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https://www.readbyqxmd.com/read/28230863/oncogenic-role-of-rab-escort-protein-1-through-egfr-and-stat3-pathway
#1
Un-Jung Yun, Jee Young Sung, Seog-Yun Park, Sang-Kyu Ye, Jaegal Shim, Jae-Seon Lee, Masahiko Hibi, Young-Ki Bae, Yong-Nyun Kim
Rab escort protein-1 (REP1) is linked to choroideremia (CHM), an X-linked degenerative disorder caused by mutations of the gene encoding REP1 (CHM). REP1 mutant zebrafish showed excessive cell death throughout the body, including the eyes, indicating that REP1 is critical for cell survival, a hallmark of cancer. In the present study, we found that REP1 is overexpressed in human tumor tissues from cervical, lung, and colorectal cancer patients, whereas it is expressed at relatively low levels in the normal tissue counterparts...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28223235/interleukin-32-inflammation-and-cancer
#2
REVIEW
Jin Tae Hong, Dong Ju Son, Chong Kil Lee, Do-Young Yoon, Dong Hun Lee, Mi Hee Park
Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. IL-32 gene consists of eight small exons, and IL-32 mRNA has nine alternative spliced isoforms, and was thought to be secreted because it contains an internal signal sequence and lacks a transmembrane region. IL-32 is initially expressed selectively in activated T cells by mitogen and activated NK cells and their expression is strongly augmented by microbes, mitogens, and other cytokines. The IL-32 is induced mainly by pathogens and pro-inflammatory cytokines, but IL-32 is more prominent in immune cells than in non-immune tissues...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28219421/regulation-of-voltage-gated-potassium-channels-attenuates-resistance-of-side-population-cells-to-gefitinib-in-the-human-lung-cancer-cell-line-nci-h460
#3
Seon Young Choi, Hang-Rae Kim, Pan Dong Ryu, So Yeong Lee
BACKGROUND: Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. METHODS: To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux...
February 21, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28212561/the-tlr7-agonist-imiquimod-induces-anti-cancer-effects-via-autophagic-cell-death-and-enhances-anti-tumoral-and-systemic-immunity-during-radiotherapy-for-melanoma
#4
Jeong Hyun Cho, Hyo-Ji Lee, Hyun-Jeong Ko, Byung-Il Yoon, Jongseon Choe, Keun-Cheol Kim, Tae-Wook Hahn, Jeong A Han, Sun Shim Choi, Young Mee Jung, Kee-Ho Lee, Yun-Sil Lee, Yu-Jin Jung
Toll-like receptor (TLR) ligands are strongly considered immune-adjuvants for cancer immunotherapy and have been shown to exert direct anti-cancer effects. This study was performed to evaluate the synergistic anti-cancer and anti-metastatic effects of the TLR7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation (IR) led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28192899/comparison-of-the-mismatch-repair-system-between-primary-and-metastatic-colorectal-cancers-using-immunohistochemistry
#5
Jiyoon Jung, Youngjin Kang, Yoo Jin Lee, Eojin Kim, Bokyung Ahn, Eunjung Lee, Joo Young Kim, Jeong Hyeon Lee, Youngseok Lee, Chul Hwan Kim, Yang-Seok Chae
Background: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Approximately 10%-15% of the CRC cases have defective DNA mismatch repair (MMR) genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC) for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has emerged as a useful technique to complement polymerase chain reaction (PCR) analyses...
February 14, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28192371/somatic-mutations-in-telomerase-promoter-counterbalance-germline-loss-of-function-mutations
#6
Lindley Maryoung, Yangbo Yue, Ashley Young, Chad A Newton, Cindy Barba, Nicolai S C van Oers, Richard C Wang, Christine Kim Garcia
Germline coding mutations in different telomere-related genes have been linked to autosomal-dominant familial pulmonary fibrosis. Individuals with these inherited mutations demonstrate incomplete penetrance of clinical phenotypes affecting the lung, blood, liver, skin, and other organs. Here, we describe the somatic acquisition of promoter mutations in telomerase reverse transcriptase (TERT) in blood leukocytes of approximately 5% of individuals with inherited loss-of-function coding mutations in TERT or poly(A)-specific ribonuclease (PARN), another gene linked to telomerase function...
February 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28146588/the-frequency-and-clinical-impact-of-her2-alterations-in-lung-adenocarcinoma
#7
Eun Kyung Kim, Kyung A Kim, Chang Young Lee, Hyo Sup Shim
Human epidermal growth factor receptor 2 (HER2 or ErbB2) can be overexpressed, amplified and/or mutated in malignant tumors, and is a candidate for therapeutic targeting. However, molecular associations and clinical significances of these alterations were controversial in lung cancer. In this study, we investigated the frequency and clinicopathological significance of HER2 dysregulation in patients with lung adenocarcinoma. HER2 protein overexpression, gene amplification, and gene mutation were evaluated by immunohistochemistry (IHC), silver in situ hybridization, and direct sequencing, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28145643/analysis-of-fifty-hotspot-mutations-of-lung-squamous-cell-carcinoma-in-never-smokers
#8
Ha Youn Lee, Se Hoon Lee, Jae Kyung Won, Dong Soo Lee, Nak Jung Kwon, Sun Mi Choi, Jinwoo Lee, Chang Hoon Lee, Sang Min Lee, Jae Joon Yim, Chul Gyu Yoo, Young Whan Kim, Sung Koo Han, Young Sik Park
Smoking is the major risk factor for lung squamous cell carcinoma (SCC), although a small number of lung SCCs occurs in never-smokers. The purpose of this study was to compare 50 hotspot mutations of lung SCCs between never-smokers and smokers. We retrospectively reviewed the medical records of patients newly diagnosed with lung SCC between January 1, 2011 and December 31, 2013 in the Seoul National University Hospital. Formalin-fixed, paraffin-embedded tumor samples were used for analysis of hotspot mutations...
March 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28092948/oral-cell-dna-adducts-as-potential-biomarkers-for-lung-cancer-susceptibility-in-cigarette-smokers
#9
Stephen S Hecht
This perspective considers the use of oral cell DNA adducts, together with exposure and genetic information, to potentially identify those cigarette smokers at highest risk for lung cancer, so that appropriate preventive measures could be initiated at a relatively young age before too much damage has been done. There are now well established and validated analytical methods for the quantitation of urinary and serum metabolites of tobacco smoke toxicants and carcinogens. These metabolites provide a profile of exposure and in some cases lung cancer risk, but they do not yield information on the critical DNA damage parameter that leads to mutations in cancer growth control genes such as KRAS and TP53...
January 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28074012/reduced-abundance-of-the-e3-ubiquitin-ligase-e6ap-contributes-to-decreased-expression-of-the-ink4-arf-locus-in-non-small-cell-lung-cancer
#10
Cristina Gamell, Twishi Gulati, Yaara Levav-Cohen, Richard J Young, Hongdo Do, Pat Pilling, Elena Takano, Neil Watkins, Stephen B Fox, Prudence Russell, Doron Ginsberg, Brendon J Monahan, Gavin Wright, Alex Dobrovic, Sue Haupt, Ben Solomon, Ygal Haupt
The tumor suppressor p16(INK4a), one protein encoded by the INK4/ARF locus, is frequently absent in multiple cancers, including non-small cell lung cancer (NSCLC). Whereas increased methylation of the encoding gene (CDKN2A) accounts for its loss in a third of patients, no molecular explanation exists for the remainder. We unraveled an alternative mechanism for the silencing of the INK4/ARF locus involving the E3 ubiquitin ligase and transcriptional cofactor E6AP (also known as UBE3A). We found that the expression of three tumor suppressor genes encoded in the INK4/ARF locus (p15(INK4b), p16(INK4a), and p19(ARF)) was decreased in E6AP(-/-) mouse embryo fibroblasts...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28042953/cervical-small-cell-neuroendocrine-tumor-mutation-profiles-via-whole-exome-sequencing
#11
Soo Young Cho, Minhye Choi, Hyo-Jeong Ban, Chang Hyeon Lee, Soojun Park, HanKyeom Kim, Young-Sik Kim, Young Seek Lee, Ji-Yun Lee
Cervical small cell neuroendocrine tumors (CSCNETs) are rare, aggressive neuroendocrine tumors (NETs). Reliable diagnostic and prognostic CSCNET markers are lacking, making diagnosis and prognosis prediction difficult, and treatment strategies limited. Here we provide mutation profiles for five tumor-normal paired CSCNETs using whole exome sequencing (WES). We expanded our assessment of frequently mutated genes to include publicly available data from 55 small intestine neuroendocrine tumors, 10 pancreatic neuroendocrine tumors, 42 small cell lung cancers, six NET cell lines, and 188 cervical cancers, along with our five CSCNETs...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28025329/association-between-gwas-identified-lung-adenocarcinoma-susceptibility-loci-and-egfr-mutations-in-never-smoking-asian-women-and-comparison-with-findings-from-western-populations
#12
Wei Jie Seow, Keitaro Matsuo, Chao Agnes Hsiung, Kouya Shiraishi, Minsun Song, Hee Nam Kim, Maria Pik Wong, Yun-Chul Hong, H Dean Hosgood, Zhaoming Wang, I-Shou Chang, Jiu-Cun Wang, Nilanjan Chatterjee, Margaret Tucker, Hu Wei, Tetsuya Mitsudomi, Wei Zheng, Jin Hee Kim, Baosen Zhou, Neil E Caporaso, Demetrius Albanes, Min-Ho Shin, Lap Ping Chung, She-Juan An, Ping Wang, Hong Zheng, Yasushi Yatabe, Xu-Chao Zhang, Young Tae Kim, Xiao-Ou Shu, Young-Chul Kim, Bryan A Bassig, Jiang Chang, James Chung Man Ho, Bu-Tian Ji, Michiaki Kubo, Yataro Daigo, Hidemi Ito, Yukihide Momozawa, Kyota Ashikawa, Yoichiro Kamatani, Takayuki Honda, Hiromi Sakamoto, Hideo Kunitoh, Koji Tsuta, Shun-Ichi Watanabe, Hiroshi Nokihara, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Masahiro Tsuboi, Koichi Goto, Zhihua Yin, Jianxin Shi, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Kimihiro Shimizu, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Jason Y Y Wong, Fumihiko Matsuda, Jian Su, Yeul Hong Kim, In-Jae Oh, Fengju Song, Victor Ho Fun Lee, Wu-Chou Su, Yuh-Min Chen, Gee-Chen Chang, Kuan-Yu Chen, Ming-Shyan Huang, Pan-Chyr Yang, Hsien-Chih Lin, Yong-Bing Xiang, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Chien-Jen Chen, Haixin Li, Yu-Tang Gao, Chen Wu, Biyun Qian, Daru Lu, Jianjun Liu, Hyo-Sung Jeon, Chin-Fu Hsiao, Jae Sook Sung, Ying-Huang Tsai, Yoo Jin Jung, Huan Guo, Zhibin Hu, Wen-Chang Wang, Charles C Chung, Charles Lawrence, Laurie Burdett, Meredith Yeager, Kevin B Jacobs, Amy Hutchinson, Sonja I Berndt, Xingzhou He, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, Chang Hyun Kang, Lingmin Hu, Chung-Hsing Chen, Tsung-Ying Yang, Jun Xu, Peng Guan, Wen Tan, Chih-Liang Wang, Alan Dart Loon Sihoe, Ying Chen, Yi Young Choi, Jen-Yu Hung, Jun Suk Kim, Ho-Il Yoon, Qiuyin Cai, Chien-Chung Lin, In Kyu Park, Ping Xu, Jing Dong, Christopher Kim, Qincheng He, Reury-Perng Perng, Chih-Yi Chen, Roel Vermeulen, Junjie Wu, Wei-Yen Lim, Kun-Chieh Chen, John K C Chan, Minjie Chu, Yao-Jen Li, Jihua Li, Hongyan Chen, Chong-Jen Yu, Li Jin, Yen-Li Lo, Ying-Hsiang Chen, Joseph F Fraumeni, Jie Liu, Taiki Yamaji, Yang Yang, Belynda Hicks, Kathleen Wyatt, Shengchao A Li, Juncheng Dai, Hongxia Ma, Guangfu Jin, Bao Song, Zhehai Wang, Sensen Cheng, Xuelian Li, Yangwu Ren, Ping Cui, Motoki Iwasaki, Taichi Shimazu, Shoichiro Tsugane, Junjie Zhu, Gening Jiang, Ke Fei, Guoping Wu, Li-Hsin Chien, Hui-Ling Chen, Yu-Chun Su, Fang-Yu Tsai, Yi-Song Chen, Jinming Yu, Victoria L Stevens, Ite A Laird-Offringa, Crystal N Marconett, Dongxin Lin, Kexin Chen, Yi-Long Wu, Maria Teresa Landi, Hongbing Shen, Nathaniel Rothman, Takashi Kohno, Stephen J Chanock, Qing Lan
To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 × 10(-8)), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21...
December 26, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27999749/growth-and-metastasis-of-lung-adenocarcinoma-is-potentiated-by-bmp4-mediated-immunosuppression
#13
Limo Chen, Xiaohui Yi, Sangeeta Goswami, Young-Ho Ahn, Jonathon D Roybal, Yongbin Yang, Lixia Diao, Di Peng, David Peng, Jared J Fradette, Jing Wang, Lauren A Byers, Jonathan M Kurie, Stephen E Ullrich, F Xiao-Feng Qin, Don L Gibbons
Cancer cells modulate the recruitment and function of inflammatory cells to create an immunosuppressive microenvironment that favors tumor growth and metastasis. However, the tumor-derived regulatory programs that promote intratumoral immunosuppression remain poorly defined. Here, we show in a Kras(LA1/+)p53(R172HΔg/+)-based mouse model that bone morphogenetic protein-4 (BMP4) augments the expression of the T cell co-inhibitory receptor ligand PD-L1 in the mesenchymal subset of lung cancer cells, leading to profound CD8(+) T cell-mediated immunosuppression, producing tumor growth and metastasis...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27983632/antimicrobial-and-antitumor-activities-of-novel-peptides-derived-from-the-lipopolysaccharide-and-%C3%AE-1-3-glucan-binding-protein-of-the-pacific-abalone-haliotis-discus-hannai
#14
Bo-Hye Nam, Ji Young Moon, Eun Hee Park, Hee Jeong Kong, Young-Ok Kim, Dong-Gyun Kim, Woo-Jin Kim, Chul Min An, Jung-Kil Seo
Antimicrobial peptides are a pivotal component of the invertebrate innate immune system. In this study, we identified a lipopolysaccharide- and β-1,3-glucan-binding protein (LGBP) gene from the pacific abalone Haliotis discus hannai (HDH), which is involved in the pattern recognition mechanism and plays avital role in the defense mechanism of invertebrates immune system. The HDH-LGBP cDNA consisted of a 1263-bp open reading frame (ORF) encoding a polypeptide of 420 amino acids, with a 20-amino-acid signal sequence...
December 14, 2016: Marine Drugs
https://www.readbyqxmd.com/read/27974707/cancer-upregulated-gene-2-induces-epithelial-mesenchymal-transition-of-human-lung-cancer-cells-via-tgf-%C3%AE-signaling
#15
Sirichat Kaowinn, Jeonghyo Kim, Jaebeom Lee, Dong Hoon Shin, Chi-Dug Kang, Dae-Kee Kim, Soojin Lee, Min Kyung Kang, Sang Seok Koh, Seong-Jin Kim, Young-Hwa Chung
Cancer upregulated gene 2 (CUG2) enhances cell migration and invasion, but the underlying mechanism has not been revealed. Herein, CUG2 decreased the expression of E-cadherin and increased the expression of N-cadherin and vimentin, characteristics of the epithelial-mesenchymal transition (EMT). A CUG2 deletion mutant, lacking interaction with nucleophosmin 1 (NPM1), or suppression of NPM1 reduced wound healing and cell invasion, indicating that CUG2-mediated EMT requires NPM1. CUG2 enhanced activation of Smad2/3 and expression of Snail and Twist, while the CUG2 silence decreased these TGF-β signaling pathways, leading to suppression of EMT...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27966653/the-accessory-proteins-reep5-and-reep6-refine-cxcr1-mediated-cellular-responses-and-lung-cancer-progression
#16
Cho Rong Park, Dong-Joo You, Sumi Park, Sunam Mander, Da-Eun Jang, Su-Cheong Yeom, Seong-Hyun Oh, Curie Ahn, Sang Heon Lee, Jae Young Seong, Jong-Ik Hwang
Some G-protein-coupled receptors have been reported to require accessory proteins with specificity for proper functional expression. In this study, we found that CXCR1 interacted with REEP5 and REEP6, but CXCR2 did not. Overexpression of REEP5 and REEP6 enhanced IL-8-stimulated cellular responses through CXCR1, whereas depletion of the proteins led to the downregulation of the responses. Although REEPs enhanced the expression of a subset of GPCRs, in the absence of REEP5 and REEP6, CXCR1 was expressed in the plasma membrane, but receptor internalization and intracellular clustering of β-arrestin2 following IL-8 treatment were impaired, suggesting that REEP5 and REEP6 might be involved in the ligand-stimulated endocytosis of CXCR1 rather than membrane expression, which resulted in strong cellular responses...
December 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27932791/migration-and-invasion-of-drug-resistant-lung-adenocarcinoma-cells-are-dependent-on-mitochondrial-activity
#17
Ji Hoon Jeon, Dong Keon Kim, Youngmi Shin, Hee Yeon Kim, Bomin Song, Eun Young Lee, Jong Kwang Kim, Hye Jin You, Heesun Cheong, Dong Hoon Shin, Seong-Tae Kim, Jae-Ho Cheong, Soo Youl Kim, Hyonchol Jang
A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated. The expression of genes associated with oxidative phosphorylation in the mitochondrial membrane was negatively correlated with the prognosis of lung adenocarcinoma. Because the mitochondrial membrane potential (MMP) reflects the functional status of mitochondria and metastasis is the principal cause of death due to cancer, the relationship between MMP and metastasis was evaluated...
December 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27866339/recurrent-tp53-missense-mutation-in-cancer-patients-of-arab-descent
#18
Aviad Zick, Luna Kadouri, Sherri Cohen, Michael Frohlinger, Tamar Hamburger, Naama Zvi, Morasha Plaser, Eilat Avital, Shani Breuier, Firase Elian, Azzam Salah, Yael Goldberg, Tamar Peretz
Hereditary cancer comprises more than 10% of all breast cancer cases. Identification of germinal mutations enables the initiation of a preventive program that can include early detection or preventive treatment and may also have a major impact on cancer therapy. Several recurrent mutations were identified in the BRCA1/2 genes in Jewish populations however, in other ethnic groups in Israel, no recurrent mutations were identified to date. Our group established panel sequencing in cancer patients to identify recurrent, founder, and new mutations in the heterogeneous and diverse populations in Israel, We evaluated five breast cancer patients of Arab descent diagnosed with cancer before the age of 50 years and identified the previously described TP53 mutation, c...
November 19, 2016: Familial Cancer
https://www.readbyqxmd.com/read/27863408/an-8-gene-signature-for-prediction-of-prognosis-and-chemoresponse-in-non-small-cell-lung-cancer
#19
Muhammad Shahid, Tae Gyu Choi, Minh Nam Nguyen, Abel Matondo, Yong Hwa Jo, Ji Youn Yoo, Ngoc Ngo Yen Nguyen, Hyeong Rok Yun, Jieun Kim, Salima Akter, Insug Kang, Joohun Ha, Chi Hoon Maeng, Si-Young Kim, Ju-Seog Lee, Jayoung Kim, Sung Soo Kim
Identification of a potential gene signature for improved diagnosis in non-small cell lung cancer (NSCLC) patient is necessary. Here, we aim to establish and validate the prognostic efficacy of a gene set that can predict prognosis and benefits of adjuvant chemotherapy (ACT) in NSCLC patients from various ethnicities. An 8-gene signature was calculated from the gene expression of 181 patients using univariate Cox proportional hazard regression analysis. The prognostic value of the signature was robustly validated in 1,477 patients from five microarray independent data sets and one RNA-seq data set...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27836576/establishment-of-a-conditional-transgenic-mouse-model-recapitulating-eml4-alk-positive-human-non-small-cell-lung-cancer
#20
Kyoung Ho Pyo, Sun Min Lim, Hye Ryun Kim, Young Hoon Sung, Mi Ran Yun, Sung-Moo Kim, Hwan Kim, Han Na Kang, Ji Min Lee, Sang Gyun Kim, Chae Won Park, Hyun Chang, Hyo Sup Shim, Han-Woong Lee, Byoung Chul Cho
BACKGROUND: Anaplastic lymphoma receptor tyrosine kinase gene (ALK) fusion is a distinct molecular subclassification of NSCLC that is targeted by anaplastic lymphoma kinase (ALK) inhibitors. We established a transgenic mouse model that expresses tumors highly resembling human NSCLC harboring echinoderm microtubule associated protein like 4 gene (EML)-ALK fusion. We aimed to test an EML4-ALK transgenic mouse model as a platform for assessing the efficacy of ALK inhibitors and examining mechanisms of acquired resistance to ALK inhibitors...
March 2017: Journal of Thoracic Oncology
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