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https://www.readbyqxmd.com/read/28088230/relationship-between-the-uptake-of-18-f-borono-l-phenylalanine-and-l-methyl-11-c-methionine-in-head-and-neck-tumors-and-normal-organs
#1
Yoshiaki Watanabe, Hiroaki Kurihara, Jun Itami, Ryohei Sasaki, Yasuaki Arai, Kazuro Sugimura
BACKGROUND AND PURPOSE: The purpose of this study was to determine the distribution of 4-borono-2-(18)F-fluoro-phenylalanine ((18)F-BPA) and L-[methyl-(11)C] methionine ((11)C-Met) in normal organs and tumors and to evaluate the usefulness of (11)C-Met/PET in screening potential candidates for boron neutron capture therapy (BNCT). MATERIAL METHODS: Seven patients who had at least one histologically confirmed head and neck tumor were included in this study. They underwent both whole-body (18)F-BPA-PET/CT and (11)C-Met-PET/CT within a span of 6 months...
January 14, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28086832/norcantharidin-inhibits-cell-growth-by-suppressing-the-expression-and-phosphorylation-of-both-egfr-and-c-met-in-human-colon-cancer-cells
#2
Peiju Qiu, Siwen Wang, Ming Liu, He Ma, Xuan Zeng, Meng Zhang, Lingling Xu, Yidi Cui, Huixin Xu, Yang Tang, Yanli He, Lijuan Zhang
BACKGROUND: Norcantharidin (NCTD) is a Chinese FDA approved, chemically synthesized drug for cancer treatment. The effect of NCTD on signaling proteins of EGFR and c-Met was systematically elucidated in current study. METHODS: Two human colon cancer cell lines, HCT116 and HT29, were used as model systems to investigate the anti-cancer molecular mechanism of NCTD. Cell cycle arrest and early/late apoptosis were analyzed by flow cytometry. The levels of EGFR, phospho-EGFR, c-Met, phospho-c-Met and other related proteins were quantified by western blot analysis...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28077801/human-papillomavirus-type-16-e6-suppresses-microrna-23b-expression-in-human-cervical-cancer-cells-through-dna-methylation-of-the-host-gene-c9orf3
#3
Chi Lam Au Yeung, Tsun Yee Tsang, Pak Lun Yau, Tim Tak Kwok
Oncogenic protein E6 of human papillomavirus type 16 (HPV-16) is believed to involve in the aberrant methylation in cervical cancer as it upregulates DNA methyltransferase 1 (DNMT1) through tumor suppressor p53. In addition, DNA demethylating agent induces the expression of one of the HPV-16 E6 regulated microRNAs (miRs), miR-23b, in human cervical carcinoma SiHa cells. Thus, the importance of DNA methylation and miR-23b in HPV-16 E6 associated cervical cancer development is investigated. In the present study, however, it is found that miR-23b is not embedded in any typical CpG island...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075467/resveratrol-suppresses-human-hepatocellular-carcinoma-via-targeting-hgf-c-met-signaling-pathway
#4
Feng Gao, Gang Deng, Wenbin Liu, Kechao Zhou, Ming Li
Resveratrol, one of the major polyphenols found in red wine, is suggested to have a role as a chemo-prevention or chemotherapy agent in various human cancer models. Herein, we report that resveratrol has a profound antitumor effect on human hepatocellular carcinoma (HCC) cells by down-regulation of the HGF-c-Met signaling pathway. Resveratrol inhibited anchorage-dependent and -independent growth of HCC cells in a dose-dependent manner. Short-term resveratrol exposure substantially decreased HGF-induced c-Met signaling pathway activation, and long-term exposure to resveratrol markedly inhibited c-Met expression on the cell membrane...
January 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28075018/c-met-as-a-potential-target-for-the-treatment-of-gastrointestinal-cancer-current-status-and-future-perspectives
#5
REVIEW
Afsaneh Bahrami, Soodabeh Shahidsales, Majid Khazaei, Majid Ghayour-Mobarhan, Mina Maftouh, Seyed Mahdi Hassanian, Amir Avan
Aberrant activation of the HGF/c-Met signalling pathways is shown to be related with cell proliferation, progression, metastasis and worse prognosis in several tumor types, including gastrointestinal cancers, suggesting its value as a stimulating-target for cancer-therapy. Several approaches have been developed for targeting HGF and/or c-Met, and one of them, crizotinib (dual c-Met/ALK inhibitor), is recently been approved by FDA for lung-cancers with ALK-rearrangement. The main aim of current review is to give an overview on the role of c-Met/HGF pathway in gastrointestinal cancer, in preclinical and clinical trials...
January 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28065241/expressions-of-cd44-cd47-and-c-met-in-ovarian-clear-cell-carcinoma-and-their-clinical-significance
#6
Hui-Min Wang, Ming-Zi Tan, Song Zhang, Xiao Li, Jian Gao, Dan-Ye Zhang, Ying-Ying Hao, Song Gao, Juan-Juan Liu, Bei Lin
Objective To investigate the expressions of CD44,CD47,and c-met in ovarian clear cell carcinoma (OCCC) tissue and their correlations with clinical variables and prognosis. Methods Immunohistochemical method was used to investigate the expressions of CD44,CD47,and c-met in tissues from 86 OCCC patients and the relationships of their expressions with the clinicopathological factors of OCCC were analyzed. Results The expressions of CD44,CD47,and c-met were significantly high in OCCC tissues (90.7%,91.9%,and 94...
December 20, 2016: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/28064436/mir-181b-5p-ets1-and-c-met-pathway-exacerbates-the-prognosis-of-pancreatic-ductal-adenocarcinoma-after-radiation-therapy
#7
Hideo Tomihara, Daisaku Yamada, Hidetoshi Eguchi, Yoshifumi Iwagami, Takehiro Noda, Tadafumi Asaoka, Hiroshi Wada, Koichi Kawamoto, Kunihito Gotoh, Yutaka Takeda, Masahiro Tanemura, Masaki Mori, Yuichiro Doki
Preoperative chemoradiation therapy (CRT) for pancreatic ductal adenocarcinoma (PDAC) has emerged as a reasonable strategy that shows good prognostic impact. However, after preoperative CRT, resected specimens exhibited remnant tumor cells, which indicated that some tumor cells had acquired or were selected for resistance to CRT. Recently, two oncological mechanisms, the epithelial-mesenchymal transition (EMT) and the presence of cancer stem cells (CSCs) were reported to be associated with resistance in various cancers...
January 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28062358/alterations-in-transcription-and-protein-expressions-of-hcc-related-genes-in-hepg2-cells-caused-by-microcystin-lr
#8
Xiaoyu Li, Xiangyang Zhang, Wenjie Xie, Chune Zhou, Yao Li, Xiuhua Zhang
Microcystin-LR (MC-LR) is the most common and toxic hepatotoxin and it could induce human hepatitis and hepatocellular carcinoma (HCC) via the route of drinking water. The aim of the present study was to determine the expressions of oncogenes c-fos, c-jun, c-myc, c-met, and N-ras and tumor suppressor gene PTEN in HepG2 cells following MC-LR-exposure to understand the possible mechanism of MC-LR-related human primary liver cancer. The results of qPCR and Western blotting showed that MC-LR-exposure at non- or sub-cytotoxic concentrations promoted the expressions of oncogenes c-fos, c-jun, c-myc, c-met, and N-ras while suppressed tumor-suppressor gene PTEN in HepG2 cells at both transcription and protein levels...
January 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28055980/immunohistochemical-profiling-of-receptor-tyrosine-kinases-med12-and-tgf-%C3%AE-rii-of-surgically-resected-small-cell-lung-cancer-and-the-potential-of-c-kit-as-a-prognostic-marker
#9
Hiroshi Yokouchi, Hiroshi Nishihara, Toshiyuki Harada, Takashi Ishida, Shigeo Yamazaki, Hajime Kikuchi, Satoshi Oizumi, Weidong Ma, Yajie Fan, Congxia Wang, Kenji Akie, Fumiko Sugaya, Yuka Fujita, Kei Takamura, Tetsuya Kojima, Mitsunori Higuchi, Osamu Honjo, Yoshinori Minami, Naomi Watanabe, Aya Goto, Hiroyuki Suzuki, Hirotoshi Dosaka-Akita, Hiroshi Isobe, Masaharu Nishimura, Mitsuru Munakata
The limited number of available treatments for patients with small-cell lung cancer (SCLC) has prompted us to further investigate the biology of SCLC by molecular profiling. We collected formalin-fixed paraffin-embedded tumor samples from 127 patients with SCLC, who had undergone surgery at 16 institutions between January 2003 and January 2013, and analyzed the association between disease-specific survival and protein expression of c-kit, c-Met, epidermal growth factor receptor, human EGFR-related 2, vascular endothelial growth factor receptor II, anaplastic lymphoma kinase, mediator complex subunit 12 (MED12), and transforming growth factor beta receptor II (TGF-βRII) by immunohistochemistry (IHC)...
December 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/28043720/discovery-of-imidazopyridine-derivatives-as-novel-c-met-kinase-inhibitors-synthesis-sar-study-and-biological-activity
#10
Yifei Yang, Yuan Zhang, LingYun Yang, Leilei Zhao, Lianghui Si, Huibin Zhang, Qingsong Liu, Jinpei Zhou
Receptor tyrosine kinase c-Met acts as an alternative angiogenic pathway in the process and contents of cancers. A series of imidazopyridine derivatives were designed and synthesized according to the established docking studies as possible c-Met inhibitors. Most of these imidazopyridine derivatives displayed nanomolar potency against c-Met in both biochemical enzymatic screens and cellular pharmacology studies. Especially, compound 7g exhibited the most inhibitory activity against c-Met with IC50 of 53.4nM and 253nM in enzymatic and cellular level, respectively...
December 19, 2016: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28035577/c-met-in-chromophobe-renal-cell-carcinoma
#11
Franziska Erlmeier, Philipp Ivanyi, Arndt Hartmann, Michael Autenrieth, Max Wiedemann, Wilko Weichert, Sandra Steffens
c-Met plays a role as a prognostic marker in clear cell renal cell carcinoma. In addition, recently the tyrosine kinase inhibitor cabozantinib targeting c-Met was approved for the treatment of advanced renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known about c-Met expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of c-Met expression on chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/28028730/exposure-response-and-tumor-growth-inhibition-analyses-of-the-monovalent-anti-c-met-antibody-onartuzumab-metmab-in-the-second-and-third-line-non-small-cell-lung-cancer
#12
Kelong Han, Pascal Chanu, Fredrik Jonsson, Helen Winter, René Bruno, Jin Jin, Mark Stroh
The phase III trial comparing onartuzumab + erlotinib vs. erlotinib in the second- and third-line non-small cell lung cancer (NSCLC) did not meet its primary endpoint of overall survival (OS). The objective was to assess whether doses higher than the phase III dose (15 mg/kg) might yield better efficacy without compromising the safety profile. Data were from 636 patients from the phase II and III NSCLC studies. Tumor growth inhibition (TGI) models were fit to longitudinal tumor size data to estimate individual TGI metrics including time to tumor re-growth (TTG)...
December 27, 2016: AAPS Journal
https://www.readbyqxmd.com/read/28011202/design-synthesis-and-biological-evaluation-of-novel-4-2-fluorophenoxy-quinoline-derivatives-as-selective-c-met-inhibitors
#13
Xiaoqiang Wang, Nan Jiang, Sijia Zhao, Shuancheng Xi, Jiao Wang, Tongfei Jing, Wenyu Zhang, Ming Guo, Ping Gong, Xin Zhai
Two novel series of 6,7-disubstituted-4-(2-fluorophenoxy)quinoline derivatives bearing 1H-imidazole-4-carboxamido or (E)-3-hydrosulfonylacrylamido motifs (16-31 and 32-42) were designed, synthesized and evaluated for their in vitro cytotoxic activity. Most of the compounds exhibited moderate to excellent potency against tested three cell lines, and fifteen compounds were further examined for their inhibitory activity against c-Met kinase. The most promising compound 16 (c-Met kinase [IC50]=1.1nM) demonstrated high selectivity and remarkable cytotoxicity against HT-29, MKN-45 and A549 cells with IC50 values of 0...
December 12, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28006830/-c-met-oncogene-in-renal-cell-carcinomas
#14
F Erlmeier, W Weichert, M Autenrieth, P Ivanyi, A Hartmann, S Steffens
c-Met plays a significant role in multiple cellular processes. Being encoded by a proto-oncogene, tyrosine kinase supports aggressive tumour behaviour such as tumour invasiveness and formation of metastases. For some subtypes of renal cell carcinoma studies have shown a association between c-Met expression and clinical outcome or prognosis. Therefore, c-Met represents a prognostic marker in renal cell carcinoma.Furthermore, c-MET will play a decisive role as a possible target for targeted therapies in the era of personalised medicine...
December 2016: Aktuelle Urologie
https://www.readbyqxmd.com/read/28004284/a-phase-i-study-of-tivantinib-in-combination-with-temsirolimus-in-patients-with-advanced-solid-tumors
#15
Christos E Kyriakopoulos, Amy M Braden, Jill M Kolesar, Jens C Eickhoff, Howard H Bailey, Jennifer Heideman, Glenn Liu, Kari B Wisinski
Background A wide variety of human cancers exhibit dysregulated c-Met activity that has implications in oncogenesis. Phosphorylation of c-Met results in activation of the PI3K/AKT/mTOR pathway. Combined blockade of c-Met and mTOR pathways has shown efficacy in preclinical studies. Tivantinib is a c-Met inhibitor and temsirolimus is a selective mTOR inhibitor. We aimed to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D), dose-limiting toxicities (DLT), adverse events (AEs), clinical activity and pharmacokinetic (PK) parameters of the combination...
December 21, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/28002685/effects-of-blood-flow-restriction-on-biomarkers-of-myogenesis-in-response-to-resistance-exercise
#16
Andrew S Layne, Kelly Larkin-Kaiser, R Gavin MacNeil, Marvin Dirain, Bhanuprasad Sandesara, Todd M Manini, Thomas W Buford
We investigated the acute myogenic response to resistance exercise with and without blood-flow restriction (BFR). Six men and women (age, 22 ± 1 years) performed unilateral knee extensions at 40% of 1-repetition maximum with or without (CNTRL) BFR applied via pressure cuff inflated to 220 mm Hg. Muscle biopsies were collected at 4 h and 24 h postexercise. Addition of BFR increased myoD and c-Met messenger RNA expression relative to CNTRL. Expression of hepatocyte growth factor protein was significantly higher following CNTRL...
January 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28002492/cell-based-screen-identifies-human-interferon-stimulated-regulators-of-listeria-monocytogenes-infection
#17
Sofya S Perelman, Michael E Abrams, Jennifer L Eitson, Didi Chen, Alyssa Jimenez, Marcel Mettlen, John W Schoggins, Neal M Alto
The type I interferon (IFN) activated transcriptional response is a critical antiviral defense mechanism, yet its role in bacterial pathogenesis remains less well characterized. Using an intracellular pathogen Listeria monocytogenes (Lm) as a model bacterial pathogen, we sought to identify the roles of individual interferon-stimulated genes (ISGs) in context of bacterial infection. Previously, IFN has been implicated in both restricting and promoting Lm growth and immune stimulatory functions in vivo. Here we adapted a gain-of-function flow cytometry based approach to screen a library of more than 350 human ISGs for inhibitors and enhancers of Lm infection...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27999896/correlation-of-pretreatment-18-f-fdg-pet-tumor-textural-features-with-gene-expression-in-pharyngeal-cancer-and-implications-for-radiotherapy-based-treatment-outcomes
#18
Shang-Wen Chen, Wei-Chih Shen, Ying-Chun Lin, Rui-Yun Chen, Te-Chun Hsieh, Kuo-Yang Yen, Chia-Hung Kao
PURPOSE: This study investigated the correlation of the matrix heterogeneity of tumors on (18)F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) with gene-expression profiling in patients with pharyngeal cancer and determined the prognostic factors for radiotherapy-based treatment outcomes. METHODS: We retrospectively reviewed the records of 57 patients with stage III-IV oropharyngeal or hypopharyngeal cancer who had completed definitive therapy...
December 20, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27994655/alteration-status-and-prognostic-value-of-met-in-head-and-neck-squamous-cell-carcinoma
#19
Yoon Ah Cho, Eun Kyung Kim, Su Jin Heo, Byoung Chul Cho, Hye Ryun Kim, Ji Myung Chung, Sun Och Yoon
The MET pathway plays a key role in various cancers, and its inhibition represents a potential treatment target. However, appropriate biomarkers are needed to facilitate the selection of patients who would benefit from MET inhibiting therapy. We herein conducted a robust confirmatory evaluation of the MET copy number alteration status and prognostic significance of c-Met expression in a large series of patients (n = 396) who underwent standard surgical resection and adjuvant chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC)...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27981621/targeting-%C3%AE-catenin-in-hepatocellular-cancers-induced-by-co-expression-of-mutant-%C3%AE-catenin-and-k-ras-in-mice
#20
Junyan Tao, Rong Zhang, Sucha Singh, Minakshi Poddar, Emily Xu, Michael Oertel, Xin Chen, Shanthi Ganesh, Marc Abrams, Satdarshan P Monga
Recently we have shown that co-expression of hMet and mutant-β-catenin using sleeping beauty transposon/transposase leads to HCC in mice that represents around 10% of human HCC. In the current study, we investigate if Ras activation, which can occur downstream of Met signaling, is sufficient to cause HCC in association with mutant-β-catenin. We also tested therapeutic efficacy of targeting β-catenin in HCC model. We show that mutant-K-Ras (G12D), which leads to Ras activation, cooperates with β-catenin mutants (S33Y, S45Y) to yield HCC in mice...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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