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EGFR mutations

Elisabeth E Fransen van de Putte, Floris Pos, Barry Doodeman, Bas W G van Rhijn, Elsbeth van der Laan, Petra Nederlof, Michiel S van der Heijden, Jolanda Bloos van der Hulst, Joyce Sanders, Annegien Broeks, J Martijn Kerst, Vincent van der Noort, Simon Horenblas, Andries M Bergman
PURPOSE: In this prospective study we evaluated safety and efficacy of concurrent radiotherapy and panitumumab following neoadjuvant/induction chemotherapy (ICT) and pelvic lymph node dissection (PLND) as a bladder preserving therapy for invasive bladder cancer (BC). MATERIALS & METHODS: Patients with cT1-4N0-2M0 bladder cancer were treated with PLND and 4 cycles of platinum-based ICT, followed by a six-and-half-week schedule of weekly panitumumab (2.5 mg/kg) and concurrent radiotherapy to the bladder (33x2 Gy)(RT/P)...
October 12, 2018: Journal of Urology
Hao Wang, Chenxin Zeng, Xin Li, Youjie Wang, Xinyi Li, Weihong Ge
AIM: To evaluate the cost-utility of gefitinib and afatinib as first-line EGFR-mutated non-small-cell lung cancer treatments from the Chinese healthcare system perspective. MATERIALS & METHODS: A Markov model was established, state transition probabilities were extracted from the LUX-Lung7 trial and utility values were from previous studies. The cost was extracted from local charge or relevant literature. Incremental cost-effectiveness ratio was calculated for intention-to-treat, EGFR exon 19 deletion (del19) and exon Leu858Arg (21L858R, L858R) muation subgroups...
October 15, 2018: Future Oncology
Y Shi, Z P Ma, W L Cui, X L Pang, W Zhang, Y Q Ma
Objective: To compare different specimen types of lung adenocarcinoma in the detection of epidermal growth factor receptor (EGFR) gene and to correlate EGFR mutations with patient clinical features. Methods: One hundred lung adenocarcinoma cases were collected from June to December in 2015, at the First Affiliated Hospital of Xinjiang Medical University.Of the 100 lung adenocarcinoma samples, 43 were male and 57 were female. The age was from 40 to 88 years old, and the average age was 66 years. One hundred lung adenocarcinoma cases were divided equally into two groups...
October 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Chun-Hua Dai, Yang Shu, Ping Chen, Jian-Nong Wu, Li-Haun Zhu, Rong-Xia Yuan, Wei-Guo Long, Yu-Min Zhu, Jian Li
Resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib and gefitinib, is a major clinical problem in the treatment of patients with non-small cell lung cancer (NSCLC). YM155 is a survivin small molecule inhibitor and has been demonstrated to induce cancer cell apoptosis and autophagy. EGFR-TKIs have been known to induce cancer cell autophagy. In this study, we showed that YM155 markedly enhanced the sensitivity of erlotinib to EGFR-TKI resistant NSCLC cell lines H1650 (EGFR exon 19 deletion and PTEN loss) and A549 (EGFR wild type and KRAS mutation) through inducing autophagy-dependent apoptosis and autophagic cell death...
October 10, 2018: Biochimica et biophysica acta. Molecular basis of disease
Michela Zamboni, Donato Civitareale
In non-small lung cancer, the expression of the transcription factor TTF-1/Nkx2.1 correlates with the presence of EGFR mutations, therefore TTF-1/Nkx2.1 expression is used to optimize an EGFR testing strategy and to guide clinical treatment. We investigate the molecular mechanisms underlying the functional connection between EGFR and TTF-1/Nkx2.1 gene expression in lung adenocarcinoma. Using the H1975 cell line as a non-small cell lung cancer model system and short hairpin RNA, we have selected clones with TTF-1/Nkx2...
October 9, 2018: Biochemical and Biophysical Research Communications
Shengyu Zhou, Xingsheng Hu, Yan Wang, Junling Li, Liqiang Zhou, Xuezhi Hao, Yutao Liu, Yuankai Shi
AIM: Most epidermal growth factor receptor (EGFR) gene mutations affecting exon 19 (inframe deletions; 19 Del) and 21 (L858R), while the rest (referred as uncommon EGFR mutation) have not been fully described due to their rarity. Here we present a retrospective study that investigated clinical characteristics and outcome of patients with different EGFR mutations. METHODS: We retrospectively analyzed the EGFR mutation pattern and its association with clinical-pathological characteristics from 100 cases of nonsmall-cell lung cancer (NSCLC) harboring EGFR mutations, and compiled the genotype response data for NSCLC patients with common and uncommon EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs)...
October 11, 2018: Asia-Pacific Journal of Clinical Oncology
Naoya Nishioka, Tadaaki Yamada, Sachi Harita, Soichi Hirai, Yuki Katayama, Takayuki Nakano, Naoko Okura, Nobuyo Tamiya, Yoshiko Kaneko, Junji Uchino, Koichi Takayama
NSCLC patients with EGFR mutations respond to EGFR-TKIs; however, the management of refractory tumors to EGFR-TKIs remains unclear. We demonstrated that repeated genetic testing might be useful for detecting resistance mechanisms as well as for decision-making in EGFR mutated NSCLC patients, following the emergence of resistance to the initial EGFR-TKIs. A 69-year-old man was diagnosed with lung adenocarcinoma with an EGFR exon 19 deletion. After tumor re-growth treated with erlotinib and chemotherapy, he was diagnosed with an SCLC transformation and administered chemotherapy to treat the SCLC...
2018: Respiratory Medicine Case Reports
Connor G O'Leary, Lynda Corrigan, Petra Martin, Anne Horgan, Miriam O'Connor, Paula Calvert
A 66-year-old non-smoker was diagnosed with stage IIIB, epidermal growth factor receptor (EGFR) mutated, squamous cell lung carcinoma. Treatment included chemotherapy, 35 fractions of radiotherapy and later Gefitinib for 3.5 years. On progression he developed a solitary brain and liver lesion. The brain lesion was excised and histology revealed adenocarcinoma of a lung primary. Afatanib was commenced for 1 further year. At the second time of progression re-biopsy identified small cell carcinoma. He completed four cycles of Carboplatin and Etoposide however deteriorated on completion of chemotherapy...
October 2018: Oxford Medical Case Reports
Fang Wei, Charles M Strom, Jordan Cheng, Chien-Chung Lin, Ching-Yun Hsu, Guy W Soo Hoo, David Chia, Yong Kim, Feng Li, David Elashoff, Tristan Grognan, Michael Tu, Wei Liao, Rena Xian, Wayne W Grody, Wu-Chou Su, David T W Wong
Previously, we detected circulating tumor DNA that contained two EGFR mutations (p.L858R and exon19 del) in plasma of patients with late-stage non-small-cell lung carcinoma (NSCLC) using the electric field-induced release and measurement (EFIRM) platform. Our aim was to determine whether EFIRM technology can detect these mutations in patients with early-stage NSCLC. Prospectively, 248 patients with radiographically determined pulmonary nodules were recruited. Plasma was collected before biopsy and histologic examination of the nodule...
September 29, 2018: Journal of Molecular Diagnostics: JMD
Yong-Hong Pan, Cai-Yu Lin, Cong-Hua Lu, Li Li, Yu-Bo Wang, Heng-Yi Chen, Yong He
PURPOSE: Third-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), rociletinib(CO-1686), is great efficacy against EGFR-mutated patients bearing the T790M resistance mutation. However, acquired resistance may emerge. There is a need to characterize acquired resistance mechanism(s) and to devise ways to overcome CO-1686 resistance. EXPERIMENTAL DESIGN: MTT assay, ki67 incorporation assay, transwell assay and TUNEL assay were employed to analyze the effects of metformin to reverse CO-1686 resistance in vitro...
October 11, 2018: Clinical Respiratory Journal
Weimin Yin, Xiaolu Yu, Xuejia Kang, Yuge Zhao, Pengfei Zhao, Hongyue Jin, Xuhong Fu, Yakun Wan, Chengyuan Peng, Yongzhuo Huang
Precision medicine has made a significant breakthrough in the past decade. The most representative success is the molecular targeting therapy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in non-small-cell lung cancer (NSCLC) with oncogenic drivers, approved by the US Food and Drug Administration (FDA) as first-line therapeutics for substituting chemotherapy. However, the rapidly developed TKI resistance invariably leads to unsustainable treatment. For example, gefitinib is the first choice for advanced NSCLC with EGFR mutation, but most patients would soon develop secondary EGFRT790M mutation and acquire gefitinib resistance...
October 11, 2018: Small
Lea Loriguet, Mony Chenda Morisse, Julie Dremaux, Louison Collet, Christophe Attencourt, Alexandre Coutte, Mathieu Boone, Henri Sevestre, Antoine Galmiche, Brigitte Gubler, Bruno Chauffert, Stephanie Trudel
BACKGROUND: Epidermal growth factor receptor (EGFR) gene alterations and amplification are frequently reported in cases of glioblastoma (GBM). However, EGFR-activating mutations that confer proven sensitivity to tyrosine kinase inhibitors (TKIs) in lung cancer have not yet been reported in GBM. CASE PRESENTATION: Using next-generation sequencing, array comparative genomic hybridization and droplet digital PCR, we identified the p.L861Q EGFR mutation in a case of GBM for the first time...
October 11, 2018: BMC Cancer
Prajish Iyer, Shailesh V Shrikhande, Malika Ranjan, Asim Joshi, Nilesh Gardi, Ratnam Prasad, Bhasker Dharavath, Rahul Thorat, Sameer Salunkhe, Bikram Sahoo, Pratik Chandrani, Hitesh Kore, Bhabani Mohanty, Vikram Chaudhari, Anuradha Choughule, Dhananjay Kawle, Pradip Chaudhari, Arvind Ingle, Shripad Banavali, Poonam Gera, Mukta R Ramadwar, Kumar Prabhash, Savio George Barreto, Shilpee Dutt, Amit Dutt
The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. Our integrated analysis of whole exome sequencing, copy number alterations, immunohistochemical, and phospho-proteome array profiling indicates ERBB2 alterations in 40% early-stage rare gallbladder tumors, among an ethnically distinct population not studied before, that occurs through overexpression in 24% (n=25) and recurrent mutations in 14% tumors (n=44); along with co-occurring KRAS mutation in 7% tumors (n=44)...
October 10, 2018: International Journal of Cancer. Journal International du Cancer
Marcel André Schneider, Janina Eden, Basile Pache, Felix Laminger, Victor Lopez-Lopez, Thomas Steffen, Martin Hübner, Friedrich Kober, Sebastian Roka, Pedro Cascales Campos, Lilian Roth, Anurag Gupta, Alexander Siebenhüner, Vahan Kepenekian, Guillaume Passot, Philippe Gertsch, Olivier Glehen, Kuno Lehmann
BACKGROUND: Adequate selection of patients with peritoneal metastasis (PM) for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains critical for successful long-term outcomes. Factors reflecting tumor biology are currently poorly represented in the selection process. The prognostic relevance of RAS/RAF mutations in patients with PM remains unclear. METHODS: Survival data of patients with colorectal PM operated in 6 European tertiary centers were retrospectively collected and predictive factors for survival identified by Cox regression analyses...
November 2018: Annals of Surgery
Giulio Riva, Christine Mian, Claudio Luchini, Ilaria Girolami, Claudio Ghimenton, Luca Cima, Luca Novelli, Esther Hanspeter, Guido Mazzoleni, Christine Schwienbacher, Stefan Pycha, Carolina D'Elia, Emanuela Trenti, Armin Pycha, Guido Martignoni, Ondrej Hes, Albino Eccher, Gabriella Nesi, Matteo Brunelli
Urachal carcinoma (UrC) is an exceedingly rare neoplasm that develops from the urachus, an embryologic remnant of the urogenital sinus and allantois. The most commonly encountered histologic subtype is adenocarcinoma. The aim of this study is to characterize a series of UrC by morphology, immunohistochemistry, and molecular analysis. We retrospectively investigated seven cases of UrCs and assessed patient symptoms, imaging, histologic features, immunohistochemical profile, molecular characteristics, pathologic stages, and type of treatment...
October 9, 2018: Virchows Archiv: An International Journal of Pathology
Emiliano Cocco, F Javier Carmona, Pedram Razavi, Helen H Won, Yanyan Cai, Valentina Rossi, Carmen Chan, James Cownie, Joanne Soong, Eneda Toska, Sophie G Shifman, Ivana Sarotto, Peter Savas, Michael J Wick, Kyriakos P Papadopoulos, Alyssa Moriarty, Richard E Cutler, Francesca Avogadri-Connors, Alshad S Lalani, Richard P Bryce, Sarat Chandarlapaty, David M Hyman, David B Solit, Valentina Boni, Sherene Loi, José Baselga, Michael F Berger, Filippo Montemurro, Maurizio Scaltriti
Mutations in ERBB2 , the gene encoding epidermal growth factor receptor (EGFR) family member HER2, are common in and drive the growth of "HER2-negative" (not ERBB2 amplified) tumors but are rare in "HER2-positive" ( ERBB2 amplified) breast cancer. We analyzed DNA-sequencing data from HER2-positive patients and used cell lines and a patient-derived xenograft model to test the consequence of HER2 mutations on the efficacy of anti-HER2 agents such as trastuzumab, lapatinib, and neratinib, an irreversible pan-EGFR inhibitor...
October 9, 2018: Science Signaling
German P Barletta, Marcia Anahi Hasenhuer, Maria Silvina Fornasari, Gustavo Parisi, Sebastian Fernandez-Alberti
Epidermal growth factor receptor (EGFR) is a prototypical cell-surface receptor that plays a key role in the regulation of cellular signaling, proliferation and differentiation. Mutations of its kinase domain have been associated with the development of a variety of cancers and, therefore, it has been the target of drug design. Single amino acid substitutions (SASs) in this domain have been proven to alter the equilibrium of pre-existing conformer populations. Despite the advances in structural descriptions of its so-called active and inactive conformations, the associated dynamics aspects that characterize them have not been thoroughly studied yet...
October 9, 2018: Journal of Computational Chemistry
Masaoki Ito, Yoshihiro Miyata, Kei Kushitani, Tomoharu Yoshiya, Yuichiro Kai, Yasuhiro Tsutani, Takeshi Mimura, Kazuo Konishi, Yukio Takeshima, Morihito Okada
BACKGROUND: This study was conducted to evaluate the prognostic and recurrent impact of EGFR mutation status in resected pN0M0 lung adenocarcinoma with consideration of the histological subtype. METHODS: Following retrospective analysis of whole 474 consecutive pathological N0M0 lung adenocarcinoma patients, the prognostic significance of EGFR mutation status was evaluated in limited 394 subjects. Overall survival and recurrence-free interval (RFI) were estimated using the Kaplan-Meier method and compared using a log-rank test...
October 8, 2018: Thoracic Cancer
Huy Gia Vuong, Thao T K Tran, Hanh T T Ngo, Thong Quang Pham, Tadao Nakazawa, Kar-Ming Fung, Lewis Hassell, Ryohei Katoh, Tetsuo Kondo
BACKGROUND: The clinical outcomes of IDH-wild type (IDH-wt) lower-grade glioma (LGG) have been the subject of debate for some time. In this meta-analysis, we aimed to assess the prognostic values of several known genetic markers (eg, TERT promoter mutation, H3F3A mutation, CDKN2A loss) in this tumor group. METHODS: Four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library were searched for relevant articles. Pooled hazard ratio (HR) and corresponding 95% confidence interval (CI) for overall survival (OS) were calculated using random effect model weighted by inverse variance method...
October 9, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Terry L Ng, Hui Yu, Derek E Smith, Theresa A Boyle, Emily R York, Scott Leedy, Dexiang Gao, Dara L Aisner, Adrie Van Bokhoven, Lynn E Heasley, Fred R Hirsch, D Ross Camidge
INTRODUCTION: Preclinically, high epidermal growth factor receptor 1 (FGFR1) messenger RNA (FGFR1-MRNA) and FGFR1 amplification (FGFR1-AMP) predicted sensitivity to fibroblast growth factor receptor inhibitors in non-small-cell lung cancer and small-cell lung cancer cell lines. KRAS mutations did not preclude sensitivity. PATIENTS AND METHODS: Metastatic EGFR- and ALK-negative lung cancers were screened for FGFR1-MRNA by in-situ hybridization (ISH) and FGFR1-AMP by silver in-situ hybridization (SISH)...
September 7, 2018: Clinical Lung Cancer
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