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Blog of Signaling Pathways

Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma

614 views | Oct 16 2019

AbuHammad S et al. provided a strong rationale for further investigation of novel combinations of CDK4/6 and PRMT5 inhibitors, not only in melanoma but other tumor types, including breast, pancreatic, and esophageal carcinoma. [Read the Full Post]

Phase I Study of Ceritinib (LDK378) in Japanese Patients with Advanced, Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer or Other Tumors

521 views | Oct 16 2019

Nishio M et al. indicated that ceritinib maximum-tolerated dose was 750 mg once daily in Japanese patients. Antitumor activity was observed irrespective of prior ALKi treatment history. Dose expansion, examining the activity of ceritinib in alectinib-resistant patients, is ongoing. [Read the Full Post]

The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis

486 views | Oct 15 2019

Barreyro FJ et al. demonstrated that in a murine model of NASH, liver injury and fibrosis are suppressed by inhibiting hepatocytes apoptosis and suggests that Emricasan may be an attractive antifibrotic therapy in NASH. [Read the Full Post]

Lapatinib Resistance in Breast Cancer Cells Is Accompanied by Phosphorylation-Mediated Reprogramming of Glycolysis

665 views | Oct 15 2019

Ruprecht B et al. offered deeper perspectives on cancer drug resistance and suggests new biomarkers and treatment options for lapatinib-resistant cancers. [Read the Full Post]

ABT-888 restores sensitivity in temozolomide resistant glioma cells and xenografts

490 views | Oct 14 2019

Yuan AL et al. indicated that in laboratory models, the addition of ABT-888 to TMZ overcame resistance to TMZ. [Read the Full Post]

Clinical relevance of a CD4+ T cell immune function assay in the diagnosis of infection in pediatric living-donor liver transplantation

0 views | Oct 14 2019

Liu W et al. suggested that low CD4+ T lymphocyte ATP levels may be an independent risk factor for infection following pediatric LDLT, and that the Immuknow assay may be used as a tool to evaluate T lymphocyte function in such patients to predict the risk of infection. [Read the Full Post]

Clinical relevance of a CD4+ T cell immune function assay in the diagnosis of infection in pediatric living-donor liver transplantation

0 views | Oct 14 2019

Liu W et al. suggested that low CD4+ T lymphocyte ATP levels may be an independent risk factor for infection following pediatric LDLT, and that the Immuknow assay may be used as a tool to evaluate T lymphocyte function in such patients to predict the risk of infection. [Read the Full Post]

KPT-330 inhibition of chromosome region maintenance 1 is cytotoxic and sensitizes chronic myeloid leukemia to Imatinib

355 views | Oct 13 2019

Nie D et al. indicated that KPT-330 showed anti-leukemic activity and sensitized CML to IM in CRM1-dependent manner in vitro and in vivo. KPT-330 represents an alternative therapy for IM-refractory CML, warranting further investigation of CRM1 as therapeutic target. [Read the Full Post]

Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer

473 views | Oct 13 2019

Coleman RL et al. indicated that across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. [Read the Full Post]

SB203580 inhibits epithelial-mesenchymal transition and pulmonary fibrosis in a rat silicosis model

353 views | Oct 12 2019

Yan W et al. suggested that p38 MAPK/ZEB-1 (ZEB-2, Twist) pathway was involved at 7days after silica instillation and p38 MAPK was pivotal for EMT in silicosis fibrosis in rats. [Read the Full Post]

NVP-BKM120 inhibits colon cancer growth via FoxO3a-dependent PUMA induction

309 views | Oct 12 2019

Yang S et al. demonstrated a key role of PUMA in mediating the anticancer effects of NVP-BKM120 and suggest that PUMA could be used as an indicator of NVP-BKM120 sensitivity, and also have important implications for it clinical applications. [Read the Full Post]

Activity of BET-proteolysis targeting chimeric (PROTAC) compounds in triple negative breast cancer

522 views | Oct 11 2019

Noblejas-López MDM et al. provided options for further clinical development of these agents in TNBC. [Read the Full Post]

Panobinostat for the Treatment of Multiple Myeloma

689 views | Oct 11 2019

Laubach JP et al. indicated The review focuses on panobinostat and its mechanism of action, pharmacokinetics, and clinical data in the treatment of relapsed or relapsed and refractory multiple myeloma. [Read the Full Post]

Suppression of Sirt1 sensitizes lung cancer cells to WEE1 inhibitor MK-1775-induced DNA damage and apoptosis

0 views | Oct 10 2019

Chen G et al. provided a novel therapeutic strategy to optimize MK-1775 treatment efficiency in lung cancers. [Read the Full Post]

Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis

498 views | Oct 10 2019

Machlus KR et al. revealed (1) the mechanism of selinexor-induced thrombocytopenia, (2) an effective way to reverse the dose-limiting thrombocytopenia, and (3) a novel role for XPO1 in megakaryopoiesis. The improved selinexor dosing regimen described herein is crucial to help reduce thrombocytopenia in selinexor patients, allowing them to continue their course of chemotherapy and have the best chance of survival. [Read the Full Post]

Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

762 views | Oct 09 2019

Sandborn WJ et al. showed that in patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. [Read the Full Post]

Screening of epidermal growth factor receptor inhibitors in natural products by capillary electrophoresis combined with high performance liquid chromatography-tandem mass spectrometry

621 views | Oct 09 2019

Li F et al. demonstrated a significant merit of our method in the identification of the bioactive compounds in natural products. [Read the Full Post]

Targeting the PI3K/Akt/mTOR-pathway with the pan-Akt inhibitor GDC-0068 in PIK3CA-mutant breast cancer brain metastases

454 views | Oct 08 2019

Ippen FM et al. suggested that the Akt-inhibitor GDC-0068 may be an encouraging targeted treatment strategy for breast cancer brain metastasis patients with activating mutations in the PI3K pathway. These data provide a rationale to further evaluate the efficacy of GDC-0068 in patients with brain metastases. [Read the Full Post]

Multicellular gene network analysis identifies a macrophage-related gene signature predictive of therapeutic response and prognosis of gliomas

289 views | Oct 08 2019

Sun X et al. identified macrophage-related gene signature has good prognostic value for predicting resistance to targeted therapeutics and survival of glioma patients, implying that combining current targeted therapies with new macrophage-targeted therapy may be beneficial for the long-term treatment outcomes of glioma patients. [Read the Full Post]

Abiraterone Acetate and Enzalutamide: Similar Efficacy in Treating Post Docetaxel Metastatic Castration-resistant Prostate Cancer: Single Center Experience

293 views | Oct 07 2019

Chang LW et al. found that AA and ENZ had a similar efficacy in treating post-docetaxel mCRPC patients. Metastatic volume and nadir PSA were independent risk factors of these patients in predicting their disease-specific survival and overall survival. [Read the Full Post]