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EGFR mutations

Xiaowei Qiu, Hang Yuan, Bin Sima
BACKGROUND: The aim of this study was to investigate the relationship between EGFR mutation and computed tomography (CT) features in patients with adenocarcinoma of the lung. METHODS: One hundred and ninety two lung adenocarcinoma patients who underwent surgery were retrospectively included in this study. Examination of EGFR gene mutation was performed on all resected tumor samples. The 192 recruited lung adenocarcinoma patients were divided into groups according to EGFR mutation status: patients with mutations in exons 18-21 (effective mutated, n = 61) and non-mutated (n = 131)...
December 5, 2018: Thoracic Cancer
Yang Zheng, Zhao Wang, Xianbin Xiong, Yi Zhong, Wei Zhang, Yibo Dong, Jialiang Li, Zaiou Zhu, Wei Zhang, Heming Wu, Wenyi Gu, Yunong Wu, Xiang Wang, Xiaomeng Song
Notch proteins are highly conserved cell surface receptors which play essential roles in cellular differentiation, proliferation, and apoptotic events at all stages of development. Recently, NOTCH1 mutations have been extensively observed in oral squamous cell carcinoma (OSCC) and are hinted to be Notch1-inactivating mutations. However, little is known about the biological effect of these reported mutations in OSCC. To mimic the inactivation of Notch1 due to inappropriate mutations and to determine the potential mechanisms, we utilized wild-type Notch1 vectors (Notch1WT ) or mutant Notch1 vectors (Notch1V1754L ) to transfect into OSCC cell lines...
December 4, 2018: Journal of Cellular Physiology
Hongbo Zhao, Yutang Huang, Jingjing Shi, Yi Dai, Lanxiang Wu, Honghao Zhou
Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI), is used clinically as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR activating mutations, but the inevitable development of acquired resistance limits its efficacy. In up to 30-40% of NSCLC cases, the mechanism underlying acquired resistance remains unknown. ATP-binding cassette (ABC) transporters are a family of membrane proteins that can significantly influence the bioavailability of numerous drugs, and have confirmed to play an essential role in multidrug resistance (MDR) in cancer chemotherapy...
2018: Frontiers in Pharmacology
Erica S Tsang, Yaoqing Shen, Negar Chooback, Cheryl Ho, Martin Jones, Daniel J Renouf, Howard Lim, Sophie Sun, Stephen Yip, Erin Pleasance, Diana N Ionescu, Karen Mungall, Katayoon Kasaian, Yussanne Ma, Yongjun Zhao, Andrew Mungall, Richard Moore, Steven J M Jones, Marco Marra, Janessa Laskin
BACKGROUND: The Personalized OncoGenomics (POG) program at the British Columbia Cancer Agency integrates whole genome (DNA) and RNA sequencing into practice for metastatic malignancies. We examined the subgroup of patients with metastatic non-small cell lung cancer (NSCLC) and report the prevalence of actionable targets, treatments, and outcomes. METHODS: We identified patients who were enrolled in the POG program between 2012-2016 who had a tumor biopsy and blood samples with comprehensive DNA (80X;40X normal) and RNA sequencing followed by in-depth bioinformatics to identify potential cancer drivers and actionable targets...
December 4, 2018: Cold Spring Harbor Molecular Case Studies
Takashi Ninomiya, Nobuhisa Ishikawa, Koji Inoue, Toshio Kubo, Masayuki Yasugi, Takuo Shibayama, Tadashi Maeda, Kazunori Fujitaka, Masahiro Kodani, Toshihide Yokoyama, Shoichi Kuyama, Nobuaki Ochi, Yutaka Ueda, Seigo Miyoshi, Toshiyuki Kozuki, Yoshihiro Amano, Tetsuya Kubota, Keisuke Sugimoto, Akihiro Bessho, Tomoya Ishii, Kazuhiko Watanabe, Isao Oze, Katsuyuki Hotta, Katsuyuki Kiura
Afatinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), has demonstrated a significant survival benefit over platinum-based chemotherapy in a first-line setting in advanced non-small-cell lung cancer (NSCLC) harboring EGFR exon 19 deletion. In addition, we and other groups have shown there to be favorable progression-free survival (PFS) outcomes, with acceptable toxicity profiles, with bevacizumab and first-generation EGFR-TKI combination therapy. On the basis of the above, we hypothesized that a combination of bevacizumab and afatinib could potentially improve efficacy...
November 1, 2018: Clinical Lung Cancer
Takahiro Nakagomi, Taichiro Goto, Yosuke Hirotsu, Daichi Shikata, Yujiro Yokoyama, Rumi Higuchi, Sotaro Otake, Kenji Amemiya, Toshio Oyama, Hitoshi Mochizuki, Masao Omata
Pulmonary invasive mucinous adenocarcinoma (IMA) is considered a variant of lung adenocarcinomas based on the current World Health Organization classification of lung tumors. However, the molecular mechanism driving IMA development and progression is not well understood. Thus, we surveyed the genomic characteristics of IMA in association with immune-checkpoint expression to investigate new potential therapeutic strategies. Tumor cells were collected from surgical specimens of primary IMA, and sequenced to survey 53 genes associated with lung cancer...
November 30, 2018: Cancers
Myung-Ju Ahn, Chun-Ming Tsai, Frances A Shepherd, Lyudmila Bazhenova, Lecia V Sequist, Toyoaki Hida, James C H Yang, Suresh S Ramalingam, Tetsuya Mitsudomi, Pasi A Jänne, Helen Mann, Mireille Cantarini, Glenwood Goss
BACKGROUND: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is selective for both EGFR-TKI-sensitizing and T790M (threonine-to-methionine substitution at codon 790)-resistance mutations. The authors present long-term follow-up data from a preplanned, pooled analysis of phase 2 studies, the AZD9291 First Time in Patients Ascending Dose Study (AURA) extension trial ( identifier NCT01802632) and the AURA2 trial (NCT02094261)...
December 4, 2018: Cancer
Sue Zann Lim, Cedric Chuan Young Ng, Vikneswari Rajasegaran, Peiyong Guan, Sathiyamoorthy Selvarajan, Aye Aye Thike, Nur Diyana Binte Md Nasir, Valerie Cui Yun Koh, Benita Kiat Tee Tan, Kong Wee Ong, Bin Tean Teh, Puay Hoon Tan
PURPOSE: We aimed to investigate the genomic profile of breast sarcomas (BS) and compare with that of malignant phyllodes tumours (MPT). METHODS: DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) specimens from 17 cases of BS diagnosed at Singapore General Hospital from January 1991 to December 2014. Targeted deep sequencing and copy number variation (CNV) analysis on 16 genes, which included recurrently mutated genes in phyllodes tumours and genes associated with breast cancer, were performed on these samples...
December 3, 2018: Breast Cancer Research and Treatment
Gaurav Goel
Colorectal cancer (CRC) is a major public health problem, both in the USA and globally. Over the past 20 years, significant advances have been made in the treatment of patients with metastatic CRC (mCRC). Recent efforts in the field of biomarkers have focused on the development of molecular diagnostics to define the subset of patients with mCRC that is likely to derive most benefit from anti-EGFR therapy. Herein, we review the recent advancements in molecular stratification of CRC and the role of current as well as emerging biomarkers in this disease...
2018: Cancer Management and Research
Thang Thanh Phan, Toan Trong Ho, Hue Thi Nguyen, Hang Thuy Nguyen, Thu Bich Tran, Son Truong Nguyen
Purpose: To identify and clarify the roles of inflammatory markers in prognosis for advanced non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitor (TKI). Patients and methods: One hundred and twelve adenocarcinoma, clinical stage IV, NSCLC patients with either EGFR exon 19 deletion (E19del) or EGFR exon 21 L858R substitution mutation (L858R) were selected for this study. The blood cell count at different stages of treatment was used to calculate the inflammatory markers...
2018: International Journal of General Medicine
R A F MacLeod, B Schneider, I Sivakova, S Nagel, W G Dirks, P Mraz, E Kubikova, A Perzelova
Glioblastoma multiforme is a highly invasive and incurable primary brain tumor. The most frequent genetic alteration therein is amplification of the epidermal growth factor receptor (EGFR) gene, the target of current clinical trials. However, EGFR amplification is poorly adapted to glioblastoma cell lines. From the 30 cultures attempted herein, we were able to establish two glioblastoma tissue cultures with permanent cell lines. The remaining cultures showed limited life span and underwent senescence between passage numbers (PN) 8 to 15...
August 9, 2018: Neoplasma
Xingxing Lv, Fusheng Gou, Yuan Shen, Hong Lu, Juan Chen, Juan Liu, Hui Chen, Xuan Zhang, Danfei Yu
RATIONALE: Advanced non-small-cell lung cancer (NSCLC) is an aggressive malignancy that generally leads to poor outcomes, with <5% long-term survival at 5 years; however, several researches have shown improvements in the progression-free survival (PFS) and overall survival (OS) on the maintenance therapy after the first-line chemotherapy. we report a case of metastatic NSCLC patient treated with maintenance therapy of gemcitabine with brilliant results. PATIENT CONCERNS: Clinical data and treatment of a 68-year-old man with NSCLC are summarized...
November 2018: Medicine (Baltimore)
Yuichiro Ohe, Fumio Imamura, Naoyuki Nogami, Isamu Okamoto, Takayasu Kurata, Terufumi Kato, Shunichi Sugawara, Suresh S Ramalingam, Hirohiko Uchida, Rachel Hodge, Sarah L Vowler, Andrew Walding, Kazuhiko Nakagawa
Background: The FLAURA study was a multicenter, double-blind, Phase 3 study in which patients with previously untreated epidermal growth factor receptor mutation-positive advanced non-small-cell lung carcinoma were randomized 1:1 to oral osimertinib 80 mg once daily or standard-of-care (gefitinib 250 mg or erlotinib 150 mg, once daily) to compare safety and efficacy. In the overall FLAURA study, significantly better progression-free survival was shown with osimertinib versus standard-of-care...
December 1, 2018: Japanese Journal of Clinical Oncology
Fasika M Tedla, Ernie Yap
PURPOSE OF REVIEW: Consistent associations between variants of the apolipoprotein L1 (APOL1) gene and nondiabetic nephropathy have been reported in individuals of African descent. Donor APOL1 genotype has also been linked to shorter renal allograft survival. This review summarizes recent advances in understanding the biology of APOL1 and their implications to kidney donors and recipients. RECENT FINDINGS: Approximately 12-13% of African Americans have two renal risk APOL1 variants but most do not develop kidney disease...
December 3, 2018: Current Opinion in Organ Transplantation
Yoshihiko Sakata, Kodai Kawamura, Naoki Shingu, Shigeo Hiroshige, Yuko Yasuda, Yoshitomo Eguchi, Keisuke Anan, Junpei Hisanaga, Tatsuya Nitawaki, Aiko Nakano, Kazuya Ichikado
BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used to treat patients with nonsmall cell lung cancer (NSCLC) and EGFR driver mutations. Although some patients discontinued these treatments because of adverse events, it is unclear whether switching EGFR-TKI because of adverse events provides a benefit. METHODS: This retrospective study evaluated data from 22 patients with EGFR mutation-positive NSCLC who received at least two EGFR-TKIs that were switched because of adverse events (March 2011 to September 2017)...
December 2, 2018: Asia-Pacific Journal of Clinical Oncology
Matt Shirley
Dacomitinib (Vizimpro® ) is an orally administered, small-molecule irreversible inhibitor of HER1 (EGFR), HER2 and HER4 that was developed by Pfizer Inc. for the treatment of solid tumours. In September 2018, dacomitinib received its first global approval, in the USA, for use in the first-line treatment of patients with metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test. Registration applications for the use of dacomitinib as first-line treatment for patients with EGFR-mutation-positive metastatic NSCLC have also been submitted in the EU and Japan...
November 30, 2018: Drugs
Frédérique Penault-Llorca, Nina Radosevic-Robin
In non-small cell lung cancer (NSCLC), the pathologist has contributed to the development of personalized medicine from the determination of the right histological type to EGFR and ALK/ROS1 molecular screening for targeted therapies. With the development of immunotherapies, pathologists intervene forefront with programmed death-ligand 1 (PD-L1) immunohistochemical testing, companion test for pembrolizumab monotherapy, first line and complementary test to the other programmed cell death-1 (PD-1) PD-L1 inhibitors...
December 2018: Translational Lung Cancer Research
Matthew Evans, Brendan O'Sullivan, Matthew Smith, Philippe Taniere
The selection of patients for immunotherapy remains challenging given the lack of highly specific and highly sensitive biomarkers. Nevertheless, it is essential that testing laboratories are able to fulfil licencing criteria by providing the tests which have been validated as providing useful predictive information. Programmed cell death protein 1 (PD-1) expression assessment is now established in routine practice, although the situation regarding the selection of a particular assay remains complex, and testing protocols are likely to change in future...
December 2018: Translational Lung Cancer Research
Yong Zhang, Ling Ye, Huijun Zhang, Xuehua Chen, Haiying Ji, Gang Chen, Lu Zhang, Tengfei Zhang, Meiling Jin
No abstract text is available yet for this article.
October 2018: Journal of Thoracic Disease
Yufang Feng, Gaohua Feng, Xiaoling Lu, Wenxia Qian, Junyi Ye, Carmen Areses Manrique, Chunping Ma, Yadong Lu
Background: The utilization of cancer-linked genetic alterations for categorizing patients against optimal treatment is becoming increasingly popular, especially in non-small cell lung cancer (NSCLC). However, disadvantages of the conventional techniques, such as the low throughput and limited detectable alteration types, lead to the demand of large-scale parallel sequencing for different forms of genetic variants. Methods: We evaluated the potential of performing next-generation sequencing (NGS)-based methods in a cohort of 61 treatment-naive NSCLC patients to profile their driver mutations, using a panel consisting of 8 well-established driver genes of lung cancer...
October 2018: Journal of Thoracic Disease
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