The Experts below are selected from a list of 47460 Experts worldwide ranked by ideXlab platform
Panchyr Yang - One of the best experts on this subject based on the ideXlab platform.
-
survival of Lung Adenocarcinoma patients with malignant pleural effusion
European Respiratory Journal, 2013Co-Authors: Mengfeng Tsai, Panchyr Yang, Weiyu Liao, Chihhsin Yang, Ishiow Jan, Jinyuan ShihAbstract:In the era of targeted therapy, the association between Lung Adenocarcinoma patient survival and malignant pleural effusions (MPEs) remains unclear. This study investigated the clinical characteristics, survival and epidermal growth factor receptor (EGFR) gene (EGFR) mutation status of Lung Adenocarcinoma patients with MPE. From June 2005 to December 2010, consecutive pleural effusions were collected prospectively. Patient clinical characteristics, EGFR mutation status, and overall survival were analysed. We collected MPEs from 448 patients in stage IV Lung Adenocarcinoma at initial diagnosis. Median overall survival for patients with MPEs at initial diagnosis and following disease progression were 14.3 months and 21.4 months, respectively (p=0.001). There were 296 (66.1%) patients harbouring EGFR mutations, the mutation rates among patients with an MPE at initial diagnosis and one following disease progression were 68.2% and 56.6%, respectively (p=0.044); the L858R mutation rate was also higher among the former (32.6% versus 18.1%; p=0.009). Multivariate analysis revealed that patients who: developed MPEs following disease progression, harboured EGFR mutations, and received EGFR-tyrosine kinase inhibitor therapy, had longer overall survival. Patients in stage IV Lung Adenocarcinoma with MPEs at initial diagnosis have shorter overall survival and higher EGFR mutation rate, especially for L858R, than patients who develop MPEs following disease progression.
-
claudin 1 is a metastasis suppressor and correlates with clinical outcome in Lung Adenocarcinoma
American Journal of Respiratory and Critical Care Medicine, 2009Co-Authors: Yu Chih Chao, Szuhua Pan, Shuenn Chen Yang, Ting Fang Che, Chungwu Lin, Mu Shiun Tsai, Geechen Chang, Yungchie Lee, Tse Ming Hong, Panchyr YangAbstract:Rationale: Claudin (CLDN)-1, a key component of tight junction complexes, was down-regulated in human Lung Adenocarcinomas.Objectives: To investigate the clinical significance of CLDN1 expression in patients with Lung Adenocarcinoma and its role in cancer invasion and metastasis.Methods: We examined the CLDN1 mRNA expression in tumor specimens from 64 patients with Lung Adenocarcinoma and protein expression by immunohistochemistry in an independent cohort of 67 patients with Lung Adenocarcinoma. CLDN1 functions in cancer cell migration, invasion, and metastatic colonization were studied by overexpression and knockdown of CLDN1. Affymetrix microarrays were performed to identify gene expression changes associated with CLDN1 overexpression.Measurements and Main Results: We found that low-CLDN1 mRNA expression had shorter overall survival (P = 0.027, log-rank test) in 64 patients with Lung Adenocarcinoma, and we confirmed by immunohistochemistry that low CLDN1 expression had shorter overall survival (P = 0.02...
-
frequent epidermal growth factor receptor gene mutations in malignant pleural effusion of Lung Adenocarcinoma
European Respiratory Journal, 2008Co-Authors: Chienhung Gow, Jinyuan Shih, Yihleong Chang, C H Yang, Y C Hsu, Y C Lee, Panchyr YangAbstract:Malignant pleural effusions (MPEs) are often observed in Lung cancer, especially Adenocarcinoma. Epidermal growth factor receptor (EGFR) gene mutations are usually detected in Lung Adenocarcinoma. The purpose of the present study was to investigate the EGFR mutation rate in MPEs of Lung Adenocarcinoma. Between June 2005 and December 2006, 136 MPEs from Lung Adenocarcinoma were collected for EGFR mutation detection. In addition, between April 2001 and November 2004, 91 surgically resected specimens of Lung Adenocarcinoma from patients without MPEs were assessed for EGFR mutation. The EGFR mutation rate was significantly higher in the patients with MPEs than in the patients without (68.4% versus 50.5%). The EGFR mutation rate in patients with MPEs was not associated with sex, smoking history, age or cancer stage. By multivariate analysis, an age of <65 yrs, never smoking, Eastern Cooperative Oncology Group performance status 0-1, and EGFR mutation were significantly associated with a longer overall survival for Lung Adenocarcinoma patients with MPEs. The patients with malignant pleural effusions related to Lung Adenocarcinoma had a higher epidermal growth factor receptor gene mutation rate than the patients from whom surgically resected specimens were taken. Epidermal growth factor receptor tyrosine kinase inhibitors may be the treatment of choice for Lung Adenocarcinoma with malignant pleural effusions in east Asia.
-
up regulated caveolin 1 accentuates the metastasis capability of Lung Adenocarcinoma by inducing filopodia formation
American Journal of Pathology, 2002Co-Authors: Peihsin Huang, Hsinyi Huang, Yenho Chen, Panchyr Yang, Suming HsuAbstract:Caveolin-1, a 21- to 24-kd integral membrane protein, is primarily implicated as a tumor suppressor gene. Transformed cells normally contain reduced or no caveolin-1. Re-expression of caveolin-1 is found in advanced human and mouse prostate Adenocarcinomas. To explore its potential role in tumorigenesis and tumor progression of human Lung cancers, we used the well-characterized cell line (CL) series of Lung Adenocarcinoma cells with increasing cellular invasiveness to show that expression of caveolin-1 mRNA and protein was up-regulated with enhanced invasion/metastatic capability of CL cells. Reintroducing the caveolin-1 gene into the less invasive, caveolin-1-negative CL cells enhanced their invasive capability at least by twofold, as revealed by an in vitro chamber invasion assay. Thus, a correlation exists for both constitutive and induced expression of caveolin-1 in CL cells. Immunohistochemical examination of caveolin-1 was performed in 95 specimens obtained retrospectively from patients who had Lung Adenocarcinoma either with (35 patients) or without (60 patients) ipsilateral hilar/peribronchial tumor-metastasized lymph nodes. Caveolin-1 immunoreactivity was either totally absent or just barely detectable in a few Lung Adenocarcinoma cells from cases diagnosed as Lung Adenocarcinoma without regional lymph node metastasis. In contrast, increased caveolin-1 immunoreactivity both in number and intensity was detected in primary Lung Adenocarcinoma cells as well as in cancer cells that metastasized to regional lymph nodes from the cases diagnosed as advanced Lung Adenocarcinoma with nodal metastases. Multivariate analysis considering caveolin-1 immunoreactivity in addition to the established prognostic parameters such as pT stage, pN in these patients confirmed that caveolin-1 is an independent functional predictor of poor survival. We further revealed that up-regulated caveolin-1 in CL cells is necessary for mediating filopodia formation, which may enhance the invasive ability of Lung Adenocarcinoma cells.
Jinyuan Shih - One of the best experts on this subject based on the ideXlab platform.
-
survival of Lung Adenocarcinoma patients with malignant pleural effusion
European Respiratory Journal, 2013Co-Authors: Mengfeng Tsai, Panchyr Yang, Weiyu Liao, Chihhsin Yang, Ishiow Jan, Jinyuan ShihAbstract:In the era of targeted therapy, the association between Lung Adenocarcinoma patient survival and malignant pleural effusions (MPEs) remains unclear. This study investigated the clinical characteristics, survival and epidermal growth factor receptor (EGFR) gene (EGFR) mutation status of Lung Adenocarcinoma patients with MPE. From June 2005 to December 2010, consecutive pleural effusions were collected prospectively. Patient clinical characteristics, EGFR mutation status, and overall survival were analysed. We collected MPEs from 448 patients in stage IV Lung Adenocarcinoma at initial diagnosis. Median overall survival for patients with MPEs at initial diagnosis and following disease progression were 14.3 months and 21.4 months, respectively (p=0.001). There were 296 (66.1%) patients harbouring EGFR mutations, the mutation rates among patients with an MPE at initial diagnosis and one following disease progression were 68.2% and 56.6%, respectively (p=0.044); the L858R mutation rate was also higher among the former (32.6% versus 18.1%; p=0.009). Multivariate analysis revealed that patients who: developed MPEs following disease progression, harboured EGFR mutations, and received EGFR-tyrosine kinase inhibitor therapy, had longer overall survival. Patients in stage IV Lung Adenocarcinoma with MPEs at initial diagnosis have shorter overall survival and higher EGFR mutation rate, especially for L858R, than patients who develop MPEs following disease progression.
-
frequent epidermal growth factor receptor gene mutations in malignant pleural effusion of Lung Adenocarcinoma
European Respiratory Journal, 2008Co-Authors: Chienhung Gow, Jinyuan Shih, Yihleong Chang, C H Yang, Y C Hsu, Y C Lee, Panchyr YangAbstract:Malignant pleural effusions (MPEs) are often observed in Lung cancer, especially Adenocarcinoma. Epidermal growth factor receptor (EGFR) gene mutations are usually detected in Lung Adenocarcinoma. The purpose of the present study was to investigate the EGFR mutation rate in MPEs of Lung Adenocarcinoma. Between June 2005 and December 2006, 136 MPEs from Lung Adenocarcinoma were collected for EGFR mutation detection. In addition, between April 2001 and November 2004, 91 surgically resected specimens of Lung Adenocarcinoma from patients without MPEs were assessed for EGFR mutation. The EGFR mutation rate was significantly higher in the patients with MPEs than in the patients without (68.4% versus 50.5%). The EGFR mutation rate in patients with MPEs was not associated with sex, smoking history, age or cancer stage. By multivariate analysis, an age of <65 yrs, never smoking, Eastern Cooperative Oncology Group performance status 0-1, and EGFR mutation were significantly associated with a longer overall survival for Lung Adenocarcinoma patients with MPEs. The patients with malignant pleural effusions related to Lung Adenocarcinoma had a higher epidermal growth factor receptor gene mutation rate than the patients from whom surgically resected specimens were taken. Epidermal growth factor receptor tyrosine kinase inhibitors may be the treatment of choice for Lung Adenocarcinoma with malignant pleural effusions in east Asia.
-
transcription repressor slug promotes carcinoma invasion and predicts outcome of patients with Lung Adenocarcinoma
Clinical Cancer Research, 2005Co-Authors: Jinyuan Shih, Mengfeng Tsai, Tzu Hua Chang, Yihleong Chang, Ang Yuan, Shin Bey Lin, Geou Yarh Liou, Meng Larn Lee, Jeremy J W ChenAbstract:Purpose: In a previous genome-wide gene expression profiling analysis using an invasion cancer cell lines model, we have identified Slug as selectively overexpressed in the highly invasive cancer cells. Here, we investigated the clinical significance of Slug in Lung Adenocarcinoma and the role of Slug in the process of cancer cell invasion and metastasis. Experimental Design: Real-time quantitative reverse transcription-PCR was used to investigate Slug mRNA in surgically resected Lung Adenocarcinoma of 54 patients and its correlation with survival. We overexpressed Slug in a Lung Adenocarcinoma cell line with very low Slug levels and investigated the in vitro and in vivo effects of Slug expression. Results: High expression of Slug mRNA in Lung cancer tissue was significantly associated with postoperative relapse ( P = 0.03) and shorter patient survival ( P Slug enhanced xenograft tumor growth and increased microvessel counts in angiogenesis assay. Both inducible and constitutive overexpression of Slug suppressed the expression of E-cadherin and increased the in vitro invasive ability. Zymography revealed increased matrix metalloproteinase-2 activity in Slug overexpressed cells. ELISA, reverse transcription-PCR, and immunohistochemistry confirmed the increase of matrix metalloproteinase-2 proteins and mRNA in Slug overexpressed cells and xenograft tumors. Conclusions: Slug expression can predict the clinical outcome of Lung Adenocarcinoma patients. Slug is a novel invasion-promoting gene in Lung Adenocarcinoma.
Kerstin W Sinkevicius - One of the best experts on this subject based on the ideXlab platform.
-
e cadherin loss accelerates tumor progression and metastasis in a mouse model of Lung Adenocarcinoma
American Journal of Respiratory Cell and Molecular Biology, 2018Co-Authors: Kerstin W Sinkevicius, Kelly J Bellaria, Juliana Barrios, Patrizia Pessina, Manav GuptaAbstract:Metastatic disease is the primary cause of death of patients with Lung cancer, but the mouse models of Lung Adenocarcinoma do not accurately recapitulate the tumor microenvironment or metastatic disease observed in patients. In this study, we conditionally deleted E-cadherin in an autochthonous Lung Adenocarcinoma mouse model driven by activated oncogenic Kras and p53 loss. Loss of E-cadherin significantly accelerated Lung Adenocarcinoma progression and decreased survival of the mice. Kras;p53;E-cadherin mice had a 41% Lung tumor burden, invasive grade 4 tumors, and a desmoplastic stroma just 8 weeks after tumor initiation. One hundred percent of the mice developed local metastases to the lymph nodes or chest wall, and 38% developed distant metastases to the liver or kidney. Lung Adenocarcinoma cancer cell lines derived from these tumors also had high migratory rates. These studies demonstrate that the Kras;p53;E-cadherin mouse model better emulates the tumor microenvironment and metastases observed in patients with Lung Adenocarcinoma than previous models and may therefore be useful for studying metastasis and testing new Lung cancer treatments in vivo.
-
neurotrophin receptor trkb promotes Lung Adenocarcinoma metastasis
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Kerstin W Sinkevicius, Kelly J Bellaria, Christina Kriegel, Jaewon J Lee, Allison N Lau, Kristen T Leeman, Pengcheng Zhou, Alexander M Beede, Christine M Fillmore, Deborah R CaswellAbstract:Lung cancer is notorious for its ability to metastasize, but the pathways regulating Lung cancer metastasis are largely unknown. An in vitro system designed to discover factors critical for Lung cancer cell migration identified brain-derived neurotrophic factor, which stimulates cell migration through activation of tropomyosin-related kinase B (TrkB; also called NTRK2). Knockdown of TrkB in human Lung cancer cell lines significantly decreased their migratory and metastatic ability in vitro and in vivo. In an autochthonous Lung Adenocarcinoma model driven by activated oncogenic Kras and p53 loss, TrkB deficiency significantly reduced metastasis. Hypoxia-inducible factor-1 directly regulated TrkB expression, and, in turn, TrkB activated Akt signaling in metastatic Lung cancer cells. Finally, TrkB expression was correlated with metastasis in patient samples, and TrkB was detected more often in tumors that did not have Kras or epidermal growth factor receptor mutations. These studies demonstrate that TrkB is an important therapeutic target in metastatic Lung Adenocarcinoma.
Kelly J Bellaria - One of the best experts on this subject based on the ideXlab platform.
-
e cadherin loss accelerates tumor progression and metastasis in a mouse model of Lung Adenocarcinoma
American Journal of Respiratory Cell and Molecular Biology, 2018Co-Authors: Kerstin W Sinkevicius, Kelly J Bellaria, Juliana Barrios, Patrizia Pessina, Manav GuptaAbstract:Metastatic disease is the primary cause of death of patients with Lung cancer, but the mouse models of Lung Adenocarcinoma do not accurately recapitulate the tumor microenvironment or metastatic disease observed in patients. In this study, we conditionally deleted E-cadherin in an autochthonous Lung Adenocarcinoma mouse model driven by activated oncogenic Kras and p53 loss. Loss of E-cadherin significantly accelerated Lung Adenocarcinoma progression and decreased survival of the mice. Kras;p53;E-cadherin mice had a 41% Lung tumor burden, invasive grade 4 tumors, and a desmoplastic stroma just 8 weeks after tumor initiation. One hundred percent of the mice developed local metastases to the lymph nodes or chest wall, and 38% developed distant metastases to the liver or kidney. Lung Adenocarcinoma cancer cell lines derived from these tumors also had high migratory rates. These studies demonstrate that the Kras;p53;E-cadherin mouse model better emulates the tumor microenvironment and metastases observed in patients with Lung Adenocarcinoma than previous models and may therefore be useful for studying metastasis and testing new Lung cancer treatments in vivo.
-
neurotrophin receptor trkb promotes Lung Adenocarcinoma metastasis
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Kerstin W Sinkevicius, Kelly J Bellaria, Christina Kriegel, Jaewon J Lee, Allison N Lau, Kristen T Leeman, Pengcheng Zhou, Alexander M Beede, Christine M Fillmore, Deborah R CaswellAbstract:Lung cancer is notorious for its ability to metastasize, but the pathways regulating Lung cancer metastasis are largely unknown. An in vitro system designed to discover factors critical for Lung cancer cell migration identified brain-derived neurotrophic factor, which stimulates cell migration through activation of tropomyosin-related kinase B (TrkB; also called NTRK2). Knockdown of TrkB in human Lung cancer cell lines significantly decreased their migratory and metastatic ability in vitro and in vivo. In an autochthonous Lung Adenocarcinoma model driven by activated oncogenic Kras and p53 loss, TrkB deficiency significantly reduced metastasis. Hypoxia-inducible factor-1 directly regulated TrkB expression, and, in turn, TrkB activated Akt signaling in metastatic Lung cancer cells. Finally, TrkB expression was correlated with metastasis in patient samples, and TrkB was detected more often in tumors that did not have Kras or epidermal growth factor receptor mutations. These studies demonstrate that TrkB is an important therapeutic target in metastatic Lung Adenocarcinoma.
Tao Ren - One of the best experts on this subject based on the ideXlab platform.
-
mir 138 5p suppresses Lung Adenocarcinoma cell epithelial mesenchymal transition proliferation and metastasis by targeting zeb2
Pathology Research and Practice, 2019Co-Authors: Dongyi Zhu, Wenjing Jin, Tao RenAbstract:Abstract Background MiR-138-5p is regarded as a tumour suppressor in many cancers. Transforming growth factor beta (TGF-β) often acts as a tumor promotor at the late stages of human cancers. However, the function of miR-138-5p on Lung Adenocarcinoma cells induced by TGF-β remains to be further confirmed. Methods RT-qPCR was used to detect the expression of human Lung Adenocarcinoma tissues, adjacent normal tissues, and relative cell lines. When the Lung Adenocarcinoma cells A549 and H1299 were transfected with negative control (NC), miR-138-5p mimics and miR-138-5p inhibitor by lipofectamine3000 and treated with or without TGF-β1, the Lung Adenocarcinoma cell function was detected by Immunofluorescence, Western blotting (WB), cell counting Kit-8 (CCK8), colony formation, EdU, Wound-healing and Transwell assays. The relation between miR-138-5p and zinc finger E-box-binding homeobox 2 (ZEB2) was detected by RT-qPCR, WB, and Luciferase reporter assays. When ZEB2 was knocked down, the Lung Adenocarcinoma cell function was detected by WB, CCK8 and Transwell assays. Results The expression of miR-138-5p was decreased in Lung Adenocarcinoma tissues and cell lines. When treated with or without TGF-β1, overexpression of miR-138-5p suppressed EMT, proliferation and metastasis of A549 and H1299. ZEB2 was verified as the direct target of miR-138-5p. Downregulation of ZEB2 suppressed EMT, proliferation and metastasis of Lung Adenocarcinoma cell, which could be reversed by miR-138-5p inhibitor. Conclusions MiR-138-5p inhibits epithelial-mesenchymal transition, growth and metastasis of Lung Adenocarcinoma cells through targeting ZEB2.
