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https://www.readbyqxmd.com/read/28647671/use-of-oncogenic-driver-mutations-in-staging-of-multiple-primary-lung-carcinomas-a-single-center-experience
#1
Ramsey Asmar, Joshua R Sonett, Gopal Singh, Mahesh M Mansukhani, Alain C Borczuk
PURPOSE: The staging of multiple pulmonary adenocarcinomas requires the distinction of intrapulmonary metastasis (IPM) from multiple primary lung cancers (MPLC). This can be challenging in some patients, and the addition of data from oncogenic driver mutations in these tumors may be helpful in this determination. PROCEDURES: As a proof of principle, molecular driver results from primary tumors and their metastases in 45 patients were compared (cohort 1). Then, 69 patients with a total of 154 synchronous or metachronous lung carcinomas were identified, with pathologic findings compared to oncogenic driver mutation...
June 21, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28646226/a-microrna-signature-of-response-to-erlotinib-is-descriptive-of-tgf%C3%AE-behaviour-in-nsclc
#2
Madeline Krentz Gober, James P Collard, Katherine Thompson, Esther P Black
Our previous work identified a 13-gene miRNA signature predictive of response to the epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in Non-Small Cell Lung Cancer cell lines. Bioinformatic analysis of the signature showed a functional convergence on TGFβ canonical signalling. We hypothesized that TGFβ signalling controls expression of the miRNA genes comprising an erlotinib response signature in NSCLC. Western analysis revealed that TGFβ signalling via Smad2/3/4 occurred differently between erlotinib-resistant A549 and erlotinib- sensitive PC9 cells...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646172/dacomitinib-a-pan-inhibitor-of-erbb-receptors-suppresses-growth-and-invasive-capacity-of-chemoresistant-ovarian-carcinoma-cells
#3
Majid Momeny, Ghazaleh Zarrinrad, Farima Moghaddaskho, Arash Poursheikhani, Ghazaleh Sankanian, Azam Zaghal, Shahab Mirshahvaladi, Fatemeh Esmaeili, Haniyeh Eyvani, Farinaz Barghi, Zahra Sabourinejad, Zivar Alishahi, Hassan Yousefi, Reza Ghasemi, Leila Dardaei, Davood Bashash, Bahram Chahardouli, Ahmad R Dehpour, Javad Tavakkoly-Bazzaz, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy worldwide. Development of chemoresistance and peritoneal dissemination of EOC cells are the major reasons for low survival rate. Targeting signal transduction pathways which promote therapy resistance and metastatic dissemination is the key to successful treatment. Members of the ErbB family of receptors are over-expressed in EOC and play key roles in chemoresistance and invasiveness. Despite this, single-targeted ErbB inhibitors have demonstrated limited activity in chemoresistant EOC...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646091/stress-specific-p38-map-kinase-activation-is-sufficient-to-drive-egf-receptor-endocytosis-but-not-nuclear-translocation
#4
Alejandra Tomas, Sylwia Jones, Simon O Vaughan, Daniel Hochhauser, Clare E Futter
P38 MAP kinase-dependent EGF receptor (EGFR) endocytosis is induced by stress. Ligand and stresses like X-rays, reportedly promote nuclear traffic of endocytosed EGFR for regulation of gene transcription and DNA repair. We fail to detect EGFR endocytosis or nuclear transport following X-ray treatment of HeLa or head and neck cancer cells, despite extensive DNA damage induction. Apparent nuclear staining with EGFR extracellular domain antibody remained present despite reduced/absent EGFR expression and so did not represent nuclear EGFR...
June 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28645631/outcomes-of-first-generation-egfr-tkis-against-non-small-cell-lung-cancer-harboring-uncommon-egfr-mutations-a-post-hoc-analysis-of-the-be-positive-study
#5
Sara Pilotto, Antonio Rossi, Tiziana Vavalà, Alessandro Follador, Marcello Tiseo, Domenico Galetta, Alessandro Morabito, Massimo Di Maio, Olga Martelli, Orazio Caffo, Pier Luigi Piovano, Diego Cortinovis, Nicoletta Zilembo, Clelia Casartelli, Giuseppe Luigi Banna, Antonio Ardizzoia, Maria Luisa Barzelloni, Alessandra Bearz, Giovenzio Genestreti, Claudia Mucciarini, Virginio Filipazzi, Jessica Menis, Elisa Rizzo, Fausto Barbieri, Erika Rijavec, Fabiana Cecere, Gianluca Spitaleri, Emilio Bria, Silvia Novello
BACKGROUND: Beyond progression after tyrosine kinase inhibitor in EGFR-positive non-small-cell lung cancer patients (BE-POSITIVE) was the first Italian multicenter observational study that reported the outcomes of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in a "real-life" Caucasian EGFR-mutated non-small-cell lung cancer (NSCLC) population. The sharing of multi-institutional experiences represents a crucial strategy to enrich knowledge about uncommon EGFR mutations...
June 1, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28644837/real-world-first-line-treatment-and-overall-survival-in-non-small-cell-lung-cancer-without-known-egfr-mutations-or-alk-rearrangements-in-us-community-oncology-setting
#6
Amy P Abernethy, Ashwini Arunachalam, Thomas Burke, Caroline McKay, Xiting Cao, Rachael Sorg, David P Carbone
PURPOSE: To establish a baseline for care and overall survival (OS) based upon contemporary first-line treatments prescribed in the era before the introduction of immune checkpoint inhibitors, for people with metastatic non-small cell lung cancer (NSCLC) without common actionable mutations. METHODS: Using a nationally representative electronic health record data from the Flatiron dataset which included 162 practices from different regions in US, we identified patients (≥18 years old) newly diagnosed with stage IV NSCLC initiating first-line anticancer therapy (November 2012- January 2015, with follow-up through July 2015)...
2017: PloS One
https://www.readbyqxmd.com/read/28643125/the-role-of-prmt1-in-egfr-methylation-and-signaling-in-mda-mb-468-triple-negative-breast-cancer-cells
#7
Katsuya Nakai, Weiya Xia, Hsin-Wei Liao, Mitsue Saito, Mien-Chie Hung, Hirohito Yamaguchi
BACKGROUND: Epidermal growth factor receptor (EGFR) is often overexpressed in triple-negative breast cancer (TNBC). However, clinical studies have shown that therapies against EGFR are not effective in patients with TNBC. Recently, it has been reported that arginine 198/200 in EGFR extracellular domain is methylated by PRMT1 and that the methylation confers resistance to EGFR monoclonal antibody cetuximab in colorectal cancer cells. To explore a potential mechanism underlying intrinsic resistance to anti-EGFR therapy in TNBC, we investigated the role of PRMT1 in EGFR methylation and signaling in MDA-MB-468 (468) TNBC cells...
June 22, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28642617/podoplanin-enhances-lung-cancer-cell-growth-in-vivo-by-inducing-platelet-aggregation
#8
Kenichi Miyata, Ai Takemoto, Sakae Okumura, Makoto Nishio, Naoya Fujita
Podoplanin/Aggrus, known as a platelet aggregation-inducing factor, is frequently overexpressed in lung squamous cell carcinomas (LSCC) and glioblastomas among other tumours, and its expression has been reported to be correlated with poor prognosis. However, the contribution of podoplanin to malignant progression has been elusive. Here we demonstrate that in podoplanin-positive LSCC cells, their growth was abrogated by podoplanin knockout in vivo but not in vitro. Conversely, ectopic expression of podoplanin promoted cell growth in vivo and facilitated intratumoral platelet activation...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642172/egfr-t790m-ctdna-testing-platforms-and-their-role-as-companion-diagnostics-correlation-with-clinical-outcomes-to-egfr-tkis
#9
Zhiyong Liang, Ying Cheng, Yuan Chen, Yanping Hu, Wei-Ping Liu, You Lu, Jie Wang, Ye Wang, Gang Wu, Jian-Ming Ying, He-Long Zhang, Xu-Chao Zhang, Yi-Long Wu
Somatic mutation in the epidermal growth factor receptor (EGFR) predict clinical response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC) and is a promising target for personalised medicine. EGFR mutations have prognostic value. Initially patients respond well to tyrosine kinase inhibitors but finally they would develop resistance and about 50% of this resistance can be attributed to the emergence of EGFR resistant mutation, T790M. This necessitates the need for genetic testing for clinical management of patients...
June 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28641700/-molecular-imaging-in-vivo-detection-of-egfr-mutations-in-non-small-cell-lung-cancer
#10
Danjing Luo, Jin'an Ma, Jinming Zhang, Yanzhong Zhao
An ever increasing number of drugs directed as epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) bring a new revolution for non-small cell lung cancer (NSCLC) therapy, and many large scales of studies show that only people with EGFR-sensitive mutation can benefit from these drugs. The main method of EGFR mutation detection is to analyze the DNA sequence of EGFR, which can be the lung cancer tissue, pleural fluid tumor cells, circulating tumor cells and peripheral blood free DNA obtained by surgery or puncture, the biggest drawback is that the heterogeneity of EGFR mutation cannot be analyzed...
June 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28640223/non-targeted-metabolomics-analysis-of-the-effects-of-tyrosine-kinase-inhibitors-sunitinib-and-erlotinib-on-heart-muscle-liver-and-serum-metabolism-in-vivo
#11
Brian C Jensen, Traci L Parry, Wei Huang, Amro Ilaiwy, James R Bain, Michael J Muehlbauer, Sara K O'Neal, Cam Patterson, Gary L Johnson, Monte S Willis
Background: More than 90 tyrosine kinases have been implicated in the pathogenesis of malignant transformation and tumor angiogenesis. Tyrosine kinase inhibitors (TKIs) have emerged as effective therapies in treating cancer by exploiting this kinase dependency. The TKI erlotinib targets the epidermal growth factor receptor (EGFR), whereas sunitinib targets primarily vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR).TKIs that impact the function of non-malignant cells and have on- and off-target toxicities, including cardiotoxicities...
June 22, 2017: Metabolites
https://www.readbyqxmd.com/read/28640116/distribution-of-somatic-mutations-of-cancer-related-genes-according-to-microsatellite-instability-status-in-korean-gastric-cancer
#12
Joonhong Park, Han Mo Yoo, Woori Jang, Soyoung Shin, Myungshin Kim, Yonggoo Kim, Seung-Woo Lee, Jeong Goo Kim
In studies of the molecular basis of gastric cancer (GC), microsatellite instability (MSI) is one of the key factors. Somatic mutations found in GC are expected to contribute to MSI-high (H) tumorigenesis. We estimated somatic mutation distribution according to MSI status in 52 matched pair GC samples using the Ion Torrent Ion S5 XL with the AmpliSeq Cancer Hotspot panel.Seventy-five (9.8%) somatic variants consisting of 34 hotspot mutations and 41 other likely pathogenic variants were identified in 34 GC samples...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28639751/gefitinib-or-erlotinib-in-previously-treated-non-small-cell-lung-cancer-patients-a-cohort-study-in-taiwan
#13
Chia-Hao Chang, Chih-Hsin Lee, Jen-Chung Ko, Lih-Yu Chang, Ming-Chia Lee, Jann-Yuan Wang, Chong-Jen Yu
Among treatment modalities for lung cancer, the most promising therapy is the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Both erlotinib and gefitinib, the two first-generation EGFR-TKIs, exhibit significant clinical responses for patients with lung adenocarcinoma. However, few studies have compared the effects of these two drugs, and results have been inconclusive because of the small sample sizes in these studies. Therefore, this study was conducted to investigate this issue...
June 22, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28639239/significant-improvement-in-detecting-braf-kras-and-egfr-mutations-using-next-generation-sequencing-as-compared-with-fda-cleared-kits
#14
Wanlong Ma, Steven Brodie, Sally Agersborg, Vincent A Funari, Maher Albitar
INTRODUCTION: We compared mutations detected in EGFR, KRAS, and BRAF genes using next-generation sequencing (NGS) and confirmed by Sanger sequencing with mutations that could be detected by FDA-cleared testing kits. METHODS: Paraffin-embedded tissue from 822 patients was tested for mutations in EGFR, KRAS, and BRAF by NGS. Sanger sequencing of hot spots was used with locked nucleic acid to increase sensitivity for specific hot-spot mutations. This included 442 (54%) lung cancers, 168 (20%) colorectal cancers, 29 (4%) brain tumors, 33 (4%) melanomas, 14 (2%) thyroid cancers, and 16% others (pancreas, head and neck, and cancer of unknown origin)...
June 21, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28638266/nuclear-expression-of-gs28-protein-a-novel-biomarker-that-predicts-prognosis-in-colorectal-cancers
#15
Sung Hak Lee, Hyung Jae Yoo, Do Eun Rim, Yinji Cui, Ahwon Lee, Eun Sun Jung, Seung Taek Oh, Jun Gi Kim, Oh-Joo Kwon, Su Young Kim, Seong-Whan Jeong
Aims: GS28 (Golgi SNARE protein, 28 kDa), a member of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) protein family, plays a critical role in mammalian endoplasmic reticulum (ER)-Golgi or intra-Golgi vesicle transport. To date, few researches on the GS28 protein in human cancer tissues have been reported. In this study, we assessed the prognostic value of GS28 in patients with colorectal cancer (CRC). Methods and results: We screened for GS28 expression using immunohistochemistry in 230 surgical CRC specimens...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28637487/the-nf1-somatic-mutational-landscape-in-sporadic-human-cancers
#16
REVIEW
Charlotte Philpott, Hannah Tovell, Ian M Frayling, David N Cooper, Meena Upadhyaya
BACKGROUND: Neurofibromatosis type 1 (NF1: Online Mendelian Inheritance in Man (OMIM) #162200) is an autosomal dominantly inherited tumour predisposition syndrome. Heritable constitutional mutations in the NF1 gene result in dysregulation of the RAS/MAPK pathway and are causative of NF1. The major known function of the NF1 gene product neurofibromin is to downregulate RAS. NF1 exhibits variable clinical expression and is characterized by benign cutaneous lesions including neurofibromas and café-au-lait macules, as well as a predisposition to various types of malignancy, such as breast cancer and leukaemia...
June 21, 2017: Human Genomics
https://www.readbyqxmd.com/read/28637019/clinicopathological-characteristics-of-ros1-and-ret-rearranged-nsclc-in-caucasian-patients-data-from-a-cohort-of-713-non-squamous-nsclc-lacking-kras-egfr-her2-braf-pik3ca-alk-alterations
#17
Frédéric Dugay, Francisco Llamas-Gutierrez, Marjory Gournay, Sarah Medane, François Mazet, Dan Christian Chiforeanu, Emmanuelle Becker, Régine Lamy, Hervé Léna, Nathalie Rioux-Leclercq, Marc-Antoine Belaud-Rotureau, Florian Cabillic
Targeted therapies have substantially changed the management of non-small cell lung cancer (NSCLC) patients with driver oncogenes. Given the high frequency, EGFR and ALK aberrations were the first to be detected and paved the way for tyrosine kinase inhibitor (TKI) treatments. Other kinases such as ROS1 and more recently RET have emerged as promising targets, and ROS1 and RET TKIs are already available for precision medicine.We screened a large cohort of 713 Caucasian non-squamous NSCLC patients lacking EGFR/KRAS/BRAF/HER2/PI3KCA/ALK aberrations for ROS1 and RET rearrangements using fluorescence in situ hybridization to determine the frequency and clinicopathological characteristics of ROS1- and RET-positive patients...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637018/the-efficacy-of-anti-pd-1-pd-l1-therapy-and-its-comparison-with-egfr-tkis-for-advanced-non-small-cell-lung-cancer
#18
REVIEW
Zhixin Sheng, Xu Zhu, Yanhua Sun, Yanxia Zhang
PURPOSE: To better understand the efficacy and safety of anti-PD-1/PD-L1 therapy (atezolizumab, pembrolizumab, nivolumab) in patients with previously treated advanced non-small-cell lung cancer (NSCLC). METHODS: The Cochrane Controlled Trial Register, Embase, Medline, and the Science Citation Index were searched for prospective published reports of atezolizumab, pembrolizumab, nivolumab in previously treated patients with advanced NSCLC. RESULTS: Finally, we identified 14 prospective published reports including four trials of atezolizumab covering 542 subjects, three trials of pembrolizumab covering 1566 subjects, seven trials of nivolumab covering 1678 subjects...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635645/cembrene-diterpenoids-with-ether-linkages-from-sarcophyton-ehrenbergi-an-anti-proliferation-and-molecular-docking-assessment
#19
Mohamed-Elamir F Hegazy, Abdelsamed I Elshamy, Tarik A Mohamed, Ahmed R Hamed, Mahmoud A A Ibrahim, Shinji Ohta, Paul W Paré
Three new cembrene diterpenoids, sarcoehrenbergilid A-C (1-3), along with four known diterpenoids, sarcophine (4), (+)-7α,8β-dihydroxydeepoxysarcophine (5), sinulolide A (6), and sinulolide B (7), and one steroid, sardisterol (8), were isolated and characterized from a solvent extract of the Red Sea soft coral Sarcophyton ehrenbergi. Chemical structures were elucidated by NMR and MS analyses with absolute stereochemistry determined by X-ray analysis. Since these isolated cembrene diterpenes contained 10 or more carbons in a large flexible ring, conformer stabilities were examined based on density functional theory calculations...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28635230/-the-expression-of-programmed-death-receptor-1-in-non-small-cell-lung-cancer-and-its-clinicopathological-features-and-prognosis-showed-a-connection-with-epidermal-growth-factor-receptor-gene-mutations
#20
H Yin, C G Liao, Y Q Wang, Z Li, L L Fan, M L Qian, N Lu
Objective: To investigate the relationships between the expression of programmed death 1 (PD-1) and the epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC). The study also attempted to investigate the clinicopathological features and prognosis in NSCLC patients. Methods: The expression of PD-1 protein in 88 cases of NSCLC tumor tissues and adjacent tissues was detected by immunohistochemistry. The mutations of EGFR in NSCLC were detected by Polymerase Chain Reaction-Amplification Refractory Mutation System(PCR-ARMS) method...
June 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
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