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Kaichao Feng, Yelei Guo, Hanren Dai, Yao Wang, Xiang Li, Hejin Jia, Weidong Han
The successes achieved by chimeric antigen receptor-modified T (CAR-T) cells in hematological malignancies raised the possibility of their use in non-small lung cancer (NSCLC). In this phase I clinical study (NCT01869166), patients with epidermal growth factor receptor (EGFR)-positive (>50% expression), relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically...
May 2016: Science China. Life Sciences
Minehiko Inomata, Ryuji Hayashi, Hiroaki Tanaka, Kazuki Shimokawa, Kotaro Tokui, Chihiro Taka, Seisuke Okazawa, Kenta Kambara, Tomomi Ichikawa, Toru Yamada, Toshiro Miwa, Tatsuhiko Kashii, Shoko Matsui, Kazuyuki Tobe
Treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been shown to prolong survival in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). The present study performed a retrospective analysis to investigate the association between the plasma lactate dehydrogenase (LDH) levels and survival in patients with EGFR mutation-positive NSCLC receiving treatment with EGFR-TKIs. The medical charts of patients with EGFR mutation-positive NSCLC who were receiving treatment with EGFR-TKIs at Toyama University Hospital between 2007 and 2014 were assessed...
May 2016: Molecular and Clinical Oncology
Takashi Hirose, Ken-ichi Fujita, Sojiro Kusumoto, Yasunari Oki, Yasunori Murata, Tomohide Sugiyama, Hiroo Ishida, Takao Shirai, Masanao Nakashima, Toshimitsu Yamaoka, Kentaro Okuda, Tohru Ohmori, Yasutsuna Sasaki
OBJECTIVES: Gefitinib is a potent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and is a key drug for patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). The pharmacokinetics of orally administered gefitinib varies greatly among patients. We prospectively evaluated the association of pharmacokinetics and pharmacogenomics with the safety and efficacy of gefitinib in patients with EGFR mutation-positive advanced NSCLC. PATIENTS AND METHODS: Pharmacokinetics was evaluated with samples of peripheral blood obtained on day 1 before treatment and 1, 3, 5, 8, and 24h after gefitinib (250 mg per day) was administered and on days 8 and 15 as the trough values...
March 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Manfred Dietel, Lukas Bubendorf, Anne-Marie C Dingemans, Christophe Dooms, Göran Elmberger, Rosa Calero García, Keith M Kerr, Eric Lim, Fernando López-Ríos, Erik Thunnissen, Paul E Van Schil, Maximilian von Laffert
BACKGROUND: There is currently no Europe-wide consensus on the appropriate preanalytical measures and workflow to optimise procedures for tissue-based molecular testing of non-small-cell lung cancer (NSCLC). To address this, a group of lung cancer experts (see list of authors) convened to discuss and propose standard operating procedures (SOPs) for NSCLC. METHODS: Based on earlier meetings and scientific expertise on lung cancer, a multidisciplinary group meeting was aligned...
February 2016: Thorax
Zhigang Wang, Pingfang Lu, Zhu Liang, Zhanfei Zhang, Weicheng Shi, Xiaobi Cai, Chunyuan Chen
Insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase receptor implicated in tumourigenesis that may be an attractive target for anti-cancer treatment. In this study, the expression and clinical significance of IGF1R were investigated in serum and lung cancer tissues from small cell lung cancinoma (SCLC). We also compared the effect of IGF1R up-regulation and IGF1R inhibition on viability and apoptosis of NCI-H446 cells. We found the concentration of IGF1R in blood serum was significantly increased and positive IGF1R protein in cancer tissue was more prevalent in SCLC...
2015: Growth Factors
Kimio Yonesaka, Keita Kudo, Satomi Nishida, Takayuki Takahama, Tsutomu Iwasa, Takeshi Yoshida, Kaoru Tanaka, Masayuki Takeda, Hiroyasu Kaneda, Isamu Okamoto, Kazuto Nishio, Kazuhiko Nakagawa
Afatinib is a second generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) characterized as an irreversible pan-human EGFR (HER) family inhibitor. Afatinib remains effective for a subpopulation of patients with non-small cell lung cancer (NSCLC) with acquired resistance to first generation EGFF-TKIs such as erlotinib. Heregulin activates HER3 in an autocrine fashion and causes erlotinib resistance in NSCLC. Here we examine whether afatinib is effective against heregulin-overexpressing NSCLCs harboring EGFR activating mutations...
October 20, 2015: Oncotarget
Koh Furugaki, Junko Fukumura, Toshiki Iwai, Keigo Yorozu, Mitsue Kurasawa, Mieko Yanagisawa, Yoichiro Moriya, Kaname Yamamoto, Kenichi Suda, Hiroshi Mizuuchi, Tetsuya Mitsudomi, Naoki Harada
Erlotinib (ERL), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, shows notable efficacy against non-small cell lung cancer (NSCLC) harboring EGFR mutations. Bevacizumab (BEV), a humanized monoclonal antibody to vascular endothelial cell growth factor (VEGF), in combination with ERL (BEV+ERL) significantly extended progression-free survival in patients with EGFR-mutated NSCLC compared with ERL alone. However, the efficacy of BEV+ERL against EGFR-mutated NSCLC harboring T790M mutation or MET amplification, is unclear...
February 15, 2016: International Journal of Cancer. Journal International du Cancer
Q Wei, Z-H Chen, L Wang, T Zhang, L Duan, C Behrens, I I Wistuba, J D Minna, B Gao, J-H Luo, Z P Liu
Lung cancer is the leading cause of cancer-related death in the United States, and metastatic behavior is largely responsible for this mortality. Mutations in multiple 'driver' oncogenes and tumor suppressors are known to contribute to the lung tumorigenesis and in some cases represent therapeutic targets. Leucine Zipper Transcription Factor-like 1 (LZTFL1) is located in the chromosome region 3p21.3 where allelic loss and genetic alterations occur early and frequently in lung cancers. Previously, we found that LZTFL1 is downregulated in epithelial tumors, including lung cancer, and functions as a tumor suppressor in gastric cancers...
May 19, 2016: Oncogene
Su Jin Lee, Jong-Mu Sun, Se Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
OBJECTIVES: After failure of first-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in patients with non-small cell lung cancer (NSCLC) harboring EGFR-activating mutation, platinum based combination chemotherapy is recommended. However, it is still unknown which chemotherapeutic regimens result in better outcomes. MATERIALS AND METHODS: A total of 63 patients who were treated with pemetrexed or pemetrexed/platinum chemotherapy after first line EGFR TKI therapy at Samsung Medical Center were included in our analysis...
November 2015: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Vishal Boolell, Muhammad Alamgeer, David N Watkins, Vinod Ganju
The landscape of advanced non-small lung cancer (NSCLC) therapies has rapidly been evolving beyond chemotherapy over the last few years. The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as offered novel therapeutic targets for anticancer therapy. Targets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with appropriate tyrosine kinase inhibitors (TKIs). Other driver mutations such as ROS, MET, RET, BRAF have also been investigated with targeted agents with some success in the early phase clinical setting...
2015: Cancers
Tomohito Kuwako, Hisao Imai, Tomomi Masuda, Yosuke Miura, Kaori Seki, Reiko Yoshino, Kyoichi Kaira, Mitsuyoshi Utsugi, Kimihiro Shimizu, Noriaki Sunaga, Yoshio Tomizawa, Shinichi Ishihara, Takao Ishizuka, Akira Mogi, Takeshi Hisada, Koichi Minato, Atsushi Takise, Ryusei Saito, Masanobu Yamada
PURPOSE: The efficacy of gefitinib [an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor] in elderly patients with non-small cell lung cancer (NSCLC) and EGFR mutation has not been elucidated. Therefore, the objective of this study was to investigate the efficacy and feasibility of gefitinib in elderly chemotherapy-naive patients with NSCLC harboring sensitive EGFR mutations. METHODS: We retrospectively evaluated the clinical effects of gefitinib as a first-line treatment for elderly (≥75 years) NSCLC patients with EGFR mutations (exon 19 deletion or exon 21 L858R mutation)...
October 2015: Cancer Chemotherapy and Pharmacology
Hengli Dou, Yan Wang, Gang Su, Song Zhao
BACKGROUND: Non-small-cell lung cancer (NSCLC) is one of the leading causes of death. The aim of the present study was to compare the expression of let-7c and miR-152 in surgically resected NSCLC cases and healthy cases to evaluate their diagnostic impact. METHODS: This hospital-based case-control study included 120 NSCLC patients and 360 healthy controls. The miRNA levels were measured via quantitative reverse transcription-polymerase chain reaction and their association with NSCLC was assessed by statistical data analysis and receiver operating characteristic curves...
2015: International Journal of Clinical and Experimental Medicine
William R Wikoff, Samir Hanash, Brian DeFelice, Suzanne Miyamoto, Matt Barnett, Yang Zhao, Gary Goodman, Ziding Feng, David Gandara, Oliver Fiehn, Ayumu Taguchi
PURPOSE: We have investigated the potential of metabolomics to discover blood-based biomarkers relevant to lung cancer screening and early detection. An untargeted metabolomics approach was applied to identify biomarker candidates using prediagnostic sera from the Beta-Carotene and Retinol Efficacy Trial (CARET) study. PATIENTS AND METHODS: A liquid chromatography/mass spectrometry hydrophilic interaction method designed to profile a wide range of metabolites was applied to prediagnostic serum samples from CARET participants (current or former heavy smokers), consisting of 100 patients who subsequently developed non-small-cell lung cancer (NSCLC) and 199 matched controls...
November 20, 2015: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Xiaoqing Zhang, Junwei Fan, Yuping Li, Shengtao Lin, Ping Shu, Jian Ni, Shengying Qin, Zhemin Zhang
This study aimed to investigate the association of epidermal growth factor receptor (EGFR) gene polymorphism and AKT1 polymorphism with the clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). The clinical outcome and the survival of NSCLC of 230 patients after treatment with EGFR-TKIs were measured. The rs712829, rs1468727 of the EGFR gene and rs1130214 of the AKT1 gene from peripheral blood cell were detected by a multiplexed single nucleotide polymorphism (SNP) MassEXTEND assay...
January 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Takaaki Hasegawa, Toshiyuki Sawa, Yohei Futamura, Akane Horiba, Takashi Ishiguro, Tsutomu Marui, Tsutomu Yoshida
OBJECTIVE: Analyses of tumor biopsy samples from non-small cell lung cancer patients with acquired epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance are expected to reveal the molecular mechanisms of resistance. However, due to limited tissue availability, performing such analyses can be challenging. We herein investigated the feasibility of tumor rebiopsy in this patient population. METHODS: From April 2004 to March 2013, 53 consecutive patients were treated with EGFR-TKIs at our department...
2015: Internal Medicine
Xiao Ma, Wei Guo, Su Yang, Xiaoli Zhu, Jiaqing Xiang, Hecheng Li
INTRODUCTION: Glucose-regulated protein 78 (78 kDa, GRP78), which is also known as immunoglobulin heavy chain binding protein (BIP), is a major chaperone in the endoplasmic reticulum (ER). The expression and clinical significance of GRP78 in the serum of non-small cell lung cancer patients have not yet been clearly described. The aims of the present study were to investigate the expression of GRP78 in the serum of non-small cell lung cancer patients, the relationships with clinicopathological parameters, and the potential implications for survival...
2015: Disease Markers
Wei Sun, Xun Yuan, Yijun Tian, Hua Wu, Hanxiao Xu, Guoqing Hu, Kongming Wu
Tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) are standard treatments for advanced non-small-cell lung cancer (NSCLC) patients harboring activating epidermal growth factor receptor (EGFR) mutations. Nowadays, tumor tissues acquired by surgery or biopsy are the routine materials for EGFR mutation analysis. However, the accessibility of tumor tissues is not always satisfactory in advanced NSCLC. Moreover, a high proportion of NSCLC patients will eventually develop resistance to EGFR-TKIs...
2015: Journal of Hematology & Oncology
Filippo Lococo, Massimiliano Paci, Cristian Rapicetta, Teresa Rossi, Valentina Sancisi, Luca Braglia, Silvio Cavuto, Alessandra Bisagni, Italia Bongarzone, Douglas M Noonan, Adriana Albini, Sally Maramotti
Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered...
2015: International Journal of Molecular Sciences
Tom Konert, Wouter Vogel, Michael P MacManus, Ursula Nestle, José Belderbos, Vincent Grégoire, Daniela Thorwarth, Elena Fidarova, Diana Paez, Arturo Chiti, Gerard G Hanna
This document describes best practice and evidence based recommendations for the use of FDG-PET/CT for the purposes of radiotherapy target volume delineation (TVD) for curative intent treatment of non-small cell lung cancer (NSCLC). These recommendations have been written by an expert advisory group, convened by the International Atomic Energy Agency (IAEA) to facilitate a Coordinated Research Project (CRP) aiming to improve the applications of PET based radiation treatment planning (RTP) in low and middle income countries...
July 2015: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Daniel P Steinfort, Tracy L Leong, Irena F Laska, Anne Beaty, Alpha Tsui, Louis B Irving
The aim of the study was to determine the accuracy of rapid on-site examinations, performed on transbronchial brushings of peripheral pulmonary lesions, in determining final bronchoscopic diagnosis. In addition to determining if rapid on-site examination impacts procedural outcomes. A prospective cohort study of consecutive patients with peripheral pulmonary lesions, which had been located by radial endobronchial ultrasound, was undertaken. Bronchoscopy was terminated if rapid on-site examination demonstrated diagnostic malignant material...
June 2015: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
2015-01-23 15:05:08
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