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Blog of Signaling Pathways

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

89 views | 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

98 views | 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]

Oncogenic role of ABHD5 in endometrial cancer

106 views | Apr 04 2019

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

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

50 views | 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]

Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial

70 views | Apr 03 2019

Planchard D et al. found that Dabrafenib plus trametinib represents a new therapy with clinically meaningful antitumour activity and a manageable safety profile in patients with previously untreated BRAFV600E-mutant NSCLC. [Read the Full Post]

White light emitting diode induces autophagy in hippocampal neuron cells through GSK-3-mediated GR and RORα pathways

94 views | Apr 03 2019

Yang Y et al. demonstrated that GSK-3-mediated GR/RORα signaling pathway is involved in white LED light-induced autophagy in hippocampal neuron cells. [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

55 views | 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]

Grem2 mediates podocyte apoptosis in high glucose milieu

102 views | Apr 02 2019

Wen H et al. indicated high glucose increases Grem2 expression in kidney cells. Grem2 mediates podocyte apoptosis through Smads. [Read the Full Post]

AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules

0 views | Apr 01 2019

Guichard SM et al. indicated the ability to dose AZD2014 intermittently, together with its ability to block signaling from both mTORC1 and mTORC2 complexes, makes this compound an ideal candidate for combining with endocrine therapies in the clinic. AZD2014 is currently in phase II clinical trials. [Read the Full Post]

Slow release of etoposide from dextran conjugation shifts etoposide activity from cytotoxicity to differentiation: A promising tool for dosage control in anticancer metronomic therapy

58 views | Apr 01 2019

De Nicola M et al. indicated slow release as a promising novel strategy for stabilizing low drug levels in metronomic regimens. [Read the Full Post]

Roxadustat in the treatment of anaemia in chronic kidney disease

93 views | Mar 31 2019

Del Vecchio L et al showed that Roxadustat is a chemical drug and thus has the potential of being cheaper than traditional ESAs. Given that the peaks of endogenous EPO are much lower than those observed with traditional ESA, it is possible to speculate the roxadustat (and more in general PHD inhibitors) will be safer than ESA on cardiovascular safety end-points. Considering that HIFs are involved in different pathways, with possible promotion of relevant side effects, their safety must be proven in long-term studies. [Read the Full Post]

Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China

106 views | Mar 31 2019

Chen N et al. showed that FG-4592 may prove an effective alternative for managing anemia of CKD. It is currently being investigated in a pivotal global Phase 3 program. [Read the Full Post]

Functional and Mechanistic Interrogation of BET Bromodomain Degraders for the Treatment of Metastatic Castration Resistant Prostate Cancer

58 views | Mar 30 2019

Kregel S et al. identified increases in polyunsaturated fatty acids (PUFAs) and Thioredoxin-interacting protein (TXNIP) as potential pharmacodynamics biomarkers for targeting BET proteins. [Read the Full Post]

Ibrutinib for the treatment of chronic lymphocytic leukemia

100 views | Mar 30 2019

Novel, extremely promising, combination strategies, based on the association of ibrutinib with chemoimmunotherapy, antiCD20 monoclonal antibody or other targeted agents, are currently being investigated, with the goal of achieving greater depth of remission, especially MRD-negativity, and removing the need for indefinite treatment. [Read the Full Post]

MYC status as a determinant of synergistic response to Olaparib and Palbociclib in ovarian cancer

99 views | Mar 29 2019

Yi J et al. show for the first time that combining PARP and CDK4/6 inhibition has synergistic effects against MYC overexpressing ovarian cancer cells both in vitro and in vivo. [Read the Full Post]

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

52 views | 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]

The SIRT1 inhibitor EX-527 suppresses mTOR activation and alleviates acute lung injury in mice with endotoxiemia

89 views | Mar 28 2019

Huang J et al. suggested that selective inhibition of SIRT1 by EX-527 might alleviate endotoxemia-associated acute lung injury partially via suppression of mTOR, which implies that SIRT1 selective inhibitors might have potential value for the pharmacological intervention of inflammatory lung injury. [Read the Full Post]

The antinociceptive effect of resveratrol in bone cancer pain is inhibited by the Silent Information Regulator 1 inhibitor selisistat

88 views | Mar 28 2019

Lux S et al. showed that acute and chronic resveratrol induces antinociceptive effect in the model of metastatic osseous oncological pain, an effect that would be mediated by SIRT1 molecular signalling. [Read the Full Post]

Effects of Combination of Estradiol with Selective Progesterone Receptor Modulators (SPRMs) on Human Breast Cancer Cells In Vitro and In Vivo

52 views | Mar 27 2019

Nair HB et al. hypothesized that a combination of estradiol (E2) with selective progesterone receptor modulator (SPRM) to exert a safer profile on endometrium will also reduce mammary gland proliferation and could be used to prevent breast cancer when used in MHT. [Read the Full Post]

Mechanisms of U46619-induced contraction in mice intrarenal arteries

149 views | Mar 27 2019

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