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https://www.readbyqxmd.com/read/29164309/pathologic-diagnosis-and-genetic-analysis-of-a-lung-tumor-needle-biopsy-specimen-obtained-immediately-after-radiofrequency-ablation
#1
Takaaki Hasegawa, Chiaki Kondo, Yozo Sato, Yoshitaka Inaba, Hidekazu Yamaura, Mina Kato, Shinichi Murata, Yui Onoda, Hiroaki Kuroda, Yukinori Sakao, Yasushi Yatabe
PURPOSE: To evaluate the possibility of pathologic diagnosis and genetic analysis of percutaneous core-needle biopsy (CNB) lung tumor specimens obtained immediately after radiofrequency ablation (RFA). MATERIALS AND METHODS: Patients who underwent CNB of lung tumors immediately after RFA from May 2013 to May 2016 were analyzed. There were 19 patients (8 men and 11 women; median age, 69 years; range, 52-88 years) and 19 lung tumors measuring 0.5-2.6 cm (median, 1...
November 21, 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/29164298/value-of-18-f-fdg-pet-ct-for-predicting-egfr-mutations-and-positive-alk-expression-in-patients-with-non-small-cell-lung-cancer-a-retrospective-analysis-of-849-chinese-patients
#2
Zhilei Lv, Jinshuo Fan, Juanjuan Xu, Feng Wu, Qi Huang, Mengfei Guo, Tingting Liao, Shuqing Liu, Xiaoli Lan, Shanshan Liao, Wei Geng, Yang Jin
PURPOSE: Epidermal growth factor receptor (EGFR) mutations and the anaplastic lymphoma kinase (ALK) rearrangement are the two most common druggable targets in non-small cell lung cancer (NSCLC). However, genetic testing is sometimes unavailable. Previous studies regarding the predictive role of (18)F-FDG PET/CT for EGFR mutations in NSCLC patients are conflicting. We investigated whether or not (18)F-FDG PET could be a valuable noninvasive method to predict EGFR mutations and ALK positivity in NSCLC using the largest patient cohort to date...
November 21, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29163853/mechanisms-of-resistance-to-irreversible-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-and-therapeutic-strategies-in-non-small-cell-lung-cancer
#3
REVIEW
Jing Xu, Jinghui Wang, Shucai Zhang
Epidermal growth factor receptor (EGFR) T790M mutation is the most frequent mechanism which accounts for about 60% of acquired resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients harboring EGFR activating mutations. Irreversible EGFR-TKIs which include the second-generation and third-generation EGFR-TKIs are developed to overcome T790M mediated resistance. The second-generation EGFR-TKIs inhibit the wide type (WT) EGFR combined with dose-limiting toxicity which limits its application in clinics, while the development of third-generation EGFR-TKIs brings inspiring efficacy either in vitro or in vivo...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163842/real-world-experience-of-afatinib-as-a-first-line-therapy-for-advanced-egfr-mutation-positive-lung-adenocarcinoma
#4
Sheng-Kai Liang, Min-Shu Hsieh, Meng-Rui Lee, Li-Ta Keng, Jen-Chung Ko, Jin-Yuan Shih
We evaluated the real-world efficacy and side effects of afatinib as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma. The medical records of patients receiving afatinib as a first-line therapy after National Health Insurance reimbursement between May 2014 and January 2016 were reviewed, and information on patient characteristics and treatment courses were collected consecutively. Rebiopsy tissue was collected for EGFR mutation and MET amplification analyses. MET amplification was detected by fluorescence in situ hybridization and immunohistochemistry...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163774/integrative-analysis-of-novel-hypomethylation-and-gene-expression-signatures-in-glioblastomas
#5
Anan Yin, Amandine Etcheverry, Yalong He, Marc Aubry, Jill Barnholtz-Sloan, Luhua Zhang, Xinggang Mao, Weijun Chen, Bolin Liu, Wei Zhang, Jean Mosser, Xiang Zhang
Molecular and clinical heterogeneity critically hinders better treatment outcome for glioblastomas (GBMs); integrative analysis of genomic and epigenomic data may provide useful information for improving personalized medicine. By applying training-validation approach, we identified a novel hypomethylation signature comprising of three CpGs at non-CpG island (CGI) open sea regions for GBMs. The hypomethylation signature consistently predicted poor prognosis of GBMs in a series of discovery and validation datasets...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163769/yap1-is-essential-for-tumor-growth-and-is-a-potential-therapeutic-target-for-egfr-dependent-lung-adenocarcinomas
#6
Ting-Fang Lee, Yu-Chi Tseng, Wei-Chin Chang, Yi-Chen Chen, Yu-Rung Kao, Teh-Ying Chou, Chao-Chi Ho, Cheng-Wen Wu
Epidermal growth factor receptor (EGFR) mutations are found in lung adenocarcinomas leading to tumor cells proliferation and survival. EGFR tyrosine kinase inhibitors (TKIs) that block EGFR activity are effective therapeutics for EGFR-mutant lung adenocarcinoma patients, but TKI-resistance inevitably occurs. The YES-associated protein (YAP1) transcription coactivator has been implicated as an oncogene and is amplified in human cancers and provides tumor cells strong proliferation and survival cues. This study investigated the roles of YAP1 in lung adenocarcinoma by exploring its regulation and functions mediated by EGFR signaling...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163686/characterization-of-distinct-types-of-kras-mutation-and-its-impact-on-first-line-platinum-based-chemotherapy-in-chinese-patients-with-advanced-non-small-cell-lung-cancer
#7
Yijun Jia, Tao Jiang, Xuefei Li, Chao Zhao, Limin Zhang, Sha Zhao, Xiaozhen Liu, Meng Qiao, Jiawei Luo, Jinpeng Shi, Hui Yang, Yan Wang, Lei Xi, Shijia Zhang, Guanghui Gao, Chunxia Su, Shengxiang Ren, Caicun Zhou
We performed this retrospective study to investigate whether the KRAS mutation status and its subtypes could predict the effect of first-line platinum-based chemotherapy in Chinese patients with non-small cell lung cancer (NSCLC). Patients received who had KRAS mutations were enrolled. Correlations between KRAS mutations, specific mutant subtypes and responses to chemotherapy were analyzed using Kaplan-Meier and Cox proportional hazard methods. A total of 2,183 cases who received KRAS mutation detection were included...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29161357/nivolumab-in-non-small-cell-lung-cancer-with-egfr-mutation
#8
H Yoshida, Y H Kim, H Ozasa, H Nagai, Y Sakamori, T Tsuji, T Nomizo, Y Yasuda, T Funazo, T Hirai
No abstract text is available yet for this article.
November 17, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29160717/reprogramming-tumor-associated-macrophages-to-reverse-egfr-t790m-resistance-by-dual-targeting-codelivery-of-gefitinib-vorinostat
#9
Huige Peng, Binfan Chen, Wei Huang, Yubo Tang, Yifan Jiang, Wenyuan Zhang, Yongzhuo Huang
Gefitinib is a first-line therapy in the EGFR-mutated nonsmall cell lung cancer (NSCLC). However, the development of drug resistance is almost unavoidable, thus leading to an unsustainable regimen. EGFR(T790M) mutation is the major cause responsible for the molecular-targeting therapy failure in NSCLC. Although the recently approved osimertinib is effective for the EGFR(T790M)-positive NSCLC, the osimertinib-resistant EGFR mutation is rapidly developed, too. In this study, we proposed a tumor-associated macrophage (TAM) reprogramming strategy for overcoming the EGFR(T790M)-associated drug resistance via a dual-targeting codelivery system of gefitinib/vorinostat that acted on both TAM with overexpression of mannose receptors and the HER-2 positive NSCLC cells...
November 21, 2017: Nano Letters
https://www.readbyqxmd.com/read/29160417/radiotherapy-modulates-expression-of-egfr-ercc1-and-p53-in-cervical-cancer
#10
V H de Almeida, A C de Melo, D D Meira, A C Pires, A Nogueira-Rodrigues, H K Pimenta-Inada, F G Alves, G Moralez, L S Thiago, C G Ferreira, C Sternberg
Cervical cancer is a public health problem and the molecular mechanisms underlying radioresistance are still poorly understood. Here, we evaluated the modulation of key molecules involved in cell proliferation, cell cycle and DNA repair in cervical cancer cell lines (CASKI and C33A) and in malignant tissues biopsied from 10 patients before and after radiotherapy. The expression patterns of epidermal growth factor receptor (EGFR), excision repair cross-complementation group 1 (ERCC1) and p53 were evaluated in cancer cell lines by quantitative PCR and western blotting, and in human malignant tissues by immunohistochemistry...
November 13, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29158469/molecular-basis-for-necitumumab-inhibition-of-egfr-variants-associated-with-acquired-cetuximab-resistance
#11
Atrish Bagchi, Jaafar N Haidar, Scott W Eastman, Michal Vieth, Michael Topper, Michelle D Iacolina, Jason M Walker, Amelie Forest, Yang Shen, Ruslan D Novosiadly, Kathryn M Ferguson
Acquired resistance to cetuximab, an antibody that targets the epidermal growth factor receptor (EGFR), impacts clinical benefit in head and neck, and colorectal cancers (CRC). One of the mechanisms of resistance to cetuximab is the acquisition of mutations that map to the cetuximab epitope on EGFR and prevent drug binding. We find that necitumumab, another FDA approved EGFR antibody, can bind to EGFR that harbors the most common cetuximab resistance substitution, S468R (or S492R, depending on the amino acid numbering system)...
November 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29156800/comparative-molecular-analyses-of-left-sided-colon-right-sided-colon-and-rectal-cancers
#12
Mohamed E Salem, Benjamin A Weinberg, Joanne Xiu, Wafik S El-Deiry, Jimmy J Hwang, Zoran Gatalica, Philip A Philip, Anthony F Shields, Heinz-Josef Lenz, John L Marshall
Tumor sidedness has emerged as an important prognostic and predictive factor in the treatment of colorectal cancer. Recent studies demonstrate that patients with advanced right-sided colon cancers have a worse prognosis than those with left-sided colon or rectal cancers, and these patient subgroups respond differently to biological therapies. Historically, management of patients with metastatic colon and rectal cancers has been similar, and colon and rectal cancer patients have been grouped together in large clinical trials...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156778/worse-disease-free-tumor-specific-and-overall-survival-in-surgically-resected-lung-adenocarcinoma-patients-with-alk-rearrangement
#13
Qiongqiong Gao, Pupu Li, Xiangli Jiang, Zhongli Zhan, Qingna Yan, Bo Zhang, Chun Huang
Introduction: This study determined the prevalence of anaplastic lymphoma kinase (ALK) rearrangement, and identified the associations of ALK rearrangement with clinicopathologic characteristics and treatment outcomes in patients with surgically-resected stage I-III lung adenocarcinoma. Methods: A total of 534 surgically-resected lung adenocarcinoma patients were studied. The prevalence of ALK protein over-expression was determined by a fully-automated immunochemistry assay (with mouse monoclonal Ventana D5F3 antibody), and the associations of ALK rearrangement with clinicopathologic characteristics and treatment outcomes were analyzed...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156777/patients-with-nsclc-may-display-a-low-ratio-of-p-t790m-vs-activating-egfr-mutations-in-plasma-at-disease-progression-implications-for-personalised-treatment
#14
Marzia Del Re, Paola Bordi, Iacopo Petrini, Eleonora Rofi, Francesca Mazzoni, Lorenzo Belluomini, Enrico Vasile, Giuliana Restante, Francesco Di Costanzo, Alfredo Falcone, Antonio Frassoldati, Ron H N van Schaik, Christi M J Steendam, Antonio Chella, Marcello Tiseo, Riccardo Morganti, Romano Danesi
Introduction: NSCLC harboring activating mutations of EGFR is highly sensitive to first-line EGFR-tyrosine kinase inhibitors (TKIs), but drug resistance depending on the EGFR mutation p.T790M will occur in about 50-60% of patients. Detailed information on the amount of p.T790M plasmatic level associated with resistance to EGFR-TKIs and guidance to treatment with p.T790M-effective TKI depending on these levels, is lacking. Methods: This study enrolled p.T790M-positive patients (n=49) affected by EGFR-mutated NSCLC at progression to first-line EGFR-TKIs and, in selected cases (n=5), after second-line treatment with osimertinib...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155348/progress-and-challenges-of-predictive-biomarkers-of-anti-pd-1-pd-l1-immunotherapy-a-systematic-review
#15
Feifei Teng, Xiangjiao Meng, Li Kong, Jinming Yu
Despite the marked success of applications of PD-1/PD-L1 checkpoint blockades in clinical, the efficacy and responsiveness of these agents varies greatly among different tumor types and across individual patients. Therefore, establishment of predictive biomarkers for checkpoint blockades is of the most importance to maximize the therapeutic benefits. In this review, we discuss the current progress and challenges of developing predictive biomarkers of immunotherapy responsiveness, aiming to provide some directions for future studies...
November 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29154817/cancer-stem-cell-like-population-is-preferentially-suppressed-by-egfr-tkis-in-egfr-mutated-pc-9-tumor-models
#16
Fan Yang, Yang Li, Bin Liu, Jiacong You, Qinghua Zhou
AIMS: Although the epidermal growth factor receptor (EGFR) and Wnt/β-catenin signaling systems synergistically regulate many essential developmental and regenerative processes in lung cancer, the mechanisms of their crosstalk remain poorly defined. Our study aimed to investigate an interaction between EGFR and the β-catenin signal. RESULTS: In this study, we described a potent activation of β-catenin by EGFR, which is dependent of the PtdIns3K/AKT pathway. We found EGF activated β-catenin signaling via phosphorylation of EGFR and AKT in EGFR-mutated PC-9 lung cancer cells...
November 14, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29153417/the-efficacy-of-transbronchial-needle-aspiration-with-endobronchial-ultrasonography-using-a-guide-sheath-for-peripheral-pulmonary-lesions-suspected-to-be-lung-cancer
#17
Ken Arimura, Yasuo Sekine, Kenzo Hiroshima, Akitoshi Sato, Mizue Hasegawa, Hideki Katsura, Etsuko Tagaya, Mitsuko Kondo, Jun Tamaoki
BACKGROUND: The efficacy of transbronchial needle aspiration (TBNA) with endobronchial ultrasonography using a guide sheath (EBUS-GS) for cases of peripheral pulmonary lesions (PPLs) has not been well established. The purpose of this study was to evaluate the efficacy of TBNA with EBUS-GS for PPLs. METHODS: We evaluated 130 patients suspected to have lung cancer who underwent transbronchial brushing (brushing), transbronchial biopsy (TBB), and TBNA with EBUS-GS...
November 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/29153372/impact-of-experimental-design-on-pet-radiomics-in-predicting-somatic-mutation-status
#18
Stephen S F Yip, Chintan Parmar, John Kim, Elizabeth Huynh, Raymond H Mak, Hugo J W L Aerts
PURPOSE: PET-based radiomic features have demonstrated great promises in predicting genetic data. However, various experimental parameters can influence the feature extraction pipeline, and hence, Here, we investigated how experimental settings affect the performance of radiomic features in predicting somatic mutation status in non-small cell lung cancer (NSCLC) patients. METHODS: 348 NSCLC patients with somatic mutation testing and diagnostic PET images were included in our analysis...
December 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/29152497/molecular-analysis-driven-video-assisted-thoracic-surgery-resections-in-bilateral-synchronous-lung-cancers-from-the-test-tube-to-the-operatory-room
#19
REVIEW
Sergio Nicola Forti Parri, Barbara Bonfanti, Alessandra Cancellieri, Dario De Biase, Rocco Trisolini, Stefania Zoboli, Luca Bertolaccini, Piergiorgio Solli, Giovanni Tallini
Synchronous cancers are not such rare clinical conditions. Nevertheless, even after the 8th edition of the TNM classification of the lung cancer, the surgical approach for patients presenting with synchronous bilateral lung cancer is still under debate. The resection of both lesions in the case of synchronous bilateral lung cancer is reasonable, but, on the other hand, is the lobectomy the correct choice in the event of the single primary with a contralateral metastatic lesion? In this case report, we describe how the molecular analysis and the detection of the EGFR, KRAS and TP53 mutations in both tumours have determined in a patient the two tumours as primary and both the right surgical approach...
October 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29152135/evaluation-of-pre-analytical-conditions-and-comparison-of-the-performance-of-several-digital-pcr-assays-for-the-detection-of-major-egfr-mutations-in-circulating-dna-from-non-small-cell-lung-cancers-the-circan_0-study
#20
Jessica Garcia, Eric Dusserre, Valérie Cheynet, Pierre Paul Bringuier, Karen Brengle-Pesce, Anne-Sophie Wozny, Claire Rodriguez-Lafrasse, Gilles Freyer, Marie Brevet, Léa Payen, Sébastien Couraud
Non invasive somatic detection assays are suitable for repetitive tumor characterization or for detecting the appearance of somatic resistance during lung cancer. Molecular diagnosis based on circulating free DNA (cfDNA) offers the opportunity to track the genomic evolution of the tumor, and was chosen to assess the molecular profile of several EGFR alterations, including deletions in exon 19 (delEX19), the L858R substitution on exon 21 and the EGFR resistance mutation T790M on exon 20. Our study aimed at determining optimal pre-analytical conditions and EGFR mutation detection assays for analyzing cfDNA using the picoliter-droplet digital polymerase chain reaction (ddPCR) assay...
October 20, 2017: Oncotarget
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