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https://www.readbyqxmd.com/read/27779808/functional-and-therapeutic-relevance-of-hepatocyte-growth-factor-c-met-signaling-in-synovial-sarcoma
#1
Yoshinori Imura, Takaaki Nakai, Shutaro Yamada, Hidetatsu Outani, Satoshi Takenaka, Kenichiro Hamada, Nobuhito Araki, Kazuyuki Itoh, Hideki Yoshikawa, Norifumi Naka
Synovial sarcoma (SS) is an aggressive soft-tissue sarcoma with a poor prognosis and thus novel therapeutic strategies for SS are urgently required. In the present study, we investigated functional and therapeutic relevance of hepatocyte growth factor (HGF)/c-MET signaling in SS. Both HGF and c-MET were highly expressed in Yamato-SS cells, resulting in activation of c-MET and its downstream AKT and extracellular signal-regulated kinase signaling pathways, whereas c-MET was expressed but not activated in SYO-1 or HS-SY-II cells...
October 24, 2016: Cancer Science
https://www.readbyqxmd.com/read/27553677/the-novel-c-met-inhibitor-capmatinib-mitigates-diethylnitrosamine-acute-liver-injury-in-mice
#2
Mohamed E Shaker, Sylvia A Ashamallah, Mohamed El-Mesery
The receptor tyrosine kinase mesenchymal-epithelial transition factor (c-Met) sits at the interface between controlled cellular division of organogenesis and uncontrolled cellular division of carcinogenesis. c-Met contribution to the initial phases of liver injury and inflammation is still not resolved. Herein, we investigated the selective pharmacological intervention of c-Met by capmatinib (formerly known as INC280) in the diethylnitrosamine (DEN) acute liver injury model in mice. c-Met inhibition by capmatinib reduced DEN-induced elevation of the pro-inflammatory cytokines TNF-α, IL-1β, IL-17A, IL-23(p19/40) and IFN-γ, which correlated well with serum markers of hepatocellular injury (ALT, AST and LDH)...
November 2, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/26791795/predictive-and-prognostic-value-of-de-novo-met-expression-in-patients-with-advanced-non-small-cell-lung-cancer
#3
Anna Li, Fei-Yu Niu, Jie-Fei Han, Na-Na Lou, Jin-Ji Yang, Xu-Chao Zhang, Qing Zhou, Zhi Xie, Jian Su, Ning Zhao, Ying Huang, Yi-Long Wu
BACKGROUND: Cellular-mesenchymal-epithelial transition (MET) protein has recently been identified as a novel target that shows promise for the treatment of non-small-cell lung cancer (NSCLC). However, the relationship between de novo MET expression and patient outcomes remains unclear. METHODS: We reviewed the data of patients who had been diagnosed with NSCLC between December 2013 and October 2014. All the patients were evaluated for MET expression status. MET-positive was defined as having an H-score ≥ 60 by immunohistochemistry analysis...
December 2015: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/26338447/cabozantinib-and-tivantinib-but-not-inc280-induce-antiproliferative-and-antimigratory-effects-in-human-neuroendocrine-tumor-cells-in-vitro-evidence-for-off-target-effects-not-mediated-by-c-met-inhibition
#4
Clemens Reuther, Vera Heinzle, Matilde Spampatti, George Vlotides, Enrico de Toni, Gerald Spöttl, Julian Maurer, Svenja Nölting, Burkhard Göke, Christoph J Auernhammer
BACKGROUND/AIMS: The hepatocyte growth factor/transmembrane tyrosine kinase receptor c-Met has been defined as a potential target in antitumoral treatment of various carcinomas. We aimed to investigate the direct effect of c-Met inhibition on neuroendocrine tumor cells in vitro. METHODS: The effects of the multi-tyrosine kinase inhibitors cabozantinib and tivantinib and of the highly specific c-Met inhibitor INC280 were investigated in human pancreatic neuroendocrine BON1, bronchopulmonary NCI-H727 and midgut GOT1 cells in vitro...
2016: Neuroendocrinology
https://www.readbyqxmd.com/read/26138303/inc280-an-orally-available-small-molecule-inhibitor-of-c-met-reduces-migration-and-adhesion-in-ovarian-cancer-cell-models
#5
Kim Moran-Jones, Laura M Brown, Goli Samimi
5-year survival rates for ovarian cancer are approximately 40%, and for women diagnosed at late stage (the majority), just 27%. This indicates a dire need for new treatments to improve survival rates. Recent molecular characterization has greatly improved our understanding of the disease and allowed the identification of potential new targets. One such pathway of interest is the HGF/c-MET axis. Activation of the HGF/c-MET axis has been demonstrated in certain ovarian tumours, and been found to be associated with decreased overall survival, suggesting its potential as a therapeutic target...
July 3, 2015: Scientific Reports
https://www.readbyqxmd.com/read/25987766/met-inhibitors-for-treatment-of-advanced-hepatocellular-carcinoma-a-review
#6
REVIEW
Xing-Shun Qi, Xiao-Zhong Guo, Guo-Hong Han, Hong-Yu Li, Jiang Chen
The current standard treatment option for advanced hepatocellular carcinoma (HCC) is sorafenib, but its clinical benefit is modest. In spite of many attempts, few drugs can provide any significant improvement of survival as the first- or second-line therapy of choice in phase III randomized controlled trials. Recently, the subgroup analysis of a phase II randomized controlled trial has shown that tivantinib, a selective MET inhibitor, can significantly improve the overall survival in patients with MET-positive advanced HCC after the failure or intolerance of a prior systemic therapy...
May 14, 2015: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/25884642/targeting-cmet-with-inc280-impairs-tumour-growth-and-improves-efficacy-of-gemcitabine-in-a-pancreatic-cancer-model
#7
Franziska Brandes, Katharina Schmidt, Christine Wagner, Julia Redekopf, Hans Jürgen Schlitt, Edward Kenneth Geissler, Sven Arke Lang
BACKGROUND: Expression and activation of the cMET receptor have been implicated in tumor progression and resistance to chemotherapy in human pancreatic cancer. In this regard we assessed the effects of targeting cMET in pancreatic cancer models in vitro and in vivo. METHODS: Human (L3.6pl, BxP3, HPAF-II, MiaPaCa2) and murine (Panc02) pancreatic cancer cell lines, endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) were used for the experiments. Furthermore, the human pancreatic cancer cell line MiaPaCa2 with acquired resistance to gemcitabine was employed (MiaPaCa2(G250))...
February 19, 2015: BMC Cancer
https://www.readbyqxmd.com/read/25098767/combined-targeting-of-mtor-and-c-met-signaling-pathways-for-effective-management-of-epithelioid-sarcoma
#8
Yoshinori Imura, Hirohiko Yasui, Hidetatsu Outani, Toru Wakamatsu, Kenichiro Hamada, Takaaki Nakai, Shutaro Yamada, Akira Myoui, Nobuhito Araki, Takafumi Ueda, Kazuyuki Itoh, Hideki Yoshikawa, Norifumi Naka
BACKGROUND: Epithelioid sarcoma (EpS) is a high-grade malignant soft-tissue sarcoma characterized by local recurrences and distant metastases. Effective treatments for EpS have not been established and thus novel therapeutic approaches against EpS are urgently required. mTOR inhibitors exert antitumor effects on several malignancies but AKT reactivation by mTOR inhibition attenuates the antitumor effects of mTOR inhibitors. This reactivation is receptor tyrosine kinase (RTK)-dependent due to a release of negative feedback inhibition...
2014: Molecular Cancer
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