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Blog of Signaling Pathways

Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK–Positive Anaplastic Large Cell Lymphoma

2310 views | Jan 23 2017

Ceccon M, et al.'s knowledge of the possible appearance of new clinically relevant mechanisms of drug resistance is a useful tool for the management of new TKI-resistant cases. [Read the Full Post]

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ

1080 views | Jan 23 2017

Zhao D, et al.'s data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ. [Read the Full Post]

Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner

1522 views | Jan 22 2017

Huyan T, et al.'s findings suggest that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy. [Read the Full Post]

Nicotine-Mediated Ca2+ -Influx Induces IL-8 Secretion in Oral Squamous Cell Carcinoma Cell

2274 views | Jan 22 2017

The results fromTsunoda K, et al.'s study indicate that the binding of nicotine to nAChR induces Ca(2+) influx, which results in the activation and phosphorylation of CaMK II and NF-κB p65, respectively. Nicotine-mediated IL-8 induction should be a trigger for the initiation of various diseases. [Read the Full Post]

Assessment of the chemotherapeutic potential of a new camptothecin derivative, ZBH-1205

0 views | Jan 21 2017

Wu D et al. found that ZBH-1205 is a promising chemotherapeutic agent to be further assessed in large-scale clinical trials. [Read the Full Post]

Antiviral activity of micafungin against enterovirus 71

0 views | Jan 21 2017

The research of Kim C et al. revealed a new indication of micafungin as an effective inhibitor of EV71, which is the first case reporting antiviral activity of micafungin, an antifungal drug. [Read the Full Post]

Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways

0 views | Jan 21 2017

In Sampson VB, et al.'s summary, potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS. [Read the Full Post]

Malassezia yeasts activate the NLRP3 inflammasome in antigen-presenting cells via Syk-kinase signalling

979 views | Jan 20 2017

Kistowska M, et al.'s results identify Malassezia spp. as potential strong inducers of pro-inflammatory responses when taken up by antigen-presenting cells and identify C-type lectin receptors and the NLRP3 inflammasome as crucial actors in this process. [Read the Full Post]

Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation

1135 views | Jan 19 2017

Angata T, et al. found that NTHi interacts with Siglec-14 to enhance proinflammatory cytokine production in a tissue culture model. Inhibitors of the Syk tyrosine kinase suppress this response. Loss of Siglec-14, due to SIGLEC14-null allele homozygosity, is associated with a reduced risk of COPD exacerbation in a Japanese patient population. Taken together, Siglec-14 and its downstream signaling pathway facilitate the "infection-inflammation-exacerbation" axis of COPD disease progression, and may represent promising targets for therapeutic intervention. [Read the Full Post]

Syk is involved in NLRP3 inflammasome-mediated caspase-1 activation through adaptor ASC phosphorylation and enhanced oligomerization

999 views | Jan 19 2017

Lin YC, et al.'s results reveal a new molecular pathway through which Syk promotes NLRP3 inflammasome formation, resulting from the phosphorylation of ASC. Thus, the control of Syk activity might be effective to modulate NLRP3 inflammasome activation and treat NLRP3-related immune diseases. [Read the Full Post]

In vitro antifungal synergy between amphiphilic aminoglycoside K20 and azoles against Candida species and Cryptococcus neoformans

1098 views | Jan 18 2017

Shrestha SK et al. suggested that combinations of K20 and azoles offer a possible strategy for developing therapies against candidiasis. [Read the Full Post]

Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells

993 views | Jan 18 2017

Chihara K, et al.'s data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr(426) following BCR stimulation. [Read the Full Post]

Gene-expression profiling elucidates molecular signaling networks that can be therapeutically targeted in vestibular schwannoma

1107 views | Jan 17 2017

Agnihotri S, et al.'s findings implicate aberrant activation of the PI3K/AKT/mTOR pathway as a molecular mechanism of pathogenesis in VS and suggest inhibition of this pathway as a potential treatment strategy. [Read the Full Post]

Targeting non-small cell lung cancer cells by dual inhibition of the insulin receptor and the insulin-like growth factor-1 receptor

1690 views | Jan 16 2017

Vincent EE et al. concluded that small molecule inhibitors targeting both the IR and IGF1R more effectively reduce NSCLC cell proliferation in a manner independent of the IR:IGF1R expression ratio, providing a therapeutic rationale for the treatment of this disease. [Read the Full Post]

Endothelial Cell Apoptosis Induces TGF-β Signaling-Dependent Host Endothelial-Mesenchymal Transition to Promote Transplant Arteriosclerosis

1378 views | Jan 16 2017

Li J et al. suggested that allograft EC apoptosis induced recipient endothelial-mesenchymal (smooth muscle) transition via TGF-β signaling, resulting in recipient EC-derived SMC accumulation as a major mechanism of vascular remodeling during TA. [Read the Full Post]

Dual PI3K/mTOR Inhibitors, GSK2126458 and PKI-587, Suppress Tumor Progression and Increase Radiosensitivity in Nasopharyngeal Carcinoma

1234 views | Jan 16 2017

Liu T, et al.'s new findings suggest the usefulness of PI3K/mTOR dual inhibition for antitumor and radiosensitizing. The combination of IR with a dual PI3K/mTOR inhibitor, GSK2126458 or PKI-587, might be a promising therapeutic strategy for NPC. [Read the Full Post]

Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeutic-mediated cell death

1499 views | Jan 15 2017

Chen H et al. found the importance of SIK3 as a mitotic regulator and underscore the potential of SIK3 as a druggable antimitotic target. [Read the Full Post]

Synergism between inhibitors of Aurora A and KIF11 overcomes KIF15-dependent drug resistance

1562 views | Jan 15 2017

Ma HT et al. provided a molecular basis for increasing the effectiveness of Aurora A and KIF11 inhibitors and tackling problems of drug resistance. [Read the Full Post]

Suppressing Cyclooxygenase-2 prevents nonalcoholic steatohepatitis and inhibits apoptosis of hepatocytes that are involved in the Akt/p53 signal pathway

0 views | Jan 14 2017

Wu J, et al.'s findings suggested that suppressing COX-2 can improve steatohepatitis by inhibiting hepatocyte apoptosis in mice via regulating the Akt/p53 pathway. Celecoxib treatment may be a favorable treatment option for NASH. [Read the Full Post]

Solitary Inhibition of the Breast Cancer Resistance Protein Efflux Transporter Results in a Clinically Significant Drug-Drug Interaction with Rosuvastatin by Causing up to a 2-Fold Increase in Statin Exposure

966 views | Jan 13 2017

Elsby R et al. found 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]