Category

Archives

PI3K

Melatonin alleviates hypoxia-induced cardiac apoptosis through PI3K/Akt pathway

1 views | Jan 19 2020

Luo GP et al. demonstrated that melatonin confers cardioprotection by inhibiting apoptosis through the activation of PI3K/Akt signaling pathway in hypoxic cardiomyocytes. [Read the Full Post]

PI3K inhibitor LY294002, as opposed to wortmannin, enhances AKT phosphorylation in gemcitabine-resistant pancreatic cancer cells

15 views | Jan 06 2020

Wang Y et al. revealed that LY294002 displays the opposite effect on PI3K-dependent AKT phosphorylation, which maintains cell survival from the cytotoxicity introduced by LY294002 itself in GEM-resistant pancreatic cancer cells. We suggest that targeting the PI3K/AKT signaling pathway with inhibitors may be counterproductive for patients with PC who have acquired GEM-resistance. [Read the Full Post]

Biomarkers of response and resistance to PI3K inhibitors in estrogen receptor-positive breast cancer patients and combination therapies involving PI3K inhibitors

7 views | Jan 04 2020

Brandão M at al. described the rational for new combination therapies involving PI3Ki and anti-HER2 agents, chemotherapy, CDK4/6 inhibitors, mTOR inhibitors or new endocrine treatments and discuss the ongoing trials in this field. [Read the Full Post]

The PI3K/mTOR dual inhibitor BEZ235 suppresses proliferation and migration and reverses multidrug resistance in acute myeloid leukemia

16 views | Dec 24 2019

Deng L et al. indicated that the PI3K/mTOR dual inhibitor BEZ235 effectively chemosensitizes AML cells via increasing miR-1-3p and subsequently down-regulating BAG4, EDN1 and ABCB1. [Read the Full Post]

NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma

19 views | Dec 24 2019

Huang JC et al. suggested NVP-BEZ235 could synergize cisplatin sensitivity in OS, combination of NVP-BEZ235 with cisplatin could represent a novel therapeutic strategy for treatment of OS. [Read the Full Post]

Dactolisib (NVP-BEZ235) toxicity in murine brain tumour models

20 views | Dec 23 2019

Netland IA et al. suggested that despite the anti-neoplastic efficacy of dactolisib in glioma treatment in vitro, its utility in vivo is questionable due to toxicity. [Read the Full Post]

First-in-Human Phase I Study of GSK2126458, an Oral Pan-Class I Phosphatidylinositol-3-Kinase Inhibitor, in Patients with Advanced Solid Tumor Malignancies

13 views | Dec 15 2019

Munster P et al. indicated although the MTD of GSK458 was 2.5 mg once daily, twice-daily dosing may increase duration of target inhibition. Fasting insulin and glucose levels served as pharmacodynamic markers of drug exposure. Select patients achieved durable responses; however,PIK3CAmutations were neither necessary nor predictive of response. Combination treatment strategies and novel biomarkers may be needed to optimally target PI3K. [Read the Full Post]

Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF

22 views | Dec 12 2019

Mercer PF et al. indicated the data define PI3K as a promising therapeutic target in IPF and provide a scientific and dosing framework for progressing GSK2126458 to clinical testing in this disease setting. A proof-of-mechanism trial of this agent is currently underway. [Read the Full Post]

PI3K inhibition reduces murine and human liver fibrogenesis in precision-cut liver slices

15 views | Dec 12 2019

Gore E et al. showed that omipalisib has antifibrotic properties in ex vivo mouse and human liver PCTS, but higher concentrations showed toxicity in jejunum PCTS. While the PI3K/mTOR pathway appears to be a promising target for the treatment of liver fibrosis, PCTS revealed likely side effects in the intestine at higher doses. [Read the Full Post]

Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks

0 views | Nov 15 2019

Zhou T et al. indicated this chromosomal hypersensitivity, as well as a small but reproducible enhancement of calicheamicin cytotoxicity following siRNA-mediated TDP1 knockdown, suggests a role for TDP1 in repair of 3'-PG double-strand breaks in vivo. [Read the Full Post]