melanoma cells

41 | Sep 19 2020

Zina Sarif et al. indicated a high relevance of Mcl-1 targeting also in melanoma therapy. [Read the Full Post]

Flavonoids Restore Platinum Drug Sensitivity to Ovarian Carcinoma Cells in a Phospho-ERK1/2-Dependent Fashion

44 | Sep 15 2020

Yifat Koren Carmi et al. showed the potential of combining flavonoids with standard therapy to restore drug sensitivity to OC cells and overcomed TME-mediated platinum drug resistance. [Read the Full Post]

FLT3 inhibition upregulates HDAC8 via FOXO to inactivate p53 and promote maintenance of FLT3-ITD+ acute myeloid leukemia

54 | Sep 14 2020

Jun Long et al. demonstrated that HDAC8 upregulation was an important mechanism to resist TKIs and promote leukemia maintenance and suggested that combining HDAC8 inhibition with TKI treatment could be a promising strategy to treat FLT3-ITD+ AML and other tyrosine kinase mutation-harboring leukemias. [Read the Full Post]

Quizartinib for the treatment of acute myeloid leukemia

49 | Sep 13 2020

Alejandro Garcia-Horton et al. reviewed the mechanism of action, pharmacology, clinical efficacy, and safety of quizartinib, a FLT3 inhibitor, for the treatment of acute myeloid leukemia. [Read the Full Post]

Anti-inflammatory Effect of AZD6244 on Acrolein-Induced Neuroinflammation

50 | Sep 10 2020

Wen-Chien Ho et al. suggested that ERK inhibition may be a neuroprotective target against acrolein-induced neuroinflammation in the CNS neurodegenerative diseases. [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

54 | 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]

Mast cells (MCs) induce ductular reaction mimicking liver injury in mice via MC-derived TGF-β1 signaling

63 | Sep 02 2020

Konstantina Kyritsi et al. demonstrated that reintroduction of MCs mimics cholestatic liver injury and MC-derived TGF-β1 might be a target in chronic cholestatic liver disease. [Read the Full Post]

Protein Kinase CK2 in Cancer Energetics

71 | Aug 27 2020

Eduardo Silva-Pavez et al. proposed that the specific inhibition of CK2 might lead to a catastrophic death of cancer cells, which could become a feasible therapeutic strategy to beat this devastating disease. [Read the Full Post]

Casein kinase 2 inhibitor CX-4945 elicits an anti-Warburg effects through the downregulation of TAp73 and inhibits gastric tumorigenesis

66 | Aug 27 2020

Shengli Tang et al. suggested that CX-4945 elicited an anti-Warburg effects in gastric cancer overexpressing Tap73 and inhibited gastric tumorigenesis. [Read the Full Post]

Cannabinoid 1 Receptor Antagonists Play a Neuroprotective Role in Chronic Alcoholic Hippocampal Injury Related to Pyroptosis Pathway

53 | Aug 26 2020

Dingang Zhang et al. indicated that cannabinoid receptors were regulated during this process, which suggested promising therapeutic strategies against alcohol-induced neurotoxicity through pharmacologic inhibition of CB1R. [Read the Full Post]

Pyroptosis is involved in the inhibitory effect of FL118 on growth and metastasis in colorectal cancer

52 | Aug 26 2020

Zhenxue Tang et al. found that FL118 restrained the growth and metastasis of colorectal cancer by inducing NLRP3-ASC-Caspase-1 mediated pyroptosis, which provided important evidence in the study on the role of pyroptosis and different tumors. [Read the Full Post]

The mTORC1 inhibitor rapamycin and the mTORC1/2 inhibitor AZD2014 impair the consolidation and persistence of contextual fear memory

57 | Aug 23 2020

Phillip E MacCallum et al. indicated the need to further understand the role of mTORC1/2 kinase activity in the molecular mechanisms underlying memory processing and also demonstrated that the effects of mTORC1 inhibition at different timepoints well after learning on memory consolidation and persistence. [Read the Full Post]

Resurrecting a p53 peptide activator - An enabling nanoengineering strategy for peptide therapeutics

84 | Aug 20 2020

Wangxiao He et al. proposed that this clinically viable drug delivery strategy could be applied not only to peptide activators of p53 for cancer therapy, but also to peptide therapeutics in general aimed at targeting intracellular protein-protein interactions for disease intervention. [Read the Full Post]

F-box protein FBXO31 modulates apoptosis and epithelial-mesenchymal transition of cervical cancer via inactivation of the PI3K/AKT-mediated MDM2/p53 axis

58 | Aug 19 2020

Keying Liu et al. revealed that FBXO31 down-regulated CC progression by blocking the PI3K/AKT-mediated MDM2/p53 axis, suggesting that FBXO31 might serve as a promising therapeutic target for CC treatment. [Read the Full Post]

GSK3β-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration

126 | Aug 19 2020

Youpei Wang et al. provided a new regulatory mechanism by which GSK3β negatively regulated human skin fibroblast cell migration. [Read the Full Post]

A phase 2 trial of buparlisib in patients with platinum-resistant metastatic urothelial carcinoma

53 | Aug 17 2020

Victor McPherson et al. proposed that given the modest clinical activity and substantial toxicity of buparlisib, future trials of PI3K inhibitors in patients with UC should focus on isoform-selective PI3K inhibitors in genomically selected patients. [Read the Full Post]

The role of CUDC-907, a dual phosphoinositide-3 kinase and histone deacetylase inhibitor, in inhibiting proliferation of adult T-cell leukemia

60 | Aug 17 2020

Chie Ishikawa et al. showed that CUDC-907 might be a potential therapeutic agent for ATL. [Read the Full Post]

Identification of MYC as an antinecroptotic protein that stifles RIPK1-RIPK3 complex formation

75 | Aug 16 2020

Daehyeon Seong et al. found that MYC-mediated suppression of necroptosis was a mechanism of necroptosis resistance in cancer, and approaches targeting MYC to induce necroptosis represent an attractive therapeutic strategy for cancer. [Read the Full Post]

Macrophages confer resistance to PI3K inhibitor GDC-0941 in breast cancer through the activation of NF-κB signaling

104 | Aug 13 2020

Muhammad Waqas Usman et al. suggested macrophages in microenvironment may contribute to the resistance of breast cancer cells to PI3K inhibition and reveal a new combination paradigm to improve the efficacy of PI3K-targeted therapy. [Read the Full Post]

A PI3K- and GTPase-independent Rac1-mTOR mechanism mediates MET-driven anchorage-independent cell growth but not migration

73 | Aug 12 2020

Alexia Hervieu et al. revealed a GTPase-independent role for Rac1 in mediating a PI3K-independent MET-to-mTOR pathway and suggested alternative or combined strategies that might overcome resistance to RTK inhibitors in patients with cancer. [Read the Full Post]

Targeting p53 for the treatment of cancer

57 | Aug 11 2020

Michael J Duffy et al. indicated that it was likely to usher in a new era in cancer treatment, especially as p53 dysfunction is so prevalent in human cancers if any of the compounds currently being evaluated in clinical trials be shown to have efficacy [Read the Full Post]

Giardia duodenalis induces extrinsic pathway of apoptosis in intestinal epithelial cells through activation of TNFR1 and K63 de-ubiquitination of RIP1 in vitro

84 | Aug 11 2020

Lin Liu et al. suggested that Giardia trophozoite stimulation could activate CASP3/8 signaling pathways via activation of TNFR1 and K63 de-ubiquitination of RIP1 caused by up-regulated expressions of CYLD and A20, and promoted Caco-2 cell apoptosis. [Read the Full Post]

Antiviral activity of PLK1-targeting siRNA delivered by lipid nanoparticles in HBV-infected hepatocytes

89 | Aug 10 2020

Adrien Foca et al. emphasized that a specific PLK1 inhibition could help in achieving an improved HBsAg loss in CHB patients, likely in combination with other HBsAg-targeting strategies. [Read the Full Post]

Targeting BCL-2 proteins in pediatric cancer: Dual inhibition of BCL-X L and MCL-1 leads to rapid induction of intrinsic apoptosis

57 | Aug 09 2020

Sarah Kehr et al. demonstrated the potency of A-1331852/S63845 in pediatric solid tumor cells and to describe the molecular mechanisms of A-1331852/S63845 co-treatment underlining the potential of BCL-XL and MCL-1 inhibition as treatment regime. [Read the Full Post]

Selumetinib for plexiform neurofibromas in neurofibromatosis type 1: a single-institution experience

59 | Aug 09 2020

Vera Espírito Santo et al. showed that the drug was associated with clinical and radiological improvement. [Read the Full Post]

Severe COVID-19 in a renal transplant recipient: A focus on pharmacokinetics

73 | Aug 08 2020

Soufian Meziyerh et al. aimed to achieve increased awareness and improved management of drug-drug interactions associated with the various treatment options for COVID-19 in renal transplant patients. [Read the Full Post]

Regorafenib for Metastatic Colorectal Cancer: An Analysis of a Registry-Based Cohort of 555 Patients

134 | Aug 06 2020

Alena Novakova-Jiresova ETAL. found that regorafenib was a safe and active treatment option for a subgroup of patients with mCRC who were progressing after other systemic therapies and maintain good performance status. [Read the Full Post]

Gemcitabine combined with cisplatin vs. taxane, cisplatin, and fluorouracil in the treatment of locally advanced nasopharyngeal carcinoma: a retrospective case-control study

103 | Aug 04 2020

Y-M Huang et al. showed that the clinical efficacy of the GP regimen combined with CCRT for the treatment of locoregionally advanced NPC might be better than that of the TPF regimen. [Read the Full Post]

Alcohol-induced CYP2E1, Mitochondrial Dynamics and Retrograde Signaling in Human Hepatic 3D Organoids

105 | Aug 03 2020

Rajesh Angireddy et al. presented a mechanistic link between CYP2E1 function and alcohol mediated mitochondrial dysfunction, retrograde signaling, and activation of hepatic steatosis in a 3D organoid system that closely recapitulated the in vivo liver response. [Read the Full Post]

In Vitro and In Vivo Efficacy of DNA Damage Repair Inhibitor Veliparib in Combination with Artesunate against Echinococcus granulosus

96 | Aug 02 2020

Y F Li et al. demonstrated that AS or AS in combination with Veliparib was effective for treating CE, especially the combination group. [Read the Full Post]

Evaluation of the Efficacy and Safety of PARP Inhibitors in Advanced-Stage Epithelial Ovarian Cancer

101 | Aug 02 2020

Yifan Jiang et al. found that PARP inhibitors were an effective and well-tolerated treatment for patients with advanced-stage epithelial ovarian cancer. [Read the Full Post]

Induction of ferroptosis in response to graphene quantum dots through mitochondrial oxidative stress in microglia

81 | Jul 26 2020

Tianshu Wu et al. not only provided new insights in the GQDs-induced cell damage performed in multiple types of cell death, but also in the influence of chemical modification on the toxicity of GQDs. [Read the Full Post]

Cigarette smoking is associated with high level of ferroptosis in seminal plasma and affects semen quality

89 | Jul 26 2020

Zhanhui Ou et al. found that cigarette smoking was associated with high level of ferroptosis in seminal plasma and affect semen quality. [Read the Full Post]

Polo-like kinase 1 as a promising diagnostic biomarker and potential therapeutic target for hepatocellular carcinoma

95 | Jul 22 2020

Eman H Yousef et al. found that Polo-like kinase 1 might be a potential biomarker for hepatocellular carcinoma diagnosis and follow-up during treatment with chemotherapies. [Read the Full Post]

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

156 | Jul 22 2020

Cristina Saura et al.showed that N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed. [Read the Full Post]

DrugSniper, a Tool to Exploit Loss-Of-Function Screens, Identifies CREBBP as a Predictive Biomarker of VOLASERTIB in Small Cell Lung Carcinoma (SCLC)

87 | Jul 21 2020

Fernando Carazo et al. showed the potential of genome-wide loss-of-function screens to identify new personalized therapeutic hypotheses in SCLC and potentially in other tumors, which was a valuable starting point for further drug development and drug repositioning projects. [Read the Full Post]

Alisertib plus induction chemotherapy in previously untreated patients with high-risk, acute myeloid leukaemia: a single-arm, phase 2 trial

121 | Jul 17 2020

Andrew M Brunner et al. suggested that alisertib combined with induction chemotherapy is active and safe in previously untreated patients with high-risk acute myeloid leukaemia. [Read the Full Post]

Phase 1 trial of carfilzomib (PR-171) in combination with vorinostat (SAHA) in patients with relapsed or refractory B-cell lymphomas

135 | Jul 16 2020

Beata Holkova et al. showed a decrease in NF-κB activation and an increase in Bim levels in some patients, but these changes did not correlate with clinical response. [Read the Full Post]

Advanced bioinformatics rapidly identifies existing therapeutics for patients with coronavirus disease-2019 (COVID-19)

129 | Jul 15 2020

Jason Kim et al. highlighted the potential use of two bioinformatics technologies to rapidly discover existing therapeutic agents that warranted further investigation for established and emerging disease processes. [Read the Full Post]

The BCL-2 family protein inhibitor ABT-737 as an additional tool for the treatment of EBV-associated post-transplant lymphoproliferative disorders

97 | Jul 14 2020

Aude Robert et al. suggested that the use of agents targeting BCL-2, either alone or in combination with other conventional drugs, represented a novel promising approach for post-transplant EBV-positive B lymphoproliferative disorders. [Read the Full Post]

Protein Acetylation Derepresses Serotonin Synthesis to Potentiate Pancreatic Beta-Cell Function Through HDAC1-PKA-Tph1 Signaling

155 | Jul 13 2020

Yuqing Zhang et al. highlighted a novel role of HDAC1-PKA-Tph1 signaling in governing β-cell functional compensation by derepressing serotonin synthesis. [Read the Full Post]

Lenvatinib and Sorafenib for Differentiated Thyroid Cancer After Radioactive Iodine: A Systematic Review and Economic Evaluation

160 | Jul 13 2020

Nigel Fleeman et al.showed that compared with placebo/BSC, treatment with lenvatinib or sorafenib results in an improvement in PFS, objective tumour response rate and possibly OS, but dose modifications were required to treat AEs. [Read the Full Post]

In Vitro Assessment of the Genotoxic Hazard of Novel Hydroxamic Acid- And Benzamide-Type Histone Deacetylase Inhibitors (HDACi)

171 | Jul 12 2020

Annabelle Friedrich et al. found that KSK64 revealed the highest genotoxic hazard and DDR stimulating potential, while TOK77 and MPK77 showed the lowest DNA damaging capacity. [Read the Full Post]

Histone Deacetylase Inhibition Prevents the Growth of Primary and Metastatic Osteosarcoma

183 | Jul 07 2020

Jeremy J McGuire et al. provided rationale for clinical trials in osteosarcoma patients using the approved therapies panobinostat or romidepsin. [Read the Full Post]

Discovery of Novel Dual c-Met/HDAC Inhibitors as a Promising Strategy for Cancer Therapy

125 | Jul 07 2020

Hao Hu et al. provided an efficient strategy for discovery of multitarget antitumor drugs. [Read the Full Post]

Combination BET Family Protein and HDAC Inhibition Synergistically Elicits Chondrosarcoma Cell Apoptosis Through RAD51-Related DNA Damage Repair

163 | Jul 06 2020

Songwei Huan et al. disclosed that BET and HDAC inhibition synergistically inhibited cell growth and induced cell apoptosis through a mechanism that involved the suppression of RAD51-related HR DNA repair in chondrosarcoma cells. [Read the Full Post]

Efficacy of Gefitinib Combined With 125 I Radioactive Particles in the Treatment of Transplanted Lung Cancer Tumors in Nude Mice

132 | Jul 02 2020

Chaojie Li et al. found that Gefitinib combined with 125I radioactive particles brachytherapy could significantly inhibit tumor growth. [Read the Full Post]

MEK Inhibitors Combined With Programmed Cell death-1 Blockade Immunotherapy for Metastatic Uveal Melanoma: Is It Warranted?

83 | Jun 30 2020

Anais Zanella et al. highlighted the need to evaluate the safety and efficacy of new treatment options such as MEKi and anti-PD-1 for mUM. [Read the Full Post]

A New Compound With Increased Antitumor Activity by Cotargeting MEK and Pim-1

85 | Jun 30 2020

Yanan Li et al. uncovered a new MEK inhibitor KZ-02 with significantly enhanced antitumor activity by co-targeting MEK and Pim-1. [Read the Full Post]

Targeting BCL-2 Proteins in Pediatric Cancer: Dual Inhibition of BCL-X L and MCL-1 Leads to Rapid Induction of Intrinsic Apoptosis

83 | Jun 29 2020

Sarah Kehr et al. demonstrated the potency of A-1331852/S63845 in pediatric solid tumor cells and to describe the molecular mechanisms of A-1331852/S63845 co-treatment underlining the potential of BCL-XL and MCL-1 inhibition as treatment regime. [Read the Full Post]

Volumetric Absorptive Microsampling (VAMS) for Assaying Immunosuppressants From Venous Whole Blood by LC-MS/MS Using a Novel Atmospheric Pressure Ionization Probe (UniSpray™)

100 | Jun 28 2020

Lucía Paniagua-González et al. showed that venous blood VAMS concentrations were correlated to those found in the original liquid venous blood, proving that the VAMS material itself will not bias blood drug concentrations. [Read the Full Post]

Notch Signaling Pathway Is a Potential Therapeutic Target for Extracranial Vascular Malformations

0 | Jun 22 2020

Reema B Davis et al. provided further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations. [Read the Full Post]

Effects of the PI3K/Akt Signaling Pathway on the Apoptosis of Early Host Cells Infected With Eimeria Tenella

194 | Jun 21 2020

Xuesong Zhang et al. investigated the role of PI3K/Akt signaling pathway on host cell apoptosis in the early infection of Eimeria tenella,the early development of E. tenella could inhibit host cell apoptosis by downregulating the Caspase-3 activity. [Read the Full Post]

A Systematic Review of the Studies That Evaluate the Performance of the DAPT Score

157 | Jun 21 2020

Chun Shing Kwok et al. showd that the DAPT score had modest predictive value for ischemic and bleeding outcomes.A prospective randomized controlled trial was needed to evaluate the clinical benefits of utilising the DAPT score in guiding continued DAPT therapy beyond 1 year. [Read the Full Post]

Inhibition of Aurora Kinase A by Alisertib Reduces Cell Proliferation and Induces Apoptosis and Autophagy in HuH-6 Human Hepatoblastoma Cells

127 | Jun 19 2020

Jingyi Tan et al. suggested that AURKA may be a novel therapeutic target and ALS a potential therapeutic drug for the treatment of HB. [Read the Full Post]

DAPT Score and the Impact of Ticagrelor Monotherapy During the Second Year After PCI

175 | Jun 18 2020

Ply Chichareon et al. found that the DAPT score can stratify ischemic but not bleeding risk in a contemporary PCI population during the second year. [Read the Full Post]

Prediction of Therapeutic Outcome and Survival in a Transgenic Mouse Model of Pancreatic Ductal Adenocarcinoma Treated With Dendritic Cell Vaccination or CDK Inhibitor Using MRI Texture: A Feasibility Study

126 | Jun 17 2020

Aydin Eresen et al. demonstrated that MRI texture features had great potential to generate diagnosis and prognosis models for monitoring early treatment response following dinaciclib drug or DC vaccine treatment and also predicting histopathological tumor markers and long-term clinical outcomes. [Read the Full Post]

Revealing the Selective Mechanisms of Inhibitors to PARP-1 and PARP-2 via Multiple Computational Methods

132 | Jun 17 2020

Hongye Hu et al. provided new insights about how inhibitors specifically bound to PARP-1 over PARP-2, which might help facilitate the design of highly selective PARP-1 inhibitors in the future. [Read the Full Post]

Cooperativity Between Orthosteric Inhibitors and Allosteric Inhibitor 8-Anilino-1-Naphthalene Sulfonic Acid (ANS) in Cyclin-Dependent Kinase 2

128 | Jun 16 2020

Erik B Faber et al. detailed the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increased the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. [Read the Full Post]

Network Indirect Comparison of 3 BRAF + MEK Inhibitors for the Treatment of Advanced BRAF Mutated Melanoma

112 | Jun 12 2020

F Consoli et al. suggested a similar efficacy and a slightly different safety profile, related to specific molecular properties of the three different BRAF and MEK inhibitors currently approved in the management of advanced MM. [Read the Full Post]

The Application of Ferroptosis in Diseases

92 | Jun 09 2020

Yangmin Qiu et al. summarized the mechanism of ferroptosis regulation and relevance to pathological physiology. [Read the Full Post]

TGF-β1-mediated Repression of SLC7A11 Drives Vulnerability to GPX4 Inhibition in Hepatocellular Carcinoma Cells

104 | Jun 09 2020

Do Hyung Kim et al. showed that TGF-β1 repressed xCT expression via Smad3 activation and enhanced lipid peroxidation in hepatocellular carcinoma cells with an early TGF-β1 signature, which would benefit from the targeting of GPX4. [Read the Full Post]

Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats

205 | Jun 05 2020

Marco Malavolta et al. explored the idea that an exacerbated inflammatory response, in particular that mediated by IL-6, migtht drive the deleterious consequences of the infection. [Read the Full Post]

HMGB1-induced Aberrant Autophagy Contributes to Insulin Resistance in Granulosa Cells in PCOS

127 | Jun 04 2020

Chuyue Zhang et al. indicated that increased HMGB1 contributes to IR development in granulosa cells of PCOS patients, which was associated with exacerbation of autophagy by HMGB1. Control of HMGB1 production might be benefical for the improvement of insulin sensitivity in granulosa cells in PCOS. [Read the Full Post]

Berberine Represses Human Gastric Cancer Cell Growth in Vitro and in Vivo by Inducing Cytostatic Autophagy via Inhibition of MAPK/mTOR/p70S6K and Akt Signaling Pathways

101 | Jun 04 2020

Qiang Zhang et al. indicated that berberine repressed human gastric cancer cell growth in vitro and in vivo by inducing cytostatic autophagy via inhibition of MAPK/mTOR/p70S6K and Akt, and provided a molecular basis for the treatment of gastric cancer. [Read the Full Post]

Cell Cycle Arrest and Apoptosis Are Not Dependent on p53 Prior to p53-dependent Embryonic Stem Cell Differentiation

257 | Jun 02 2020

Sushil K Jaiswal et al. found that the multiple roles of p53 in cell cycle regulation and apoptosis were first acquired during pluripotent stem cell differentiation. [Read the Full Post]

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

145 | 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]

Inhibition of Apoptosis by Caspase Inhibitor Z-VAD-FMK Improves Cryotolerance of in Vitro Derived Bovine Embryos

0 | May 26 2020

Maria Elena Pero et al. found that the addition of 20 μM Z-VAD-FMK during vitrification/warming and post-warming culture partially inhibited cryopreservation-induced apoptosis by reducing the level of active caspase 3, suggesting a potential used as an additive to ameliorate the efficiency of embryo cryopreservation in cattle, critical for a further diffusion of IVEP technology in the field. [Read the Full Post]

ABT-263 Exhibits Apoptosis-Inducing Potential in Oral Cancer Cells by Targeting C/EBP-homologous Protein

119 | May 20 2020

In-Hyoung Yang et al. provided evidence that ABT-263 may serve as an effective therapeutic agent for the treatment of human oral cancer. [Read the Full Post]

Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic.

0 | May 19 2020

Galiana I et al. supported targeted senolysis as a new therapeutic opportunity to improve outcomes in breast cancer patients [Read the Full Post]

Endoplasmic reticulum stress mediates resistance to BCL-2 inhibitor in uveal melanoma cells

118 | May 16 2020

Bellini L et al. identified ABT-263 as a valid therapeutic option for patients suffering from uveal melanoma. [Read the Full Post]

Discovery of IAP-recruiting BCL-XL PROTACs as potent degraders across multiple cancer cell lines

119 | May 16 2020

Zhang X et al. expanded the anti-tumor spectra of BCL-XL degraders and further highlight the importance of selecting suitable E3 members to achieve effective cellular activity. [Read the Full Post]

Toll-like Receptor 4 Deficiency Aggravates Airway Hyperresponsiveness and Inflammation by Impairing Neutrophil Apoptosis in a Toluene Diisocyanate-Induced Murine Asthma Model.

100 | May 15 2020

Chen S et al. indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation. [Read the Full Post]

"Direct to Drug" screening as a precision medicine tool in multiple myeloma.

81 | May 14 2020

Bonolo de Campos C et al. found that this "direct to drug" screening resource, paired with functional genomics, had the potential to successfully direct appropriate individualized therapeutic approaches in MM and to enrich clinical trials for likely responders. [Read the Full Post]

Dual targeting of BCL2 and MCL1 rescues myeloma cells resistant to BCL2 and MCL1 inhibitors associated with the formation of BAX/BAK hetero-complexes

85 | May 12 2020

Seiller C et al. found that BCLXL remains a major resistant factor of cell death induced by this combination. [Read the Full Post]

FBP1 loss disrupts liver metabolism and promotes tumorigenesis through a hepatic stellate cell senescence secretome

95 | May 09 2020

Li F et.al provided genetic evidence for FBP1 as a metabolic tumour suppressor in liver cancer and establish a critical crosstalk between hepatocyte metabolism and HSC senescence that promotes tumour growth. [Read the Full Post]

Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic

94 | May 08 2020

Galiana I et al. supported targeted senolysis as a new therapeutic opportunity to improve outcomes in breast cancer patients. [Read the Full Post]

Necrostatin-1 protects C2C12 myotubes from CoCl2-induced hypoxia

104 | May 03 2020

Chen R et al. suggested that Nec‑1 protected C2C12 myotubes under conditions of CoCl2-induced hypoxia. [Read the Full Post]

Caspase-3 Inhibitor Z-DEVD-FMK Enhances Retinal Ganglion Cell Survival and Vision Restoration After Rabbit Traumatic Optic Nerve Injury

140 | Apr 28 2020

Yuanyuan Liu et al. showed the caspase-3 inhibitor Z-DEVD-FMK is neuroprotective by inhibiting RGCs apoptosis when injected 30 min after optic nerve damage and significantly promotes restoration of vision. A controlled clinical trial is now needed to evaluate the efficacy and safety of Z-DEVD-FMK in humans. [Read the Full Post]

Multiple myeloma with 1q21 amplification is highly sensitive to MCL-1 targeting

0 | Mar 29 2020

Slomp A et al. indicated that amplification of 1q21 identifies an MM subset highly sensitive to MCL-1 inhibitor treatment and can be used as a predictive marker to guide selection of therapy. [Read the Full Post]

An in vitro assay for biomarker discovery and dose prediction applied to ibrutinib plus venetoclax treatment of CLL

96 | Feb 27 2020

Eide CA et al. suggested that IBR + VEN may represent an effective therapeutic option for patients with AML. [Read the Full Post]

Venetoclax, a BCL-2 Inhibitor, Enhances the Efficacy of Chemotherapeutic Agents in Wild-Type ABCG2-Overexpression-Mediated MDR Cancer Cells

103 | Feb 27 2020

Wang JQ et al. provided useful guidance in combination therapy against wild-type ABCG2-mediated MDR cancer in clinical practice. [Read the Full Post]

Multiple myeloma with 1q21 amplification is highly sensitive to MCL-1 targeting

123 | Feb 14 2020

Slomp A et al. indicated that amplification of 1q21 identifies an MM subset highly sensitive to MCL-1 inhibitor treatment and can be used as a predictive marker to guide selection of therapy. [Read the Full Post]

L-Cystathionine Protects against Homocysteine-Induced Mitochondria-Dependent Apoptosis of Vascular Endothelial Cells

111 | Feb 13 2020

Wang X et al. indicated that L-cystathionine could protect against homocysteine-induced mitochondria-dependent apoptosis of HUVECs. [Read the Full Post]

Venetoclax in acute myeloid leukemia - current and future directions

127 | Feb 11 2020

Lachowiez C et al. provided biological and clinical rationale for current venetoclax based treatments in AML, addresses common adverse events encountered with venetoclax based therapy, and explores emerging clinical data regarding combinations of novel targeted therapeutics used in conjunction with venetoclax for the treatment of AML. [Read the Full Post]

Anticancer drug candidate CBL0137, which inhibits histone chaperone FACT, is efficacious in preclinical orthotopic models of temozolomide-responsive and -resistant glioblastoma

187 | Feb 05 2020

Barone TA et al. indicated that CBL0137 targets GBM according to its proposed mechanism of action, crosses the blood-brain barrier, and is efficacious in both TMZ-responsive and -resistant orthotopic models, making it an attractive new therapy for GBM. [Read the Full Post]

Proteomic Analysis of an Induced Pluripotent Stem Cell Model Reveals Strategies to Treat Juvenile Myelomonocytic Leukemia

176 | Feb 05 2020

Pearson S et al. demonstrated these small molecular inhibitors, JQ1 and CBL0137, preferentially extinguish primitive hematopoietic cells from sporadic JMML patients as opposed to cells from healthy individuals. [Read the Full Post]

Isoflavones Isolated from the Seeds of Millettia ferruginea Induced Apoptotic Cell Death in Human Ovarian Cancer Cells

175 | Jan 18 2020

Wang YY et al. suggested that DMI induced apoptotic cell death through the intrinsic pathway via ROS production, while ferrugone stimulated the extrinsic pathway in human ovarian cancer cells. [Read the Full Post]

Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties

0 | Jan 12 2020

Lawrence CP and Chow SC demonstrated that both z-VAD-FMK and z-IETD-FMK are immunosuppressive in vitro and inhibit T cell proliferation without blocking the processing of caspase-8 and caspase-3. [Read the Full Post]

P53 inhibitor pifithrin-α prevents the renal tubular epithelial cells against injury

381 | Jan 02 2020

Shen YL et al. indicated that pifithrin-α can facilitate the progression of renal tubular epithelial cells through G2/M phase, protecting them against injury. [Read the Full Post]

Sesamin suppresses NSCLC cell proliferation and induces apoptosis via Akt/p53 pathway

196 | Jan 02 2020

Chen Y et al. demonstrated that sesamin suppresses NSCLC cell proliferation by induction of G1 phase cell cycle arrest and apoptosis via Akt/p53 pathway. Therefore, sesamin may be a promising adjuvant treatment for NSCLC therapy. [Read the Full Post]

On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death

0 | Dec 23 2019

Zilka O et al. demonstrated that potent RTAs subvert ferroptosis and suggest that lipid peroxidation (autoxidation) may play a central role in the process. [Read the Full Post]

CDK5 Inhibitor Downregulates Mcl-1 and Sensitizes Pancreatic Cancer Cell Lines to Navitoclax

146 | Dec 13 2019

Kour S et al. reported the discovery of an aminopyrazole, 2-([1,1'-biphenyl]-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)acetamide (analog 24), which selectively inhibited cyclin-dependent kinase (CDK) 5 over CDK2 in cancer cell lines. [Read the Full Post]

MCL-1 antagonism enhances the anti-invasive effects of dasatinib in pancreatic adenocarcinoma

133 | Nov 25 2019

Castillo L et al. suggested that MCL-1 antagonism, while reducing cell viability, may have an additional benefit in increasing the antimetastatic efficacy of dasatinib for the treatment of PDAC. [Read the Full Post]

Isovitexin Suppresses Cancer Stemness Property And Induces Apoptosis Of Osteosarcoma Cells By Disruption Of The DNMT1/miR-34a/Bcl-2 Axis

128 | Nov 23 2019

Liang X et al. suggested that ISOV-mediated epigenetic regulation involved the DNMT1/miR-34a/Bcl-2 axis and caused the suppression of stemness and induction of apoptosis in the spheres derived from OS cells. The data indicated that ISOV exhibited a novel efficient potential for the treatment of OS. [Read the Full Post]

An integrative pharmacogenomics analysis identifies therapeutic targets in KRAS-mutant lung cancer

234 | Nov 07 2019

Wang H et al. developed a genotype-based strategy that identifies CK2 as a promising co-target in KRAS(G12C) mutant NSCLC by using available pharmacogenomics gene expression datasets. This approach is applicable to other oncogene driven cancers. [Read the Full Post]

The Caspase 1 Inhibitor VX-765 Protects the Isolated Rat Heart via the RISK Pathway

0 | Nov 06 2019

Do Carmo H et al. indicated the caspase 1 inhibitor, VX-765, was able to reduce myocardial infarction in a model of IR injury. However, the addition of IPC did not demonstrate any further protection. [Read the Full Post]

Nutlin-3 enhances the bortezomib sensitivity of p53-defective cancer cells by inducing paraptosis

224 | Nov 01 2019

Lee DM et al. suggested that bortezomib/nutlin-3 perturbs proteostasis, triggering ER/mitochondria stress and irrecoverable impairments in their structure and function, ultimately leading to paraptotic cell death. [Read the Full Post]

Nutlin-3a selects for cells harbouring TP53 mutations

0 | Oct 29 2019

Kucab JE et al. suggested that including a Nutlin-3a counter-screen significantly improves the specificity and efficiency of the HIMA, whereby TP53-mutated clones are selected prior to sequencing and TP53-WT clones can be discarded. [Read the Full Post]

The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia

0 | Oct 24 2019

Brumatti G et al. demonstrated antileukemic efficacy and safety of the birinapant/emricasan combination in vivo suggest that induction of necroptosis warrants clinical investigation as a therapeutic opportunity in AML. [Read the Full Post]

Prolonged Idasanutlin (RG7388) Treatment Leads to the Generation of p53-Mutated Cells

163 | Oct 20 2019

Skalniak L et al. showed that although idasanutlin presents much improved activities compared to its precursor, it displays the similar weaknesses, which are limited elimination of cancer cells and the generation of p53-mutated drug-resistant subpopulations. [Read the Full Post]

The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques

263 | Oct 20 2019

Laforge M et al. demonstrated that Q-VD-OPH injection in SIV-infected RMs may represent an adjunctive therapeutic agent to control HIV infection and delaying disease progression to AIDS. [Read the Full Post]

Genome-wide CRISPR/Cas9 library screening identified PHGDH as a critical driver for Sorafenib resistance in HCC

349 | Oct 18 2019

Wei L et al. demonstrated that targeting PHGDH is an effective approach to overcome TKI drug resistance in HCC. [Read the Full Post]

The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis

271 | Oct 15 2019

Barreyro FJ et al. demonstrated that in a murine model of NASH, liver injury and fibrosis are suppressed by inhibiting hepatocytes apoptosis and suggests that Emricasan may be an attractive antifibrotic therapy in NASH. [Read the Full Post]

Recent developments in the treatment of blastic plasmacytoid dendritic cell neoplasm

148 | Oct 06 2019

Future directions in therapy approaches for patients with BPDCN will include the development of other CD123-targeted agents, agents targeting beyond CD123 and investigation of rational combination approaches of CD123-directed therapy with other therapies. [Read the Full Post]

LncRNA FER1L4 induces apoptosis and suppresses EMT and the activation of PI3K/AKT pathway in osteosarcoma cells via inhibiting miR-18a-5p to promote SOCS5

173 | Oct 03 2019

Ye F et al. indicated thatthe overexpression of FER1L4 promoted apoptosis and inhibited the EMT markers expression and PI3K/AKT signaling pathway activation in OS cells via downregulating miR-18a-5p to promote SOCS5. [Read the Full Post]

On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death

0 | Oct 02 2019

Zilka O et al. demonstrated that potent RTAs subvert ferroptosis and suggest that lipid peroxidation (autoxidation) may play a central role in the process. [Read the Full Post]

ABT-737 potentiates cisplatin-induced apoptosis in human osteosarcoma cells via the mitochondrial apoptotic pathway

222 | Sep 22 2019

Zhang F et al. demonstrated that ABT-737 alone has a nominal influence on human U-2OS cells when treated within the clinically administered range, but when combined with DDP, it can inhibit the proliferation of human U-2OS cells by inducing apoptosis via the mitochondrial apoptotic pathway. [Read the Full Post]

Fenretinide via NOXA induction, enhanced activity of the BCL-2 inhibitor venetoclax in high BCL-2-expressing neuroblastoma preclinical models

173 | Sep 06 2019

Reynolds CP et al. found that fenretinide + ventoclax is a synergistic combination that warrants clinical testing in high BCL-2 expressing neuroblastoma. [Read the Full Post]

An in vitro assay for biomarker discovery and dose prediction applied to ibrutinib plus venetoclax treatment of CLL

44 | Sep 06 2019

Skånland SS et al. suggested that phospho flow should be considered as a novel approach for dose and synergy prediction in a precision medicine setting for CLL. [Read the Full Post]

XPO1 inhibitor KPT-330 synergizes with Bcl-xL inhibitor to induce cancer cell apoptosis by perturbing rRNA processing and Mcl-1 protein synthesis

171 | Aug 28 2019

Zhu ZC et al. clarify the reason of apoptosis resistance of cancer cells to XPO1 inhibition and develop a potential strategy for treating solid tumors. [Read the Full Post]

Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death

206 | Aug 06 2019

Kwon MY et al. showed that hemin and CORM accelerate the HO-1 expression in the presence of Erastin and increase membranous lipid peroxidation. Thus, HO-1 is an essential enzyme for iron-dependent lipid peroxidation during ferroptotic cell death. [Read the Full Post]

RSL3 and Erastin differentially regulate redox signaling to promote Smac mimetic-induced cell death

0 | Aug 06 2019

Dächert J et al. showed that RSL3/BV6 and Erastin/BV6 differentially regulate redox signaling and cell death in ALL cells. While RSL3/BV6 cotreatment induces ferroptotic cell death, Erastin/BV6 stimulates oxidative cell death independently of iron. These findings have important implications for the therapeutic targeting of redox signaling to enhance Smac mimetic-induced cell death in ALL. [Read the Full Post]

Inhibition of apoptosis by caspase inhibitor Z-VAD-FMK improves cryotolerance of in vitro derived bovine embryos

0 | Jul 22 2019

Pero ME et al. indicated the addition of 20 μM Z-VAD-FMK during vitrification/warming and post-warming culture partially inhibits cryopreservation-induced apoptosis by reducing the level of active caspase 3, suggesting a potential use as an additive to ameliorate the efficiency of embryo cryopreservation in cattle, critical for a further diffusion of IVEP technology in the field. Further studies are though needed to evaluate the effect of Z-VAD-FMK on post-transfer embryo development before considering a commercial application. [Read the Full Post]

Inhibition of Bcl-2/xl With ABT-263 Selectively Kills Senescent Type II Pneumocytes and Reverses Persistent Pulmonary Fibrosis Induced by Ionizing Radiation in Mice

186 | Jul 16 2019

Pan J et al. demonstrated that PF can be reversed by a senolytic drug such as ABT-263 after it becomes a progressive disease. Therefore, ABT-263 has the potential to be developed as a new treatment for PF. [Read the Full Post]

Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors

169 | Jul 15 2019

Zhu Y et al. showed the hypothesis-driven, bioinformatics-based approach we used to discover that dasatinib (D) and quercetin (Q) are senolytic can be extended to increase the repertoire of senolytic drugs, including additional cell type-specific senolytic agents. [Read the Full Post]

Flavopiridol enhances ABT-199 sensitivity in unfavourable-risk multiple myeloma cells in vitro and in vivo

176 | Jul 12 2019

Zhou L et al. argue that CDK9 inhibitors, for example, FP may increase the antimyeloma activity of ABT-199, including in unfavourable-risk MM minimally responsive to ABT-199 alone. [Read the Full Post]

Therapeutics targeting Bcl-2 in hematological malignancies

182 | Jul 12 2019

Ruefli-Brasse A et al. review recent progress in direct and selective targeting of Bcl-2 family proteins for cancer therapy and the search for rationale combinations. [Read the Full Post]

Structural States of Hdm2 and HdmX: X-ray Elucidation of Adaptations and Binding Interactions for Different Chemical Compound Classes

192 | Jun 26 2019

Kallen J et al. used the same numbering for Hdm2 (as in Q00987) and HdmX (as in O15151, but minus 1). Taken together, these structural insights should prove useful for the design and optimization of further selective and/or dual Hdm2/HdmX inhibitors. [Read the Full Post]

Direct Activation of BAX by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia

201 | Jun 24 2019

Reyna DE et al. provides proof-of-concept for direct BAX activation as a treatment strategy in AML. [Read the Full Post]

Curaxin CBL0137 has the potential to reverse HIV-1 latency

318 | Jun 24 2019

Jean MJ et al. indicated that CBL0137 possesses capabilities as a LRA and could be considered for the "shock and kill" approach. [Read the Full Post]

Increased MCL-1 expression predicts poor prognosis and disease recurrence in acute myeloid leukemia

201 | Jun 13 2019

Li XX et al. suggested that higher expression of MCL-1 predicts poor prognosis and can be used for disease monitoring. [Read the Full Post]

Combination of Emricasan with Ponatinib Synergistically Reduces Ischemia/Reperfusion Injury in Rat Brain Through Simultaneous Prevention of Apoptosis and Necroptosis

293 | Jun 10 2019

Tian J et al. concluded that combination of emricasan with ponatinib could synergistically reduce I/R injury in rat brain through simultaneous prevention of apoptosis and necroptosis. Our findings might lay a basis on extension of the clinical indications for emricasan and ponatinib in treating ischemic stroke. [Read the Full Post]

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models

385 | Jun 08 2019

Lehmann C et al provided functional and molecular insight on the superior anti-tumor activity of combined idasanutlin and venetoclax treatment in AML and support its further exploration in clinical studies. [Read the Full Post]

Hemin-induced platelet activation and ferroptosis is mediated through ROS-driven proteasomal activity and inflammasome activation: Protection by Melatonin

237 | May 26 2019

NaveenKumar SK et al. demonstrated an association of platelet activation/ferroptosis with proteasome activity and inflammasome activation. Although, high-throughput screening has recognized ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) as potent ferroptosis inhibitors, having an endogenous antioxidant such as MLT as ferroptosis inhibitor is of high interest. MLT is a well-known chronobiotic hormone that regulates the circadian rhythms in vertebrates. It is also known to exhibit potent antioxidant and ROS quenching capabilities. MLT can regulate fundamental cellular functions by exhibiting cytoprotective, oncostatic, antiaging, anti-venom, and immunomodulatory activities. The ROS scavenging capacity of MLT is key for its cytoprotective and anti-apoptotic properties. Considering the anti-ferroptotic and anti-apoptotic potentials MLT, it could be a promising clinical application to treat hemolytic, thrombotic and thrombocytopenic conditions. Therefore, we propose MLT as a pharmacological and therapeutic agent to inhibit ferroptosis and platelet activation. [Read the Full Post]

Inhibition of apoptosis by caspase inhibitor Z-VAD-FMK improves cryotolerance of in vitro derived bovine embryos

437 | May 17 2019

Pero ME et al. found that the addition of 20 μM Z-VAD-FMK during vitrification/warming and post-warming culture partially inhibits cryopreservation-induced apoptosis by reducing the level of active caspase 3, suggesting a potential use as an additive to ameliorate the efficiency of embryo cryopreservation in cattle, critical for a further diffusion of IVEP technology in the field. [Read the Full Post]

MPP+ induces necrostatin-1- and ferrostatin-1-sensitive necrotic death of neuronal SH-SY5Y cells

0 | May 06 2019

Ito K et al. found that MPP+ predominantly induced non-apoptotic death of neuronally differentiated SH-SY5Y cells. This cell death was strongly inhibited by necrostatin-1 (Nec-1), a necroptosis inhibitor, and by an indole-containing compound (3,3'-diindolylmethane: DIM). However, it occurred independently of receptor-interacting serine/threonine-protein kinase 1/3 (RIP1/RIP3), indicating that this form of cell death was not necroptosis. MPP+-induced cell death was also inhibited by several inhibitors of ferroptosis, including ferrostatin-1 (Fer-1). Although MPP+-induced death and ferroptosis shared some features, such as occurrence of lipid peroxidation and inhibition by Fer-1, MPP+-induced death seemed to be distinct from ferroptosis because MPP+-induced death (but not ferroptosis) was inhibited by Nec-1, was independent of p53, and was accompanied by ATP depletion and mitochondrial swelling. Further investigation of MPP+-induced non-apoptotic cell death may be useful for understanding the mechanisms of neuronal loss and for treatment of neurodegenerative diseases such as Parkinson's disease. [Read the Full Post]

Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties

433 | May 04 2019

Lawrence CP et al. demonstrated that both z-VAD-FMK and z-IETD-FMK are immunosuppressive in vitro and inhibit T cell proliferation without blocking the processing of caspase-8 and caspase-3. [Read the Full Post]

On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death

305 | Apr 30 2019

Zilka O et al. demonstrated that potent RTAs subvert ferroptosis and suggest that lipid peroxidation (autoxidation) may play a central role in the process. [Read the Full Post]

The Caspase 1 Inhibitor VX-765 Protects the Isolated Rat Heart via the RISK Pathway

412 | Apr 22 2019

Do Carmo H et al. indicated the caspase 1 inhibitor, VX-765, was able to reduce myocardial infarction in a model of IR injury. However, the addition of IPC did not demonstrate any further protection. [Read the Full Post]

Lipoxygenase-mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3

249 | Apr 08 2019

Shintoku R et al suggested that tumor ferroptosis is promoted by LOX-catalyzed lipid hydroperoxide generation in cellular membranes. [Read the Full Post]

Bcl-xL inhibition enhances Dinaciclib-induced cell death in soft-tissue sarcomas

275 | Apr 05 2019

Rello-Varona S et al showed that Bcl-xL inhibitor A-1331852 also synergized with conventional chemotherapy drugs as Gemcitabine. Thus, Bcl-xL targeted therapy arises as a major opportunity to the treatment of STS. [Read the Full Post]

Memantine and Q-VD-OPh Treatments in Experimental Spinal Cord Injury: Combined Inhibition of Necrosis and Apoptosis

370 | Apr 05 2019

Aydoseli A et al showed that combined use of memantine and Q-VD-OPh provides better histological and clinical results. The combined inhibition of the two major pathways, necrosis and apoptosis, needs to be further assessed with in-vivo or in-vitro studies. [Read the Full Post]

Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction

202 | Apr 04 2019

Walaszczyk A et al. provided proof-of-concept evidence that senescent cells are major contributors to impaired function and increased mortality following MI and that senolytics are a potential new therapeutic avenue for MI. [Read the Full Post]

MCL-1 or BCL-xL-dependent resistance to the BCL-2 antagonist (ABT-199) can be overcome by specific inhibitor as single agents and in combination with ABT-199 in acute myeloid leukemia cells

202 | Apr 02 2019

Wang Q et al. showed that ABT-199 could synergize with A-1210477 in vitro or in vivo. [Read the Full Post]

Targeting Oxidative Stress With Auranofin or Prima-1Met to Circumvent p53 or Bax/Bak Deficiency in Myeloma Cells

197 | Mar 29 2019

Tessoulin B et al. showed that auranofin and Prima-1Metsimilarly overcome cell death resistance in myeloma cells due to either p53 deficiency or to mitochondrial dysfunction. [Read the Full Post]

Down-regulation of JMJD5 suppresses metastasis and induces apoptosis in oral squamous cell carcinoma by regulating p53/NF-κB pathway

905 | Mar 19 2019

Yao Y et al. supplied mechanistic insights into the effects of JMJD5 on the modulation of OSCC development, illustrating that JMJD5 might be an essential prognostic indicator and therapeutic target against OSCC progression. [Read the Full Post]

Neuroprotection with the P53-Inhibitor Pifithrin-μ after Cardiac Arrest in a Rodent Model

943 | Mar 18 2019

Glas M et al. indicated that temporarily inhibition of apoptosis with pifithrin-μ after cardiac arrest decreases the number of injured neurons in the CA1 segment of hippocampus in a cardiac arrest rat model, without clinical correlate. Further studies should elucidate the role of this neuroprotective agent in different settings and with longer cardiac arrest. [Read the Full Post]

Nutlin-3a selects for cells harbouring TP53 mutations

274 | Mar 04 2019

Kucab JE et al. suggested that including a Nutlin-3a counter-screen significantly improves the specificity and efficiency of the HIMA, whereby TP53-mutated clones are selected prior to sequencing and TP53-WT clones can be discarded. [Read the Full Post]

RSL3 and Erastin differentially regulate redox signaling to promote Smac mimetic-induced cell death

311 | Feb 25 2019

Dächert J et al. indicated that RSL3/BV6 and Erastin/BV6 differentially regulate redox signaling and cell death in ALL cells. While RSL3/BV6 cotreatment induces ferroptotic cell death, Erastin/BV6 stimulates oxidative cell death independently of iron. These findings have important implications for the therapeutic targeting of redox signaling to enhance Smac mimetic-induced cell death in ALL. [Read the Full Post]

Practice patterns and outcomes with the use of regorafenib in metastatic colorectal cancer: Results from the Regorafenib in Metastatic colorectal cancer - An Indian exploratory analysis study

573 | Feb 19 2019

Ramaswamy A et al. indicated duration of treatment with regorafenib as an efficacy end point in this study is similar to available data from other regions as it is the side effect profile. [Read the Full Post]

Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial

683 | Feb 18 2019

Bruix J et al. indicated that regorafenib is the only systemic treatment shown to provide survival benefit in HCC patients progressing on sorafenib treatment. Future trials should explore combinations of regorafenib with other systemic agents and third-line treatments for patients who fail or who do not tolerate the sequence of sorafenib and regorafenib. [Read the Full Post]

Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia

392 | Feb 13 2019

Wu X et al. indicated taht they conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution. [Read the Full Post]

Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment

452 | Feb 05 2019

Yee-Lin V et al. Nutlin-3, a small molecule inhibitor that specifically targets p53-Mdm2 interaction offers new therapeutic opportunities by enhancing cancer cell growth arrest and apoptosis through the restoration of the p53-mediated tumor suppression pathway while producing minimal cytotoxicity and side effects. [Read the Full Post]

The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia

315 | Feb 01 2019

Brumatti G et al. demonstrated antileukemic efficacy and safety of the birinapant/emricasan combination in vivo suggest that induction of necroptosis warrants clinical investigation as a therapeutic opportunity in AML. [Read the Full Post]

MDM2 is implicated in high-glucose-induced podocyte mitotic catastrophe via Notch1 signalling

271 | Jan 29 2019

Tang H, et al. found that high glucose up-regulates MDM2 expression and leads to podocyte MC. Notch1 signalling is an essential downstream pathway of MDM2 in mediating HG-induced MC in podocytes. [Read the Full Post]

Drp1 mediates compression-induced programmed necrosis of rat nucleus pulposus cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF

279 | Jan 28 2019

Lin H et al. indicated that Drp1 mediates compression-induced programmed necrosis of NP cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF. [Read the Full Post]

Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis

248 | Jan 06 2019

Yu X et al. suggested that MCL-1 contributes to the development of ESCC and is a promising therapeutic target for chemosensitization of ESCC cells to cisplatin. This might provide a scientific basis for developing effective approaches to treat the subset of ESCCs patients with MCL-1 overexpression. [Read the Full Post]

RNA Polymerase I Inhibition with CX-5461 as a Novel Therapeutic Strategy to Target MYC in Multiple Myeloma

327 | Dec 24 2018

Lee HC et al. provided a rationale for the clinical translation of CX-5461 as a novel therapeutic approach to target MYC in myeloma. [Read the Full Post]

WIP1 modulates responsiveness to Sonic Hedgehog signaling in neuronal precursor cells and medulloblastoma

0 | Dec 23 2018

Wen J et al. found that Wip1 knockdown or treatment with a WIP1 inhibitor suppressed the effects of Shh stimulation and potentiated the growth inhibitory effects of SHH pathway-inhibiting drugs in Shh-activated MB cells in vitro. [Read the Full Post]

Regulation of XIAP Turnover Reveals a Role for USP11 in Promotion of Tumorigenesis

0 | Dec 22 2018

Zhou Z et al. proposed that aberrant USP11, via stabilization of XIAP, promotes tumor initiation and progression. [Read the Full Post]

Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells

293 | Dec 13 2018

Adedoyin O et al. demonstrated an important antiferroptotic role of HO-1 in renal epithelial cells. [Read the Full Post]

Parthenolide inhibits the initiation of experimental autoimmune neuritis

870 | Dec 09 2018

Zhang M et al. indicated that PAR plays dual roles in EAN and it is not proper to be applied in autoimmune diseases of nervous system. [Read the Full Post]

Inhibitors of ubiquitin E3 ligase as potential new antimalarial drug leads

517 | Dec 04 2018

Jain J et al. provided better understanding regarding the importance of E3 ligase functions in the malaria parasite as a potential new antimalarial drug target and a new class of antimalarial drug leads. [Read the Full Post]

RCN1 suppresses ER stress-induced apoptosis via calcium homeostasis and PERK-CHOP signaling

510 | Nov 24 2018

Xu S et al. indicated that RCN1, a target of NF-κB, suppresses ER calcium release by binding to IP3R1 and decreases the UPR, thereby inhibiting ER stress-induced apoptosis. [Read the Full Post]

Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine

363 | Nov 18 2018

Pagel R et al. suggested that circadian rhythm stability is pivotal for the maintenance of mucosal barrier function. CRD increases intestinal necroptosis, thus rendering the gut epithelium more susceptible to inflammatory processes.-Pagel, R., Bär, F., Schröder, T., Sünderhauf, A., Künstner, A., Ibrahim, S. M., Autenrieth, S. E., Kalies, K., König, P., Tsang, A. H., Bettenworth, D., Divanovic, S., Lehnert, H., Fellermann, K., Oster, H., Derer, S., Sina, C. Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine. [Read the Full Post]

BIM mediates synergistic killing of B-cell acute lymphoblastic leukemia cells by BCL-2 and MEK inhibitors

0 | Oct 30 2018

Korfi K et al. observed in B-ALL cells driven by a range of genetic abnormalities and therefore has significant therapeutic potential. [Read the Full Post]

AT101 exerts a synergetic efficacy in gastric cancer patients with 5-FU based treatment through promoting apoptosis and autophagy

456 | Oct 29 2018

Wei X et al. showed APE1 is guided as a potential therapeutic target for gastric cancer. AT101 could be regarded as a potent inhibitor to promote chemotherapeutic sensitivity in patients with gastric cancer. [Read the Full Post]

Loss of XIAP facilitates switch to TNFα-induced necroptosis in mouse neutrophils

1256 | Oct 28 2018

Wicki S et al. may implicated an important role of neutrophils in the development of hyperinflammation and disease progression of patients diagnosed with X-linked lymphoproliferative syndrome type 2, which are deficient in XIAP. [Read the Full Post]

FANCD2 protects against bone marrow injury from ferroptosis

314 | Oct 27 2018

Song X et al. indicate that FANCD2 plays a novel role in the negative regulation of ferroptosis. [Read the Full Post]

Identification of mTOR as a primary resistance factor of the IAP antagonist AT406 in hepatocellular carcinoma cells

0 | Oct 24 2018

Zhen MC et al. concluded that mTOR could be a key resistance factor of AT406 in HCC cells. [Read the Full Post]

AT-101 inhibits hedgehog pathway activity and cancer growth

0 | Oct 02 2018

Wang J et al. revealed a novel molecular mechanism responsible for the anticancer action of AT-101 and contributes to the further development of AT-101 as an anticancer drug. [Read the Full Post]

A NOXA/MCL-1 Imbalance Underlies Chemoresistance of Malignant Rhabdoid Tumor Cells

552 | Aug 19 2018

Ouchi K et al. suggested that modulation of the NOXA/MCL-1 pathway may be a potential strategy for the treatment of patients with MRT. [Read the Full Post]

DRP-1 is required for BH3 mimetic-mediated mitochondrial fragmentation and apoptosis

442 | Aug 19 2018

Milani M et al. provided new insights into MCL-1 ligands, and the interplay between DRP-1 and the anti-apoptotic BCL-2 family members in the regulation of apoptosis. [Read the Full Post]

Combined treatment of carfilzomib and z-VAD-fmk inhibits skeletal proteolysis and apoptosis and ameliorates cancer cachexia

679 | Aug 06 2018

Wang Q et al. found that Combined treatment with CFZ and z-VAD-fmk early in the development of cachexia was associated with signs of less proteolysis and apoptosis and less severe cachexia in a mouse model of cancer-induced cachexia. [Read the Full Post]

Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152

488 | Jul 23 2018

Tchoghandjian A et al. revealed for the first time that ML-IAP protein expression correlates with GBM patient survival and that its antagonist GDC-0152 improves outcome in xenografted mouse. [Read the Full Post]

Anti-apoptotic Bcl-XL but not Mcl-1 contributes to protection against virus-induced apoptosis

463 | Jul 17 2018

Ohmer M et al. showed that Mcl-1 is dispensable for the regulation of apoptosis during infection with different large DNA viruses, either because the viruses replace its function (in fibroblasts and epithelial cells) or because the pro-apoptotic activity generated by the infection appears not to be blocked by it (in macrophages). [Read the Full Post]

Ferroptosis is an autophagic cell death process

538 | Jul 12 2018

Gao M et al. indicated that ferroptosis is an autophagic cell death process, and NCOA4-mediated ferritinophagy supports ferroptosis by controlling cellular iron homeostasis. [Read the Full Post]

BIM mediates synergistic killing of B-cell acute lymphoblastic leukemia cells by BCL-2 and MEK inhibitors

657 | Jun 13 2018

Korfi K et al. observed in B-ALL cells driven by a range of genetic abnormalities and therefore has significant therapeutic potential. [Read the Full Post]

Calcineurin complex isolated from T-cell acute lymphoblastic leukemia (T-ALL) cells identifies new signaling pathways including mTOR/AKT/S6K whose inhibition synergize with calcineurin inhibition to promote T-ALL cell death

0 | May 31 2018

Tosello V et al. identified AKT inhibition as a novel promising drug combination to potentiate the pro-apoptotic effects of Cn inhibitors. [Read the Full Post]

Etoposide Induces Apoptosis in Activated Human Hepatic Stellate Cells via ER Stress

783 | May 31 2018

Wang C et al. demonstrated that VP-16 exerts a proapoptotic effect on LX-2 cells and has an antifibrogenic effect on collagen deposition, suggesting a new strategy for the treatment of liver fibrosis. [Read the Full Post]

Glucocorticoids Prevent Enterovirus 71 Capsid Protein VP1 Induced Calreticulin Surface Exposure by Alleviating Neuronal ER Stress

740 | May 29 2018

Hu DD et al. identified VP1-promoted Ecto-CRT upregulation as a novel mechanism of EV71-induced neuronal cell damage and highlight the potential of the use of glucocorticoids to treat severe HFMD patients with CNS complications. [Read the Full Post]

Pharmacological Inhibition of PERK Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats Through the Activation of Akt

791 | May 19 2018

Yan F et al. found that PERK might serve as a promising target for future therapeutic intervention. [Read the Full Post]

Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue

2115 | May 16 2018

Liu Z et al. revealed a novel function of melatonin on adipocyte pyroptosis, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory response. [Read the Full Post]

Myosin IIA-related Actomyosin Contractility Mediates Oxidative Stress-induced Neuronal Apoptosis

754 | May 16 2018

Wang Y et al. unraveled the biochemical and mechanistic mechanisms during oxidative stress-induced neuronal apoptosis and may be applicable for the development of therapies for CNS diseases. [Read the Full Post]

Nutlin-3a: A Potential Therapeutic Opportunity for TP53 Wild-Type Ovarian Carcinomas

618 | May 15 2018

Crane EK et al. found that Nutlin-3a could be a potential therapeutic agent for ovarian carcinomas expressing wild-type TP53 and warrants further investigation. [Read the Full Post]

p53-related protein kinase confers poor prognosis and represents a novel therapeutic target in multiple myeloma

856 | Apr 23 2018

Hideshima T et al. demonstrated that either genetic or pharmacological inhibition of TP53RK triggers MM cell apoptosis via both p53-Myc axis-dependent and axis-independent pathways, validating TP53RK as a novel therapeutic target in patients with poor-prognosis MM. [Read the Full Post]

Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway

0 | Apr 23 2018

Wang L et al. revealed that p38 MAPK inhibitors may provide a novel intervention strategy for diabetic pancreatic cancer treatment. [Read the Full Post]

4-Hydroxy-2-nonenal induces apoptosis by activating ERK1/2 signaling and depleting intracellular glutathione in intestinal epithelial cells

1058 | Apr 08 2018

Ji Y et al. provided new insights into a functional role of MKP-1 in oxidative stress-induced cell death by regulating ERK1/2 MAP kinase in intestinal epithelial 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

2557 | 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]

Targeting Autophagy Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib

762 | Apr 05 2018

Wang W et al. demonstrated that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib. [Read the Full Post]

Novel MDM2 inhibitor SAR405838 (MI-773) induces p53-mediated apoptosis in neuroblastoma

688 | Apr 03 2018

Lu J et al. suggested that MDM2-specific inhibitors like SAR405838 may serve not only as a stand-alone therapy, but also as an effective adjunct to current chemotherapeutic regimens for treating NB with an intact MDM2-p53 axis. [Read the Full Post]

Downregulation of B-myb promotes senescence via the ROS-mediated p53/p21 pathway, in vascular endothelial cells

1254 | Mar 24 2018

Zhou Z et al. suggested that B-myb may be a novel candidate for regulating cell senescence to protect against endothelial senescence-related cardiovascular diseases. [Read the Full Post]

Late-stage inhibition of autophagy enhances calreticulin surface exposure

845 | Mar 07 2018

Li DD et al. highlight the potential of the combined use of ER stress inducers and autophagy late-stage inhibitors to reestablish and strengthen both the CRT exposure and immunogenicity of chemotherapeutic agents induced death cells. [Read the Full Post]

HSPA5 Regulates Ferroptotic Cell Death in Cancer Cells

0 | Mar 07 2018

Zhu S et al. identified a novel role of HSPA5 in ferroptosis and suggest a potential therapeutic strategy for overcoming gemcitabine resistance. [Read the Full Post]

UMI-77 primes glioma cells for TRAIL-induced apoptosis by unsequestering Bim and Bak from Mcl-1

555 | Mar 01 2018

Liu JW et al. showed that UMI-77 enhances TRAIL-induced apoptosis by unsequestering Bim and Bak, which provides a novel therapeutic strategy for the treatment of gliomas. [Read the Full Post]

Strain- and host species-specific inflammasome activation, IL-1β release, and cell death in macrophages infected with uropathogenic Escherichia coli

2198 | Feb 26 2018

Schaale K et al. indicated in mouse macrophages, CFT073-triggered inflammasome responses are completely NLRP3-dependent, and largely α-hemolysin-dependent. In contrast, UPEC activates an NLRP3-independent cell death pathway and an α-hemolysin-independent IL-1β secretion pathway in human macrophages. This has important implications for understanding UTI in [Read the Full Post]

Pharmacological inhibition of Bcl-xL sensitizes osteosarcoma to doxorubicin

558 | Feb 21 2018

Baranski Z et al. identified Bcl-xL as a candidate drug target for sensitization to chemotherapy in patients with osteosarcoma. [Read the Full Post]

Nanoparticle-Mediated Mitochondrial Damage Induces Apoptosis in Cancer

835 | Jan 28 2018

Mallick A et al. presented here clearly stimulate the usage of multiple drugs to perturb simultaneously diverse targets, selectively in mitochondria, as next-generation cancer therapeutics. [Read the Full Post]

Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration

717 | Jan 26 2018

Hambright WS et al. suggested that ferroptosis may be an important neurodegenerative mechanism in diseases such as AD. [Read the Full Post]

Chenodeoxycholic acid activates NLRP3 inflammasome and contributes to cholestatic liver fibrosis

1107 | Jan 12 2018

Gong Z et al. offered a mechanistic basis to ameliorate cholestatic liver fibrosis by targeting inflammasome activation. [Read the Full Post]

AKT is indispensable for coordinating Par-4/JNK cross talk in p21 downmodulation during ER stress

1039 | Jan 10 2018

Rasool RU et al. found that 3-AWA inhibits colorectal tumor growth and formation of colorectal polyps at a tolerable dose, similar to the first-line drug for colorectal cancer-5-fluorouracil. [Read the Full Post]

Biliary tract instillation of a SMAC mimetic induces TRAIL-dependent acute sclerosing cholangitis-like injury in mice

671 | Jan 08 2018

Guicciardi ME et al. contributed to the development of the disease. Our results also indicate that inhibition of TRAIL signaling pathways may be beneficial in the treatment of PSC. [Read the Full Post]

Human Papillomavirus Downregulates the Expression of IFITM1 and RIPK3 to Escape from IFNγ- and TNFα-Mediated Antiproliferative Effects and Necroptosis

1632 | Jan 07 2018

Ma W et al. revealed how hrHPV deregulates two pathways involved in cell death and growth regulation to withstand immune-mediated control of hrHPV-infected cells. [Read the Full Post]

Blocking EZH2 methylation transferase activity by GSK126 decreases stem cell-like myeloma cells

1336 | Jan 05 2018

Zeng D et al. suggested that EZH2 inactivation by GSK126 is effective in killing MM cells and CSCs as a single agent or in combination with bortezomib. Clinical trial of GSK126 in patients with MM may be warranted. [Read the Full Post]

Activation of oncogenic pathways in classical Hodgkin lymphoma by decitabine: A rationale for combination with small molecular weight inhibitors.

1147 | Dec 29 2017

Swerev TM et al. concluded that targeting of oncogenic pathways of cHL may improve efficacy of DNA-demethylating therapy in cHL. [Read the Full Post]

Matrine induces Akt/mTOR signalling inhibition-mediated autophagy and apoptosis in acute myeloid leukaemia cells

999 | Dec 20 2017

Wu J et al. indicated that matrine exerts antitumour effect through apoptosis and autophagy, and the latter one might be a potential therapeutic strategy for AML. [Read the Full Post]

E platinum, a newly synthesized platinum compound, induces apoptosis through ROS-triggered ER stress in gastric carcinoma cells

1242 | Dec 09 2017

Wang X et al. indicated that E Platinum may be a potential and effective treatment for gastric cancer in clinical. [Read the Full Post]

Histone Deacetylase Inhibitor Trichostatin a Promotes the Apoptosis of Osteosarcoma Cells through p53 Signaling Pathway Activation

874 | Dec 07 2017

Deng Z et al. indicated class I HDACs play a central role in the pathogenesis of osteosarcoma, and HDAC inhibitors may thus have promise as new therapeutic agents against osteosarcoma. [Read the Full Post]

High efficacy of the BCL-2 inhibitor ABT199 (venetoclax) in BCL-2 high-expressing neuroblastoma cell lines and xenografts and rational for combination with MCL-1 inhibition

810 | Dec 03 2017

Bate-Eya LT et al. suggested that neuroblastoma patients with high BCL-2 and BIM/BCL-2 complex levels might benefit from combination treatment with ABT199 and compounds that inhibit MCL-1 expression. [Read the Full Post]

HSPA5 Regulates Ferroptotic Cell Death in Cancer Cells

766 | Oct 23 2017

Zhu S et al. identified a novel role of HSPA5 in ferroptosis and suggest a potential therapeutic strategy for overcoming gemcitabine resistance. [Read the Full Post]

Chemotherapy-induced Dkk-1 expression by primary human mesenchymal stem cells is p53 dependent

1278 | Oct 23 2017

Hare I et al. indicated that Dkk-1 has been shown to promote tumor growth in several models of malignancy, suggesting that MSC-derived Dkk-1 could counteract the intent of cytotoxic chemotherapy, and that pharmacologic inhibition of Dkk-1 in patients receiving chemotherapy treatment for certain malignancies may be warranted. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

0 | Oct 18 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]

Protective effect of necrostatin-1 on myocardial tissue in rats with acute myocardial infarction

0 | Oct 13 2017

Liu YR et al. found that necrostatin-1 can inhibit myocardial tissue apoptosis and necrosis in acute myocardial infarct rats and has a protective effect on myocardial tissue. [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

0 | Sep 29 2017

Liu SH et al. found that LIPUS stimulation might play a crucial and beneficial role in neurodegenerative diseases. [Read the Full Post]

Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts

0 | Sep 27 2017

Virakul S et al. found that multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO. [Read the Full Post]

K45A mutation of RIPK1 results in poor necroptosis and cytokine signaling in macrophages, which impacts inflammatory responses in vivo

0 | Sep 18 2017

Shutinoski B et al. indicated that K45 mediated kinase activity of RIPK1 is not only important for necroptosis but it also has a key role in promoting cytokine signaling and host response to inflammatory stimuli. [Read the Full Post]

Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells.

0 | Sep 07 2017

Zhang W et al. provided evidence showing that YM155 could act as a small molecule survivin inhibitor on survivin-rich expressed SCC9 cells in culture as well as when grown as tumor in a xenograft model. [Read the Full Post]

Embelin Reduces Systemic Inflammation and Ameliorates Organ Injuries in Septic Rats Through Downregulating STAT3 and NF-κB Pathways

1675 | Sep 05 2017

Zhou XL et al. indicated that embelin ameliorates sepsis in rats through suppressing STAT3 and NF-κB pathways. [Read the Full Post]

Role of BmDredd during Apoptosis of Silk Gland in Silkworm, Bombyx mori

1267 | Sep 04 2017

Chen RT et al. suggested that BmDredd plays a critical role in SG apoptosis. [Read the Full Post]

Calcineurin and GSK-3 inhibition sensitizes T-cell acute lymphoblastic leukemia cells to apoptosis through X-linked inhibitor of apoptosis protein degradation

921 | Sep 04 2017

Tosello V et al. showed that dual Cn and GSK-3 inhibitor treatment in vitro and in vivo is effective against available models of T-ALL, indicating an insofar untapped therapeutic opportunity. [Read the Full Post]

The Role of the Active Oxygen Produced from Gp91phox NADPH Oxidase on the Newborn Weight of Mouse Pups

1343 | Sep 03 2017

Keiichi Hiramoto et al. indicated that gp91phox NADPH oxidase produces ROS during graviditas. The ROS activate NLRP3, and NLRP3 leads to the production of caspase-1, which subsequently increases IL-1, thereby finally inducing IGF-1. Because the newborn weight is determined by IGF-1, gp91phox appears to be important for promoting fetal growth during graviditas. [Read the Full Post]

Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells

0 | Aug 30 2017

Zhang W et al. suggested that survivin could be further developed as a potential therapeutic agent for the treatment of survivin-rich expressed OSCC. [Read the Full Post]

Assessment of the chemotherapeutic potential of a new camptothecin derivative, ZBH-1205

0 | Aug 11 2017

Wu D, et al. found that ZBH-1205 is a promising chemotherapeutic agent to be further assessed in large-scale clinical trials. [Read the Full Post]

Bcl-2 phosphorylation confers resistance on chronic lymphocytic leukaemia cells to the BH3 mimetics ABT-737, ABT-263 and ABT-199 by impeding direct binding

1437 | Aug 03 2017

Song T et al. suggested that a structural alteration in the BH3-binding groove was induced by phosphorylation of Bcl-2. Our data also provided a framework to overcome resistance of CLL cells to the ABT compounds by combining pBcl-2 kinase inhibitors with the ABT compounds. [Read the Full Post]

Sorafenib potentiates ABT-737-induced apoptosis in human oral cancer cells

1219 | Aug 02 2017

Kim LH et al. suggest that sorafenib may effectively overcome ABT-737 resistance to apoptotic cell death, which can be a new potential chemotherapeutic strategy against human oral cancer. [Read the Full Post]

Profiling B cell chronic lymphocytic leukemia by reverse phase protein array: Focus on apoptotic proteins

0 | Jul 24 2017

Frezzato F et al. identified some molecules, particularly those involved in apoptosis control, which could be considered for further studies to design new therapeutic strategies in CLL. [Read the Full Post]

Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity

0 | Jun 26 2017

Li Y et al. suggested that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors. [Read the Full Post]

Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs

0 | Jun 03 2017

Huang Y et al. provided a rationale for the development of TRAIL-induced apoptosis-based cancer therapies. [Read the Full Post]

Erastin Disrupts Mitochondrial Permeability Transition Pore (mPTP) and Induces Apoptotic Death of Colorectal Cancer Cells

0 | May 25 2017

Huo H et al. found that erastin is cytotoxic and pro-apoptotic to colorectal cancer cells. [Read the Full Post]

Targeting survivin as a potential new treatment for chondrosarcoma of bone

0 | May 19 2017

de Jong Y et al. found that survivin is important for chondrosarcoma survival and chondrosarcoma patients might benefit from survivin inhibition using YM155, for which TP53 mutational status can serve as a predictive biomarker. [Read the Full Post]

The apoptotic members CD95, BclxL, and Bcl-2 cooperate to promote cell migration by inducing Ca(2+) flux from the endoplasmic reticulum to mitochondria.

957 | May 04 2017

Fouqué A et al. revealed a novel molecular mechanism controlled by BclxL to promote cancer cell migration. [Read the Full Post]

The small-molecule IAP antagonist AT406 inhibits pancreatic cancer cells in vitro and in vivo

0 | May 02 2017

Jiang Y et al. suggested that AT406 could be further evaluated as a promising anti-pancreatic cancer agent. [Read the Full Post]

The apoptotic members CD95, BclxL, and Bcl-2 cooperate to promote cell migration by inducing Ca(2+) flux from the endoplasmic reticulum to mitochondria

911 | Apr 27 2017

Fouqué A et al. revealed a novel molecular mechanism controlled by BclxL to promote cancer cell migration and supports the use of BH3 mimetics as therapeutic options not only to kill tumor cells but also to prevent metastatic dissemination in TNBCs. [Read the Full Post]

The small-molecule IAP antagonist AT406 inhibits pancreatic cancer cells in vitro and in vivo

1472 | Apr 25 2017

Jiang Y et al. suggested that AT406 could be further evaluated as a promising anti-pancreatic cancer agent. [Read the Full Post]

Inhibition of Bcl-2 family members sensitises soft tissue leiomyosarcomas to chemotherapy

1548 | Apr 15 2017

In conclusion,de Graaff MA et al found Bcl-2 family proteins contribute to soft tissue leiomyosarcoma chemoresistance. Antiapoptotic proteins are highly expressed in leiomyosarcoma of soft tissue, and inhibition of these proteins using a BH3 mimetic increases leiomyosarcoma sensitivity to doxorubicin. [Read the Full Post]

BH3 mimetic ABT-737 sensitizes colorectal cancer cells to ixazomib through MCL-1 downregulation and autophagy inhibition

1465 | Apr 12 2017

Yang L et al. found that the combination of ABT-737 with MLN9708 is a promising therapeutic strategy for human colorectal cancer. [Read the Full Post]

Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells

0 | Apr 12 2017

Fu J et al disclosed novel signaling cascades of macrophage-mediated bilateral bystander responses that the release of TNF-α and IL-8 regulated by MAPK and NF-κB pathways synergistically increased cellular injury after α-particle irradiation. [Read the Full Post]

Resveratrol delays polycystic kidney disease progression through attenuation of nuclear factor κB-induced inflammation

0 | Apr 09 2017

Wu M et al found that the NF-κB signaling pathway is activated and partly responsible for inflammation in polycystic kidney tissues. Targeting inflammation through resveratrol could be a new strategy for PKD treatment in the future. [Read the Full Post]

A synthetic cell-penetrating dominant-negative ATF5 peptide exerts anti-cancer activity against a broad spectrum of treatment resistant cancers

1023 | Apr 02 2017

Karpel-Massler G et al found the idea that CP-d/n-ATF5-S1, administered as a single reagent or in combination with other drugs, holds promise as an innovative, safe, and efficient antineoplastic agent against treatment-resistant cancers. Clin Cancer Res; 22(18); 4698-711. ©2016 AACR. [Read the Full Post]

AT-101 inhibits hedgehog pathway activity and cancer growth

1050 | Mar 17 2017

Wang J et al. demonstrated that AT-101 significantly and selectively inhibits Hh pathway activity by potentially targeting Smo and consequently suppresses the growth of Hh-driven cancer. [Read the Full Post]

Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis

1523 | Mar 10 2017

Sun X et al. found that knockdown of MT-1G by RNA interference increases glutathione depletion and lipid peroxidation, which contributes to sorafenib-induced ferroptosis. [Read the Full Post]

Identification of baicalein as a ferroptosis inhibitor by natural product library screening

1138 | Mar 10 2017

Xie Y et al. found that baicalein enhances cellular anti-ferroptosis capacity and could be a potential therapeutic agent for ferroptosis-associated tissue injury. [Read the Full Post]

Lenalidomide, Thalidomide, and Pomalidomide Reactivate the Epstein-Barr Virus Lytic Cycle through Phosphoinositide 3-Kinase Signaling and Ikaros Expression

1736 | Mar 09 2017

Jones RJ et al. concluded LTP may reactivate EBV-positive resting memory B cells thereby enhancing EBV lytic cycle and host immune suppression. [Read the Full Post]

Assessment of the chemotherapeutic potential of a new camptothecin derivative, ZBH-1205

0 | Mar 04 2017

Wu D et al. found that ZBH-1205 is a promising chemotherapeutic agent to be further assessed in large-scale clinical trials. [Read the Full Post]

Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites

2125 | Feb 19 2017

Douglass AN, et al.'s data demonstrate that host-based prophylaxis could be developed into an effective intervention strategy that eliminates LS parasites before the onset of clinical disease and thus opens a [Read the Full Post]

Palmitate increases musclin gene expression through activation of PERK signaling pathway in C2C12 myotubes

0 | Feb 14 2017

Gu N, et al.'s findings suggest that palmitate increases musclin gene expression via the activation of the PERK signaling pathway in C2C12 myotubes. [Read the Full Post]

Activation of the p62-Keap1-NRF2 Pathway Protects Against Ferroptosis in Hepatocellular Carcinoma Cells

0 | Feb 11 2017

Sun X, et al.'s findings demonstrate novel molecular mechanisms and signaling pathways of ferroptosis; the status of NRF2 is a key factor that determines the therapeutic response to ferroptosis-targeted therapies in HCC cells. [Read the Full Post]

Assessment of the chemotherapeutic potential of a new camptothecin derivative, ZBH-1205

0 | Jan 21 2017

Wu D et al. found that ZBH-1205 is a promising chemotherapeutic agent to be further assessed in large-scale clinical trials. [Read the Full Post]

Endothelial Cell Apoptosis Induces TGF-β Signaling-Dependent Host Endothelial-Mesenchymal Transition to Promote Transplant Arteriosclerosis

1593 | Jan 16 2017

Li J et al. suggested that allograft EC apoptosis induced recipient endothelial-mesenchymal (smooth muscle) transition via TGF-β signaling, resulting in recipient EC-derived SMC accumulation as a major mechanism of vascular remodeling during TA. [Read the Full Post]

Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites

2321 | Jan 08 2017

Douglass AN, et al.‘’s data demonstrate that host-based prophylaxis could be developed into an effective intervention strategy that eliminates LS parasites before the onset of clinical disease and thus opens a new avenue to prevent malaria. [Read the Full Post]

Palmitate increases musclin gene expression through activation of PERK signaling pathway in C2C12 myotubes

1417 | Jan 07 2017

Gu N et al. suggested that palmitate increases musclin gene expression via the activation of the PERK signaling pathway in C2C12 myotubes. [Read the Full Post]

Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells

0 | Dec 24 2016

Zhang W et al. suggested that survivin could be further developed as a potential therapeutic agent for the treatment of survivin-rich expressed OSCC. [Read the Full Post]

Profiling B cell chronic lymphocytic leukemia by reverse phase protein array: Focus on apoptotic proteins

1376 | Dec 14 2016

Frezzato F, et al. identified some molecules, particularly those involved in apoptosis control, which could be considered for further studies to design new therapeutic strategies in CLL. [Read the Full Post]

Assessment of the chemotherapeutic potential of a new camptothecin derivative, ZBH-1205

2259 | Dec 10 2016

Wu D et al. found that ZBH-1205 is a promising chemotherapeutic agent to be further assessed in large-scale clinical trials. [Read the Full Post]

Acute Sensitivity of Ph-like Acute Lymphoblastic Leukemia to the SMAC-Mimetic Birinapant.

0 | Dec 09 2016

In combination therapy, birinapant enhanced the in vivo efficacy of an induction-type regimen of vincristine, dexamethasone, and L-asparaginase against Ph-like ALL xenografts, offering a preclinical rationale to further evaluate this SMAC mimetic for BCP-ALL treatment. [Read the Full Post]

Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells

1534 | Dec 03 2016

Zhang W et al. suggested that survivin could be further developed as a potential therapeutic agent for the treatment of survivin-rich expressed OSCC. [Read the Full Post]

K45A mutation of RIPK1 results in poor necroptosis and cytokine signaling in macrophages, which impacts inflammatory responses in vivo

1488 | Nov 27 2016

Shutinoski B et al.'s results indicated that K45 mediated kinase activity of RIPK1 is not only important for necroptosis but it also has a key role in promoting cytokine signaling and host response to inflammatory stimuli. [Read the Full Post]

Protective effect of necrostatin-1 on myocardial tissue in rats with acute myocardial infarction

1442 | Nov 15 2016

Liu YR et al. found that necrostatin-1 can inhibit myocardial tissue apoptosis and necrosis in acute myocardial infarct rats and has a protective effect on myocardial tissue. [Read the Full Post]

Overcoming resistance to TRAIL-induced apoptosis in solid tumor cells by simultaneously targeting death receptors, c-FLIP and IAPs

2362 | Nov 01 2016

Huang Y et al. provided a rationale for the development of TRAIL-induced apoptosis-based cancer therapies. [Read the Full Post]

Erastin Disrupts Mitochondrial Permeability Transition Pore (mPTP) and Induces Apoptotic Death of Colorectal Cancer Cells

1474 | Oct 24 2016

Huo H et al. demonstrated that erastin is cytotoxic and pro-apoptotic to colorectal cancer cells. [Read the Full Post]

Targeting survivin as a potential new treatment for chondrosarcoma of bone

1437 | Oct 17 2016

De Jong Y et al. found that survivin is important for chondrosarcoma survival and chondrosarcoma patients might benefit from survivin inhibition using YM155, for which TP53 mutational status can serve as a predictive biomarker. [Read the Full Post]

Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity

2657 | Sep 30 2016

Li Y et al. suggest that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors. [Read the Full Post]

Inhibition of Bcl-2 family members sensitises soft tissue leiomyosarcomas to chemotherapy

1738 | Sep 18 2016

De Graaff MA, et al. found that Bcl-2 family proteins contribute to soft tissue leiomyosarcoma chemoresistance. [Read the Full Post]

Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells

7489 | Sep 14 2016

[Read the Full Post]

A Synthetic Cell-Penetrating Dominant-Negative ATF5 Peptide Exerts Anticancer Activity against a Broad Spectrum of Treatment-Resistant Cancers

1337 | Sep 07 2016

Karpel-Massler G, et al. found that CP-d/n-ATF5-S1, administered as a single reagent or in combination with other drugs, holds promise as an innovative, safe, and efficient antineoplastic agent against treatment-resistant cancers. [Read the Full Post]

Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells

2731 | Aug 31 2016

Sun X, et al. demonstrated novel molecular mechanisms and signaling pathways of ferroptosis; the status of NRF2 is a key factor that determines the therapeutic response to ferroptosis-targeted therapies in HCC cells. [Read the Full Post]

The roles of Bim and Bmf in B-cell development and apoptosis in TACI-lg transgenic mice

4351 | Mar 11 2015

Woess et al. demonstrated B-cell lymphoma 2 (Bcl2) interacting mediator of cell death (Bim) and Bcl2 modifying factor (Bmf), the two pro-apoptotic members of Bcl2 family, mediate apoptosis in the context of lacking BAFF and APRIL. [Read the Full Post]

The role of heat shock protein beta-1 in erastin-induced ferroptosis

4078 | Mar 09 2015

Sun et al. found heat shock protein beta-1 (HSPB1) as a key negative mediator of ferroptotic cancer cell death. [Read the Full Post]

RIP1, a novel oncogenic driver in melanoma

4612 | Mar 06 2015

u et al. found that RIP1 plays a role as an oncogenic driver in human melanoma. [Read the Full Post]

The binding of mutant p53 and DAB2IP increase the invasion of inflammation induced cancer cells

4434 | Dec 08 2014

Minin et al. inflammatory cytokines can increase the invasive behavior of cancer cells with p53 missense mutants (mutp53). [Read the Full Post]

At101 was developed to put requirements in place for CPA

2392 | Mar 03 2014

AT-101 inhibits a panel of different lymphoproliferative malignancies with IC50 ranged from 1.2 μM to 7.4 μM. [Read the Full Post]

Lenalidomide is effective in induring complete response

2519 | Feb 28 2014

Lenalidomide (Revlimid, CC-5013) is a TNF-α secretion inhibitor with IC50 of 13 nM. [Read the Full Post]

BCL 2 inhibition with ABT 737 prolongs survival in an NRAS

2339 | Feb 26 2014

ABT-737 is a BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w with EC50 of 78.7 nM, 30.3 nM and 197.8 nM [Read the Full Post]

Abt199 is designed to block the function of the protein Bcl2

2679 | Feb 14 2014

ABT-199 (GDC-0199) is a Bcl-2-selective inhibitor with Ki of <0.01 nM, >4800-fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. [Read the Full Post]

Nutlin 3 is a cis imidazoline analog

3992 | Jan 26 2014

Nutlin-3 is a potent and selective Mdm2 (RING finger-dependent ubiquitin protein ligase for itself and p53) antagonist with IC50 of 90 nM; stabilizes p73 in p53-deficient cells. [Read the Full Post]

Abt 199 is designed to block the protein Bcl 2

2699 | Jan 16 2014

ABT-199 (GDC-0199) is a Bcl-2-selective inhibitor with Ki of <0.01 nM, >4800-fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. [Read the Full Post]

ABT 737 is a small molecule that acts as a selective inhibitor of Bcl 2

2695 | Dec 23 2013

ABT-737 shows low activity to Bcl-B and no effects to Mcl-1 and BFL-1. [Read the Full Post]

Abt199 is designed to block the function of the protein Bcl 2

2340 | Dec 17 2013

ABT-199 (GDC-0199) is a Bcl-2-selective inhibitor with Ki of <0.01 nM, >4800-fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. [Read the Full Post]

AT101 was developed to put requirements in place for CPAs

2478 | Dec 13 2013

AT-101 inhibits a panel of different lymphoproliferative malignancies with IC50 ranged from 1.2 μM to 7.4 μM. [Read the Full Post]

ABT 263 was formulated in 10 ethano

2610 | Dec 05 2013

ABT-263 is structurally related to ABT-737; it is a disruptor of Bcl-2/Bcl-xL interactions with pro-apoptotic proteins. [Read the Full Post]

Nutlin 3 inhibits the interaction between the proteins p53 and MDM2

3874 | Nov 29 2013

Nutlin-3 is a potent and selective Mdm2 (RING finger-dependent ubiquitin protein ligase for itself and p53) antagonist with IC50 of 90 nM; stabilizes p73 in p53-deficient cells. [Read the Full Post]

ABT 199 is designed to block the function of the protein Bcl 2

3086 | Nov 18 2013

ABT-199 (GDC-0199) is a Bcl-2-selective inhibitor with Ki of <0.01 nM, >4800-fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. [Read the Full Post]

Nutlin3 inhibits the MDM2 p53 interaction and activates p5

3801 | Sep 26 2013

Nutlin-3 is a potent and selective Mdm2 (RING finger-dependent ubiquitin protein ligase for itself and p53) antagonist with IC50 of 90 nM; stabilizes p73 in p53-deficient cells. [Read the Full Post]

TW37 is a Bcl2 inhibitor that has been shown to inhibit the angiogenic potential of endothelial cells

2505 | Jun 24 2013

TW-37 is a novel nonpeptide inhibitor to recombinant Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.29 μM, 1.11 μM and 0.26 μM, respectively. [Read the Full Post]

BCL-2 INHIBITORS HARMONIZING APOPTOSIS

2864 | Sep 18 2012

IMPROPER REGULATION OF BCL-2 PATHWAY IN TUMORS: Bcl-2 protein is abbreviated on basis of chromosomal translocations for the B-cell lymphoma 2 is a major apoptosis regulatory protein and is seen to be associated with it in the follicular lymphoma. Bcl-2 protein along with its other family members keeps a tight check on balancing the cell growth and apoptosis of the cells by keeping an interaction with each other. Any disturbance in the homeostatic balance between apoptosis and growth of cells usually results in the aberrations associated with various types of cancers. Hence using the Bcl-2 inhibitors to achieve Bcl-2 inhibition seems to be an attractive and promising strategy for the treatment of many types of cancers. Different Bcl-2 antagonists are designed on the basis of this strategy among them some are showing promising results at the pre-clinical and clinical levels. As the decrease in apoptosis is a key feature of the development of some sort of cancer, so it was not very surprising to find an association between the Bcl-2 gene, breast cancer, melanoma, prostate cancer and lung carcinomas along with the neurodegenerative problems like autoimmune disorders and schizophrenia. [Read the Full Post]

LENALIDOMIDE – AN ANTI-INFLAMMATORY DRUG

3673 | Sep 05 2012

LENALIDOMIDE: INTRODUCTION Tumor Necrosis factor (TNF) is a pro-inflammatory cytokine, the high levels of which signify inflammation in several disease conditions like autoimmune disorders (e.g. - rheumatoid arthritis, Crohn's disease and ankylosing spondylitis etc.), numerous cancers, skin diseases like psoriasis and refractory asthma. This is often the rationale that TNF-alpha inhibitors are given such importance in medical literature. Starting from natural compounds like curcumin, cannabis and green tea to xanthine derivatives, hallucination inducing compounds and also the best of all monoclonal antibodies, several TNF inhibitors are being studied in several and physiological conditions.As a result of its significance, TNF-alpha inhibition in cancers researchers got abundant attention. [Read the Full Post]

LENALIDOMIDE – AN INHIBITOR OF INFLAMMATION

5242 | Aug 29 2012

LENALIDOMIDE Tumor necrosis factor or TNF is amongst the pro-inflammatory cytokines, in varied forms of diseases associated with cancer, autoimmune diseases (like ankylosing spondylitis and Crohn's disease etc.) and skin diseases e: g refractory asthma and psoriasis high levels of TNF are being observed. From medical point of view due to this reality inhibitors of TNF-alpha are being given lots of value. Different inhibitors of tumor necrosis factor are being studied from numerous physiological and medical point of view these inhibitors include illusion inducing compounds, natural compounds comprising cannabis, curcumin and green tea whereas artificial include xanthine derivatives and most significantly monoclonal antibodies. Lots of emphasize is being placed on these inhibitors for cancer therapy. [Read the Full Post]

LENALIDOMIDE – AN ANTI-INFLAMMATORY DRUG

4578 | Jul 10 2012

LENALIDOMIDE: INTRODUCTION Tumor Necrosis factor (TNF) is a pro-inflammatory cytokine, the high levels of which signify inflammation in several disease conditions like autoimmune disorders (e.g. - rheumatoid arthritis, Crohn's disease and ankylosing spondylitis etc.), numerous cancers, skin diseases like psoriasis and refractory asthma. This is often the rationale that TNF inhibitors are given such importance in medical literature. Starting from natural compounds like curcumin, cannabis and green tea to xanthine derivatives, hallucination inducing compounds and also the best of all monoclonal antibodies, several TNF inhibitors are being studied in several and physiological conditions.As a result of its significance, TNF inhibition in cancers researchers got abundant attention. [Read the Full Post]

LENALIDOMIDE AND INFALAMATION

3067 | Apr 12 2012

ROLE OF TUMOR NECROSIS FACTOR Different types of molecules are there in the body for the purpose of communication between cells. Cytokines are one of such molecules that can induce a change such as growth, differentiation, movement or cell death. Tumor Necrosis factor abbreviated as TNF is one of such cytokines that plays a role in the development of inflammation at the site of disease or microbial attack. Its high levels are associated with the development of inflammation in many types of diseased conditions e.g., different types of cancers, autoimmune disorders (rheumatoid arthritis, ankylosing spondylitis and Crohn's disease etc.), and skin diseases e.g., refractory asthma and psoriasis. Due to its relatedness to many diseases, TNF-alpha is given importance in medical research as well as literature. [Read the Full Post]

OBATOCLAX AGAINST BCL-2 PATHWAYS IN CANCER

3295 | Mar 13 2012

Importance of Bcl-2 Pathway in Cancer: The pro-survival protein Bcl-2 and its related family members activate pro-survival pathways in cancer that are often associated with uncontrolled proliferation of cancer cells. Apart from this direct effect, stress pathways are also reported to be converging with Bcl-2 signaling pathways which makes the development of various Bcl-2 inhibitors an attractive approach to target cancer by inducing mitochondrial apoptotic pathways. [Read the Full Post]

ABT-263: THE BH-3 MIMETIC

4596 | Mar 13 2012

ABT-263 – Introduction: ABT-263 is a small molecule Bcl-2/Bcl-XL inhibitor marketed by Abbott laboratories under the generic name of Navitoclax. Similar in nature to ABT-737, also marketed by Abbott laboratories, ABT-263 inhibits the anti – intrinsic apoptotic pathway via the BH3 domain. Bcl-2/Bcl-XL bind with pro-apoptotic proteins (BID) with the single BH3 domain and thereby regulate the apoptotic process. However, it has been observed in numerous cancer types that Bcl-2 is over expressed which leads to the survival of cells that would normally be removed via apoptosis. ABT-263 Bcl-2 inhibitor have been demonstrated to be effective against small cell lung cancer xenographs, acute lymphoblastic leukemia and hematologic tumors. [Read the Full Post]

BCL-2 INHIBITOR – SMALL YET EFFECTIVE

3553 | Mar 13 2012

INHIBITION OF BCL-2 PROTEINS: Apoptosis is the natural system for the removal of cellular material from the body. This could be due to damage by invasion, age or injury. There are two mechanisms which regulate this process, the Intrinsic and the Extrinsic pathways. The extrinsic pathway is a cascade of signal originating from outside the cell via death receptors on the cellular membrane. The intrinsic pathway is initiated within the cell whereby pro-apoptotic proteins are released to activate the caspase cascade from the mitochondria. Part of the caspase cascade is the family of Bcl-2 proteins which regulate the process towards apoptosis or survival. Bcl-2 family consists of anti-apoptotic members such as Bcl-2, Mcl-1, Bcl-XL and Bcl2a1, other members are the pro-apoptotic proteins such as BAX, BAK, BAD, BIM, PUMA, BID, BIK, NOXA and BMF. In many forms of cancer it has been demonstrated that Bcl-2 is over expressed such as lung, breast, prostate, renal, ovarian and glioblastoma cancer, melanoma and leukemia are the highest report over expressers of Bcl-2. [Read the Full Post]

ABT-737: THE SMALL BCL-2 INHIBITOR

4064 | Mar 13 2012

BCL-2 INHIBITION AND ITS IMPLICATIONS: Bcl-2 family of proteins are a series of regulator proteins governing the pro-survival pathway. Characteristically Bcl-2 has been discovered to be over expressed in a variety of tumor types such small cell lung cancer, melanoma, prostate and breast cancer. The concept of targeted chemotherapy is to focus drug inhibition against a target that is over expressed in the cancer cell in comparison to normal cellular material; Bcl-2 is a clear target for inhibition. Over expression of this protein disrupts the regulation of the intrinsic apoptotic pathway, creating chemotherapeutic resistance. By inhibiting the sequestering of pro-apoptotic proteins by the Bcl-2 family (anti-apoptotic proteins) normal apoptotic processes can be utilized to trigger tumor cell death. Significantly there have been several now molecules introduced into the clinic in recent years which target Bcl-2 and have demonstrated clear benefits in chemotherapeutic action. One of these small molecules is ABT-737, while others are Navitoclax (ABT-263), Obatoclax (GX15-070) and TW-37. [Read the Full Post]

Survivin, the novel target for the treatment of fibrotic disease

5485 | Nov 06 2011

A fibroblast is a type of mesenchymal cells that synthesize the extracellular matrix(ECM) and collagen, and plays a key role in wound healing by differentiating into alpha-smooth muscle actin expressing myofibroblasts. At last, the normal wound repair progress following injury requires the elimination of myofibroblasts by apoptosis. However, in abnormal state, this excessive ECM can result in the progressive destruction of tissue architecture and lead to impaired organ function. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive form of lung disease caused by fibrosis of the lungs. [Read the Full Post]

The roles of p53 in hematopoietic stem cell rate

3468 | Nov 03 2011

At present, p53 is the star gene of the cancer studies, since more than half of cancer development and progression are reported to be related to the p53 mutation. p53 is a tumor suppressor protein, and is originally isolated as a cellular partner of simian virus 40(SV-40)-derived tumor antigens[1]. p53 has regulated several signaling pathways involved in the cell’s response to stress, and plays a role in apoptosis, genomic stability, senescence, inducing cell-cycle arrest and inhibition of angiogenesis. [Read the Full Post]

Chipuk, J. E., T. Moldoveanu, et al. (2010). "The BCL-2 family reunion." Mol Cell 37(3): 299-310.

2919 | Jul 9 2011

The newest review which give a overview of the BCL-2 family proteins including detail data of bcl-2 proteins, the signal transduction related to the bcl-2 and Pharmacological Regulation of the Bcl-2 Proteins [Read the Full Post]

Altieri, D. C. (2008). "Survivin, cancer networks and pathway-directed drug discovery." Nat Rev Cancer 8(1): 61-70.

3577 | Jun 11 2011

A fantastic review about survivin which was published in NATURE REVIEW CANCER. It concludes nearly all the important pathways which survivin is involved in. We can find wonderful pictures of pathways in this review [Read the Full Post]

Kruse, J. P. and W. Gu (2009). "Modes of p53 regulation." Cell 137(4): 609-622.

3623 | Jun 4 2011

This article which was published in CELL gives us a overview of p53 regulation. It give a introduction of the Classical Model of p53 regulation, Mdm2 Regulation, promoter-Specific Activation, p53 Transcriptional Activation. We can get detail information for p53 regulation from this article. [Read the Full Post]

He, L., X. He, et al. (2007). "A microRNA component of the p53 tumour suppressor network." Nature 447(7148): 1130-1134.

3274 | May 15 2011

The article which was published in NATURE uses miRNA to study p53 network. The article which was citied by 562 provides a new way to study target. [Read the Full Post]

Wheatley, S. P. and I. A. McNeish (2005). "Survivin: a protein with dual roles in mitosis and apoptosis." Int Rev Cytol 247: 35-88.

3579 | Apr 22 2011

a review give us a detail information of survivin’s role in mitosis and apoptosis.54 pages content include main information and data about survivin. [Read the Full Post]

Bouwmeester, T., A. Bauch, et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway." Nat Cell Biol 6(2): 97-105.

3430 | Apr 20 2011

How the TNF-α triggers the NF-KB ? [Read the Full Post]

Chen, G. and D. V. Goeddel (2002). "TNF-R1 signaling: a beautiful pathway." Science 296(5573): 1634-1635.

3623 | Mar 26 2011

This short article introduce TNF-R1 signaling pathway and the targets which are regulated by TNF-R1 signaling pathway. [Read the Full Post]

Lane, D. P. and T. R. Hupp (2003). "Drug discovery and p53." Drug Discov Today 8(8): 347-355.

3196 | Mar 19 2011

The article try to explain the relationship between p53 structure and drug discovery of p53. [Read the Full Post]

Coultas, L. and A. Strasser (2003). "The role of the Bcl-2 protein family in cancer." Semin Cancer Biol 13(2): 115-123.

2548 | Mar 11 2011

A review which gives a systematic description of the relationship between bcl-2 and cancer. [Read the Full Post]

Adams, J. M. and S. Cory (1998). "The Bcl-2 protein family: arbiters of cell survival." Science 281(5381): 1322-1326.

2369 | Mar 2 2011

A article about bcl-2 family proteins which is citied more than 3500.One of the most classical articles about bcl-2 family proteins which is published in science. [Read the Full Post]