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Blog of Signaling Pathways

The HDAC Inhibitor Quisinostat (JNJ-26481585) Supresses Hepatocellular Carcinoma alone and Synergistically in Combination with Sorafenib by G0/G1 phase arrest and Apoptosis induction

165 views | Mar 17 2020

He B et al. indicated that quisinostat, as a novel chemotherapy for HCC, exhibited excellent antitumor activity in vitro and vivo, which was even enhanced by the addition of sorafenib, implying combination of quisinostat with sorafenib a promising and alternative therapy for patients with advanced hepatocellular carcinoma. [Read the Full Post]

Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

147 views | Mar 16 2020

Tian X et al.demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment. [Read the Full Post]

Structure of the intact ATM/Tel1 kinase

161 views | Mar 16 2020

Wang X et al. provided a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents. [Read the Full Post]

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

207 views | Mar 15 2020

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

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

196 views | Mar 15 2020

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

WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance

91 views | Mar 14 2020

Zheng H et al. demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes. [Read the Full Post]

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

359 views | Mar 14 2020

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

ATM induces MacroD2 nuclear export upon DNA damage

159 views | Mar 13 2020

Golia B et al. identified a novel feedback regulation between two crucial DNA damage-induced signaling pathways: ADP-ribosylation and ATM activation. [Read the Full Post]

mbined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet

139 views | Mar 13 2020

Luo F et al. suggested that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages. [Read the Full Post]

PXD101 significantly improves nuclear reprogramming and the in vitro developmental competence of porcine SCNT embryos

179 views | Mar 12 2020

Jin JX et al. demonstrated that PXD101 can significantly improve the in vitro and in vivo developmental competence of porcine SCNT embryos and can enhance their nuclear reprogramming. [Read the Full Post]

How Does Empagliflozin Reduce Cardiovascular Mortality? Insights From a Mediation Analysis of the EMPA-REG OUTCOME Trial

106 views | Mar 12 2020

Inzucchi SE et al. indicated in this exploratory analysis from the EMPA-REG OUTCOME trial, changes in markers of plasma volume were the most important mediators of the reduction in risk of CV death with empagliflozin versus placebo. [Read the Full Post]

Molecular alterations and poziotinib efficacy, a pan-HER inhibitor, in human epidermal growth factor receptor 2 (HER2)-positive breast cancers: Combined exploratory biomarker analysis from a phase II clinical trial of poziotinib for refractory HER2-positive breast cancer patients

205 views | Mar 11 2020

Koga T et al. identified HER2 CN amplification, PIK3CA pathway alteration, and ERBB3 cytoplasmic mutation showed predictive roles on clinical outcomes of HER2-positive MBC treated with poziotinib. [Read the Full Post]

Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study

187 views | Mar 11 2020

O'Connor OA et al. showed that monotherapy with belinostat produced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across the major subtypes, irrespective of number or type of prior therapies. These results have led to US Food and Drug Administration approval of belinostat for this indication. [Read the Full Post]

Activity of a novel HER2 inhibitor, poziotinib, for HER2 exon 20 mutations in lung cancer and mechanism of acquired resistance: An in vitro study

218 views | Mar 10 2020

Koga T et al. identified the secondary C805S at the covalent binding site of HER2 to poziotinib as a potential mechanism of acquired resistance. HSP90 inhibitors might be a therapeutic strategy for the C805S secondary mutation. [Read the Full Post]

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

93 views | Mar 09 2020

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

The Role and Mechanism of CRT0066101 as an Effective Drug for Treatment of Triple-Negative Breast Cancer

165 views | Mar 09 2020

Liu Y et al. indicated that PRKD inhibitor CRT0066101 exhibits anti-TNBC effects via modulating a phosphor-signaling network and inhibiting the phosphorylation of many cancer-driving factors, including MYC, MAPK1/3, AKT, YAP, and CDC2, providing insight into the important roles as well as the molecular mechanism of CRT0066101 as an effective drug for TNBC. [Read the Full Post]

MGCD0103, a selective histone deacetylase inhibitor, coameliorates oligomeric Aβ25-35 -induced anxiety and cognitive deficits in a mouse model

333 views | Mar 08 2020

Huang HJ et al. revealed MGCD0103 could be a potential therapeutic agent against AD. [Read the Full Post]

Simultaneous inhibition of JAK and SYK kinases ameliorates chronic and destructive arthritis in mice

94 views | Mar 08 2020

Llop-Guevara A et al. showed that concurrent JAK + SYK inhibition resulted in higher efficacy than single kinase inhibition and TNF blockade in a chronic and severe arthritis model. Thus, blockade of multiple immune signals with dual JAK + SYK inhibition represents a reasonable therapeutic strategy for RA, in particular in patients with inadequate responses to current treatments. Our data supports the multiplicity of events underlying this heterogeneous and complex disease. [Read the Full Post]

An Ilomastat-CD Eye Drop Formulation to Treat Ocular Scarring

105 views | Mar 06 2020

Mohamed-Ahmed AHA et al. showed that Ilomastat-CD has the potential to be formulated as an eye drop for use as an antifibrotic, which may have implications for the prevention of scarring in many settings, for example glaucoma filtration surgery. [Read the Full Post]

The class I/IV HDAC inhibitor mocetinostat increases tumor antigen presentation, decreases immune suppressive cell types and augments checkpoint inhibitor therapy

167 views | Mar 06 2020

Briere D et al. provided evidence that mocetinostat modulates immune-related genes in tumor cells as well as immune cell types in the tumor microenvironment and enhances checkpoint inhibitor therapy. [Read the Full Post]