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https://www.readbyqxmd.com/read/28333239/small-bowel-carcinomas-in-coeliac-or-crohn-s-disease-clinico-pathological-molecular-and-prognostic-features-a-study-from-the-small-bowel-cancer-italian-consortium
#1
Alessandro Vanoli, Antonio Di Sabatino, Daniela Furlan, Catherine Klersy, Federica Grillo, Roberto Fiocca, Claudia Mescoli, Massimo Rugge, Gabriella Nesi, Paolo Fociani, Gianluca Sampietro, Sandro Ardizzone, Ombretta Luinetti, Antonio Calabrò, Francesco Tonelli, Umberto Volta, Donatella Santini, Giacomo Caio, Paolo Giuffrida, Luca Elli, Stefano Ferrero, Giovanni Latella, Antonio Ciardi, Roberto Caronna, Gaspare Solina, Aroldo Rizzo, Carolina Ciacci, Francesco P D'Armiento, Marianna Salemme, Vincenzo Villanacci, Renato Cannizzaro, Vincenzo Canzonieri, Luca Reggiani Bonetti, Livia Biancone, Giovanni Monteleone, Augusto Orlandi, Giuseppe Santeusanio, Maria C Macciomei, Renata D'Incà, Vittorio Perfetti, Giancarlo Sandri, Marco Silano, Ada M Florena, Antonino G Giannone, Claudio Papi, Luigi Coppola, Paolo Usai, Antonio Maccioni, Marco Astegiano, Paola Migliora, Rachele Manca, Michele Martino, Davide Trapani, Roberta Cerutti, Paola Alberizzi, Roberta Riboni, Fausto Sessa, Marco Paulli, Enrico Solcia, Gino R Corazza
Background and Aims.: An increased risk of small bowel carcinoma (SBC) has been reported in coeliac disease (CD) and Crohn's disease (CrD). We explored clinico-pathologic, molecular and prognostic features of CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) in comparison with sporadic SBC (spo-SBC). Methods.: Seventy-six patients undergoing surgical resection for non-familial SBC (26 CD-SBC, 25 CrD-SBC, 25 spo-SBC) were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability (MSI) and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations...
February 24, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28332309/effects-of-mir-145-5p-through-nras-on-the-cell-proliferation-apoptosis-migration-and-invasion-in-melanoma-by-inhibiting-mapk-and-pi3k-akt-pathways
#2
Sha Liu, Guozhen Gao, Dexiong Yan, Xiangjun Chen, Xingwei Yao, Shuzhong Guo, Guirong Li, Yu Zhao
We aimed to detect the effects of miR-145-5p on the cell proliferation, apoptosis, migration, and invasion in NRAS-mutant, BRAF-mutant, and wild-type melanoma cells, in order to figure out the potential mechanisms and provide a novel therapeutic target of melanoma. RT-qPCR and western blot were used to detect the expression of miR-145-5p and NRAS in melanoma tumor tissues and cells, respectively. Luciferase assay was performed to determine whether miR-145-5p directly targeted NRAS. After transfecting miR-145-5p mimics, miR-145-5p inhibitors, NRAS cDNA and NRAS siRNA into CHL-1, VMM917 and SK-mel-28 cells, functional assays were used to detect the proliferation, apoptosis, invasion and migration, including MTT, flow cytometry, Transwell and wound healing assays...
March 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28326956/clinical-pathologic-and-genetic-features-of-wilms-tumors-with-wtx-gene-mutation
#3
Sanda Alexandrescu, Sara Akhavanfard, Marian H Harris, Sara O Vargas
Clinical and pathologic features of patients with WTX-mutated Wilms tumor (WT) have not been studied in detail. We characterize the clinical and pathologic findings in WT with WTX abnormalities and provide comparison with WT without WTX mutation. Clinical, gross, and microscopic features in 35 patients with WT were examined. Karyotype was examined in a subset of cases. All cases had been previously analyzed for WTX, WT1, and CTNNB1 aberrations via array comparative genomic hybridization; OncoMap 4 high throughput genotyping was performed on 18 cases...
March 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28325255/mucosal-melanoma-of-the-head-and-neck
#4
REVIEW
Paolo Antonio Ascierto, Remo Accorona, Gerardo Botti, Davide Farina, Piero Fossati, Gemma Gatta, Helen Gogas, Davide Lombardi, Roberto Maroldi, Piero Nicolai, Marco Ravanelli, Vito Vanella
Mucosal melanoma of the head and neck is a very rare and aggressive malignancy with a very poor prognosis. The nasal cavity, paranasal sinuses, and oral cavity are the most common locations. One-, 3- and 5-year survival rates between 2000 and 2007 were 63%, 30% and 20%, respectively. Cigarette smoking seems to be a risk factor even though the evidence for this is very low. Clinical signs and symptoms are usually nonspecific. While surgery is considered the mainstay of treatment for most mucosal melanomas of the head and neck region, radiotherapy has a role in local control of the disease after surgery...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28323937/tert-braf-and-nras-in-primary-thyroid-cancer-and-metastatic-disease
#5
Miguel Melo, Adriana Gaspar da Rocha, Rui Batista, João Vinagre, Maria João Martins, Gracinda Costa, Cristina Ribeiro, Francisco Carrilho, Valeriano Leite, Cláudia Lobo, José Manuel Cameselle-Teijeiro, Bruno Cavadas, Luísa Pereira, Manuel Sobrinho-Simões, Paula Soares
Context: Little is known about the frequency of key mutations in thyroid cancer metastases and its relationship with the primary tumor genotype. Objectives: To evaluate the frequency of TERT promoter (TERTp), BRAF and NRAS mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors, lymph node metastases (LNM) and distant metastases. Design and patients: Mutation analysis was performed in 437 tissue samples from 204 patients, mainly with papillary thyroid carcinomas (PTC) (n=180), including 196 LNM and 56 distant metastases...
March 6, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28314739/intratumorous-heterogeneity-for-ras-mutations-in-a-treatment-na%C3%A3-ve-colorectal-tumour
#6
Sebastian Lunke, Belinda Lee, Sevastjan Kranz, Peter Gibbs, Paul Waring, Michael Christie
Activating mutations in KRAS and NRAS genes in patients with colorectal cancer (CRC) are associated with a lack of response to treatment with anti-epidermal growth factor receptor (EGFR) therapies. Mutations in these genes are thought to be mutually exclusive, however reports have described CRCs with two activating rat sarcoma (RAS) mutations. This has fuelled discussion about whether these mutations are the result of intratumorous heterogeneity, or if they are co-occurring in the same cancer cell clone. We present a case of a colorectal tumour with three RAS mutations detected during routine diagnostic testing...
March 17, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28314085/targeted-next-generation-sequencing-and-identification-of-risk-factors-in-world-health-organization-defined-atypical-chronic-myeloid-leukemia
#7
Mrinal M Patnaik, Daniela Barraco, Terra L Lasho, Christy M Finke, Kaaren Reichard, Katherine P Hoversten, Rhett P Ketterling, Naseema Gangat, Ayalew Tefferi
Atypical chronic myeloid leukemia (aCML) is an aggressive myeloid neoplasm with overlapping features of myelodysplastic syndromes (prominent granulocytic dysplasia) and myeloproliferative neoplasms (neutrophilic leukocytosis). We studied 25 molecularly-annotated and World Health Organization defined aCML patients; median age 70 years, 84% males. Cytogenetic abnormalities were seen in 36% and gene mutations in 100%. Mutational frequencies were, ASXL1 28%, TET2 16%, NRAS 16%, SETBP1 12%, RUNX1 12%, ETNK1 8% and PTPN11 4%...
March 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28297630/genomics-of-multiple-myeloma
#8
Sebastien Robiou du Pont, Alice Cleynen, Charlotte Fontan, Michel Attal, Nikhil Munshi, Jill Corre, Hervé Avet-Loiseau
Multiple myeloma (MM) is characterized by wide variability in the chromosomal/genetic changes present in tumor plasma cells. Genetically, MM can be divided into two groups according to ploidy and hyperdiploidy versus nonhyperdiploidy. Several studies in gene expression profiling attempted to identify subentities in MM without convincing results. These studies mostly confirmed the cytogenetic data and subclassified patients according to 14q32 translocations and ploidy. More-recent data that are based on whole-exome sequencing have confirmed this heterogeneity and show many gene mutations but without a unifying mutation...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28292978/validating-a-fully-automated-real-time-pcr-based-system-for-use-in-the-molecular-diagnostic-analysis-of-colorectal-carcinoma-a-comparison-with-ngs-and-ihc
#9
Richard Colling, Lai Mun Wang, Elizabeth Soilleux
BACKGROUND: Molecular testing is increasingly needed in colorectal carcinoma (CRC) and the current clinically relevant mutations are in BRAF, KRAS and NRAS. This study aimed to further validate a new alternative polymerase chain reaction (PCR) platform (Idylla, Biocartis) against existing next-generation sequencing (NGS) and immunohistochemistry (IHC) assays. METHODS: 56 Idylla tests were performed on 43 CRC cases, in a total of 74 comparisons against an NGS panel (Ion Torrent) and the VE1 (anti-BRAF) antibody IHC...
March 14, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28284558/a-step-forward-for-patients-with-nras-mutant-melanoma
#10
Michael A Postow, Paul B Chapman
No abstract text is available yet for this article.
March 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28284557/binimetinib-versus-dacarbazine-in-patients-with-advanced-nras-mutant-melanoma-nemo-a-multicentre-open-label-randomised-phase-3-trial
#11
Reinhard Dummer, Dirk Schadendorf, Paolo A Ascierto, Ana Arance, Caroline Dutriaux, Anna Maria Di Giacomo, Piotr Rutkowski, Michele Del Vecchio, Ralf Gutzmer, Mario Mandala, Luc Thomas, Lev Demidov, Claus Garbe, David Hogg, Gabriella Liszkay, Paola Queirolo, Ernesto Wasserman, James Ford, Marine Weill, L Andres Sirulnik, Valentine Jehl, Viviana Bozón, Georgina V Long, Keith Flaherty
BACKGROUND: There are no established therapies specific for NRAS-mutant melanoma despite the emergence of immunotherapy. We aimed to assess the efficacy and safety of the MEK inhibitor binimetinib versus that of dacarbazine in patients with advanced NRAS-mutant melanoma. METHODS: NEMO is an ongoing, randomised, open-label phase 3 study done at 118 hospitals in 26 countries. Patients with advanced, unresectable, American Joint Committee on Cancer stage IIIC or stage IV NRAS-mutant melanoma who were previously untreated or had progressed on or after previous immunotherapy were randomised (2:1) to receive either binimetinib 45 mg orally twice daily or dacarbazine 1000 mg/m(2) intravenously every 3 weeks...
March 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28280605/next-generation-sequencing-identifies-interactome-signatures-in-relapsed-and-refractory-metastatic-colorectal-cancer
#12
Benny Johnson, Laurence Cooke, Daruka Mahadevan
BACKGROUND: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. METHODS: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28278423/digoxin-plus-trametinib-therapy-achieves-disease-control-in-braf-wild-type-metastatic-melanoma-patients
#13
Arthur E Frankel, Ugur Eskiocak, Jennifer G Gill, Stacy Yuan, Vijayashree Ramesh, Thomas W Froehlich, Chul Ahn, Sean J Morrison
This is the first prospective study of a combination therapy involving a cardenolide and a MEK inhibitor for metastatic melanoma. Whereas BRAF mutant melanomas can exhibit profound responses to treatment with BRAF and MEK inhibitors, there are fewer options for BRAF wild-type melanomas. In preclinical studies, we discovered that cardenolides synergize with MEK inhibitor to promote the regression of patient-derived xenografts irrespective of BRAF mutation status. We therefore conducted a phase 1B study of digoxin 0...
March 6, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28277830/can-binimetinib-encorafenib-and-masitinib-be-more-efficacious-than-currently-available-mutation-based-targeted-therapies-for-melanoma-treatment
#14
Megan C Turner, Kara Rossfeld, April K S Salama, Douglas Tyler, Georgia Beasley
Historically, there were few effective and durable treatments for metastatic melanoma. Recently, mutation based targeted therapies have revolutionized treatment and outcomes for patients with metastatic melanoma. Specifically, inhibitors aimed at BRAF, NRAS, and C-KIT mutations are now commonly used in treatment for patients harboring the specific mutations. Areas covered: A brief review of current BRAF, NRAS, and C-KIT inhibitors provides background for a thorough review of newly developed agents namely binimetinib, a MEK inhibitor, encorafenib a BRAF inhibitor, and masitinib which inhibits C-KIT...
March 22, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28275037/colon-cancer-version-1-2017-nccn-clinical-practice-guidelines-in-oncology
#15
Al B Benson, Alan P Venook, Lynette Cederquist, Emily Chan, Yi-Jen Chen, Harry S Cooper, Dustin Deming, Paul F Engstrom, Peter C Enzinger, Alessandro Fichera, Jean L Grem, Axel Grothey, Howard S Hochster, Sarah Hoffe, Steven Hunt, Ahmed Kamel, Natalie Kirilcuk, Smitha Krishnamurthi, Wells A Messersmith, Mary F Mulcahy, James D Murphy, Steven Nurkin, Leonard Saltz, Sunil Sharma, David Shibata, John M Skibber, Constantinos T Sofocleous, Elena M Stoffel, Eden Stotsky-Himelfarb, Christopher G Willett, Christina S Wu, Kristina M Gregory, Deborah Freedman-Cass
This portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease. Considerations for treatment selection among 32 different monotherapies and combination regimens in up to 7 lines of therapy have included treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences. Location of the primary tumor, the BRAF mutation status, and tumor microsatellite stability should also be considered in treatment decisions...
March 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28267766/association-of-smad4-mutation-with-patient-demographics-tumor-characteristics-and-clinical-outcomes-in-colorectal-cancer
#16
Amir Mehrvarz Sarshekeh, Shailesh Advani, Michael J Overman, Ganiraju Manyam, Bryan K Kee, David R Fogelman, Arvind Dasari, Kanwal Raghav, Eduardo Vilar, Shanequa Manuel, Imad Shureiqi, Robert A Wolff, Keyur P Patel, Raja Luthra, Kenna Shaw, Cathy Eng, Dipen M Maru, Mark J Routbort, Funda Meric-Bernstam, Scott Kopetz
SMAD4 is an essential mediator in the transforming growth factor-β pathway. Sporadic mutations of SMAD4 are present in 2.1-20.0% of colorectal cancers (CRCs) but data are limited. In this study, we aimed to evaluate clinicopathologic characteristics, prognosis, and clinical outcome associated with this mutation in CRC cases. Data for patients with metastatic or unresectable CRC who underwent genotyping for SMAD4 mutation and received treatment at The University of Texas MD Anderson Cancer Center from 2000 to 2014 were reviewed...
2017: PloS One
https://www.readbyqxmd.com/read/28262927/targeting-the-ras-signaling-pathway-as-a-potential-therapeutic-target-in-the-treatment-of-colorectal-cancer
#17
REVIEW
Afsane Bahrami, Seyed Mahdi Hassanian, Soodabeh ShahidSales, Zahra Farjami, Malihe Hasanzadeh, Kazem Anvari, Amir Aledavood, Mina Maftouh, Gordon A Ferns, Majid Khazaei, Amir Avan
The V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is an important pathways that is frequently dysregulated in colorectal cancer (CRC). It is involved in the modulation of several downstream effectors, that include: Raf/Mek/Erk, PI3K/Akt, RalGDS/p38MAPK and Rac/Rho, and thereby influences tumorigenesis, the invasive behaviors of tumor cell, and resistance to therapy. There is growing evidence exploring the use of drugs that target these pathways in the treatment of CRC. Cetuximab has been approved for CRC patients without a KRAS mutation, or for EGFR-expressing metastatic CRC, although most of the patients have a mutation of KRAS and NRAS...
March 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28262675/genomic-characterisation-of-e%C3%AE-myc-mouse-lymphomas-identifies-bcor-as-a-myc-co-operative-tumour-suppressor-gene
#18
Marcus Lefebure, Richard W Tothill, Elizabeth Kruse, Edwin D Hawkins, Jake Shortt, Geoffrey M Matthews, Gareth P Gregory, Benjamin P Martin, Madison J Kelly, Izabela Todorovski, Maria A Doyle, Richard Lupat, Jason Li, Jan Schroeder, Meaghan Wall, Stuart Craig, Gretchen Poortinga, Don Cameron, Megan Bywater, Lev Kats, Micah D Gearhart, Vivian J Bardwell, Ross A Dickins, Ross D Hannan, Anthony T Papenfuss, Ricky W Johnstone
The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28259104/association-of-oncogenic-mutations-in-patients-with-advanced-cutaneous-squamous-cell-carcinomas-treated-with-cetuximab
#19
Alexandra Picard, Florence Pedeutour, Frédéric Peyrade, Laurence Saudes, Valérie Duranton-Tanneur, Emmanuel Chamorey, Nathalie Cardot-Leccia, Anne Sudaka, Marc Ettaiche, Maxime Benchetrit, Gilles Poissonnet, Nicolas Weinbreck, Bérengère Dadone, Jean-Philippe Lacour, Thierry Passeron, Henri Montaudié
Importance: Cetuximab was recently proposed for advanced cutaneous squamous cell carcinomas (cSCC); however, its efficacy is inconsistent and identification of predictive biomarkers for response is necessary. Objective: To search for somatic mutations of the HRAS, KRAS, NRAS, BRAF, and EGFR genes in patients with advanced cSCC treated with cetuximab; and to investigate the efficacy and tolerance of cetuximab according to these mutations. Design, Setting, and Participants: A multicentric and retrospective study of 31 patients (22 men, 9 women) with histologically confirmed advanced cSCC carried out in 1 department of dermatology and 2 departments of medical oncology in France between January 2008 and December 2014...
March 4, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28255113/-multiple-lncrnas-affect-the-incidence-and-%C3%A2-development-of-melanoma
#20
Han Yan, Dan Tan, Pan Xie, Zhaoqian Liu, Xi Li
To find the relationship between long non-coding RNA (lncRNA) based on data mining methods.
 Methods: We use a whole genome mRNA expression data set (GSE15605) from the gene expression ominibus database to find the lncRNAs which relate to melanoma.
 Results: Four lncRNAs (LINC01213, PGM5-AS1, LINC01133 and LOC284578) were significantly associated with the incidence and development of melanoma. Meanwhile, LINC01213, LINC01133 and LOC284578 were correlated with BRAF mutation, and PGM5-AS1 was related to NRAS mutation...
February 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
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