Blog of Signaling Pathways

Inhibition of 6-phosphofructo-2-kinase suppresses fibroblast-like synoviocytes-mediated synovial inflammation and joint destruction in rheumatoid arthritis

499 views | Oct 16 2018

Zou Y et al. showed that elevated PFKFB3 expression might contribute to synovial inflammation and aggressive behaviours of RA FLSs, suggesting a novel strategy of targeting PFKFB3 to prevent synovial inflammation and joint destruction in RA. [Read the Full Post]

Blockage of glycolysis by targeting PFKFB3 suppresses tumor growth and metastasis in head and neck squamous cell carcinoma

456 views | Oct 16 2018

Li HM et al. indicated the pharmacological inhibition of PFKFB3 via PFK15 suppressed tumor growth and alleviated metastasis in HNSCC, offering a promising strategy for cancer therapy. [Read the Full Post]

A sensitive virus yield assay for evaluation of Antivirals against Zika Virus

762 views | Oct 15 2018

Goebel S et al. showed qPCR associated higher sensitivity and short duration of the assay time, this novel cell based assay will be very useful for confirming the activity of antivirals against ZIKV. [Read the Full Post]

Retinoic acid and TGF-β signalling cooperate to overcome MYCN-induced retinoid resistance

2071 views | Oct 15 2018

Duffy DJ et al. provided a powerful precision oncology tool for identifying the driving signalling networks for malignancies not primarily driven by somatic mutations, such as paediatric cancers. By applying global omics approaches to the signalling networks regulating neuroblastoma differentiation and stemness, we have determined the pathways involved in the MYCN-mediated retinoid resistance, with TGF-β signalling being a key regulator. These findings revealed a number of combination treatments likely to improve clinical response to retinoid therapy, including co-treatment with retinoids and KGN, which may prove valuable in the treatment of high-risk MYCN-amplified neuroblastoma. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 views | Oct 14 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Acquired resistance to combination treatment through loss of synergy with MEK and PI3K inhibitors in colorectal cancer

0 views | Oct 14 2018

Bhattacharya B et al. highlight that AQR to combination treatment may develop through alternative mechanisms to those of single agent treatment, including a change in drug interaction. [Read the Full Post]

Romidepsin induces G2/M phase arrest via Erk/cdc25C/cdc2/cyclinB pathway and apoptosis induction through JNK/c-Jun/caspase3 pathway in hepatocellular carcinoma cells

956 views | Oct 13 2018

Sun WJ et al. offered proof-of-concept for use of Romidepsin as a novel class of chemotherapy in the treatment of HCC. [Read the Full Post]

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

493 views | Oct 13 2018

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]

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

1793 views | Oct 12 2018

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]

Epigenetic repression of miR-375 is the dominant mechanism for constitutive activation of the PDPK1/RPS6KA3 signalling axis in multiple myeloma.

966 views | Oct 12 2018

Tatekawa S et al. showed the universal involvement of overlapping epigenetic dysregulation for abnormal miR-375 repression in MM, which is likely to contribute to myelomagenesis and to subsequent myeloma progression by activating oncogenic signalling pathways. [Read the Full Post]

Activation of Wnt/β-catenin signalling is required for TGF-β/Smad2/3 signalling during myofibroblast proliferation

857 views | Oct 12 2018

Xu L et al. found that a major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFβ1-smad2/3 signalling through Wnt/β-catenin contribute to lung fibrosis. [Read the Full Post]

Tumor Necrosis Factor Inhibits Spread of Hepatitis C Virus Among Liver Cells, Independent From Interferons

939 views | Oct 10 2018

Laidlaw SM et al. found TNF to have antiviral effects independently of, as well as in combination with, IFNs. TNF inhibits HCV infection despite increased HCV envelope glycoprotein-mediated infection of liver cells. These findings contradict those from other studies, which have reported that TNF blocks signal transduction in response to IFNs. The destructive inflammatory effects of TNF must be considered along with its antiviral effects. [Read the Full Post]

Targeting Hsp90 with FS-108 circumvents gefitinib resistance in EGFR mutant non-small cell lung cancer cells

564 views | Oct 10 2018

Wang YQ et al. indicated that FS-108 is a powerful agent that impacts the survival of gefitinib-resistant cells in vitro and in vivo through targeting Hsp90. [Read the Full Post]

A multi-targeted liquid chromatography-mass spectrometry screening procedure for the detection in human urine of drugs non-prohibited in sport commonly used by the athletes

780 views | Oct 09 2018

Mazzarino M et al. indicated this work presents an analytical method for the simultaneous analysis in human urine of 38 pharmacologically active compounds (19 benzodiazepine-like substances, 7 selective serotonin reuptake inhibitors, 4 azole antifungal drugs, 5 inhibitors of the phosphodiesterases type 4 and 3 inhibitors of the phosphodiesterase type 5) by liquid-chromatography coupled with tandem mass spectrometry. [Read the Full Post]

PTC725, an NS4B-Targeting Compound, Inhibits a Hepatitis C Virus Genotype 3 Replicon, as Predicted by Genome Sequence Analysis and Determined Experimentally

0 views | Oct 09 2018

Graci JD et al. identified previously unreported amino acid substitutions selected by PTC725 treatment which further demonstrate that these compounds target the NS4B first transmembrane region. [Read the Full Post]

Cyclic tensile strain promotes the osteogenic differentiation of a bone marrow stromal cell and vascular endothelial cell co-culture system

908 views | Oct 08 2018

Jiang Y et al. demonstrated that cyclic tensile strain promotes osteogenic differentiation in BMSC/VEC co-culture systems, possibly via a VEC-mediated paracrine effect of VEGF on BMSCs. [Read the Full Post]

The phosphodiesterase 4 inhibitor roflumilast augments the Th17-promoting capability of dendritic cells by enhancing IL-23 production, and impairs their T cell stimulatory activity due to elevated IL-10

573 views | Oct 08 2018

Bros M et al. suggested that PDE4 inhibitors aside from their broad overall anti-inflammatory effects may enhance the Th17-polarizing capacity in DCs as an unwanted side effect. [Read the Full Post]

Synergistic cytotoxicity of BIIB021 with triptolide through suppression of PI3K/Akt/mTOR and NF-κB signal pathways in thyroid carcinoma cells

3330 views | Oct 07 2018

Kim SH et al. suggested that BIIB021 has a cytotoxic activity accompanied by regulation of hsp90 client proteins in thyroid carcinoma cells. Moreover, the synergism between BIIB021 and triptolide in induction of cytotoxicity is associated with the inhibition of PI3K/Akt/mTOR and NF-κB signal pathways, the underexpression of survivin and the activation of DNA damage response in thyroid carcinoma cells. [Read the Full Post]

Artesunate enhances the therapeutic response of glioma cells to temozolomide by inhibition of homologous recombination and senescence

902 views | Oct 07 2018

Berte N et al. showed the amelioration of TMZ-induced cell death upon ART co-treatment provides a rational basis for a combination regime of TMZ and ART in glioblastoma therapy. [Read the Full Post]

Inactivation of Lsd1 triggers senescence in trophoblast stem cells by induction of Sirt4

695 views | Oct 06 2018

Castex J et al. showed that by repression of Sirt4, Lsd1 directs the epigenetic control of TSC immortality via maintenance of metabolic flexibility. [Read the Full Post]