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https://www.readbyqxmd.com/read/28237182/correlation-of-c-met-expression-and-outcome-in-patients-with-renal-cell-carcinoma-treated-with-sunitinib
#1
Katriina Johanna Peltola, Patrick Penttilä, Juhana Rautiola, Heikki Joensuu, Erkki Hänninen, Ari Ristimäki, Petri Bono
BACKGROUND: Treatment of patients with metastatic renal cell carcinoma (mRCC) has improved substantially since the introduction of targeted therapies, but no predictive biomarkers are available. The proto-oncogene c-Met is involved in tumor angiogenesis, development, and metastasis. The main objective was to evaluate c-Met expression in sunitinib-treated patients with mRCC, including patients with bone metastases. METHODS: c-Met expression was analyzed from 137 formalin-fixed paraffin-embedded tumor samples using a validated immunostaining protocol...
February 1, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28223547/cabozantinib-targets-bone-microenvironment-modulating-human-osteoclast-and-osteoblast-functions
#2
Marco Fioramonti, Daniele Santini, Michele Iuliani, Giulia Ribelli, Paolo Manca, Nicola Papapietro, Filippo Spiezia, Bruno Vincenzi, Vincenzo Denaro, Antonio Russo, Giuseppe Tonini, Francesco Pantano
Cabozantinib, a c-MET and vascular endothelial growth factor receptor 2 inhibitor, demonstrated to prolong progression free survival and improve skeletal disease-related endpoints in castration-resistant prostate cancer and in metastatic renal carcinoma. Our purpose is to investigate the direct effect of cabozantinib on bone microenvironment using a total human model of primary osteoclasts and osteoblasts.Osteoclasts were differentiated from monocytes isolated from healthy donors; osteoblasts were derived from human mesenchymal stem cells obtained from bone fragments of orthopedic surgery patients...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212996/analysis-of-a-panel-of-druggable-gene-mutations-and-of-alk-and-pd-l1-expression-in-a-series-of-thymic-epithelial-tumors-tets
#3
Marcello Tiseo, Angela Damato, Lucia Longo, Fausto Barbieri, Federica Bertolini, Alessandro Stefani, Mario Migaldi, Letizia Gnetti, Roberta Camisa, Paola Bordi, Sebastiano Buti, Giulio Rossi
INTRODUCTION: Thymic epithelial tumors (TETs) are rare neoplasms with different prognosis lacking consistent molecular alterations possibly leading to targeted therapy. We collected a consecutive series of TETs aimed at investigating the mutational status of druggable genes (EGFR, c-KIT, KRAS, BRAF, PDGFR-alpha and -beta, HER2 and c-MET) and the expression of ALK and PD-L1. PATIENTS AND METHODS: One hundred twelve consecutive cases of TETs and relative clinico-pathologic features were collected...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212658/c-met-expression-and-activity-in-urogenital-cancers-novel-aspects-of-signal-transduction-and-medical-implications
#4
REVIEW
Ralf Hass, Susanne Jennek, Yuanyuan Yang, Karlheinz Friedrich
C-Met is a receptor tyrosine kinase with multiple functions throughout embryonic development, organogenesis and wound healing and is expressed in various epithelia. The ligand of c-Met is Hepatocyte Growth Factor (HGF) which is secreted among others by mesenchymal stroma/stem (MSC) cells.Physiological c-Met functions are centred around processes that underly cellular motility and invasive growth. Aberrant c-Met expression and activity is observed in numerous cancers and makes major contributions to cell malignancy...
February 17, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28205613/pak4-interacts-with-p85-alpha-implications-for-pancreatic-cancer-cell-migration
#5
Helen King, Kiruthikah Thillai, Andrew Whale, Prabhu Arumugam, Hesham Eldaly, Hemant M Kocher, Claire M Wells
It has been reported that p21-activated kinase 4 (PAK4) is amplified in pancreatic cancer tissue. PAK4 is a member of the PAK family of serine/threonine kinases, which act as effectors for several small GTPases, and has been specifically identified to function downstream of HGF-mediated c-Met activation in a PI3K dependent manner. However, the functionality of PAK4 in pancreatic cancer and the contribution made by HGF signalling to pancreatic cancer cell motility remain to be elucidated. We now find that elevated PAK4 expression is coincident with increased expression levels of c-Met and the p85α subunit of PI3K...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28192399/c-met-mir-130b-axis-as-novel-mechanism-and-biomarker-for-castration-resistance-state-acquisition
#6
A Cannistraci, G Federici, A Addario, A L Di Pace, L Grassi, G Muto, D Collura, M Signore, L De Salvo, S Sentinelli, G Simone, M Costantini, S Nanni, A Farsetti, V Coppola, R De Maria, D Bonci
Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28188446/treatment-options-for-egfr-t790m-negative-egfr-tyrosine-kinase-inhibitor-resistant-non-small-cell-lung-cancer
#7
Salvatore Corallo, Ettore D'Argento, Antonia Strippoli, Michele Basso, Santa Monterisi, Sabrina Rossi, Alessandra Cassano, Carlo M Barone
The introduction of first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib and afatinib) for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC) has dramatically improved patients' prognosis and quality of life (QoL). Unfortunately, after an initial and sometimes durable benefit from EGFR-TKI therapy, all patients with EGFR-mutant lung cancer eventually become resistant to the treatment and experience disease progression. In approximately 50% of these patients, genomic alterations in the EGFR kinase domain resulting in the mutant T790M are responsible for the resistance and this has led to the development of novel EGFR inhibitors active against mutant-T790M EGFR...
February 10, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28175520/340%C3%A2-c-met-%C3%AE-1-integrin-a-receptor-complex-driving-invasive-glioblastoma-resistance-to-antiangiogenic-therapy
#8
Maxim Sidorov, Arman Jahangiri, Sung-Won Han, Michael De Lay, Jeffrey Wagner, Brandyn Castro, Patrick Michael Flanigan, Brandon S Imber, William A Weiss, Manish Kumar Aghi
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
https://www.readbyqxmd.com/read/28170202/autologous-neohep-derived-from-chronic-hepatitis-b-virus-patients-blood-monocytes-by-upregulation-of-c-met-signaling
#9
Jashdeep Bhattacharjee, Barun Das, Disha Sharma, Preeti Sahay, Kshama Jain, Alaknanda Mishra, Srikanth Iyer, Puja Nagpal, Vinod Scaria, Perumal Nagarajan, Prakash Khanduri, Asok Mukhopadhyay, Pramod Upadhyay
In view of the escalating need for autologous cell-based therapy for treatment of liver diseases, a novel candidate has been explored in the present study. The monocytes isolated from hepatitis B surface antigen (HBsAg) nucleic acid test (NAT)-positive (HNP) blood were differentiated to hepatocyte-like cells (NeoHep) in vitro by a two-step culture procedure. The excess neutrophils present in HNP blood were removed before setting up the culture. In the first step of culture, apoptotic cells were depleted and genes involved in hypoxia were induced, which was followed by the upregulation of genes involved in the c-MET signaling pathway in the second step...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28164434/dual-inhibition-of-akt-and-c-met-as-a-second-line-therapy-following-acquired-resistance-to-sorafenib-in-hepatocellular-carcinoma-cells
#10
Peng Han, Hali Li, Xian Jiang, Bo Zhai, Gang Tan, Dali Zhao, Haiquan Qiao, Bing Liu, Hongchi Jiang, Xueying Sun
Sorafenib displays a limited efficacy for advanced hepatocellular carcinoma (HCC). Some HCC patients initially respond to sorafenib but eventually succumb to the disease, indicating that the acquired resistance to sorafenib reduces its beneficial effects. No alternative drugs are available after the failure of sorafenib therapy. Therefore, investigation of the mechanisms underlying the acquired resistance and development of second-line treatments for sorafenib-resistant HCC are urgently required. In the present study, sorafenib-resistant HCC cells generated from sorafenib-sensitive human HCC cells were shown to overproduce hepatocyte growth factor (HGF) and overexpress c-Met kinase and its phosphorylated form, leading to the activation of Akt and ERK (extracellular signaling-regulated kinase) pathways...
February 6, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28154329/the-pharmacological-actions-of-ephedrine-alkaloids-free-ephreda-herb-extract-and-preparation-for-clinical-application
#11
Sumiko Hyuga
 Ephedra Herb is defined in the 17th edition of the Japanese Pharmacopoeia as the terrestrial stem of Ephedra sinica STAPF., Ephedra intermedia SCHRENK et C.A. MEYER, or Ephedra equisetina BUNGE (Ephedraceae) which contains more than 0.7% ephedrine alkaloids (ephedrine and pseudoephedrine). The primary effects and adverse effects of Ephedra Herb are traditionally believed to be mediated by ephedrine alkaloids. We recently reported that Ephedra Herb extract (EHE) exhibits antimetastatic and antitumor effects by suppressing the hepatocyte growth factor-c-Met signaling pathway through the inhibition of c-Met tyrosine kinase activity...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28148897/germacrone-derivatives-synthesis-biological-activity-molecular-docking-studies-and-molecular-dynamics-simulations
#12
Jie Wu, Yu Feng, Chao Han, Wu Huang, Zhibin Shen, Mengdie Yang, Weiqiang Chen, Lianbao Ye
Germacrone is one of the major bioactive components in the Curcuma zedoaria oil product, which is extracted from Curcuma zedoaria Roscoe, known as zedoary. The present study designed some novel germacrone derivatives based on combination principles, synthesized these compounds, and investigated their inhibitions on Bel-7402, HepG2, A549 and HeLa cells. Meanwhile, the study evaluated inhibitions of these derivatives on c-Met kinase, which has been detected in a number of cancers. The results suggested that the majority of the compounds showed stronger inhibitory effect on cancers and c-Met kinase than germacrone...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28146421/the-hdac-inhibitor-ar42-interacts-with-pazopanib-to-kill-trametinib-dabrafenib-resistant-melanoma-cells-in-vitro-and-in-vivo
#13
Laurence Booth, Jane L Roberts, Cindy Sander, John Lee, John M Kirkwood, Andrew Poklepovic, Paul Dent
Studies focused on the killing of activated B-RAF melanoma cells by the histone deacetylase (HDAC) inhibitor AR42. Compared to other tumor cell lines, PDX melanoma isolates were significantly more sensitive to AR42-induced killing. AR42 and the multi-kinase inhibitor pazopanib interacted to activate: an eIF2α-Beclin1 pathway causing autophagosome formation; an eIF2α-DR4/DR5/CD95 pathway; and an eIF2α-dependent reduction in the expression of c-FLIP-s, MCL-1 and BCL-XL. AR42 did not alter basal chaperone activity but increased the ability of pazopanib to inhibit HSP90, HSP70 and GRP78...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28133784/design-and-synthesis-of-novel-4-phenoxyquinolines-bearing-3-hydrosulfonylacrylamido-or-1h-imidazole-4-carboxamido-scaffolds-as-c-met-kinase-inhibitors
#14
Jiao Wang, Lijun Xie, Yu Wang, Xiaoqiang Wang, Shuancheng Xi, Tianfang Zeng, Ping Gong, Xin Zhai
A series of novel 6,7-disubstituted-4-phenoxyquinoline derivatives bearing (E)-3-hydrosulfonylacrylamido or 1H-imidazole-4-carboxamido moieties were designed, synthesized and evaluated for their cytotoxicity against A549, MKN-45, and HT-29 cancer cell lines in vitro. All the target compounds showed moderate to significant cytotoxic activity against the tested cells with IC50 values ranging from 0.13 to 2.65 µM. Five of them were further examined for their inhibitory activity against c-Met kinase, which identified compound 30 as a promising agent (c-Met IC50  = 1...
January 30, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28131876/modulating-the-function-of-atp-binding-cassette-subfamily-g-member-2-abcg2-with-inhibitor-cabozantinib
#15
Guan-Nan Zhang, Yun-Kai Zhang, Yi-Jun Wang, Anna Maria Barbuti, Xi-Jun Zhu, Xin-Yue Yu, Ai-Wen Wen, John N D Wurpel, Zhe-Sheng Chen
Cabozantinib (XL184) is a small molecule tyrosine kinase receptor inhibitor, which targets c-Met and VEGFR2. Cabozantinib has been approved by the Food and Drug Administration to treat advanced medullary thyroid cancer and renal cell carcinoma. In the present study, we evaluated the ability of cabozantinib to modulate the function of the ATP-binding cassette subfamily G member 2 (ABCG2) by sensitizing cells that are resistant to ABCG2 substrate antineoplastic drugs. We used a drug-selected resistant cell line H460/MX20 and three ABCG2 stable transfected cell lines ABCG2-482-R2, ABCG2-482-G2, and ABCG2-482-T7, which overexpress ABCG2...
January 25, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28129786/metformin-promotes-the-survival-of-transplanted-cardiosphere-derived-cells-thereby-enhancing-their-therapeutic-effect-against-myocardial-infarction
#16
Rongchuan Yue, Wenbin Fu, Xiang Liao, Cong Lan, Qiao Liao, Liangpeng Li, Dezhong Yang, Xuewei Xia, Xiongwen Chen, Chunyu Zeng, Wei Eric Wang
BACKGROUND: Transplantation of cardiosphere-derived cells (CDCs) has been shown to exert a therapeutic effect in patients with myocardial infarction (MI). However, poor survival of transplanted CDCs limits their beneficial effect. Metformin (MET) activates AMP-activated protein kinase (AMPK) which is associated with cell survival. The aim of this study is to determine whether MET improves CDC survival in the transplantation microenvironment and enhances the therapeutic effect of CDC transplantation against MI...
January 28, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28118080/oncogene-dependent-requirement-of-fatty-acid-synthase-in-hepatocellular-carcinoma
#17
Li Che, Maria G Pilo, Antonio Cigliano, Gavinella Latte, Maria M Simile, Silvia Ribback, Frank Dombrowski, Matthias Evert, Xin Chen, Diego F Calvisi
Hepatocellular carcinoma (HCC), the most frequent primary tumor of the liver, is an aggressive cancer type with limited treatment options. Cumulating evidence underlines a crucial role of aberrant lipid biosynthesis (a process known as de novo lipogenesis) along carcinogenesis. Previous studies showed that suppression of fatty acid synthase (FASN), the major enzyme responsible for de novo lipogenesis, is highly detrimental for the in vitro growth of HCC cell lines. To assess whether de novo lipogenesis is required for liver carcinogenesis, we have generated various mouse models of liver cancer by stably overexpressing candidate oncogenes in the mouse liver via hydrodynamic gene delivery...
January 24, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28114366/progressive-enrichment-of-stemness-features-and-tumor-stromal-alterations-in-multistep-hepatocarcinogenesis
#18
Jeong Eun Yoo, Young-Joo Kim, Hyungjin Rhee, Haeryoung Kim, Ei Yong Ahn, Jin Sub Choi, Massimo Roncalli, Young Nyun Park
Cancer stem cells (CSCs), a subset of tumor cells, contribute to an aggressive biological behavior, which is also affected by the tumor stroma. Despite the role of CSCs and the tumor stroma in hepatocellular carcinoma (HCC), features of stemness have not yet been studied in relation to tumor stromal alterations in multistep hepatocarcinogenesis. We investigated the expression status of stemness markers and tumor stromal changes in B viral carcinogenesis, which is the main etiology of HCC in Asia. Stemness features of tumoral hepatocytes (EpCAM, K19, Oct3/4, c-KIT, c-MET, and CD133), and tumor stromal cells expressing α-smooth muscle actin (α-SMA), CD68, CD163, and IL-6 were analyzed in 36 low grade dysplastic nodules (DNs), 48 high grade DNs, 30 early HCCs (eHCCs), and 51 progressed HCCs (pHCCs) by immunohistochemistry or real-time PCR...
2017: PloS One
https://www.readbyqxmd.com/read/28107696/a-mini-review-of-c-met-as-a-potential-therapeutic-target-in-melanoma
#19
REVIEW
Doa'a G F Al-U'datt, Belal A A Al-Husein, Ghazi Raji Qasaimeh
Melanoma is the third highest rated cancer in prevalence. Surgery, radiotherapy and targeted/biological therapies in addition to chemotherapy are available options for management of this cancer. Met is an appealing target for management of this type of cancer, since it targets many cancer vital processors, such as angiogenesis, cell growth, scattering and differentiation. In this review, we provide an overview about pathway abnormalities associated with melanoma. We also provide a summary about the events involved in Met signaling and related signaling molecules...
January 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28104777/naturally-occurring-inlb-variants-that-support-intragastric-listeria-monocytogenes-infection-in-mice
#20
Konstantin Sobyanin, Elena Sysolyatina, Mikhail Krivozubov, Yaroslava Chalenko, Anna Karyagina, Svetlana Ermolaeva
Listeria monocytogenes is a causative agent of foodborne infection in humans and animals. The virulence factor InlB interacts with mammalian receptor c-Met via its internalin domain to provide L. monocytogenes invasion in non-professional phagocytes. Naturally occurring InlB internalin domain variants form 4 subclusters on the maximal likelihood tree. Four variants belonging to distinct subclusters were cloned into the vector carrying 3' and 5'-flanking sequences to restore full length inlB and expressed in the L...
January 18, 2017: FEMS Microbiology Letters
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