Blog of Signaling Pathways

Cotargeting MNK and MEK kinases induces the regression of NF1-mutant cancers

598 views | Aug 15 2018

Lock R et al. demonstrated that combined MNK and MEK suppression represents a promising therapeutic strategy for these incurable Ras-driven tumors and highlight the utility of developing selective MNK inhibitors for these and possibly other malignancies. [Read the Full Post]

Acquired CDK6 amplification promotes breast cancer resistance to CDK4/6 inhibitors and loss of ER signaling and dependence

0 views | Aug 14 2018

Yang C et al. suggested that the clinical paradigm of sequential endocrine-based therapy may be ineffective in some settings of acquired CDK4/6 resistance. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

0 views | Aug 14 2018

Song M et al. indicated that small interfering RNA (siRNA)-based screening of ∼4800 druggable genes in 3-dimensional CSLC cultures in comparison to 2-dimensional bulk cultures of U87 glioma cells revealed 3 groups of genes essential for the following: survival of the CSLC population only, bulk-cultured population only, or both populations. [Read the Full Post]

Hepatitis C Virus NS4B Can Suppress STING Accumulation To Evade Innate Immune Responses

1241 views | Aug 13 2018

Yi G et al. showed that 2a/JFH1 NS4B has an additional mechanism to evade STING signaling through suppressing STING accumulation. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

0 views | Aug 13 2018

Song M et al. provided a useful resource that can be exploited for the selective elimination of CSLCs.-Song, M., Lee, H., Nam, M.-H., Jeong, E., Kim, S., Hong, Y., Kim, N., Yim, H. Y., Yoo, Y.-J., Kim, J. S., Kim, J.-S., Cho, Y.-Y., Mills, G. B., Kim, W.-Y., Yoon, S. Loss-of-function screens of druggable targetome against cancer stem-like cells. [Read the Full Post]

A profiling study of a newly developed HCVcc strain PR63cc's sensitivity to direct-acting antivirals

1233 views | Aug 12 2018

Tao W et al. showed that PR63cc was more resistant than JFH1 to the asunaprevir/daclatasvir combination treatment. In summary, our study systemically analyzed the DAA sensitivity of a new HCVcc strain and identified critical RAVs. These results are not only important for monitoring the emergence of drug-resistant mutations of current DAA therapies, but also valuable for developing next-generation DAAs. [Read the Full Post]

VCP inhibitors induce endoplasmic reticulum stress, cause cell cycle arrest, trigger caspase-mediated cell death and synergistically kill ovarian cancer cells in combination with Salubrinal

657 views | Aug 12 2018

Bastola P et al. provided a proof-of-concept that VCP inhibitors can be used as a single agent and can be synergized with compounds that enhance CHOP expression to induce cell death in ovarian cancer cells. [Read the Full Post]

The cKit Inhibitor, Masitinib, Prevents Diabetes-Induced Retinal Vascular Leakage

1008 views | Aug 10 2018

Kim SR et al. provided the first demonstration that cKit inhibitors, such as masitinib, might be promising therapeutics for prevention of diabetes-induced breakdown of the BRB. [Read the Full Post]

Proliferation Markers Are Associated with MET Expression in Hepatocellular Carcinoma and Predict Tivantinib Sensitivity In Vitro

0 views | Aug 10 2018

Rebouissou S et al. indicated that Tivantinib acts as an antimitotic compound, and cell proliferation markers are the best predictors of its antitumor efficacy in cell lines. Ki67 expression should be tested in clinical trials to predict tivantinib response. [Read the Full Post]

Local release of masitinib alters in vivo implantable continuous glucose sensor performance

889 views | Aug 09 2018

Avula M et al. showed that the mast cell-targeting tyrosine kinase inhibitor, masitinib, was released from degradable polymer microspheres delivered from the surfaces of FDA-approved human commercial CGM needle-type implanted sensors in a rodent subcutaneous test bed. By targeting the mast cell c-Kit receptor and inhibiting mast cell activation and degranulation, local masitinib penetration around the CGM to several hundred microns sought to reduce sensor fibrosis to extend CGM functional lifetimes in subcutaneous sites. Drug-releasing and control CGM implants were compared in murine percutaneous implant sites for 21 days using direct-wire continuous glucose reporting. Drug-releasing implants exhibited no significant difference in CGM fibrosis at implant sites but showed relatively stable continuous sensor responses over the study period compared to blank microsphere control CGM implants. [Read the Full Post]

Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis

0 views | Aug 09 2018

Sun X et al. showed that metallothionein (MT)-1G is a critical regulator and promising therapeutic target of sorafenib resistance in human HCC cells. [Read the Full Post]

Characterization of cholesterol homeostasis in sphingosine-1-phosphate lyase-deficient fibroblasts reveals a Niemann-Pick disease type C-like phenotype with enhanced lysosomal Ca2+ storage

0 views | Aug 08 2018

Vienken H et al. showed that both a primary defect in cholesterol trafficking and S1P lyase deficiency cause overlapping phenotypic alterations, and challenge the present view on the role of sphingosine in lysosomal Ca2+ homeostasis. [Read the Full Post]

Histone Deacetylase Inhibitor RGFP109 Overcomes Temozolomide Resistance by Blocking NF-κB-Dependent Transcription in Glioblastoma Cell Lines

0 views | Aug 08 2018

Li ZY et al. showed that RGFP109, an HDAC inhibitor, in combination with TMZ may be a therapeutic candidate for patients with temozolomide-resistant GBM. [Read the Full Post]

BMS-708163 and Nilotinib restore synaptic dysfunction in human embryonic stem cell-derived Alzheimer's disease models

1552 views | Aug 07 2018

Nishioka H et al. suggested that the AD models we developed are promising materials for the discovery of AD drugs that target the expression of pre-synaptic proteins and synaptic function. [Read the Full Post]

A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells

701 views | Aug 07 2018

Lo Cicero A et al. highlight the potential of high-throughput drug screening using HGPS iPS-derived cells, in order to find therapeutic compounds for HGPS and, potentially, for other aging-related disorders. [Read the Full Post]

Combined treatment of carfilzomib and z-VAD-fmk inhibits skeletal proteolysis and apoptosis and ameliorates cancer cachexia

968 views | Aug 06 2018

Wang Q et al. found that Combined treatment with CFZ and z-VAD-fmk early in the development of cachexia was associated with signs of less proteolysis and apoptosis and less severe cachexia in a mouse model of cancer-induced cachexia. [Read the Full Post]

CDK inhibitors suppress Th17 and promote iTreg differentiation, and ameliorate experimental autoimmune encephalomyelitis in mice

608 views | Aug 06 2018

Yoshida H et al. suggested that CDK inhibitors modulate TGF-β-signaling pathways, which restore TGF-β-mediated suppression of IL-2 production, thereby modifying the Th17/iTreg balance. [Read the Full Post]

The role of Runx2 in facilitating autophagy in metastatic breast cancer cells

1347 views | Aug 05 2018

Tandon M et al. revealed a novel regulatory mechanism of autophagy via Runx2 and provide molecular insights into the role of autophagy in metastatic cancer cells. [Read the Full Post]

MKP1 mediates chemosensitizer effects of E1a in response to cisplatin in non-small cell lung carcinoma cells

1116 views | Aug 05 2018

Cimas FJ et al. indicated that the present work reinforce the critical role of MKP1 in the cellular response to cisplatin highlighting the importance of this phosphatase in future gene therapy approach based on E1a gene. [Read the Full Post]

Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma

704 views | Aug 04 2018

Mersch S et al. described for the first time the establishment and characterization of a liposarcoma cell line derived from a peritoneal sarcomatosis. Hence, in the future, the newly established cell line Lipo-DUE1 might serve as a useful in vitro and in vivo model to investigate the biological behavior of liposarcoma and to assess novel targeted therapies. [Read the Full Post]