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Apoptosis

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

14 | 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

13 | 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]

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

13 | Nov 21 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]

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

29 | 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

23 | 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

27 | 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

36 | 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

57 | 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

67 | 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

29 | 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]

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

67 | 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

40 | 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

10 | 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

49 | 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]

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

62 | 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

59 | 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

67 | 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

67 | 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

54 | 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

74 | 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

92 | 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]

RIP3 inhibition protects locomotion function through ameliorating mitochondrial antioxidative capacity after spinal cord injury

98 | Jun 17 2019

Wang Y et al. suggested improving antioxidative capacity as a potential multifunctional treatment after SCI and the broader possibility of targeting RIP3 activity as a therapeutic window for spinal neuroprotective intervention. [Read the Full Post]

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

80 | 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

109 | 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

161 | 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]

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

127 | 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]

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

175 | 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]

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

172 | 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]

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

154 | 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

201 | 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

107 | 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

104 | 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

90 | 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

453 | 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

478 | 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

128 | 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]

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

346 | 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

324 | 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

213 | 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

231 | 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

163 | 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

143 | 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

148 | 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

145 | 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

199 | 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]

Parthenolide inhibits the initiation of experimental autoimmune neuritis

558 | 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

311 | 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

316 | 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

219 | 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

319 | 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

801 | 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]

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

430 | 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

323 | 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

515 | 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

330 | 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

352 | 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]

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

507 | 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

599 | 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

548 | 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

589 | 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

1665 | 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

591 | 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

485 | 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

658 | 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

806 | 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

2095 | 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

545 | 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

566 | 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

1052 | 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

625 | 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]

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

448 | 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

1770 | 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

454 | 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

696 | 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]

Chenodeoxycholic acid activates NLRP3 inflammasome and contributes to cholestatic liver fibrosis

938 | 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

815 | 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

544 | 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

1341 | 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

1034 | 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.

959 | 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

854 | 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

1105 | 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

713 | 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

691 | 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]

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

1082 | 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]

Inhibition of glioblastoma cell proliferation, migration and invasion by the proteasome antagonist carfilzomib

965 | Sep 22 2017

Areeb Z et al. showed that carfilzomib represents a novel, yet FDA-approved agent for the treatment of glioblastoma multiforme. [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

1400 | 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

1089 | 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

808 | 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

1203 | 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

1280 | 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

1084 | 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]

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.

837 | 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

801 | 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

1324 | 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

1385 | 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

1329 | 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

886 | 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

907 | 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]

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

1529 | 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

1959 | 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]

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

1443 | 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

2141 | 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

1222 | 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

1264 | 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

2016 | 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

1390 | 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

1347 | 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

1318 | 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

2149 | Nov 01 2016

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

Targeting survivin as a potential new treatment for chondrosarcoma of bone

1318 | 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

2474 | 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

1595 | 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

6520 | 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

1197 | 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]

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

3966 | 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]

RIP1, a novel oncogenic driver in melanoma

4294 | 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

4131 | 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

2257 | 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

2398 | 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

2233 | 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

2573 | 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

3823 | 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

2529 | 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

2616 | 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

2214 | 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

2334 | 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

2466 | 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

3736 | 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

2951 | 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

3662 | 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

2413 | 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

2729 | 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

3502 | 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

4982 | 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

4405 | 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

2903 | 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

3112 | 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

4355 | 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

3412 | 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

3883 | 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

5307 | 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

3363 | 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.

2755 | 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.

3433 | 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.

3484 | 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.

3176 | 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.

3388 | 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.

3279 | 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.

3460 | 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.

3084 | 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.

2457 | 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.

2261 | 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]