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Blog of Signaling Pathways

The Phosphodiesterase 10A Inhibitor PF-2545920 Enhances Hippocampal Excitability and Seizure Activity Involving the Upregulation of GluA1 and NR2A in Post-synaptic Densities

78 views | Feb 15 2019

Zhang Y et al. suggested it would be detrimental to use the drug in seizure patients and might cause neuronal hyperexcitability in non-epileptic individuals. [Read the Full Post]

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours

63 views | Feb 14 2019

Xu H et al. indicated these data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. [Read the Full Post]

Nano-emulsions as vehicles for topical delivery of forskolin

81 views | Feb 14 2019

Miastkowska M et al. showed that the nano-emulsions developed in this study could be used as effective carriers for topical administration of forskolin. [Read the Full Post]

Two mTOR inhibitors, rapamycin and Torin 1, differentially regulate iron-induced generation of mitochondrial ROS

143 views | Feb 13 2019

Huang H et al. suggested that mTOR inhibition may not be able to alleviate iron-induced neurotoxicity. [Read the Full Post]

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

114 views | 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]

Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9

75 views | Feb 12 2019

Guo D et al. found that pancreatic differentiation of ABCC8-deficient cells recapitulated the CHI disease phenotype in vitro, which represents an attractive model to further elucidate the function of SUR1 and to develop and screen for novel therapeutic drugs. [Read the Full Post]

Upregulation of hydroxysteroid sulfotransferase 2B1b promotes hepatic oval cell proliferation by modulating oxysterol-induced LXR activation in a mouse model of liver injury

0 views | Feb 12 2019

Wang Z et al. indicated that upregulation of SULT2B1b might promote HOC proliferation and aggravate liver injury via the suppression of oxysterol-induced LXR activation in chemically induced mouse liver injury. [Read the Full Post]

Mechanisms of Pinometostat (EPZ-5676) Treatment-Emergent Resistance in MLL-Rearranged Leukemia

65 views | Feb 11 2019

Campbell CT et al. demonstrated TER models of the DOT1L inhibitor pinometostat and provided useful tools for investigating clinical resistance. [Read the Full Post]

In vivo activation of invariant natural killer T cells induces systemic and local alterations in T-cell subsets prior to preterm birth

85 views | Feb 11 2019

Gomez-Lopez N et al. found that iNKT-cell activation altered the systemic and local T-cell subsets prior to preterm labour/birth; however, treatment with rosiglitazone partially reversed such effects. [Read the Full Post]

Vascular Endothelial Growth Factor-A Increases the Aqueous Humor Outflow Facility

0 views | Feb 10 2019

Fujimoto T et al. suggested that VEGF-A may regulate the conventional aqueous outflow of SCE cells through VEGFR2. [Read the Full Post]

Leukotriene B₄ Metabolism and p70S6 Kinase 1 Inhibitors: PF-4708671 but Not LY2584702 Inhibits CYP4F3A and the ω-Oxidation of Leukotriene B₄ In Vitro and In Cellulo

95 views | Feb 10 2019

Archambault AS et al. showed that PF-4708671 inhibits CYP4F3A and prevents the ω-oxidation of LTB4 in cellulo, which might result in increased LTB4 levels in vivo. [Read the Full Post]

Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells

71 views | Feb 09 2019

Vallo S et al. suggested that the overexpression of ABCB1 confers resistance to nab-paclitaxel in urothelial cancer cells. Additionally, small molecules may overcome resistance to anticancer drugs that are substrates of ABCB1. [Read the Full Post]

An Oncogenic ALK Fusion and an RRAS Mutation in KRAS Mutation-Negative Pancreatic Ductal Adenocarcinoma

0 views | Feb 09 2019

Shimada Y et al. found that rare oncogenic aberrations, such as the ALK fusion and RRAS mutation, may drive pancreatic carcinogenesis independent of the KRAS mutation. [Read the Full Post]

PBX3 is essential for leukemia stem cell maintenance in MLL-rearranged leukemia

80 views | Feb 08 2019

Guo H et al. found that PBX3 is epigenetically aberrant in the LSCs of MLL-r AML and is essential for leukemia development. Significantly, the differential expression of PBX3 in normal and malignant hematopoietic cells suggests PBX3 as a potential prognostic marker and therapeutic target for MLL-r leukemia. [Read the Full Post]

MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic Implications and Prognostic Values

67 views | Feb 08 2019

Lee GD et al. found that the prognosis of patients with METex14 skipping was similar to that of patients with major driver mutations. siRNA targeting the junction of METex14 skipping could inhibit MET-driven signaling pathways in cells with METex14 skipping. [Read the Full Post]

Inhibition of oxidative phosphorylation suppresses the development of osimertinib resistance in a preclinical model of EGFR-driven lung adenocarcinoma

139 views | Feb 07 2019

Martin MJ et al. supported a model in which the combination of osimertinib and OxPhos inhibitors can delay or prevent resistance in osimertinib-naïve tumour cells, and represents a novel strategy that warrants further pre-clinical investigation. [Read the Full Post]

Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors

189 views | Feb 07 2019

CXCL12 competition binding studies were proven to be highly valuable as an initial screening assay and indicative for the pharmacological and functional profile of competitive CXCR4 antagonists, which will help the design of new potent CXCR4 inhibitors. [Read the Full Post]

Fatty acid translocase promoted hepatitis B virus replication by upregulating the levels of hepatic cytosolic calcium

159 views | Feb 06 2019

Huang J et al. identified a novel link between CD36 and HBV replication, which is associated with cytosolic calcium and the Src kinase pathway. [Read the Full Post]

The energy sensing LKB1-AMPKα1 pathway regulates IGF1 secretion and consequent activation of the IGF1R-PKB pathway in primary hepatocytes

69 views | Feb 06 2019

Chen L et al. demonstrated that the energy-sensing LKB1-AMPK pathway regulates IGF1 secretion in mouse primary hepatocytes, which in turn regulates activation of the IGF1R-PKB pathway. [Read the Full Post]

Inhibition of the NOTCH pathway using γ-secretase inhibitor RO4929097 has limited antitumor activity in established glial tumors

554 views | Feb 05 2019

Dantas-Barbosa C et al. indicated that RO4929097-mediated effects were independent of NOTCH1 mutation status or expression levels, but associated with low IL-6 levels. In established glial tumor models, NOTCH inhibition had limited effects as a single agent, but enhanced efficacy when combined with DNA-interfering agents. These preclinical data need to be considered for further clinical development of NOTCH inhibitors in glial tumors. [Read the Full Post]