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https://www.readbyqxmd.com/read/29683947/encephalocraniocutaneous-lipomatosis
#1
Abhishek Bavle, Rikin Shah, Naina Gross, Theresa Gavula, Alejandro Ruiz-Elizalde, Klaas Wierenga, Rene McNall-Knapp
A 5-year-old boy presented with worsening headaches for 3 months. On examination, he was found to have a hairless fatty tissue nevus of the scalp (nevus psiloliparus), subcutaneous soft tissue masses on the right side of his face, neck, mandible and right buttock and epibulbar dermoid of the right eye (choristoma) (Figs. 1A, B). Magnetic resonance imaging revealed a large suprasellar mass, which was debulked and found to be a pilocytic astrocytoma. Testing was not performed for the BRAF/KIAA1549 fusion or BRAFV600E mutation...
April 20, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29682243/frequency-of-nras-gene-mutation-in-wild-type-kras-and-braf-colorectal-cancers-a-single-center-study
#2
Hooria Momenzadeh, Mitra Mirzai, Zahra Jowkar, Bita Geramizadeh
BACKGROUND Incidence of colorectal cancer is increasing in countries such as Iran. Molecular biomarkers play very important role in the diagnosis, treatment, and prognosis of this cancer. Mutation in the RAS family (including KRAS and NRAS) is one of these important molecular biomarkers, which should be tested before starting treatment with anti-EGRF (Epidermal growth factor) drugs. Objectives: There has been very few reports about the frequency of NRAS mutation from Iran and no study from south of the country...
January 2018: Middle East Journal of Digestive Diseases
https://www.readbyqxmd.com/read/29674508/combined-braf-and-hsp90-inhibition-in-patients-with-unresectable-braf-v600e-mutant-melanoma
#3
Zeynep Eroglu, Yian Ann Chen, Geoffrey T Gibney, Jeffrey S Weber, Ragini R Kudchadkar, Nikhil I Khushalani, Joseph Markowitz, Andrew S Brohl, Leticia F Tetteh, Howida Ramadan, Gina Arnone, Jiannong Li, Xiuhua Zhao, Ritin Sharma, Lancia N F Darville, Bin Fang, Inna Smalley, Jane L Messina, John M Koomen, Vernon K Sondak, Keiran S M Smalley
PURPOSE: BRAF inhibitors are clinically active in patients with advanced BRAFV600 -mutant melanoma, although acquired resistance remains common. Preclinical studies demonstrated that resistance could be overcome using concurrent treatment with the HSP90 inhibitor XL888. METHODS: Vemurafenib (960 mg PO BID) combined with escalating doses of XL888 (30, 45, 90 or 135 mg PO twice weekly) was investigated in 21 patients with advanced BRAFV600 -mutant melanoma. Primary endpoints were safety and determination of a maximum tolerated dose...
April 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29672836/pathogenic-and-targetable-genetic-alterations-in-70-urachal-adenocarcinomas
#4
Henning Reis, Kristan E van der Vos, Christian Niedworok, Thomas Herold, Orsolya Módos, Attila Szendrői, Thomas Hager, Marc Ingenwerth, Daniël J Vis, Mark A Behrendt, Jeroen de Jong, Michiel S van der Heijden, Benoit Peyronnet, Romain Mathieu, Marcel Wiesweg, Jason Ablat, Krzysztof Okon, Yuri Tolkach, David Keresztes, Nikolett Nagy, Felix Bremmer, Nadine T Gaisa, Piotr Chlosta, Joerg Kriegsmann, Ilona Kovalszky, József Timar, Glen Kristiansen, Heinz-Joachim Radzun, Ruth Knüchel, Martin Schuler, Peter Black, Herbert Rübben, Boris Hadaschik, Kurt Werner Schmid, Bas W G van Rhijn, Péter Nyirády, Tibor Szarvas
Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy. We therefore subjected 70 urachal adenocarcinomas to targeted next-generation sequencing, conducted in situ and immunohistochemical analyses (including PD-L1 and DNA mismatch repair proteins (MMR)) and evaluated the microsatellite instability (MSI) status...
April 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29666465/molecular-epidemiology-of-lung-cancer-in-iran-implications-for-drug-development-and-cancer-prevention
#5
REVIEW
Zahra Fathi, Nicholas L Syn, Jian-Guo Zhou, Raheleh Roudi
Epidemiological studies undertaken over the past decades reveal a gradual but progressive increase in the incidence and mortality attributable to lung cancer in the Islamic Republic of Iran, a sovereign state geographically situated at the crossroads of Central Eurasia and Western Asia. We identified references published in English and Persian through searches of PubMed, EMBASE, Web of Science, Scopus, and the Scientific Information Database (SID)-a specialized Iranian database, which indexes Iranian scientific journals-between inception and 15 September 2017...
April 18, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29660527/the-association-between-mutations-in-braf-and-colorectal-cancer-specific-survival-depends-on-microsatellite-status-and-tumor-stage
#6
Hendrik Bläker, Elizabeth Alwers, Alexander Arnold, Esther Herpel, Katrin E Tagscherer, Wilfried Roth, Lina Jansen, Viola Walter, Matthias Kloor, Jenny Chang-Claude, Hermann Brenner, Michael Hoffmeister
BACKGROUND & AIMS: Colorectal tumors with mutations in BRAF and microsatellite stability (MSS) have been associated with adverse outcomes of patients. Combined tests for microsatellite instability (MSI-H) and BRAF mutations might therefore be used in risk assessment, particularly for patients with stage II tumors. We investigate the stage-specific prognostic value of combined testing for MSI-H and BRAF for patients with colorectal cancer (CRC). METHODS: We performed a retrospective analysis of colorectal tumor samples collected from 1995 patients at 22 hospitals in Germany, between 2003 and 2010...
April 13, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29658453/-braf-v600e-mutation-and-its-clinical-significance-in-children-with-langerhans-cell-histiocytosis
#7
Xue Tang, Xia Guo, Lin-Yong Sun, Yuan Ai, Xue Yang, Jing-Jing Sun, Jian-Rong Wu, Ju Gao
OBJECTIVE: To investigate the clinical significance of BRAF-V600E mutation in children with Langerhans cell histiocytosis (LCH). METHODS: Real-time fluorescence quantitative PCR was used to detect BRAF-V600E mutation in paraffin-embedded tissue samples from 26 children with LCH. A retrospective analysis was performed for the association of BRAF-V600E mutation with clinical features and prognosis of children with LCH. RESULTS: Of the 26 children, 25 received standard chemotherapy, with a 2-year overall survival (OS) rate of 100% and a 2-year event-free survival (EFS) rate of 88%...
April 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29653212/improving-classification-of-melanocytic-nevi-braf-v600e-expression-associated-with-distinct-histomorphologic-features
#8
Maija Kiuru, Danielle M Tartar, Lihong Qi, Danyang Chen, Lan Yu, Thomas Konia, John D McPherson, William J Murphy, Maxwell A Fung
BACKGROUND: A subset of melanomas carrying a BRAF V600E mutation, the most common targetable mutation in melanoma, arises in association with a melanocytic nevus also harboring a BRAF V600E mutation. The detailed histomorphologic characteristics of BRAF V600E-positive nevi are not systematically documented. OBJECTIVE: To identify histomorphologic features correlating with BRAF V600E status in nevi. METHODS: We retrospectively identified melanocytic nevi from our laboratory reporting system...
April 10, 2018: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29628290/the-immune-landscape-of-cancer
#9
Vésteinn Thorsson, David L Gibbs, Scott D Brown, Denise Wolf, Dante S Bortone, Tai-Hsien Ou Yang, Eduard Porta-Pardo, Galen F Gao, Christopher L Plaisier, James A Eddy, Elad Ziv, Aedin C Culhane, Evan O Paull, I K Ashok Sivakumar, Andrew J Gentles, Raunaq Malhotra, Farshad Farshidfar, Antonio Colaprico, Joel S Parker, Lisle E Mose, Nam Sy Vo, Jianfang Liu, Yuexin Liu, Janet Rader, Varsha Dhankani, Sheila M Reynolds, Reanne Bowlby, Andrea Califano, Andrew D Cherniack, Dimitris Anastassiou, Davide Bedognetti, Arvind Rao, Ken Chen, Alexander Krasnitz, Hai Hu, Tathiane M Malta, Houtan Noushmehr, Chandra Sekhar Pedamallu, Susan Bullman, Akinyemi I Ojesina, Andrew Lamb, Wanding Zhou, Hui Shen, Toni K Choueiri, John N Weinstein, Justin Guinney, Joel Saltz, Robert A Holt, Charles E Rabkin, Alexander J Lazar, Jonathan S Serody, Elizabeth G Demicco, Mary L Disis, Benjamin G Vincent, Llya Shmulevich
We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis...
April 4, 2018: Immunity
https://www.readbyqxmd.com/read/29626621/first-in-human-phase-i-study-of-ac0010-a-mutant-selective-egfr-inhibitor-in-non-small-cell-lung-cancer-safety-efficacy-and-potential-mechanism-of-resistance
#10
Yuxiang Ma, Xin Zheng, Hongyun Zhao, Wenfeng Fang, Yang Zhang, Jieying Ge, Lu Wang, Weicong Wang, Ji Jiang, Shaokun Chuai, Zhou Zhang, Wanhong Xu, Xiao Xu, Pei Hu, Li Zhang
INTRODUCTION: AC0010 is a mutation-selective, third-generation EGFR tyrosine kinase inhibitor (TKI). This first-in-human phase I trial determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AC0010 in patients with advanced or recurrent NSCLC and acquired resistance to the first-generation EGFR-TKI. METHODS: Patients received escalating daily doses of AC0010 (50 to 600 mg) throughout 28-day cycles...
April 4, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29622700/hybrid-capture-based-tumor-sequencing-and-copy-number-analysis-to-confirm-origin-of-metachronous-metastases-in-brca1-mutant-cholangiocarcinoma-harboring-a-novel-ywhaz-braf-fusion
#11
Huat C Lim, Meagan Montesion, Thomas Botton, Eric A Collisson, Sarah E Umetsu, Spencer C Behr, John D Gordan, Phil J Stephens, Robin K Kelley
Biliary tract cancers such as cholangiocarcinoma represent a heterogeneous group of cancers that can be difficult to diagnose. Recent comprehensive genomic analyses in large cholangiocarcinoma cohorts have defined important molecular subgroups within cholangiocarcinoma that may relate to anatomic location and etiology [1-4] and may predict responsiveness to targeted therapies in development [5-7]. These emerging data highlight the potential for tumor genomics to inform diagnosis and treatment options in this challenging tumor type...
April 5, 2018: Oncologist
https://www.readbyqxmd.com/read/29618685/-splenic-diffuse-red-pulp-small-b-cell-lymphoma-diagnosed-by-splenectomy-initially-mimicking-hairy-cell-leukemia-japanese-variant
#12
Yukika Yamada, Miyoko Miura, Mayu Tagari, Kazuo Oshimi, Tomokazu Shiragata, Wataru Suga, Tatsurou Takahashi, Kazuyoshi Shimizu, Kouichi Ohshima, Keizou Kajiwara
A 62-year-old man presented to the hospital with thrombocytopenia, and splenomegaly was detected. His blood films prepared by natural air drying revealed medium-sized lymphocytes with unevenly distributed large and small villous projections. The cytoplasm was basophilic, nuclei were oval with clumped chromatin, and nucleoli were absent in most cells. Immune phenotypes CD19+, CD20+, CD11c+, FMC7+, IgM+, and Igκ+ were detected. TRAP stain appeared negative, IgH JH chain genes were monoclonally rearranged, and BRAF V600E mutation was not detected...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29617661/integrated-genomic-analysis-of-the-ubiquitin-pathway-across-cancer-types
#13
Zhongqi Ge, Jake S Leighton, Yumeng Wang, Xinxin Peng, Zhongyuan Chen, Hu Chen, Yutong Sun, Fan Yao, Jun Li, Huiwen Zhang, Jianfang Liu, Craig D Shriver, Hai Hu, Helen Piwnica-Worms, Li Ma, Han Liang
Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atlas, we perform comprehensive molecular characterization of 929 ubiquitin-related genes and 95 deubiquitinase genes. Among them, we systematically identify top somatic driver candidates, including mutated FBXW7 with cancer-type-specific patterns and amplified MDM2 showing a mutually exclusive pattern with BRAF mutations...
April 3, 2018: Cell Reports
https://www.readbyqxmd.com/read/29616327/whole-exome-sequencing-identifies-key-mutated-genes-in-t790m-wildtype-cmet-unamplified-lung-adenocarcinoma-with-acquired-resistance-to-first-generation-egfr-tyrosine-kinase-inhibitors
#14
Chenguang Li, Hailin Liu, Bin Zhang, Liqun Gong, Yanjun Su, Zhenfa Zhang, Changli Wang
PURPOSE: Lung cancer is the leading cause of cancer-related death worldwide. Lung adenocarcinoma harboring EGFR-activating mutations will inevitably acquire resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs). EGFR T790M mutation and cMET amplification are common mechanisms. Further study is needed to explore unknown genomic alterations contributing to drug resistance. METHODS: Tumor and blood samples from 69 stage IIIB-IV NSCLC patients defined as acquired resistance to first-generation EGFR TKIs (gefitinib, erlotinib or ecotinib) were collected...
April 3, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29616135/egfr-inhibition-enhances-the-antitumor-efficacy-of-a-selective-braf-v600e-inhibitor-in-thyroid-cancer-cell-lines
#15
Yongsheng Jia, Cuicui Zhang, Chuanxiang Hu, Yang Yu, Xiangqian Zheng, Yigong Li, Ming Gao
BRAF V600E is the most common genetic alteration in thyroid cancer and is indicative of a relatively poor prognosis. A selective inhibitor of BRAF V600E has been proposed as a novel treatment for patients with thyroid cancer exhibiting BRAF V600E mutations. However, this inhibitor has demonstrated a limited therapeutic effect. In the present study, possible adaptive mechanisms of resistance of thyroid cancer cells to the specific BRAF V600E inhibitor, PLX4032, were investigated. MTT assays were performed to determine the anti-proliferative efficiencies and half maximal inhibitory concentration (IC50 ) of inhibitory treatments...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29615337/immunohistochemical-and-molecular-genetic-study-on-epithelioid-glioblastoma-series-of-seven-cases-with-review-of-literature
#16
Gaurav Khanna, Pankaj Pathak, Vaishali Suri, Mehar Chand Sharma, Sujata Chaturvedi, Arvind Ahuja, M Bhardwaj, Ajay Garg, Chitra Sarkar, Rajeev Sharma
Epithelioid glioblastoma (e-gbm) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of CNStumors. About half of these tumors show characteristic BRAF-V600E mutation. However, unlike conventional GBMs, e-gbm lack specific diagnostic and prognostic markers. Hence, we aimed to molecularly characterize these tumors. An extensive review of literature was performed.In a multi-institutional effort, all the cases of glioblastoma of year 2017 were reviewed...
March 22, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29599670/dermoscopic-assessment-of-skin-toxicities-in-patients-with-melanoma-during-treatment-with-vemurafenib
#17
Marcin Rajczykowski, Grazyna Kaminska-Winciorek, Elzbieta Nowara, Marzenna Samborska-Plewicka, Sebastian Giebel
Introduction: The use of vemurafenib in melanoma has improved the survival of patients; however, it is associated with skin toxicities. Aim: To assess skin toxicities by dermoscopy in patients treated with vemurafenib. Material and methods: Eight patients with BRAF V600 mutation positive metastatic melanoma were examined dermoscopically during vemurafenib treatment. All skin lesions occurring during therapy were assessed clinically and dermoscopically using a hand-held dermoscope with polarised and non-polarised light...
February 2018: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/29596542/assessment-of-tumor-sequencing-as-a-replacement-for-lynch-syndrome-screening-and-current-molecular-tests-for-patients-with-colorectal-cancer
#18
Heather Hampel, Rachel Pearlman, Mallory Beightol, Weiqiang Zhao, Daniel Jones, Wendy L Frankel, Paul J Goodfellow, Ahmet Yilmaz, Kristin Miller, Jason Bacher, Angela Jacobson, Electra Paskett, Peter G Shields, Richard M Goldberg, Albert de la Chapelle, Brian H Shirts, Colin C Pritchard
Importance: Universal tumor screening for Lynch syndrome (LS) in colorectal cancer (CRC) is recommended and involves up to 6 sequential tests. Somatic gene testing is performed on stage IV CRCs for treatment determination. The diagnostic workup for patients with CRC could be simplified and improved using a single up-front tumor next-generation sequencing test if it has higher sensitivity and specificity than the current screening protocol. Objective: To determine whether up-front tumor sequencing (TS) could replace the current multiple sequential test approach for universal tumor screening for LS...
March 29, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29589315/molecular-testing-for-the-treatment-of-advanced-colorectal-cancer-an-overview
#19
Patrick S Lin, Thomas J Semrad
Concurrent with an expansion in the number of agents available for the treatment of advanced CRC, there has been an increase in our understanding of selection biomarkers to optimize the management of patients with this disease. For CRC patients being considered for anti-EGFR therapy, expanded RAS testing is the standard of care to determine the subset of patients who can benefit from cetuximab or panitumumab in conjunction with chemotherapy. A small fraction of patients have HER2 amplification where emerging data suggest treatment with drugs targeting this alteration...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29589138/mutational-analysis-of-triple-negative-breast-cancers-within-the-international-breast-cancer-study-group-ibcsg-trial-22-00
#20
Elisabetta Munzone, Kathryn P Gray, Caterina Fumagalli, Elena Guerini-Rocco, István Láng, Thomas Ruhstaller, Lorenzo Gianni, Roswitha Kammler, Giuseppe Viale, Angelo Di Leo, Alan S Coates, Richard D Gelber, Meredith M Regan, Aron Goldhirsch, Massimo Barberis, Marco Colleoni
PURPOSE: We investigated the occurrence and the prognostic and predictive relationship of a selected number of somatic mutations in triple-negative breast cancer (TNBC) patients having known clinical outcomes treated within the IBCSG Trial 22-00. METHODS: A matched case-control sampling selected patients enrolled in the IBCSG Trial 22-00 who had TNBC tumors, based on local assessment. Cases had invasive breast cancer recurrence (at local, regional, or distant site) according to the protocol definition...
March 27, 2018: Breast Cancer Research and Treatment
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