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https://www.readbyqxmd.com/read/28336956/preclinical-development-of-a-humanized-neutralizing-antibody-targeting-hgf
#1
Hyori Kim, Sung Hee Hong, Jung Yong Kim, In-Chull Kim, Young-Whan Park, Song-Jae Lee, Seong-Won Song, Jung Ju Kim, Gunwoo Park, Tae Min Kim, Yun-Hee Kim, Jong Bae Park, Junho Chung, In-Hoo Kim
Hepatocyte growth factor (HGF) and its receptor, cMET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. We therefore examined the anti-tumor activity of the humanized monoclonal anti-HGF antibody, YYB-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. HGF neutralization, The extracellular signal-related kinases 1 and 2 (ERK1/2) phosphorylation, and HGF-induced scattering were assessed in HGF-expressing cell lines treated with YYB-101...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336955/progress-of-antibody-based-inhibitors-of-the-hgf-cmet-axis-in-cancer-therapy
#2
REVIEW
Ki-Hyun Kim, Hyori Kim
Dysregulated receptor tyrosine kinase signaling in human cancer cells leads to tumor progression, invasion and metastasis. The receptor tyrosine kinase cMET is frequently overexpressed in cancer tissue, and activation of cMET signaling is related to drug resistance and the processes of carcinogenesis, invasion and metastasis. For that reason, cMET and its ligand, hepatocyte growth factor (HGF), are considered prime targets for the development of anticancer drugs. At least eight anti-cMET and four anti-HGF antibodies have been tested or are being tested in clinical trials...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28292264/establishment-of-patient-derived-gastric-cancer-xenografts-a-useful-tool-for-preclinical-evaluation-of-targeted-therapies-involving-alterations-in-her-2-met-and-fgfr2-signaling-pathways
#3
Haiyong Wang, Jun Lu, Jian Tang, Shitu Chen, Kuifeng He, Xiaoxia Jiang, Weiqin Jiang, Lisong Teng
BACKGROUND: Targeted therapies are emerging treatment options for gastric cancer (GC). Patient-derived tumor xenograft(PDX) models of GC closely retain the features of the original clinical cancer, offering a powerful tool for preclinical drug efficacy testing. This study aimed to establish PDX GC models, and explore therapeutics targeting Her2, MET(cMet), and FGFR2, which may assist doctor to select the proper target therapy for selected patients. METHODS: GC tissues from 32 patients were collected and implanted into immuno-deficient mice...
March 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28263231/appendix-derived-pseudomyxoma-peritonei-pmp-molecular-profiling-toward-treatment-of-a-rare-malignancy
#4
Elizabeth M Gleeson, Rebecca Feldman, Beth L Mapow, Lynn T Mackovick, Kristine M Ward, William F Morano, Rene R Rubin, Wilbur B Bowne
OBJECTIVES: Pseudomyxoma peritonei (PMP) is a rare malignancy originating from the appendix, characterized by disseminated mucinous tumor implants on peritoneal surfaces. We examined the role of multiplatform molecular profiling to study biomarker-guided treatment strategies for this rare malignancy. METHODS: A total of 54 patients with appendix-derived PMP were included in the study. Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing), protein expression (immunohistochemistry), and gene amplification (C/fluorescent in situ hybridization)...
March 3, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28238725/functional-and-structural-analysis-of-programmed-c-methylation-in-the-biosynthesis-of-the-fungal-polyketide-citrinin
#5
Philip A Storm, Dominik A Herbst, Timm Maier, Craig A Townsend
Fungal polyketide synthases (PKSs) are large, multidomain enzymes that biosynthesize a wide range of natural products. A hallmark of these megasynthases is the iterative use of catalytic domains to extend and modify a series of enzyme-bound intermediates. A subset of these iterative PKSs (iPKSs) contains a C-methyltransferase (CMeT) domain that adds one or more S-adenosylmethionine (SAM)-derived methyl groups to the carbon framework. Neither the basis by which only specific positions on the growing intermediate are methylated ("programming") nor the mechanism of methylation are well understood...
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28155605/met-activating-genetically-improved-chimeric-factor-1-promotes-angiogenesis-and-hypertrophy-in-adult-myogenesis
#6
Flavio Ronzoni, Gabriele Ceccarelli, Ilaria Perini, Laura Benedetti, Daniela Galli, Francesca Mulas, Martina Balli, Giovanni Magenes, Riccardo Bellazzi, Gabriella Cusella De Angelis, Maurilio Sampaolesi
BACKGROUND: Myogenic progenitor cells (activated satellite cells) are able to express both HGF and its receptor cMet. After muscle injury, HGF-Met stimulation promotes activation and primary division of satellite cells. MAGIC-F1 (Met-Activating Genetically Improved Chimeric Factor-1) is an engineered protein that contains two human Met-binding domains that promotes muscle hypertrophy. MAGIC-F1 protects myogenic precursors against apoptosis and increases their fusion ability enhancing muscle differentiation...
February 1, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28143872/musashi-rna-binding-proteins-as-cancer-drivers-and-novel-therapeutic-targets
#7
Alexander E Kudinov, John Karanicolas, Erica A Golemis, Yanis Boumber
Aberrant gene expression that drives human cancer can arise from epigenetic dysregulation. While much attention has focused on altered activity of transcription factors and chromatin-modulating proteins, proteins that act post-transcriptionally can potently affect expression of oncogenic signaling proteins. The RNA-binding proteins (RBPs) Musashi-1 (MSI1) and Musashi-2 (MSI2) are emerging as regulators of multiple critical biological processes relevant to cancer initiation, progression, and drug resistance...
January 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28138035/co-targeting-hgf-cmet-signaling-with-mek-inhibitors-in-metastatic-uveal-melanoma
#8
Hanyin Cheng, Vivian Chua, Connie Liao, Timothy J Purwin, Mizue Terai, Ken Kageyama, Michael A Davies, Takami Sato, Andrew E Aplin
Patients with metastatic uveal melanoma usually die within 1 year of diagnosis, emphasizing an urgent need to develop new treatment strategies. The liver is the most common site of metastasis. Mitogen-activated protein kinase kinase (MEK) inhibitors improve survival in V600 BRAF-mutated cutaneous melanoma patients but have limited efficacy in patients with uveal melanoma. Our previous work showed that hepatocyte growth factor (HGF) signaling elicits resistance to MEK inhibitors in metastatic uveal melanoma...
March 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28118734/metabolic-risk-score-and-vascular-mortality-among-korean-adults
#9
Keum Ji Jung, Yon Ho Jee, Sun Ha Jee
Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors. However, rather than using a dichotomous scale, a continuous metabolic syndrome (cMetS) score has been proposed to evaluate MetS because current MetS criteria do not function well in identifying those at high risk of cardiovascular mortality. The objective of this study was to examine the association between cMetS score and vascular mortality among Korean population. We included 441 411 individuals who visited health promotion centers and were given a medical examination from 1994 to 2004...
January 1, 2017: Asia-Pacific Journal of Public Health
https://www.readbyqxmd.com/read/28078108/egfr-family-and-cmet-expression-profiles-and-prognostic-significance-in-esophagogastric-adenocarcinoma
#10
Ellie Chan, Ahmad Alkhasawneh, Lizette Vila Duckworth, Tabish Aijaz, Tania Zuluaga Toro, Xiaomin Lu, Steven J Hughes, Amy Collinsworth, Thomas J George
BACKGROUND: Targeted therapy with anti-human epidermal growth factor receptor-2 (HER2) monoclonal antibody in patients with HER2 overexpressed esophagogastric adenocarcinoma (EGA) improves survival; however, the effect is transient due to the development of resistance. Some studies suggest that cMet overexpression provides cross talk for epidermal growth factor receptor (EGFR) and HER2 inhibition. We sought to characterize the expression profile of the EGFR family and cMet receptors in untreated, resected EGA...
December 2016: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28008383/better-to-be-alone-than-in-bad-company-the-antagonistic-effect-of-cisplatin-and-crizotinib-combination-therapy-in-non-small-cell-lung-cancer
#11
Nele Van Der Steen, Christophe Deben, Vanessa Deschoolmeester, An Wouters, Filip Lardon, Christian Rolfo, Paul Germonpré, Elisa Giovannetti, Godefridus J Peters, Patrick Pauwels
AIM: To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies. METHODS: We tested three different treatment schemes in four non-small cell lung cancer (NSCLC) cell lines with a different cMET/epidermal growth factor receptor genetic background by means of the sulforhodamine B assay and performed analysis with Calcusyn. RESULTS: All treatment schemes showed an antagonistic effect in all cell lines, independent of the cMET status...
December 10, 2016: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27969527/ps01-60-ph-ib-ii-trial-of-inc280-%C3%A2-erlotinib-vs-platinum-pemetrexed-in-adult-pts-with-egfr-mutated-cmet-amplified-egfr-tki-resistant-advanced-nsclc-topic-medical-oncology
#12
Igor I Rybkin, Egbert Smit, Hans-Georg Kopp, Dong-Wan Kim, Alexander Spira, Alfredo Berruti, Dae Ho Lee, Noemí Reguart, Mikhail Akimov, Karl Schumacher, Allison Upalawanna, Matthew Squires, Daniel S-W Tan
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27969451/mini01-03-phase-ph-i-study-of-the-safety-and-efficacy-of-the-cmet-inhibitor-capmatinib-inc280-in-patients-with-advanced-cmet-nsclc-topic-medical-oncology
#13
Todd M Bauer, Martin Schuler, Rossana Berardi, Wan-Teck Lim, Robin Van Geel, Maja De Jonge, Analia Azaro, Maya Gottfried, Ji-Youn Han, Dae Ho Lee, Mira Wollner, David Hong, Arndt Vogel, Angelo Delmonte, Alexander Krohn, Yong Zhang, Matthew Squires, Monica Giovannini, Mikhail Akimov, Dong-Wan Kim
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27869528/the-association-between-measures-of-fitness-and-metabolic-health-in-treatment-seeking-youth-with-obesity
#14
Emily Hill Guseman, Samuel P Cauffman, Jared M Tucker, Lucie Smith, Joey C Eisenmann, William Stratbucker
BACKGROUND: Both cardiorespiratory fitness (CRF) and measures of muscular fitness are associated with metabolic syndrome in adults. However, limited information exists about these relationships in youth with severe obesity who are at increased risk of metabolic dysfunction. The purpose of this study was to examine the relationship between fitness and metabolic health in treatment-seeking youth with obesity. METHODS: Data for this analysis were collected at the time of baseline visits at a stage 3 pediatric weight management center...
April 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/27801981/heterogeneity-of-the-resistance-to-gefitinib-treatment-in-a-non-small-cell-lung-cancer-patient-with-active-epidermal-growth-factor-receptor-mutation
#15
Chong-Rui Xu, Wen-Zhao Zhong, Qing Zhou, Xu-Chao Zhang, Jin-Ji Yang, Yi-Long Wu
We report the case of a 37-year-old male non-small cell lung cancer patient with an active epidermal growth factor receptor (EGFR) mutation who received gefitinib as first-line treatment. After 13.7 months, the patient experienced disease progression and was treated with platinum-based doublet chemotherapy plus gefitinib for 5.4 months. A subsequent lung biopsy showed cMET overexpression; therefore, the patient received a cMET inhibitor with the gefitinib. The response in the different lesions of several organs was diverse...
January 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/27740533/%C3%A2-reply-to-the-letter-to-the-editor
#16
Sara Bignulin, Edmondo Falleti, Sara Cmet, Dario Cappello, Annarosa Cussigh, Ilaria Lenisa, Denis Dissegna, Fabio Pugliese, Cinzia Vivarelli, Carlo Fabris, Pierluigi Toniutto
No abstract text is available yet for this article.
November 2016: Annals of Hepatology
https://www.readbyqxmd.com/read/27703030/the-gas6-axl-signaling-network-is-a-mesenchymal-mes-molecular-subtype-specific-therapeutic-target-for-ovarian-cancer
#17
Jane Antony, Tuan Zea Tan, Zoe Kelly, Jeffrey Low, Mahesh Choolani, Chiara Recchi, Hani Gabra, Jean Paul Thiery, Ruby Yun-Ju Huang
Ovarian cancer is a complex disease with heterogeneity among the gene expression molecular subtypes (GEMS) between patients. Patients with tumors of a mesenchymal ("Mes") subtype have a poorer prognosis than patients with tumors of an epithelial ("Epi") subtype. We evaluated GEMS of ovarian cancer patients for molecular signaling profiles and assessed how the differences in these profiles could be leveraged to improve patient clinical outcome. Kinome enrichment analysis identified AXL as a particularly abundant kinase in Mes-subtype tumor tissue and cell lines...
October 4, 2016: Science Signaling
https://www.readbyqxmd.com/read/27689874/hepatocyte-growth-factor-renders-braf-mutant-human-melanoma-cell-lines-resistant-to-plx4032-by-downregulating-the-pro-apoptotic-bh3-only-proteins-puma-and-bim
#18
Leona Rohrbeck, Jia-Nan Gong, Erinna F Lee, Andrew J Kueh, Andreas Behren, Lin Tai, Guillaume Lessene, David C S Huang, Walter D Fairlie, Andreas Strasser, Marco J Herold
A large proportion of melanomas harbour the activating BRAF(V600E) mutation that renders these cells dependent on MAPK signalling for their survival. Although the highly specific and clinically approved BRAF(V600E) kinase inhibitor, PLX4032, induces apoptosis of melanoma cells bearing this mutation, the underlying molecular mechanisms are not fully understood. Here, we reveal that PLX4032-induced apoptosis depends on the induction of the pro-apoptotic BH3-only protein PUMA with a minor contribution of its relative BIM...
December 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27687593/carp-1-functional-mimetics-are-novel-inhibitors-of-drug-resistant-triple-negative-breast-cancers
#19
Vino T Cheriyan, Magesh Muthu, Ketan Patel, Sreeja Sekhar, Walajapet Rajeswaran, Scott D Larsen, Lisa Polin, Edi Levi, Mandip Singh, Arun K Rishi
Doxorubicin and Cisplatin are the frontline therapeutics for treatment of the triple negative breast cancers (TNBCs). Emergence of drug-resistance often contributes to failure of drugs and poor prognosis, and thus necessitates development of new and improved modalities to treat TNBCs. We generated and characterized chemotherapy-resistant TNBC cells following their culture in chronic presence of Doxorubicin or Cisplatin, and tested whether their viabilities were inhibited by a novel class of CARP- 1 functional mimetic (CFM) compounds...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27676546/p2-09-cmet-in-nsclc-expression-amplification-and-mutations-track-biology-and-pathogenesis
#20
Nele Van Der Steen, Christian Rolfo, Elisa Giovannetti, Pablo Reclusa, Godefridus J Peters, Patrick Pauwels
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
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