Blog of Signaling Pathways

X66, a novel N-terminal heat shock protein 90 inhibitor, exerts antitumor effects without induction of heat shock response

1881 views | Feb 25 2017

The HSP90 inhibitory action and the potent antitumor activity, with the anti-HSR action, promise X66 a novel HSP90-targeted agent, which merits further research and development. [Read the Full Post]

Solitary inhibition of the breast cancer resistance protein (BCRP) efflux transporter results in a clinically significant drug-drug interaction with rosuvastatin by causing up to a two-fold increase in statin exposure

2603 views | Feb 25 2017

Elsby R, et al.'s result shows that solitary inhibition of the intestinal BCRP transporter can result in clinically significant DDIs with rosuvastatin, causing up to a maximum 2-fold increase in exposure, which may warrant statin dose adjustment in clinical practice [Read the Full Post]

Relative cytotoxic potencies and cell death mechanisms of α1 -adrenoceptor antagonists in prostate cancer cell lines

2459 views | Feb 24 2017

Prazosin and doxazosin demonstrated cytotoxic actions on both castration-resistant PC-3 and androgen-sensitive LNCap prostate cancer cells. The mechanisms involved included changes in a number of proliferation and apoptosis regulatory proteins. The role of autophagy depended on the cell type, but contributed to cell death in PC3 cells. [Read the Full Post]

Hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) mediates radiation-induced invasiveness through the SDF-1α/CXCR4 pathway in non-small cell lung carcinoma cells

3069 views | Feb 24 2017

Gu Q et al.'s findings have elucidated the underlying mechanisms of the irradiation-enhanced invasiveness of NSCLC cells. [Read the Full Post]

Metformin regulates differentiation of bone marrow-derived endothelial progenitor cells via multiple mechanisms

1372 views | Feb 23 2017

Li WD, et al.'s results here showed that metformin could regulate the differentiation of EPCs. Autophagy related pathway and AMPK-eNOS-NO pathway were involved in the mechanisms. [Read the Full Post]

Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent

0 views | Feb 22 2017

Thangamani S, et al.'s study lays the foundation for further investigation of repurposing simvastatin as a topical antibacterial agent to treat skin infections. [Read the Full Post]

Mutant p53 in concert with an interleukin-27 receptor alpha deficiency causes spontaneous liver inflammation, fibrosis, and steatosis in mice

1473 views | Feb 22 2017

The combination of mutant p53 and IL27RA(-/-) causes spontaneous liver inflammation, steatosis, and fibrosis in vivo, whereas either gene alone in vivo has no effects on the liver. [Read the Full Post]

SMO Gene Amplification and Activation of the Hedgehog Pathway as Novel Mechanisms of Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Lung Cancer

1870 views | Feb 21 2017

Della Corte CM, et al.'s result supports the role of the Hh pathway in mediating resistance to anti-EGFR-TKIs through the induction of EMT and suggests new opportunities to design new treatment strategies in lung cancer. [Read the Full Post]

Repurposing celecoxib as a topical antimicrobial agent

0 views | Feb 21 2017

Thangamani S, et al.'s results demonstrate that celecoxib alone, or in combination with traditional antimicrobials, has a potential to use as a topical drug for the treatment of bacterial skin infections. [Read the Full Post]

Targeting hedgehog signaling reduces self-renewal in embryonal rhabdomyosarcoma

0 views | Feb 20 2017

Satheesha S, et al.‘s ’ work identifies novel functional aspects of hedgehog signaling in ERMS, redefines the rationale for its targeting as means to control ERMS self-renewal and underscores the importance of studying functional tumor heterogeneity in pediatric cancers. [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

0 views | Feb 20 2017

Mathur R, et al.‘s’ results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. [Read the Full Post]

Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites

2465 views | Feb 19 2017

Douglass AN, et al.'s data demonstrate that host-based prophylaxis could be developed into an effective intervention strategy that eliminates LS parasites before the onset of clinical disease and thus opens a [Read the Full Post]

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma

0 views | Feb 19 2017

Brun SN, et al.'s studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease. [Read the Full Post]

Phosphoinositide 3-Kinase δ Regulates Dectin-2 Signaling and the Generation of Th2 and Th17 Immunity

1219 views | Feb 18 2017

Lee MJ et al. demonstrated that PI3Kδ regulates Dectin-2 signaling and its dendritic cell function. [Read the Full Post]

Anidulafungin-Induced Suicidal Erythrocyte Death

0 views | Feb 18 2017

Anidulafungin triggers hemolysis and eryptosis with cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to Ca2+ entry and activation of p38 kinase. [Read the Full Post]

Icaritin activates JNK-dependent mPTP necrosis pathway in colorectal cancer cells

1727 views | Feb 18 2017

Zhou C, et al.'s results showed that ICT exerts potent inhibitory effect against CRC cells in vitro and in vivo. JNK-dependent mPTP necrosis pathway could be key mechanism responsible for ICT's actions. [Read the Full Post]

Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer

0 views | Feb 17 2017

Manteghi S et al. establish HD-PTP/PTPN23 as a prominent haploinsufficient tumor suppressor gene preventing tumor progression through control of integrin trafficking. [Read the Full Post]

Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition

0 views | Feb 17 2017

When compared to the SW13- subtype, SW13+ cells have restored BRM expression, increased metastatic capacity, and significantly different expression of a variety of chromatin remodeling factors including those involved with histone acetylation and methylation. These data are consistent with a multistep mechanism of SW13- to SW13+ conversion and subtype stabilization: histone hypermodification results in the altered expression of chromatin remodeling factors and chromatin epigenetic enzymes and the re-expression of BRM which results in restoration of SWI/SNF complex function and leads to changes in chromatin structure and gene expression that stabilize the SW13+ phenotype. [Read the Full Post]

MEK Inhibition Sensitizes Precursor B-Cell Acute Lymphoblastic Leukemia (B-ALL) Cells to Dexamethasone through Modulation of mTOR Activity and Stimulation of Autophagy

0 views | Feb 16 2017

Polak A et al. demonstrated that modulation of MEK/ERK pathway is an attractive therapeutic strategy overcoming GC resistance in B-ALL patients. [Read the Full Post]

The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells

1244 views | Feb 16 2017

Lou HZ, et al. found that a low concentration of INK-128 significantly increased the sensitivity of pancreatic cancer cells to gemcitabine. Together, our in vitro results suggest that INK-128 might be further investigated as a novel anti-cancer agent or chemo-adjuvant for pancreatic cancer treatment. [Read the Full Post]