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“hepatocyte growth factor” AND “lung cancer”

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https://www.readbyqxmd.com/read/30047303/in-silico-guided-development-of-imine-based-inhibitors-for-resistance-deriving-kinases
#1
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
https://www.readbyqxmd.com/read/29986736/mir-182-suppresses-invadopodia-formation-and-metastasis-in-non-small-cell-lung-cancer-by-targeting-cortactin-gene
#2
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
https://www.readbyqxmd.com/read/29943841/microrna-198-inhibition-of-hgf-c-met-signaling-pathway-overcomes-resistance-to-radiotherapy-and-induces-apoptosis-in-human-non-small-cell-lung-cancer
#3
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
https://www.readbyqxmd.com/read/29928062/novel-antibody-reagents-for-characterization-of-drug-and-tumor-microenvironment-induced-changes-in-epithelial-mesenchymal-transition-and-cancer-stem-cells
#4
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
https://www.readbyqxmd.com/read/29717265/identification-of-a-met-eif4g1-translational-regulation-axis-that-controls-hif-1%C3%AE-levels-under-hypoxia
#5
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...
May 2, 2018: Oncogene
https://www.readbyqxmd.com/read/29664235/mir-1-3p-and-mir-206-sensitizes-hgf-induced-gefitinib-resistant-human-lung-cancer-cells-through-inhibition-of-c-met-signalling-and-emt
#6
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
https://www.readbyqxmd.com/read/29616122/plasmodium-circumsporozoite-protein-suppresses-the-growth-of-a549-cells-via-inhibiting-nuclear-transcription-factor-%C3%AE%C2%BAb
#7
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
https://www.readbyqxmd.com/read/29416720/targeting-the-golgi-apparatus-to-overcome-acquired-resistance-of-non-small-cell-lung-cancer-cells-to-egfr-tyrosine-kinase-inhibitors
#8
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
https://www.readbyqxmd.com/read/29398577/cell-death-inflammation-tumor-burden-and-proliferation-blood-biomarkers-predict-lung-cancer-radiotherapy-response-and-correlate-with-tumor-volume-and-proliferation-imaging
#9
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
https://www.readbyqxmd.com/read/29371783/evaluation-of-a-serum-lung-cancer-biomarker-panel
#10
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
https://www.readbyqxmd.com/read/29346833/phase-1b-trial-of-ficlatuzumab-a-humanized-hepatocyte-growth-factor-inhibitory-monoclonal-antibody-in-combination-with-gefitinib-in-asian-patients-with-nsclc
#11
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
https://www.readbyqxmd.com/read/29248440/jtc801-induces-ph-dependent-death-specifically-in-cancer-cells-and-slows-growth-of-tumors-in-mice
#12
Xinxin Song, Shan Zhu, Yangchun Xie, Jiao Liu, Lingyi Sun, Dexing Zeng, Pengcheng Wang, Xiaochao Ma, Guido Kroemer, David L Bartlett, Timothy R Billiar, Michael T Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Maintenance of acid-base homeostasis is required for normal physiology, metabolism, and development. It is not clear how cell death is activated in response to changes in pH. We performed a screen to identify agents that induce cell death in a pH-dependent manner (we call this alkaliptosis) in pancreatic ductal adenocarcinoma cancer (PDAC) cells and tested their effects in mice. METHODS: We screened a library of 254 compounds that interact with G-protein-coupled receptors (GPCRs) to identify those with cytotoxic activity against a human PDAC cell line (PANC1)...
April 2018: Gastroenterology
https://www.readbyqxmd.com/read/29187584/a-novel-bispecific-c-met-ctla-4-antibody-targeting-lung-cancer-stem-cell-like-cells-with-therapeutic-potential-in-human-non-small-cell-lung-cancer
#13
Jian-Feng Li, Yuan-Yuan Niu, Yan-Li Xing, Feng Liu
A novel paradigm in tumor biology suggests that non-small cell lung cancer (NSCLC) growth is driven by lung cancer stem cell-like cells (LCSCs), but here are still not any effective strategies to remove LCSCs. The bispecific antibody is a novel antibody, which can target two different antigens and mediate specific killing effects by selectively redirecting effector cells to the target cells. Here, we designed and synthesized a new bispecific antibody (BsAb), BsAb-5, that can target cellular-mesenchymal to epithelial transition factor (c-MET) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) in CD166+ LCSCs with high affinity and specificity, for the first time...
November 29, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29168346/cancer-testis-gene-piwil1-promotes-cell-proliferation-migration-and-invasion-in-lung-adenocarcinoma
#14
Kaipeng Xie, Kai Zhang, Jing Kong, Cheng Wang, Yayun Gu, Cheng Liang, Tingting Jiang, Na Qin, Jibin Liu, Xuejiang Guo, Ran Huo, Mingxi Liu, Hongxia Ma, Juncheng Dai, Zhibin Hu
Piwi-like RNA-mediated gene silencing 1 (PIWIL1) has been identified as a novel extremely highly expressed cancer-testis (CT) gene in lung adenocarcinoma. However, the exact function and mechanism of PIWIL1 in lung adenocarcinoma remains unclear. Herein, we sought to investigate the role of PIWIL1 in the occurrence and development of lung adenocarcinoma. We examined the expression pattern of PIWIL1 in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples, and validated it by Real-Time PCR (RT-PCR) in additional 21 paired lung adenocarcinoma tissues and 16 normal tissues...
January 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29125233/in-vivo-imaging-xenograft-models-for-the-evaluation-of-anti-brain-tumor-efficacy-of-targeted-drugs
#15
COMPARATIVE STUDY
Kenji Kita, Sachiko Arai, Akihiro Nishiyama, Hirokazu Taniguchi, Koji Fukuda, Rong Wang, Tadaaki Yamada, Shinji Takeuchi, Shoichiro Tange, Atsushi Tajima, Mitsutoshi Nakada, Kazuo Yasumoto, Yoshiharu Motoo, Takashi Murakami, Seiji Yano
Molecular-targeted drugs are generally effective against tumors containing driver oncogenes, such as EGFR, ALK, and NTRK1. However, patients harboring these oncogenes frequently experience a progression of brain metastases during treatment. Here, we present an in vivo imaging model for brain tumors using human cancer cell lines, including the EGFR-L858R/T790M-positive H1975 lung adenocarcinoma cells, the NUGC4 hepatocyte growth factor (HGF)-dependent gastric cancer cells, and the KM12SM colorectal cancer cells containing the TPM3-NTRK1 gene fusion...
December 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29121501/does-c-met-remain-a-rational-target-for-therapy-in-patients-with-egfr-tki-resistant-non-small-cell-lung-cancer
#16
REVIEW
Yi-Long Wu, Ross Andrew Soo, Giuseppe Locatelli, Uz Stammberger, Giorgio Scagliotti, Keunchil Park
Non-small cell lung cancer (NSCLC) inevitably develops resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. In 5-20% of cases, this can be attributed to aberrant c-Met activity, providing a clear rationale for the use of c-Met inhibitors in these patients. EGFR TKI-resistant tumors often remain sensitive to EGFR signaling, such that c-Met inhibitors are likely to be most effective when combined with continued EGFR TKI therapy. The phase III trials of the c-Met inhibitors onartuzumab and tivantinib, which failed to demonstrate significant benefit in patients with NSCLC but excluded patients with EGFR TKI-resistant disease, do not allow c-Met to be dismissed as a rational target in EGFR TKI-resistant NSCLC...
December 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29069748/clinical-impact-of-high-serum-hepatocyte-growth-factor-in-advanced-non-small-cell-lung-cancer
#17
Takahiro Tsuji, Yuichi Sakamori, Hiroaki Ozasa, Yoshitaka Yagi, Hitomi Ajimizu, Yuto Yasuda, Tomoko Funazo, Takashi Nomizo, Hironori Yoshida, Hiroki Nagai, Ken Maeno, Tetsuya Oguri, Toyohiro Hirai, Young Hak Kim
Activation of c-MET through hepatocyte growth factor (HGF) increases tumorigenesis, induces resistance, and is associated with poor prognosis in various solid tumors. However, the clinical value of serum HGF (sHGF) in patients with advanced non-small cell lung cancer (NSCLC), especially those receiving cytotoxic chemotherapy, remains unknown. Here, we show that sHGF may be useful to predict tumor response and progression-free survival (PFS) in patients with advanced NSCLC. A total of 81 patients with NSCLC were investigated...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29063069/targeting-met-in-cancer-therapy
#18
REVIEW
Hong-Nan Mo, Peng Liu
MET encodes a receptor tyrosine kinase c-MET for hepatocyte growth factor (HGF). The specific combination of c-MET and HGF activates downstream signaling pathways to trigger cell migration, proliferation, and angiogenesis. MET exon 14 alterations and MET gene amplification play a critical role in the origin of cancer. Several monoclonal antibodies and small-molecule inhibitors of c-MET have been evaluated in clinical trials. In patients with advanced non-small cell lung cancer, cabozantinib and crizotinib showed clear efficacy with a generally tolerable adverse events profile...
September 2017: Chronic Diseases and Translational Medicine
https://www.readbyqxmd.com/read/28964418/serum-biomarkers-may-prognosticate-recurrence-in-node-negative-non-small-cell-lung-cancers-less-than-4-centimeters
#19
COMPARATIVE STUDY
Christopher W Seder, Andrew T Arndt, Lia Jordano, Sanjib Basu, Cristina L Fhied, Selina Sayidine, Gary W Chmielewski, Kelsey Gallo, Michael J Liptay, Jeffrey A Borgia
BACKGROUND: A significant proportion of patients who undergo lung resection for less than 4 cm non-small cell lung cancer (NSCLC) will die of disease recurrence within 5 years. The ability to identify patients at greatest risk for recurrence may help individualize treatment and surveillance regimens and improve outcomes. We hypothesized that a serum-based biomarker panel could help risk stratify patients with node-negative NSCLC less than 4 cm for recurrence after lung resection. METHODS: An institutional biorepository of more than 1,800 cases was used to identify patients with resected, node-negative NSCLC less than 4 cm in size...
November 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28944826/macc%C3%A2-1-antibody-target-therapy-suppresses-growth-and-migration-of-non%C3%A2-small-cell-lung-cancer
#20
Woda Shi, Jianxiang Song, Wencai Wang, Yajun Zhang, Shiying Zheng
Non‑small‑cell lung cancer (NSCLC) accounts for ~80% of human lung cancers that result in mortalities worldwide. Metastasis‑associated in colon cancer‑1 (MACC‑1) has been demonstrated to be significantly expressed in cases of NSCLC and promotes tumor cell migration and metastasis through transactivation of the metastasis‑inducing hepatocyte growth factor/MET proto‑gene, receptor tyrosine kinase (HGF/MET) signaling pathway. The present study constructed a chimeric antibody (Chanti‑MACC‑1) targeting MACC‑1 and investigated its potential as a molecular therapeutic target in the treatment of NSCLC therapy...
November 2017: Molecular Medicine Reports
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