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https://www.readbyqxmd.com/read/28926605/assessment-of-common-somatic-mutations-of-egfr-kras-braf-nras-in-pulmonary-non-small-cell-carcinoma-using-iplex%C3%A2-hs-a-new-highly-sensitive-assay-for-the-massarray%C3%A2-system
#1
Bobbie C Sutton, Ryan T Birse, Kevin Maggert, Tammy Ray, Jessica Hobbs, Amobi Ezenekwe, Jason Kazmierczak, Michael Mosko, Joan Kish, Andrew Bullock, Zonggao Shi, M Sharon Stack, Darryl Irwin
Increased early detection and personalized therapy for lung cancer have coincided with greater use of minimally invasive sampling techniques such as endobronchial ultrasound-guided biopsy (EBUS), endoscopic ultrasound-guided biopsy (EUS), and navigational biopsy, as well as thin needle core biopsies. As many lung cancer patients have late stage disease and other comorbidities that make open surgical procedures hazardous, the least invasive biopsy technique with the highest potential specimen yield is now the preferred first diagnostic study...
2017: PloS One
https://www.readbyqxmd.com/read/28921051/fine-particle-matters-induce-dna-damage-and-g2-m-cell-cycle-arrest-in-human-bronchial-epithelial-beas-2b-cells
#2
Jing Wu, Yanfeng Shi, Collins Otieno Asweto, Lin Feng, Xiaozhe Yang, Yannan Zhang, Hejing Hu, Junchao Duan, Zhiwei Sun
There is compelling evidence that exposure to particulate matter (PM) is linked to lung tumorigenesis. However, there is not enough experimental evidence to support the specific mechanisms of PM2.5-induced DNA damage and cell cycle arrest in lung tumorigenesis. In this study, we investigated the toxic effects and molecular mechanisms of PM2.5 on bronchial epithelial (BEAS-2B) cells. PM2.5 exposure reduced cell viability and enhanced LDH activity. The cell growth curves of BEAS-2B cells decreased gradually with the increase in PM2...
September 18, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28919011/dabrafenib-plus-trametinib-in-patients-with-previously-untreated-braf-v600e-mutant-metastatic-non-small-cell-lung-cancer-an-open-label-phase-2-trial
#3
David Planchard, Egbert F Smit, Harry J M Groen, Julien Mazieres, Benjamin Besse, Åslaug Helland, Vanessa Giannone, Anthony M D'Amelio, Pingkuan Zhang, Bijoyesh Mookerjee, Bruce E Johnson
BACKGROUND: BRAF(V600E) mutation occurs in 1-2% of lung adenocarcinomas and acts as an oncogenic driver. Dabrafenib, alone or combined with trametinib, has shown substantial antitumour activity in patients with previously treated BRAF(V600E)-mutant metastatic non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of dabrafenib plus trametinib treatment in previously untreated patients with BRAF(V600E)-mutant metastatic NSCLC. METHODS: In this phase 2, sequentially enrolled, multicohort, multicentre, non-randomised, open-label study, adults (≥18 years of age) with previously untreated metastatic BRAF(V600E)-mutant NSCLC were enrolled into cohort C from 19 centres in eight countries within North America, Europe, and Asia...
September 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28915716/implementation-and-utilization-of-the-molecular-tumor-board-to-guide-precision-medicine
#4
REVIEW
Shuko Harada, Rebecca Arend, Qian Dai, Jessica A Levesque, Thomas S Winokur, Rongjun Guo, Martin J Heslin, Lisle Nabell, L Burt Nabors, Nita A Limdi, Kevin A Roth, Edward E Partridge, Gene P Siegal, Eddy S Yang
BACKGROUND: With rapid advances in genomic medicine, the complexity of delivering precision medicine to oncology patients across a university health system demanded the creation of a Molecular Tumor Board (MTB) for patient selection and assessment of treatment options. The objective of this report is to analyze our progress to date and discuss the importance of the MTB in the implementation of personalized medicine. MATERIALS AND METHODS: Patients were reviewed in the MTB for appropriateness for comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that were in place...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881815/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
#5
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...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881604/impact-of-country-of-birth-on-genetic-testing-of-metastatic-lung-adenocarcinomas-in-france-african-women-exhibit-a-mutational-spectrum-more-similar-to-asians-than-to-caucasians
#6
Raphael Saffroy, Jean-François Morère, Nelly Bosselut, Pasquale F Innominato, Jocelyne Hamelin, Jean Trédaniel, Sophie Masse, Véronique Dussaule-Duchatelle, André Balaton, Pierre Validire, Catherine Guettier, Mohamed Bouchahda, Antoinette Lemoine
BACKGROUND: Limited data are available on the prevalence of oncogenic driver mutations in Caucasian populations, and especially in Europeans. AIM: To evaluate the targetable mutational spectra in unselected patients with lung adenocarcinoma in routine clinical practice from several French hospitals, using the same molecular platform. PATIENTS AND METHODS: Samples from 2,219 consecutive patients with histologically-proven advanced lung adenocarcinoma were centrally analysed at a referenced and certified diagnostic platform in order to test for activating and resistance mutations in EGFR, KRAS, BRAF, ERBB2 and PI3KCA...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877978/how-i-manage-pulmonary-langerhans-cell-histiocytosis
#7
Gwenaël Lorillon, Abdellatif Tazi
Pulmonary Langerhans cell histiocytosis (PLCH) is a rare sporadic cystic lung disease of unknown aetiology that is characterised by the infiltration and destruction of the wall of distal bronchioles by CD1a(+) Langerhans-like cells. In adults, PLCH is frequently isolated and affects young smokers of both sexes. Recent multicentre studies have led to the more standardised management of patients in clinical practice. Smoking cessation is essential and is occasionally the only suitable intervention. Serial lung function testing is important because a significant proportion of patients may experience an early decline in forced expiratory volume in 1 s and develop airflow obstruction...
September 30, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28866070/next-generation-sequencing-a-novel-approach-to-distinguish-multifocal-primary-lung-adenocarcinomas-from-intrapulmonary-metastases
#8
Snehal B Patel, Wendy Kadi, Ann E Walts, Alberto M Marchevsky, Andy Pao, Angela Aguiluz, Tudor Mudalige, Zhenqui Liu, Nan Deng, Jean Lopategui
Distinguishing between multiple lung primaries and intrapulmonary metastases is imperative for accurate staging. The American Joint Committee on Cancer (AJCC) criteria are routinely used for this purpose but can yield equivocal conclusions. We evaluated whether next generation sequencing (NGS) using the 50 gene AmpliSeq Cancer Hotspot Panel v2 can be used to facilitate this distinction. NGS was performed on known primary-metastatic pairs (8 patients) and multiple lung adenocarcinomas (11 patients). Primary-metastatic pairs showed high mutational concordance: Seven pairs shared mutations, and 1 was concordant for having no mutations...
August 30, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28862766/genomic-profiles-of-lung-cancer-associated-with-idiopathic-pulmonary-fibrosis
#9
Ji An Hwang, Deokhoon Kim, Sung-Min Chun, SooHyun Bae, Joon Seon Song, Mi Young Kim, Hyun Jung Koo, Jin Woo Song, Woo Sung Kim, Jae Cheol Lee, Hyeong Ryul Kim, Chang-Min Choi, Se Jin Jang
Little is known on the pathogenesis or molecular profiles of idiopathic pulmonary fibrosis-associated lung cancer (IPF-LC). This study was performed to investigate the genomic profiles of IPF-LC and to explore the possibility of defining potential therapeutic targets in IPF-LC. We assessed genomic profiles of IPF-LC using targeted exome sequencing (OncoPanel version 2) in 35 matched tumor/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling was performed using GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively...
September 1, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28857272/acanthoma-planoepitheliale-hyperkeratoticum-lesions-associated-with-braf-inhibitor-in-metastatic-melanoma
#10
M Sokołowska-Wojdyło, B Olszewska, M Sobjanek, M Sławińska, K Sosińska-Mielcarek, W Biernat, R Nowicki
A 68-year-old woman was diagnosed with BRAF V600 mutation positive melanoma of unknown primary (MUP) with metastasis to the lung, liver and brain. According to local standards dabrafenib monotherapy was started in July 2016. Control CT performed after two months revealed disease stabilization. The tolerance of therapy was good, but after 2 months of treatment with dabrafenib the patient developed disseminated skin lesions with extended seborrheic keratosis G2 (according to international common toxicity criteria CTC)...
August 30, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28840016/lung-adenocarcinoma-from-molecular-basis-to-genome-guided-therapy-and-immunotherapy
#11
REVIEW
Roberto Chalela, Víctor Curull, César Enríquez, Lara Pijuan, Beatriz Bellosillo, Joaquim Gea
Although adenocarcinoma (ADC) is the most frequent lung cancer, its diagnosis is often late, when the local invasion is important and/or the metastases have already appeared. Therefore, the mortality at 5 years is still very high, ranging from 51% to 99%, depending on the stage. The implementation of different molecular techniques has allowed genomic studies even in relatively small histological samples such as obtained with non-invasive or minimally invasive techniques, facilitating a better phenotyping of lung ADC...
July 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28840008/differences-between-low-and-high-grade-fetal-adenocarcinoma-of-the-lung-a-clinicopathological-and-molecular-study
#12
Jing Zhang, Jian Sun, Xiao-Long Liang, Jun-Liang Lu, Yu-Feng Luo, Zhi-Yong Liang
BACKGROUND: Fetal adenocarcinoma of the lung (FLAC) is a rare entity of lung cancer. It is classified into low-grade fetal adenocarcinoma (L-FLAC) and high-grade fetal adenocarcinoma (H-FLAC). We aim to report the clinicopathological and molecular features of FLAC in Chinese patients. METHODS: FLACs were screened from a consecutive lung adenocarcinoma series comprising 920 cases. The clinicopathological features L-FLAC and H-FLAC were retrospectively reviewed via immunohistochemical study and mutation analysis...
July 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28838394/molecular-profiling-in-italian-patients-with-advanced-non-small-cell-lung-cancer-an-observational-prospective-study
#13
Elisa Gobbini, Domenico Galetta, Marcello Tiseo, Paolo Graziano, Antonio Rossi, Emilio Bria, Massimo Di Maio, Giulio Rossi, Vanesa Gregorc, Ferdinando Riccardi, Vieri Scotti, Anna Ceribelli, Lucio Buffoni, Angelo Delmonte, Tindara Franchina, Maria Rita Migliorino, Diego Cortinovis, Salvatore Pisconti, Paola Bordi, Annamaria Catino, Evaristo Maiello, Francesca Arizio, Silvia Novello
OBJECTIVES: Molecular profiling of advanced non-small-cell lung cancer (NSCLC) is recommended according to European and Italian guidelines. However, molecular routine assessment remains still heterogeneous. This observational study aimed to take a picture of the real clinical practice in molecular testing and therapeutic choices in advanced Italian NSCLCs. MATERIALS AND METHODS: This study prospectively enrolled newly diagnosed advanced or recurrent NSCLCs referred to 38 Italian centres, from November 2014 to November 2015...
September 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28834810/braf-v600e-mutations-occur-in-a-subset-of-glomus-tumors-and-are-associated-with-malignant-histologic-characteristics
#14
Nooshin Karamzadeh Dashti, Armita Bahrami, Seung J Lee, Sarah M Jenkins, Fausto J Rodriguez, Andrew L Folpe, Jennifer M Boland
Glomus tumors are rare mesenchymal neoplasms with a phenotype akin to the modified smooth muscle cells of the glomus body. Most are benign, but rare examples show malignant histologic characteristics and aggressive behavior. We recently encountered a malignant glomus tumor with BRAF V600E mutation. We sought to study a large cohort for this mutation, with particular attention to associated malignant histologic characteristics. Tumors were classified based on WHO criteria as benign, uncertain malignant potential (glomus tumors of uncertain malignant potential-GT-UMP), or malignant...
August 22, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28830562/ciliated-muconodular-papillary-tumors-of-the-lung-with-kras-braf-akt1-mutation
#15
Emiko Udo, Bungo Furusato, Kazuko Sakai, Leah M Prentice, Tomonori Tanaka, Yuka Kitamura, Tomoshi Tsuchiya, Naoya Yamasaki, Takeshi Nagayasu, Kazuto Nishio, Junya Fukuoka
BACKGROUND: Ciliated muconodular papillary tumors (CMPTs) are newly recognized rare peripheral lung nodules that are histologically characterized by ciliated columnar, goblet, and basal cells. Although recent studies have shown that CMPTs constitute a neoplastic disease, the complete histogenesis of CMPTs is not fully understood and molecular data are limited. METHODS: We reviewed four cases of CMPT and performed immunohistochemical and genomic analyses to establish CMPT profiles...
August 22, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28821955/targeted-next-generation-sequencing-for-analyzing-the-genetic-alterations-in-atypical-adenomatous-hyperplasia-and-adenocarcinoma-in-situ
#16
Xuan Xu, Na Li, Ruiying Zhao, Lei Zhu, Jinchen Shao, Jie Zhang
PURPOSE: Atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) have been defined as preinvasive pulmonary adenocarcinoma lesions according to the 2015 World Health Organization lung adenocarcinoma classification. We aimed to search for the most common gene mutations in patients with AAH and AIS and investigate the distinctions between the two groups at the molecular level. METHODS: We performed targeted next-generation sequencing on 18 cases with AAH and 28 cases with AIS to screen for mutations with the Ion Torrent Oncomine Solid Tumor DNA panel...
August 18, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28811082/correlation-between-molecular-analysis-diagnosis-according-to-the-2015-who-classification-of-unresected-lung-tumours-and-ttf1-expression-in-small-biopsies-and-cytology-specimens-from-344-non-small-cell-lung-carcinoma-patients
#17
Prudence A Russell, Toni-Maree Rogers, Benjamin Solomon, Naveed Alam, Stephen A Barnett, Vivek Rathi, Richard A Williams, Gavin M Wright, Matthew Conron
We investigated correlations between diagnosis according to the 2015 World Health Organization (WHO) classification of unresected lung tumours, molecular analysis and TTF1 expression in small biopsy and cytology specimens from 344 non-small cell lung carcinoma (NSCLC) patients. One case failed testing for EGFR, KRAS and ALK abnormalities and six had insufficient tumour for ALK testing. Overall mutation rate in 343 cases was 48% for the genes tested, with 19% EGFR, 33% KRAS and 4% BRAF mutations, and 5% ALK rearrangements detected...
August 12, 2017: Pathology
https://www.readbyqxmd.com/read/28783725/a-braf-kinase-inactive-mutant-induces-lung-adenocarcinoma
#18
Patricia Nieto, Chiara Ambrogio, Laura Esteban-Burgos, Gonzalo Gómez-López, María Teresa Blasco, Zhan Yao, Richard Marais, Neal Rosen, Roberto Chiarle, David G Pisano, Mariano Barbacid, David Santamaría
The initiating oncogenic event in almost half of human lung adenocarcinomas is still unknown, a fact that complicates the development of selective targeted therapies. Yet these tumours harbour a number of alterations without obvious oncogenic function including BRAF-inactivating mutations. Inactivating BRAF mutants in lung predominate over the activating V600E mutant that is frequently observed in other tumour types. Here we demonstrate that the expression of an endogenous Braf(D631A) kinase-inactive isoform in mice (corresponding to the human BRAF(D594A) mutation) triggers lung adenocarcinoma in vivo, indicating that BRAF-inactivating mutations are initiating events in lung oncogenesis...
August 10, 2017: Nature
https://www.readbyqxmd.com/read/28783719/tumours-with-class-3-braf-mutants-are-sensitive-to-the-inhibition-of-activated-ras
#19
Zhan Yao, Rona Yaeger, Vanessa S Rodrik-Outmezguine, Anthony Tao, Neilawattie M Torres, Matthew T Chang, Matthias Drosten, Huiyong Zhao, Fabiola Cecchi, Todd Hembrough, Judith Michels, Hervé Baumert, Linde Miles, Naomi M Campbell, Elisa de Stanchina, David B Solit, Mariano Barbacid, Barry S Taylor, Neal Rosen
Approximately 200 BRAF mutant alleles have been identified in human tumours. Activating BRAF mutants cause feedback inhibition of GTP-bound RAS, are RAS-independent and signal either as active monomers (class 1) or constitutively active dimers (class 2). Here we characterize a third class of BRAF mutants-those that have impaired kinase activity or are kinase-dead. These mutants are sensitive to ERK-mediated feedback and their activation of signalling is RAS-dependent. The mutants bind more tightly than wild-type BRAF to RAS-GTP, and their binding to and activation of wild-type CRAF is enhanced, leading to increased ERK signalling...
August 2, 2017: Nature
https://www.readbyqxmd.com/read/28782530/chemotherapeutics-resistance-arms-race-an-update-on-mechanisms-involved-in-resistance-limiting-egfr-inhibitors-in-lung-cancer
#20
REVIEW
Pankaj Kumar Singh, Om Silakari
Clinical reports suggest that EGFR-mutated lung cancer usually respond significantly towards small molecule tyrosine kinase inhibitors. Same studies also report the eventual development of acquired resistance within a median time interval of 9 to 14months. One of the major mechanisms involved in this acquired resistance was found to be a secondary point mutation at gate-keeper residue, EGFR T790M. However, there are other recent studies which disclose the role of few other novel key players such as, ZEB1, TOPK etc...
October 1, 2017: Life Sciences
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