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https://www.readbyqxmd.com/read/29355391/updated-molecular-testing-guideline-for-the-selection-of-lung-cancer-patients-for-treatment-with-targeted-tyrosine-kinase-inhibitors-guideline-from-the-college-of-american-pathologists-the-international-association-for-the-study-of-lung-cancer-and-the-association
#1
Neal I Lindeman, Philip T Cagle, Dara L Aisner, Maria E Arcila, Mary Beth Beasley, Eric Bernicker, Carol Colasacco, Sanja Dacic, Fred R Hirsch, Keith Kerr, David J Kwiatkowski, Marc Ladanyi, Jan A Nowak, Lynette Sholl, Robyn Temple-Smolkin, Benjamin Solomon, Lesley H Souter, Erik Thunnissen, Ming S Tsao, Christina B Ventura, Murry W Wynes, Yasushi Yatabe
CONTEXT: - In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. OBJECTIVE: - To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update...
January 22, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29354805/current-progress-and-outcomes-of-clinical-trials-on-using-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-therapy-in-non-small-cell-lung-cancer-patients-with-brain-metastases
#2
Ling-Ling Kong, Lin-Lin Wang, Li-Gang Xing, Jin-Ming Yu
Non-small cell lung cancer (NSCLC) continues to be one of the major causes of cancer-related deaths worldwide, and brain metastases are the major cause of death in NSCLC patients. With recent advances in understanding the underlying molecular mechanism of NSCLC development and progression, mutations in epidermal growth factor receptor (EGFR) have been recognized as a key predictor of therapeutic sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Using EGFR-TKI alone or in combination with standard treatments such as whole-brain radiotherapy and surgery has been an effective strategy for the management of brain metastasis...
December 2017: Chronic Diseases and Translational Medicine
https://www.readbyqxmd.com/read/29353978/survival-difference-between-egfr-del19-and-l858r-mutant-advanced-non-small-cell-lung-cancer-patients-receiving-gefitinib-a-propensity-score-matching-analysis
#3
Minglei Zhuo, Qiwen Zheng, Jun Zhao, Meina Wu, Tongtong An, Yuyan Wang, Jianjie Li, Shuhang Wang, Jia Zhong, Xue Yang, Hanxiao Chen, Bo Jia, Zhi Dong, Emei Gao, Jingjing Wang, Ziping Wang
Objective: Although superior clinical benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of advanced non-small-cell lung cancer (NSCLC) had been reported, the survival difference between exon 19 deletion (Del19) and exon 21 Leu858Arg substitution (L858R) remains controversial. The purpose of this study is to investigate the differences in progression-free survival (PFS) and overall survival (OS) between different EGFR mutant subtypes among advanced NSCLC patients receiving gefitinib...
December 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/29353977/uncommon-egfr-mutations-in-a-cohort-of-chinese-nsclc-patients-and-outcomes-of-first-line-egfr-tkis-and-platinum-based-chemotherapy
#4
Jinpeng Shi, Hui Yang, Tao Jiang, Xuefei Li, Chao Zhao, Limin Zhang, Sha Zhao, Xiaozhen Liu, Yijun Jia, Yan Wang, Lei Xi, Shijia Zhang, Chunxia Su, Shengxiang Ren, Caicun Zhou
Objective: Data on the clinical activity of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer (NSCLC) and uncommon EGFR mutations remain insufficient. This study aimed to investigate the effect of first-line EGFR-TKIs or platinum-based chemotherapy in NSCLC patients with uncommon EGFR mutations. Methods: We retrospectively enrolled 504 patients with EGFR-mutant NSCLC. The clinical characteristics and treatment outcomes were collected and compared between patients with common and uncommon EGFR-mutant NSCLC...
December 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/29352819/dietary-fibre-intake-in-relation-to-the-risk-of-incident-chronic-kidney-disease
#5
Parvin Mirmiran, Emad Yuzbashian, Golaleh Asghari, Shaghayegh Sarverzadeh, Fereidoun Azizi
The purpose of this study was primarily to evaluate the association of total fibre intake with the risk of incident chronic kidney disease (CKD). We also evaluated the association of dietary fibre from fruits, vegetables, cereals and legumes with the incidence of CKD in a population-based prospective study. We followed up 1630 participants of the Tehran Lipid and Glucose Study for 6·1 years, who were initially free of CKD. Baseline diet was assessed by a valid and reliable FFQ. Estimated glomerular filtration rate (eGFR) was calculated, using the Modification of Diet in Renal Disease Study equation, and CKD was defined as eGFR <60 ml/min per 1·73 m2...
January 21, 2018: British Journal of Nutrition
https://www.readbyqxmd.com/read/29351901/xiap-regulation-by-mnk-links-mapk-and-nf%C3%AE%C2%BAb-signaling-to-determine-an-aggressive-breast-cancer-phenotype
#6
Myron K Evans, Michael C Brown, Joseph Geradts, Xuhui Bao, Timothy J Robinson, Mohit Kumar Jolly, Peter Vermeulen, Gregory M Palmer, Matthias Gromeier, Herbert Levine, Michael A Morse, Steven Van Laere, Gayathri R Devi
Hyperactivation of the NFκB pathway is a distinct feature of inflammatory breast cancer (IBC), a highly proliferative and lethal disease. Gene expression studies in IBC patient tissue have linked epidermal growth factor receptor (EGFR/HER2)-mediated MAPK signaling to NFκB hyperactivity, but the mechanism(s) by which this occurs remain unclear. Here, we report that the X-linked inhibitor of apoptosis protein (XIAP) plays a central role in linking these two pathways. XIAP overexpression correlated with poor prognoses in breast cancer patients and was frequently observed in untreated IBC patient primary tumors...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29351356/epha2-ephrin-a1-mediate-corneal-epithelial-cell-compartmentalization-via-adam10-regulation-of-egfr-signaling
#7
Nihal Kaplan, Rosa Ventrella, Han Peng, Sonali Pal-Ghosh, Constadina Arvanitis, Joshua Z Rappoport, Brian J Mitchell, Mary Ann Stepp, Robert M Lavker, Spiro Getsios
Purpose: Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal-corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal-corneal epithelial boundary organization...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29349588/amphiregulin-enhances-cardiac-fibrosis-and-aggravates-cardiac-dysfunction-in-mice-with-experimental-myocardial-infarction-partly-through-activating-egfr-dependent-pathway
#8
Liang Liu, Xian Jin, Cui-Fen Hu, Ya-Ping Zhang, Zhong'e Zhou, Rong Li, Cheng-Xing Shen
Cardiac fibrosis (CF), a main process of ventricular remodeling after myocardial infarction (MI), plays a crucial role in the pathogenesis of heart failure (HF) post-MI. It is known that amphiregulin (AR) is involved in fibrosis of several organs. However, the expression of AR and its role post-MI are yet to be determined. This study aimed to investigate the impact of AR on CF post-MI and related mechanisms. Significantly upregulated AR expression was evidenced in the infarct border zone of MI mice in vivo and the AR secretion was enhanced in macrophages, but not in cardiac fibroblasts...
January 18, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29348482/egfr-activation-triggers-cellular-hypertrophy-and-lysosomal-disease-in-naglu-depleted-cardiomyoblasts-mimicking-the-hallmarks-of-mucopolysaccharidosis-iiib
#9
Valeria De Pasquale, Antonio Pezone, Patrizia Sarogni, Alfonso Tramontano, Gabriele Giacomo Schiattarella, Vittorio Enrico Avvedimento, Simona Paladino, Luigi Michele Pavone
Mucopolysaccharidosis (MPS) IIIB is an inherited lysosomal storage disease caused by the deficiency of the enzyme α-N-acetylglucosaminidase (NAGLU) required for heparan sulfate (HS) degradation. The defective lysosomal clearance of undigested HS results in dysfunction of multiple tissues and organs. We recently demonstrated that the murine model of MPS IIIB develops cardiac disease, valvular abnormalities, and ultimately heart failure. To address the molecular mechanisms governing cardiac dysfunctions in MPS IIIB, we generated a model of the disease by silencing NAGLU gene expression in H9C2 rat cardiomyoblasts...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348459/distinct-dependencies-on-receptor-tyrosine-kinases-in-the-regulation-of-mapk-signaling-between-braf-v600e-and-non-v600e-mutant-lung-cancers
#10
Hiroshi Kotani, Yuta Adachi, Hidenori Kitai, Shuta Tomida, Hideaki Bando, Anthony C Faber, Takayuki Yoshino, Dominic C Voon, Seiji Yano, Hiromichi Ebi
BRAF is one of the most frequently mutated genes across a number of different cancers, with the best-characterized mutation being V600E. Despite the successes of treating BRAF mutant V600E lung cancer with BRAF pathway inhibitors, treatment strategies targeting tumors with non-V600E mutations are yet to be established. We studied cellular signaling differences between lung cancers with different BRAF mutations and determined their sensitivities to BRAF pathway inhibitors. Here, we observed that MEK inhibition induced feedback activation of the receptor tyrosine kinase (RTK) EGFR, and in some cases the RTK FGFR, resulting in transient suppression of ERK phosphorylation in BRAF non-V600E, but not BRAF V600E, mutant cells...
January 19, 2018: Oncogene
https://www.readbyqxmd.com/read/29346833/phase-1b-trial-of-ficlatuzumab-a-humanized-hepatocyte-growth-factor-inhibitory-monoclonal-antibody-in-combination-with-gefitinib-in-asian-patients-with-nsclc
#11
Eng-Huat Tan, Wan-Teck Lim, Myung-Ju Ahn, Quan-Sing Ng, Jin Seok Ahn, Daniel Shao-Weng Tan, Jong-Mu Sun, May Han, Francis C Payumo, Krista McKee, Wei Yin, Marc Credi, Shefali Agarwal, Jaroslaw Jac, Keunchil Park
Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 κ HGF inhibitory monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC)...
January 18, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29346631/anticardiolipin-antibodies-and-12-month-graft-function-in-kidney-transplant-recipients-a-prognosis-cohort-survey
#12
Marion Gauthier, Florence Canoui-Poitrine, Esther Guéry, Dominique Desvaux, Sophie Hue, Guillaume Canaud, Thomas Stehle, Philippe Lang, Tomek Kofman, Philippe Grimbert, Marie Matignon
Background: In kidney transplant recipients, anticardiolipin (ACL) antibodies without antiphospholipid syndrome (APS) are found in up to 38% of patients and could be associated with thrombotic events (TEs). However, the prognostic role of ACL regarding kidney transplant and patients outcomes have still not been well defined. Methods: We conducted an observational, monocentric, retrospective cohort study including 446 kidney transplant recipients and standardized follow-up: 36-month allograft and patient survival, 12-month estimated glomerular filtration rate (eGFR) and 3- and 12-month screening biopsies...
January 16, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29345400/fludrocortisone-a-treatment-for-tubulopathy-post-paediatric-renal-transplantation-a-national-paediatric-nephrology-unit-experience
#13
S R Ali, I Shaheen, D Young, I Ramage, H Maxwell, D A Hughes, D Athavale, M G Shaikh
Calcineurin inhibitors post-renal transplantation are recognized to cause tubulopathies in the form of hyponatremia, hyperkalemia, and acidosis. Sodium supplementation may be required, increasing medication burden and potentially resulting in poor compliance. Fludrocortisone has been beneficial in addressing tubulopathies in adult studies, with limited paediatric data available. A retrospective review of data from an electronic renal database from December 2014 to January 2016 was carried out. Forty-seven post-transplant patients were reviewed with 23 (49%) patients on sodium chloride or bicarbonate...
January 18, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29344641/inhibition-of-rptor-overcomes-resistance-to-egfr-inhibition-in-triple-negative-breast-cancer-cells
#14
Kyu Sic You, Yong Weon Yi, Sahng-June Kwak, Yeon-Sun Seong
Triple-negative breast cancer (TNBC) cells frequently exhibit activated growth factor signaling and resistance to inhibitors for epidermal growth factor receptor (EGFR), despite the overexpression of EGFR protein, and this is associated with a malignant behavior and a poor prognosis. In this study, to elucidate the underlying mechanisms of resistance to EGFR inhibitor and identify inhibitors that exert a synergistic effect with EGFR inhibition, we examined the inhibitory effects of selected protein kinase inhibitors (PKIs) in combination with gefitinib on the viability of a mesenchymal stem-like (MSL) subtype TNBC cell line...
January 15, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344640/over-regulation-of-microrna-133b-inhibits-cell-proliferation-of-cisplatin-induced-non-small-cell-lung-cancer-cells-through-pi3k-akt-and-jak2-stat3-signaling-pathway-by-targeting-egfr
#15
Bin Li, Cui-Min Ding, Yan-Xiao Li, Jing-Cui Peng, Nan Geng, Wen-Wen Qin
The present study determined the anticancer activity and its mechanism of microRNA‑133b on cell proliferation of cisplatin-induced non-small cell lung cancer cells. The expression of microRNA-133b cisplatin‑induced non-small cell lung cancer (NSCLC) tissue was lower than that of para-carcinoma tissue in patients. Overall survival of higher expression in cisplatin-induced NSCLC patients was higher than that of lower expression in cisplatin‑induced NSCLC patients. Over-regulation of microRNA-133b inhibited cell proliferation and LDH activity, induced apoptosis and caspase-3 activity, suppressed the protein expression of EGFR, PI3K, p-Akt, p-JAK2 and p-STAT3, decreased cyclin D1 and increased Bax protein expression in cisplatin‑induced A549 cells...
January 15, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29344206/impact-of-metastatic-status-on-the-prognosis-of-egfr-mutation-positive-non-small-cell-lung-cancer-patients-treated-with-first-generation-egfr-tyrosine-kinase-inhibitors
#16
Yoshihiko Taniguchi, Akihiro Tamiya, Kenji Nakahama, Yoko Naoki, Masaki Kanazu, Naoki Omachi, Kyoichi Okishio, Takahiko Kasai, Shinji Atagi
The aim of the present study was to analyze the impact of metastatic status on the prognosis of epithelial growth factor receptor (EGFR) mutation-positive patients with non-small cell lung cancer (NSCLC) treated with first-generation EGFR-tyrosine kinase inhibitors (TKIs). A total of 178 EGFR mutation-positive patients with stage IIIB-IV and relapsed NSCLC who were treated with gefitinib or erlotinib as the first-line treatment were enrolled in the present study. Metastatic status, progression-free survival (PFS), overall survival (OS) and treatment-response rates were investigated...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343688/wee1-inhibitor-mk1775-sensitizes-kras-mutated-nsclc-cells-to-sorafenib
#17
Elisa Caiola, Roberta Frapolli, Michele Tomanelli, Rossana Valerio, Alice Iezzi, Marina C Garassino, Massimo Broggini, Mirko Marabese
Non-Small-Cell Lung Cancer (NSCLC) is a poorly chemosensitive tumor and targeted therapies are only used for about 15% of patients where a specific driving and druggable lesion is observed (EGFR, ALK, ROS). KRAS is one of the most frequently mutated genes in NSCLC and patients harboring these mutations do not benefit from specific treatments. Sorafenib, a multi-target tyrosine kinase inhibitor, was proposed as a potentially active drug in KRAS-mutated NSCLC patients, but clinical trials results were not conclusive...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29341459/multicenter-study-of-diagnostic-procedures-genetic-aberration-analysis-and-first-line-treatment-of-lung-cancer-in-jiangsu-province-china
#18
YangBo Hu, Huan Hu, LiYun Miao, Xin Zhao, Wei Gu, Wei Heng, ZiLi Meng, Jian Feng, Yi You, XingXiang Xu, Rong Hu, HaiQuan Li, Jie Zhao, XiaoLi Zhu, MeiQi Shi, Li Shen, XiuWei Zhang, XiaoWei Yin, Hang Ma, MinHua Shi, Yong Yu, Hong Lv, LiMing Cai, GaoHua Feng, YeQing Zhang, Feng Wu, TangFeng Lv, Yong Song
BACKGROUND: Jiangsu Province, China, is highly developed economically and culturally, and has a high prevalence of lung cancer. We aimed to evaluate the diagnostic procedures, genetic aberration analysis status, and first-line treatment models of lung cancer in Jiangsu Province. METHODS: Lung cancer patients diagnosed in 2016 at 22 tertiary care hospitals were evaluated. Demographic characteristics, tumor histology, staging, family history of lung cancer, auxiliary examinations, genetic testing, and first-line treatment were collected on discharge...
January 17, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29341374/validation-of-the-digital-pcr-system-in-tyrosine-kinase-inhibitor-resistant-egfr-mutant-non-small-cell-lung-cancer
#19
Katsuhiro Masago, Shiro Fujita, Akito Hata, Chiyuki Okuda, Yuko Yoshizumi, Reiko Kaji, Nobuyuki Katakami, Yukio Hirata, Yasushi Yatabe
The aim of this study was to compare the accuracy of the QuantStudio 3D Digital polymerase chain reaction (dPCR) system and a PCR-based next generation sequencing (NGS) system for detecting a secondary mutation in the epidermal growth factor receptor (EGFR) gene T790M in non-small cell lung cancer (NSCLC) patients previously diagnosed with EGFR-activating mutations. Twenty-five patients with NSCLC previously treated with EGFR-TKIs were examined. The patients were treated daily with either erlotinib or gefitinib...
January 17, 2018: Pathology International
https://www.readbyqxmd.com/read/29340107/a-comparison-of-arms-plus-and-droplet-digital-pcr-for-detecting-egfr-activating-mutations-in-plasma
#20
Xinxin Zhang, Ning Chang, Guohua Yang, Yong Zhang, Mingxiang Ye, Jing Cao, Jie Xiong, Zhiping Han, Shuo Wu, Lei Shang, Jian Zhang
In this study, we introduce a novel amplification refractory mutation system (ARMS)-based assay, namely ARMS-Plus, for the detection of epidermal growth factor receptor (EGFR) mutations in plasma samples. We evaluated the performance of ARMS-Plus in comparison with droplet digital PCR (ddPCR) and assessed the significance of plasma EGFR mutations in predicting efficacy of EGFR-tyrosine kinase inhibitor (TKI) regimen. A total of 122 advanced non-small cell lung cancer (NSCLC) patients were enrolled in this study...
December 19, 2017: Oncotarget
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