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Blog of Signaling Pathways

PQ401, an IGF-1R inhibitor, induces apoptosis and inhibits growth, proliferation and migration of glioma cells

437 views | Apr 26 2018

Zhou X et al. suggested that PQ401 may serve as a promising leading drug for treating glioma patients with elevated IGF-1R signalling. [Read the Full Post]

Lumiracoxib metabolism in male C57bl/6J mice: characterisation of novel in vivo metabolites

717 views | Apr 25 2018

P Dickie A et al. found that while there was significant overlap with reported human metabolites, a number of unique mouse metabolites were detected, particularly taurine conjugates of lumiracoxib and its oxidative metabolites. [Read the Full Post]

Suppression of chronic lymphocytic leukemia progression by CXCR4 inhibitor WZ811

911 views | Apr 25 2018

Li SH et al. demonstrated that WZ811 may be a novel approach in the treatment of chronic lymphocytic leukemia. [Read the Full Post]

Mechanism for neurotropic action of vorinostat, a pan histone deacetylase inhibitor.

489 views | Apr 24 2018

Shukla S et al. suggested that vorinostat exerts a positive effect on the neuritogenesis via activation of MEK1/2 & PI3K pathways involving an upstream kinase, TrkA. Bioactive small molecules with neurotrophic and neuritogenic actions, like vorinostat identified in the present study, hold great promise as therapeutic agents for treatment of neurodegenerative diseases and neuronal injuries by virtue of their ability to stimulate neuritic outgrowth. [Read the Full Post]

Pharmacologic Inhibition of JAK1/JAK2 Signaling Reduces Experimental Murine Acute GVHD While Preserving GVT Effects

1068 views | Apr 24 2018

Carniti C et al. provided further evidence that JAK inhibition represents a new and potentially clinically relevant approach to GVHD prevention. [Read the Full Post]

p53-related protein kinase confers poor prognosis and represents a novel therapeutic target in multiple myeloma

679 views | 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 views | 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]

Connexin 32-mediated cell-cell communication is essential for hepatic differentiation from human embryonic stem cells

582 views | Apr 22 2018

Qin J et al. suggested that Cx32 is essential for cell-cell interactions that facilitate driving hESCs through hepatic-lineage maturation. Regulators of both Cx32 and other members of its pathways maybe used as a promising approach on regulating hepatic lineage restriction of pluripotent stem cells and optimizing their functional maturation. [Read the Full Post]

Targeting synthetic lethality between the SRC kinase and the EPHB6 receptor may benefit cancer treatment

657 views | Apr 22 2018

Paul JM et al. indicated the observations are of potential practical importance, since TNBC is an aggressive heterogeneous malignancy with a very high rate of patient mortality due to the lack of targeted therapies, and our work indicates that FDA-approved SRC inhibitors may potentially be used in a personalized manner for treating patients with EPHB6-deficient TNBC. Our findings are also of a general interest, as EPHB6 is downregulated in multiple malignancies and our data serve as a proof of principle that EPHB6 deficiency may be targeted by small molecule inhibitors in the SL approach. [Read the Full Post]

TGF-β1 activates the canonical NF-κB signaling to promote cell survival and proliferation in dystrophic muscle fibroblasts in vitro.

0 views | Apr 21 2018

Ma ZY et al. suggested that TGF-β1 prevents apoptosis and cell cycle arrest in dystrophic muscle fibroblasts through the canonical NF-κB signaling pathway. [Read the Full Post]

Activation of carbonic anhydrase IX by alternatively spliced tissue factor under late-stage tumor conditions.

428 views | Apr 21 2018

Ramchandani D et al. found that CAIX is a novel downstream mediator of asTF in pancreatic cancer, particularly under hypoxic conditions that model late-stage tumor microenvironment. [Read the Full Post]

In silico prediction and in vitro and in vivo validation of acaricide fluazuron as a potential inhibitor of FGFR3 and a candidate anticancer drug for bladder carcinoma

515 views | Apr 20 2018

Ke K et al. suggested for the first time that fluazuron is a potential inhibitor of FGFR3 and a candidate anticancer drug for the treatment of BC. [Read the Full Post]

BET Bromodomain Inhibition as a Therapeutic Strategy in Ovarian Cancer by Downregulating FoxM1

548 views | Apr 20 2018

Zhang Z et al. provide a mechanistic rationale for the clinical investigation of BET bromodomain inhibitors in this deadly disease. [Read the Full Post]

UCN-01 enhances cytotoxicity of irinotecan in colorectal cancer stem-like cells by impairing DNA damage response

587 views | Apr 19 2018

Signore M et al. showed that combination of LY2603618, a specific Chk1/2 inhibitor, with irinotecan resulted in a significant reduction of CRC-SC growth in vivo, confirming that irinotecan treatment coupled to inhibition of Chk1 represents a potentially effective therapeutic approach for CRC treatment. [Read the Full Post]

Abl2 kinase phosphorylates Bi-organellar regulator MNRR1 in mitochondria, stimulating respiration

856 views | Apr 19 2018

Aras S et al. showed that binding of MNRR1 to COX is promoted by phosphorylation at tyrosine-99 and that this interaction stimulates respiration. We show that phosphorylation of MNRR1 takes place in mitochondria and is mediated by Abl2 kinase (ARG). A family with Charcot-Marie-Tooth disease type 1A with an exaggerated phenotype harbors a Q112H mutation in MNRR1, located in a domain that is necessary for transcriptional activation by MNRR1. Furthermore, the mutation causes the protein to function suboptimally in the mitochondria in response to cellular stress. The Q112H mutation hinders the ability of the protein to interact with Abl kinase, leading to defective tyrosine phosphorylation and a resultant defect in respiration. [Read the Full Post]

Evaluation of cardioprotective effect of aqueous extract of Garcinia indica Linn. fruit rinds on isoprenaline-induced myocardial injury in Wistar albino rats

706 views | Apr 18 2018

Patel KJ et al. found that the aqueous extract of G. indica was not found to be cardioprotective against myocardial injury. [Read the Full Post]

P53-dependent upregulation of neutral sphingomyelinase-2: role in doxorubicin-induced growth arrest

546 views | Apr 18 2018

Shamseddine AA et al. identifyd nSMase2 as a novel p53 target gene, regulated by the DNA damage pathway to induce cell growth arrest. [Read the Full Post]

Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment

382 views | Apr 17 2018

Chaudhari U et al. revealed early expression signatures of genes involved in formation of sarcomeric structures, regulation of ion homeostasis and induction of apoptosis. Eighty-four significantly deregulated genes related to cardiac functions, stress and apoptosis were validated using real-time PCR. The expression of the 84 genes was further studied by real-time PCR in hiPSC-CMs incubated with daunorubicin and mitoxantrone, further anthracycline family members that are also known to induce cardiotoxicity. A panel of 35 genes was deregulated by all three anthracycline family members and can therefore be expected to predict the cardiotoxicity of compounds acting by similar mechanisms as doxorubicin, daunorubicin or mitoxantrone. The identified gene panel can be applied in the safety assessment of novel drug candidates as well as available therapeutics to identify compounds that may cause cardiotoxicity. [Read the Full Post]

CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours

378 views | Apr 17 2018

Costa-Cabral S et al. suggested that the KRAS/CDK1 interaction is a robust synthetic lethal effect worthy of further investigation. [Read the Full Post]

Mdivi-1 Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats, Possibly via Inhibition of Drp1-Activated Mitochondrial Fission and Oxidative Stress

376 views | Apr 16 2018

Wu P et al. suggested that Mdivi-1 exerts neuroprotective effects against cell death induced by SAH and the underlying mechanism may be inhibition of Drp1-activated mitochondrial fission and oxidative stress. [Read the Full Post]