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“hepatocyte growth factor” AND “lung cancer”

Niki Karachaliou, Andres Felipe Cardona, Jillian Wilhelmina Paulina Bracht, Erika Aldeguer, Ana Drozdowskyj, Manuel Fernandez-Bruno, Imane Chaib, Jordi Berenguer, Mariacarmela Santarpia, Masaoki Ito, Jordi Codony-Servat, Rafael Rosell
BACKGROUND: The activation of multiple signaling pathways jeopardizes the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutation positive non-small cell lung cancer (NSCLC). Integrin-linked kinase (ILK) regulates the interactions between tumor cells and extracellular environment to activate signaling pathways and promote cell proliferation, migration, and epithelial-mesenchymal transition. Src homology 2 domain-containing phosphatase 2 (SHP2) is essential for receptor tyrosine kinase signaling and mitogen-activated protein kinase (MAPK) pathway activation...
November 22, 2018: EBioMedicine
Jongmin Sim, You Jeong Heo, Hyunsik Bae, Hyeong Chan Shin, Binnari Kim, Junhun Cho, Seung Tae Kim, Jeeyun Lee, Won Ki Kang, Kyoung-Mee Kim
BACKGROUND: MET is a tyrosine kinase receptor for the hepatocyte growth factor, and its overexpression is a poor prognostic factor in gastric carcinomas. Programmed death-ligand 1 (PD-L1) is an important biomarker of immunotherapy and is frequently positive in microsatellite instability-high (MSI-H) gastric carcinomas. In lung cancers, MET activation up-regulates PD-L1 expression. In this study, we investigated expression of MET and PD-L1 in MSI-H gastric carcinoma and the effects on prognosis...
November 12, 2018: Pathology, Research and Practice
Tatsuya Nagano, Motoko Tachihara, Yoshihiro Nishimura
Treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) improves the overall survival of patients with EGFR -mutated non-small-cell lung cancer (NSCLC). First-generation EGFR-TKIs (e.g., gefitinib and erlotinib) or second-generation EGFR-TKIs (e.g., afatinib and dacomitinib) are effective for the treatment of EGFR -mutated NSCLC, especially in patients with EGFR exon 19 deletions or an exon 21 L858R mutation. However, almost all cases experience disease recurrence after 1 to 2 years due to acquired resistance...
November 15, 2018: Cells
Yijun Jia, Xuefei Li, Chao Zhao, Tao Jiang, Sha Zhao, Limin Zhang, Xiaozhen Liu, Jinpeng Shi, Meng Qiao, Jiawei Luo, Sangtian Liu, Ruoshuang Han, Xiaoxia Chen, Caicun Zhou
BACKGROUND: Although EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are the standard treatment for patients with EGFR-mutant non-small-cell lung cancer (NSCLC), responses vary within individuals. The current study aimed to investigate whether serum levels of several cytokines and their dynamic changes during TKI treatment could be used to predict the efficacy of EGFR-TKIs. MATERIALS AND METHODS: Pre-treatment and one-month post-treatment serum levels of hepatocyte growth factor (HGF), interleukin-10 (IL-10), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), interferon gamma (IFN-γ) and monocyte chemotactic protein-1 (MCP-1) were measured using enzyme-linked immunosorbent assay and U-plex biomarker group assays in patients with EGFR-mutant NSCLC received first-line EGFR-TKIs...
November 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Gurudeeban Selvaraj, Satyavani Kaliamurthi, Aman Chandra Kaushik, Abbas Khan, Yong-Kai Wei, William C Cho, Keren Gu, Dong-Qing Wei
BACKGROUND: Lung adenocarcinoma (LUAD) is a heterogeneous disease with poor survival in the advanced stage and a high incidence rate in the world. Novel drug targets are urgently required to improve patient treatment. Therefore, we aimed to identify therapeutic targets for LUAD based on protein-protein and protein-drug interaction network analysis with neural network algorithms using mRNA expression profiles. RESULTS: A comprehensive meta-analysis of selective non-small cell lung cancer (NSCLC) mRNA expression profile datasets from Gene Expression Omnibus were used to identify potential biomarkers and the molecular mechanisms related to the prognosis of NSCLC patients...
October 2018: Journal of Biomedical Informatics
Maria Apicella, Elisa Giannoni, Stephany Fiore, Karin Johanna Ferrari, Daniel Fernández-Pérez, Claudio Isella, Carlotta Granchi, Filippo Minutolo, Antonino Sottile, Paolo Maria Comoglio, Enzo Medico, Filippo Pietrantonio, Marco Volante, Diego Pasini, Paola Chiarugi, Silvia Giordano, Simona Corso
The microenvironment influences cancer drug response and sustains resistance to therapies targeting receptor-tyrosine kinases. However, if and how the tumor microenvironment can be altered during treatment, contributing to resistance onset, is not known. We show that, under prolonged treatment with tyrosine kinase inhibitors (TKIs), EGFR- or MET-addicted cancer cells displayed a metabolic shift toward increased glycolysis and lactate production. We identified secreted lactate as the key molecule instructing cancer-associated fibroblasts to produce hepatocyte growth factor (HGF) in a nuclear factor κB-dependent manner...
August 30, 2018: Cell Metabolism
Oshin Miranda, Mariya Farooqui, Jill M Siegfried
Hepatocyte growth factor (HGF) is the ligand for the tyrosine kinase receptor c-Met (Mesenchymal Epithelial Transition Factor also known as Hepatocyte Growth Factor Receptor, HGFR), a receptor with expression throughout epithelial and endothelial cell types. Activation of c-Met enhances cell proliferation, invasion, survival, angiogenesis, and motility. The c-Met pathway also stimulates tissue repair in normal cells. A body of past research shows that increased levels of HGF and/or overexpression of c-Met are associated with poor prognosis in several solid tumors, including lung cancer, as well as cancers of the head and neck, gastro-intestinal tract, breast, ovary and cervix...
August 21, 2018: Cancers
Dorra Amor, Sébastien Goutal, Solène Marie, Fabien Caillé, Martin Bauer, Oliver Langer, Sylvain Auvity, Nicolas Tournier
BACKGROUND: Erlotinib is an epidermal growth factor receptor (EGFR)-targeting tyrosine kinase inhibitor approved for treatment of non-small cell lung cancer. The wide inter-individual pharmacokinetic (PK) variability of erlotinib may impact treatment outcome and/or toxicity. Recent in vivo studies reported a nonlinear uptake transport of erlotinib into the liver, suggesting carrier-mediated system(s) to mediate its hepatobiliary clearance. Erlotinib has been identified in vitro as a substrate of organic anion-transporting polypeptide (OATP) transporters which expression does not restrict to hepatocytes and may impact the tissue uptake of erlotinib in vivo...
August 16, 2018: EJNMMI Research
Xinpeng Li, Naxin Yuan, Lingdan Lin, Lixia Yin, Yiqing Qu
Non-small cell lung cancer (NSCLC) is the most frequent type of human lung cancer; lung cancer is responsible for the highest rates of cancer-associated mortality in the world. Cysteine-rich angiogenic inducer-61 (CYR-61) has been identified as a tumorigenesis-, development- and metastasis-related gene, and is reported to enhance proliferation, migration and invasion through hepatocyte growth factor (HGF)-induced scattering and the metastasis-inducing HGF/Met signaling pathway in tumor cells and xenograft models...
August 2018: Experimental and Therapeutic Medicine
Pankaj Kumar Singh, Om Silakari
Two major mechanisms involved in resistant NSCLC (Non-small cell lung cancer) include secondary acquired mutation in EGFR (epidermal growth factor receptor), i.e., EGFR T790M and amplification of c-MET (hepatocyte growth factor receptor). Thus, already established pharmacophore models of EGFR T790M and c-MET were employed to filter-out an in-house database. Further fitness score led to selection of imino-pyrimidine scaffold. Followed by sketching of imino-pyrimidine derivatives having varied aryl substitutions, which were then docked and subjected to molecular dynamic simulations, to study the orientations and conformations of the designed molecules in the catalytic domain...
July 26, 2018: Journal of Biomolecular Structure & Dynamics
Yongwen Li, Hongbing Zhang, Hao Gong, Yin Yuan, Ying Li, Cong Wang, Weiting Li, Zihe Zhang, Minghui Liu, Hongyu Liu, Jun Chen
BACKGROUND: Metastasis is the leading cause of cancer mortality and is a major hurdle for lung cancer treatment. Invadopodia, which are cancer-specific protrusive structures, play a crucial role in the metastatic cascade through degradation of the basement membrane and surrounding stroma. Cortactin, a critical component of invadopodia, frequently used as an invadopodia marker, a universally important player in invadopodia function, and is frequently overexpressed in cancer, but the exact mechanism of regulation is not yet fully understood...
July 9, 2018: Journal of Experimental & Clinical Cancer Research: CR
Lin Zhu, Feng Xue, Xiangying Xu, Jianyu Xu, Songliu Hu, Shanshan Liu, Ying Cui, Chunzi Gao
Non-small-cell lung cancer (NSCLC) is the most common cause of death from cancer worldwide. MicroRNAs (miRNAs) are a group of important regulators in NSCLC, including miR-198. However, the underlying molecular mechanisms of miR-198 involvement in intrinsic resistance to radiotherapy in NSCLC remain to be elucidated. In this study, to investigate the clinical significance of miR-198 in NSCLC in relation to the response to radiotherapy, we determined the expression patterns of miR-198 between responders and nonresponders after 2 months of radiotherapy and found that decreased expressions of miR-198 were associated with radiotherapy resistance...
June 26, 2018: Journal of Cellular Biochemistry
Tony Navas, Thomas D Pfister, Simona Colantonio, Amina Aziz, Lynda Dieckman, Richard G Saul, Jan Kaczmarczyk, Suzanne Borgel, Sergio Y Alcoser, Melinda G Hollingshead, Young H Lee, Donald P Bottaro, Tara Hiltke, Gordon Whiteley, Naoko Takebe, Robert J Kinders, Ralph E Parchment, Joseph E Tomaszewski, James H Doroshow
The presence of cancer stem cells (CSCs) and the induction of epithelial-to-mesenchymal transition (EMT) in tumors are associated with tumor aggressiveness, metastasis, drug resistance, and poor prognosis, necessitating the development of reagents for unambiguous detection of CSC- and EMT-associated proteins in tumor specimens. To this end, we generated novel antibodies to EMT- and CSC-associated proteins, including Goosecoid, Sox9, Slug, Snail, and CD133. Importantly, unlike several widely used antibodies to CD133, the anti-CD133 antibodies we generated recognize epitopes distal to known glycosylation sites, enabling analyses that are not confounded by differences in CD133 glycosylation...
2018: PloS One
Astrid A Glück, Eleonora Orlando, Dominic Leiser, Michaela Poliaková, Lluís Nisa, Aurélie Quintin, Jacopo Gavini, Deborah M Stroka, Sabina Berezowska, Lukas Bubendorf, Andree Blaukat, Daniel M Aebersold, Michaela Medová, Yitzhak Zimmer
Poor oxygenation is a common hallmark of solid cancers that strongly associates with aggressive tumor progression and treatment resistance. While a hypoxia-inducible factor 1α (HIF-1α)-associated transcriptional overexpression of the hepatocyte growth factor (HGF) receptor tyrosine kinase (RTK) MET has been previously documented, any regulation of the HIF-1α system through MET downstream signaling in hypoxic tumors has not been yet described. By using MET-driven in vitro as well as ex vivo tumor organotypic fresh tissue models we report that MET targeting results in depletion of HIF-1α and its various downstream targets...
July 2018: Oncogene
Demin Jiao, Jun Chen, Yu Li, Xiali Tang, Jian Wang, Wei Xu, Jia Song, You Li, Huimin Tao, Qingyong Chen
Hepatocyte growth factor (HGF) overexpression is an important mechanism in acquired epidermal growth factor receptor (EGFR) kinase inhibitor gefitinib resistance in lung cancers with EGFR activating mutations. MiR-1-3p and miR-206 act as suppressors in lung cancer proliferation and metastasis. However, whether miR-1-3p and miR-206 can overcome HGF-induced gefitinib resistance in EGFR mutant lung cancer is not clear. In this study, we showed that miR-1-3p and miR-206 restored the sensitivities of lung cancer cells PC-9 and HCC-827 to gefitinib in present of HGF...
July 2018: Journal of Cellular and Molecular Medicine
Xu-Feng Deng, Dong Zhou, Quan-Xing Liu, Hong Zheng, Yan Ding, Wen-Yue Xu, Jia-Xin Min, Ji-Gang Dai
Blocking the activation of nuclear factor κB (NF-κB) is a promising strategy for the treatment of non-small cell lung cancer. The circumsporozoite protein (CSP), a key component of the sporozoite stage of the malaria parasite, was previously reported to block NF-κB activation in hepatocytes. Therefore, in the present study, the effect of CSP on the growth of the human lung cancer cell line, A549, was investigated. It was demonstrated that transfection with a recombinant plasmid expressing CSP was able to inhibit the proliferation of A549 cells in a dose-dependent manner and induce the apoptosis of A549 cells...
May 2018: Oncology Letters
Yoshimi Ohashi, Mutsumi Okamura, Ryohei Katayama, Siyang Fang, Saki Tsutsui, Akinobu Akatsuka, Mingde Shan, Hyeong-Wook Choi, Naoya Fujita, Kentaro Yoshimatsu, Isamu Shiina, Takao Yamori, Shingo Dan
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) were demonstrated to provide survival benefit in patients with non-small cell lung cancer (NSCLC) harboring activating mutations of EGFR; however, emergence of acquired resistance to EGFR-TKIs has been shown to cause poor outcome. To overcome the TKI resistance, drugs with different mode of action are required. We previously reported that M-COPA (2-methylcoprophilinamide), a Golgi disruptor, suppressed the growth of gastric cancers overexpressing receptor tyrosine kinases (RTKs) such as hepatocyte growth factor receptor (MET) via downregulating their cell surface expression...
January 5, 2018: Oncotarget
Ahmed Salem, Hitesh Mistry, Alison Backen, Clare Hodgson, Pek Koh, Emma Dean, Lynsey Priest, Kate Haslett, Ioannis Trigonis, Alan Jackson, Marie-Claude Asselin, Caroline Dive, Andrew Renehan, Corinne Faivre-Finn, Fiona Blackhall
INTRODUCTION: There is an unmet need to develop noninvasive biomarkers to stratify patients in drug-radiotherapy trials. In this pilot study we investigated lung cancer radiotherapy response and toxicity blood biomarkers and correlated findings with tumor volume and proliferation imaging. PATIENTS AND METHODS: Blood samples were collected before and during (day 21) radiotherapy. Twenty-six cell-death, hypoxia, angiogenesis, inflammation, proliferation, invasion, and tumor-burden biomarkers were evaluated...
May 2018: Clinical Lung Cancer
Peter J Mazzone, Xiao-Feng Wang, Xiaozhen Han, Humberto Choi, Meredith Seeley, Richard Scherer, Victoria Doseeva
Background: A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact of combining molecular and clinical variables. Methods: The training set of serum samples was purchased from commercially available biorepositories. The testing set was from a biorepository at the Cleveland Clinic...
2018: Biomarker Insights
Eng-Huat Tan, Wan-Teck Lim, Myung-Ju Ahn, Quan-Sing Ng, Jin Seok Ahn, Daniel Shao-Weng Tan, Jong-Mu Sun, May Han, Francis C Payumo, Krista McKee, Wei Yin, Marc Credi, Shefali Agarwal, Jaroslaw Jac, Keunchil Park
Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 κ HGF inhibitory monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC)...
June 2018: Clinical Pharmacology in Drug Development
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