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Blog of Signaling Pathways

An RNA interference screen identifies new avenues for nephroprotection

0 views | Mar 29 2017

Zynda ER et al shed new light on the mechanisms of stress response in mammalian cells, and open new avenues to reduce the morbidity and mortality associated with renal injury. [Read the Full Post]

The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid

0 views | Mar 28 2017

Hiramoto K et al suggested that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. [Read the Full Post]

DNA Topoisomerase IIα contributes to the early steps of adipogenesis in 3T3-L1 cells

0 views | Mar 28 2017

Jacobsen RG et al. found that treatment of cancer with Topo II inhibitors may alter metabolic processes in the adipose tissue. [Read the Full Post]

A Repurposing Strategy for Hsp90 Inhibitors Demonstrates Their Potency against Filarial Nematodes

1 views | Mar 27 2017

Gillan V et al provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

Beneficial metabolic actions of a stable GIP agonist following pretreatment with a SGLT2 inhibitor in high fat fed diabetic mice

987 views | Mar 26 2017

Millar PJ et al demonstratd that (DAla(2))GIP can exert beneficial metabolic control in high fat fed diabetic mice pre-treated with DAPA. The results highlight possibility of a targeted and personalized approach using a GIP agonist and SGLT2 inhibitor for the treatment of type 2 diabetes. [Read the Full Post]

Inhibition of Human UDP-Glucuronosyltransferase Enzymes by Canagliflozin and Dapagliflozin: Implications for Drug-Drug Interactions

3 views | Mar 26 2017

Pattanawongsa A et al found that since the sodium-glucose cotransporter 2 inhibitors share common structural features, notably a glycoside moiety, investigation of drugs in this class for effects on UGT to identify (or exclude) potential drug-drug interactions is warranted. [Read the Full Post]

Small-Molecule Induction of Canine Embryonic Stem Cells Toward Naïve Pluripotency

738 views | Mar 25 2017

Tobias IC et al. suggested that 2iL culture conditions promote the conversion of cESCs toward an epigenetically distinct pluripotent state resembling naïve PSCs. [Read the Full Post]

DNA Topoisomerase IIα contributes to the early steps of adipogenesis in 3T3-L1 cells

832 views | Mar 25 2017

Jacobsen RG et al. found that treatment of cancer with Topo II inhibitors may alter metabolic processes in the adipose tissue. [Read the Full Post]

Reversal of Dabigatran Effects in Models of Thrombin Generation and Hemostasis by Factor VIIa and Prothrombin Complex Concentrate

0 views | Mar 25 2017

Hoffman M et al suggested that a cell-based model reflects the effects on thrombin generation of clinically relevant levels of FVIIa and PCC in the presence of dabigatran. Enhancing the rate of thrombin generation and peak thrombin level appear to correlate best with hemostasis in vivo. The ineffectiveness of FVIIa at supratherapeutic dabigatran levels may explain conflicting reports of its efficacy in dabigatran reversal. [Read the Full Post]

MITF depletion elevates expression levels of ERBB3 receptor and its cognate ligand NRG1-beta in melanoma

948 views | Mar 24 2017

Alver TN et al. suggested that MITF may play a role in the development of acquired drug resistance through hyper-activation of the PI3K pathway. [Read the Full Post]

Silymarin improved diet-induced liver damage and insulin resistance by decreasing inflammation in mice

878 views | Mar 24 2017

Guo Y et al. suggested that silymarin-induced alleviation of inflammatory response could be a mechanism responsible for its benefits against liver damage and insulin resistance. [Read the Full Post]

Linifanib (ABT-869) Potentiates the Efficacy of Chemotherapeutic Agents through the Suppression of Receptor Tyrosine Kinase-Mediated AKT/mTOR Signaling Pathways in Gastric Cancer

838 views | Mar 23 2017

Chen J et al. suggested that the addition of ABT-869 to traditional chemotherapies may be a promising strategy for the treatment of human gastric cancer. [Read the Full Post]

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

0 views | Mar 23 2017

Meng Z et al indicated that PTEN activation by inhibiting HDAC6 significantly contributed to tumour inhibition. Therefore, non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. [Read the Full Post]

Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression

1368 views | Mar 22 2017

Duckworth C et al suggestec that overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating expression of CXCL1, CXCL2 and CXCL8 that is IKKβ-dependent. Co-targeting IKKβ and PI3K pathways downstream of GAB2 might be a promising therapeutic strategy for ovarian cancer that overexpresses GAB2. [Read the Full Post]

FBW7 mutations mediate resistance of colorectal cancer to targeted therapies by blocking Mcl-1 degradation

1996 views | Mar 21 2017

Tong J et al. demonstrate FBW7 mutational status as a key genetic determinant of CRC response to targeted therapies, and Mcl-1 as an attractive therapeutic target. [Read the Full Post]

Tivantinib induces G2/M arrest and apoptosis by disrupting tubulin polymerization in hepatocellular carcinoma

0 views | Mar 21 2017

Xiang Q et al suggested that the potent anti-tumor activity of tivantinib in HCC was achieved by targeting microtubule. Tivantinib treatment for patients with HCC should not be selected based on MET status. [Read the Full Post]

CD4+ T cell–dependent and –independent cytokine-chemokine network changes in the immune responses of HIV-infected individuals

2269 views | Mar 20 2017

Arnold KB et al identified a critical deficiency in NK cell responses of HIV-infected individuals, independent of CD4(+) T cell depletion, which directs secreted profiles. Our findings illustrate a broad approach for identifying key disease-associated nodes in a multicellular, multivariate signaling network. [Read the Full Post]

Discovery of Diverse Small-Molecule Inhibitors of Mammalian Sterile20-like Kinase 3 (MST3).

305 views | Mar 19 2017

Olesen SH et al. suggested key roles for members of the mammalian Sterile20-like (MST) family of kinases in many aspects of biology. [Read the Full Post]

Synthetic Lethal Screens Identify Vulnerabilities in GPCR Signaling and Cytoskeletal Organization in E-Cadherin-Deficient Cells

298 views | Mar 19 2017

Telford BJ, et al. demonstrated that E-cadherin loss creates druggable vulnerabilities that have the potential to improve the management of both sporadic and familial LBC and DGC. [Read the Full Post]

The-cyclic-GMP-protein-kinase-G-pathway-as-a-therapeutic-target-in-head-and-neck-squamous-cell-carcinoma

819 views | Mar 19 2017

Tuttle TR et al found that Tadalafil substantially reduced the growth of CAL27-derived tumors in athymic mice. Several drugs which either activate sGC or inhibit PDE5 are approved for treatment of nonmalignant conditions. These drugs could be repurposed as novel and effective therapeutics in patients with head and neck cancer. [Read the Full Post]