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“hepatocyte growth factor” AND “lung cancer”

Shang-Ru Wu, Chia-Hao Lin, Han-Po Shih, Chun-Jung Ko, Hsin-Ying Lin, Shao-Wei Lan, Hsin-Hsien Lin, Hsin-Fang Tu, Chao-Chi Ho, Hsiang-Po Huang, Ming-Shyue Lee
BACKGROUND: Dysregulation of pericellular proteolysis usually accounts for cancer cell invasion and metastasis. Isolation of a cell-surface protease system for lung cancer metastasis is an important issue for mechanistic studies and therapeutic target identification. METHODS: Immunohistochemistry of a tissue array (n = 64) and TCGA database (n = 255) were employed to assess the correlation between serine protease inhibitors (SPIs) and lung adenocarcinoma progression...
February 15, 2019: British Journal of Cancer
Xiaojuan Ai, Xialing Guo, Jun Wang, Andreea L Stancu, Patrick M N Joslin, Dianzheng Zhang, Shudong Zhu
Lung cancer is a serious health problem and the leading cause of cancer death worldwide, due to its high incidence and mortality. 85% of lung cancers are represented by the non-small cell lung cancer (NSCLC). Traditional chemotherapy has been the main treatment option in NSCLC. However, it is often associated with limited efficacy and overall poor patient survival. In recent years, molecular targeting has achieved great progress in therapeutic treatment of cancer and plays a crucial role in the current clinical treatment of NSCLC, due to enhanced efficacy on cancer tissues and reduced toxicity for normal tissues...
December 25, 2018: Oncotarget
Sabrina Baltschukat, Barbara Schacher Engstler, Alan Huang, Huai-Xiang Hao, Angela Tam, Hui Qin Wang, Jinsheng Liang, Matthew T DiMare, Hyo-Eun C Bhang, Youzhen Wang, Pascal Furet, William R Sellers, Francesco Hofmann, Joseph Schoepfer, Ralph Tiedt
PURPOSE: The selective MET inhibitor capmatinib is being investigated in multiple clinical trials, both as a single agent and in combination. Here, we describe the preclinical data of capmatinib that supported the clinical biomarker strategy for rational patient selection. EXPERIMENTAL DESIGN: The selectivity and cellular activity of capmatinib were assessed in large cellular screening panels. Antitumor efficacy was quantified in a large set of cell line- or patient-derived xenograft models, testing single agent or combination treatment depending on the genomic profile of the respective models...
January 23, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Young Mi Whang, Seung Pil Jung, Meyoung-Kon Kim, In Ho Chang, Serk In Park
Bone metastasis is the terminal stage disease of prostate, breast, renal, and lung cancers, and currently no therapeutic approach effectively cures or prevents its progression to bone metastasis. One of the hurdles to the development of new drugs for bone metastasis is the complexity and heterogeneity of the cellular components in the metastatic bone microenvironment. For example, bone cells, including osteoblasts, osteoclasts, and osteocytes, and the bone marrow cells of diverse hematopoietic lineages interact with each other via numerous cytokines and receptors...
January 17, 2019: International Journal of Molecular Sciences
Akira Naito, Seiichiro Sakao, Irene M Lang, Norbert F Voelkel, Takayuki Jujo, Keiichi Ishida, Toshihiko Sugiura, Goro Matsumiya, Ichiro Yoshino, Nobuhiro Tanabe, Koichiro Tatsumi
BACKGROUND: Impaired angiogenesis is assumed to be an important factor in the development of chronic thromboembolic pulmonary hypertension (CTEPH). However, the role of endothelial cells (ECs) in CTEPH remains unclear. The aim of this study was to investigate the angiogenic potential of ECs from pulmonary endarterectomy (PEA) specimens. METHODS: We isolated ECs from PEA specimens (CTEPH-ECs) and control EC lines from the intact pulmonary arteries of patients with peripheral lung cancers, using a MACS system...
December 29, 2018: BMC Pulmonary Medicine
Menghua Du, Jin Wang, Huan Chen, Shouli Wang, Liesong Chen, Yichang Xu, Fengtao Su, Xueguan Lu
Hepatocyte growth factor (HGF), an activator of the c‑Met signaling pathway, is involved in tumor invasiveness, metastasis and radiotherapy resistance. In the present study, a novel HGF regulatory pathway in lung cancer involving micro-RNAs (miRNAs/miR) is described. Immunohistochemical staining and western blot analyses demonstrated that HGF was upregulated and associated with miR‑200a downregulation in non‑small cell lung cancer (NSCLC) samples compared with normal lung tissues. The association between HGF and miR‑200a was associated with the degree of tumor malignancy and cell migration and invasion...
December 12, 2018: Oncology Reports
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
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