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https://www.readbyqxmd.com/read/29774876/-clinicopathological-features-for-epithelioid-glioblastoma-a-newly-defined-tumor-by-the-2016-world-health-organization-classification-of-tumors-of-the-central-nervous-system
#1
Juan Li, Xuebing Ling, Mingyao Lai, Qingjun Hu, Changguo Shan, Linbo Cai
To retrospectively summarize the clinicopathological features of epithelioid glioblastoma (Ep-GBM) and to explore new treatment for Ep-GBM.
 Methods: The clinical data of 13 patients with Ep-GBM, who were treated in our department from March 2016 to July 2017, were retrospectively analyzed. The clinicopathological features were summarized and the efficacy was evaluated.
 Results: The positive rate of BRAFV600E mutant and INI-1 was 76.9% (10/13) and 80% (8/10), respectively, while the median Ki-67 index was 30%...
April 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29774030/changes-in-the-tcr%C3%AE-repertoire-and-tumor-immune-signature-from-a-cutaneous-melanoma-patient-immunized-with-the-csf-470-vaccine-a-case-report
#2
Mariana Aris, Alicia Inés Bravo, María Betina Pampena, Paula Alejandra Blanco, Ibel Carri, Daniel Koile, Patricio Yankilevich, Estrella Mariel Levy, María Marcela Barrio, José Mordoh
The allogeneic therapeutic vaccine CSF-470 has demonstrated a significant benefit over medium-dose IFNα2b in the distant metastasis-free survival for stages IIB-IIC-III cutaneous melanoma patients in a randomized phase II/III clinical trial (CASVAC-0401, NCT01729663). At the end of the 2-year CSF-470 immunization protocol, patient #006 developed several lung and one subcutaneous melanoma metastases; this later was excised. In this report, we analyzed the changes throughout vaccination of immune populations in blood and in the tumor tissue, with special focus on the T-cell repertoire...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29768105/identification-of-a-recurrent-lmo7-braf-fusion-in-papillary-thyroid-carcinoma
#3
Huiling He, Wei Li, Pearlly Yan, Ralf Bundschuh, Jackson A Killian, Jadwiga Labanowska, Pamela Brock, Rulong Shen, Nyla A Heerema, Albert de la Chapelle
BACKGROUND: The BRAFV600E mutation is the most common driver in papillary thyroid carcinoma (PTC) tumors. In recent years, gene fusions have also been recognized as important drivers of cancer in PTC. Previous studies have suggested that thyroid tumors with fusion genes frequently display an aggressive course. These observations prompted further exploration of gene fusions in PTC tumors. The aim was to search for previously unrecognized gene fusions using thyroid tissue samples from PTC patients...
May 16, 2018: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29762246/brafv600e-mutation-does-not-significantly-affect-the-efficacy-of-radioiodine-therapy-in-patients-with-papillary-thyroid-carcinoma-without-known-distant-metastases
#4
Guohua Shen, Ying Kou, Bin Liu, Rui Huang, Anren Kuang
PURPOSE: The BRAF mutation is the most common and specific oncogenic event in papillary thyroid carcinoma (PTC). However, its role in radioiodine therapy decision making has yet to be established. This study aimed to evaluate the impact of the BRAF mutation on the clinical response to radioiodine therapy. METHODS: This retrospective study included PTC patients who received total thyroidectomy with lymph node dissection, radioiodine therapy, and thyroid-stimulating hormone suppression between January 2012 and March 2016...
May 14, 2018: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29744727/immunohistochemical-biomarkers-in-thyroid-pathology
#5
REVIEW
Zubair Baloch, Ozgur Mete, Sylvia L Asa
The application of immunohistochemistry to the diagnosis of thyroid lesions has increased as new biomarkers have emerged. In this review, we discuss the biomarkers that are critical for accurate diagnosis, prognosis, and management. Immunohistochemical markers are used to confirm that an unusual tumor in the thyroid is indeed of thyroid origin, either of follicular epithelial or C-cell differentiation; the various mimics include nonthyroidal lesions such as parathyroid tumors, paragangliomas, thymic neoplasms, and metastatic malignancies...
May 9, 2018: Endocrine Pathology
https://www.readbyqxmd.com/read/29737325/the-mek1-2-inhibitor-azd6244-sensitizes-braf-mutant-thyroid-cancer-to-vemurafenib
#6
Hao Song, Jinna Zhang, Liang Ning, Honglai Zhang, Dong Chen, Xuelong Jiao, Kejun Zhang
BACKGROUND [i]BRAF[/i]V600E mutation occurs in approximately 45% of papillary thyroid cancer (PTC) cases, and 25% of anaplastic thyroid cancer (ATC) cases. Vemurafenib/PLX4032, a selective BRAF inhibitor, suppresses extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase 1/2 (MEK/ERK1/2) signaling and shows beneficial effects in patients with metastatic melanoma harboring the [i]BRAFV600E[/i] mutation. However, the response to vemurafenib is limited in BRAF-mutant thyroid cancer. The present study evaluated the effect of vemurafenib in combination with the selective MEK1/2 inhibitor AZD6244 on cell survival and explored the mechanism underlying the combined effect of vemurafenib and AZD6244 on thyroid cancer cells harboring BRAFV600E...
May 8, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29736852/thoracic-involvement-in-erdheim-chester-disease-computed-tomography-imaging-findings-and-their-association-with-the-braf-v600e-mutation
#7
S Mojdeh Mirmomen, Arlene Sirajuddin, Moozhan Nikpanah, Rolf Symons, Anna K Paschall, Ioannis Papageorgiou, William A Gahl, Kevin O'Brien, Juvianee I Estrada-Veras, Ashkan A Malayeri
OBJECTIVES: To investigate the computed tomography (CT) thoracic findings in Erdheim-Chester disease (ECD) and evaluate the association of these findings with the BRAFV600E mutation. METHODS: This was a prospective study of patients with ECD (n=61, men=46) who underwent thoracic CT imaging. CT examinations were independently interpreted by two experienced radiologists. Association of imaging findings with BRAFV600E was achieved via the Chi-square or Fisher's exact test and odds ratios (OR) with 95% confidence intervals (CI), as appropriate...
May 7, 2018: European Radiology
https://www.readbyqxmd.com/read/29729495/braf-in-non-small-cell-lung-cancer-nsclc-pickaxing-another-brick-in-the-wall
#8
REVIEW
Alessandro Leonetti, Francesco Facchinetti, Giulio Rossi, Roberta Minari, Antonia Conti, Luc Friboulet, Marcello Tiseo, David Planchard
Molecular characterization of non-small cell lung cancer (NSCLC) marked an historical turning point for the treatment of lung tumors harboring kinase alterations suitable for specific targeted drugs inhibition, translating into major clinical improvements. Besides EGFR, ALK and ROS1, BRAF represents a novel therapeutic target for the treatment of advanced NSCLC. BRAF mutations, found in 1.5-3.5% of NSCLC, are responsible of the constitutive activation of mitogen activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway...
April 24, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29727562/n-7-cyano-6-4-fluoro-3-3-trifluoromethyl-phenyl-acetyl-amino-phenoxy-1-3-benzothiazol-2-yl-cyclopropanecarboxamide-tak632-promotes-inhibition-of-braf-through-the-induction-of-inhibited-dimers
#9
Michael Grasso, Michelle A Estrada, Kiara N Berrios, Jeffrey D Winkler, Ronen Marmorstein
BRAFV600E is the most common activating mutation in melanoma and patients treated with BRAFV600E inhibitors all develop resistance within 1 year. A significant resistance pathway is paradoxical activation (transactivation) involving BRAF dimers, whereby an inhibitor bound protein subunit allosterically activates the other subunit. We recently reported on bivalent BRAFV600E -selective vemurafenib inhibitors that stabilize an inactive αC-out/αC-out homodimeric conformation with improved inhibitor potency and selectivity in vitro...
May 4, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29724167/vemurafenib-in-chinese-patients-with-braf-v600-mutation-positive-unresectable-or-metastatic-melanoma-an-open-label-multicenter-phase-i-study
#10
Lu Si, Xiaoshi Zhang, Zhen Xu, Qiudi Jiang, Lilian Bu, Xuan Wang, Lili Mao, Weijiang Zhang, Nicole Richie, Jun Guo
BACKGROUND: Melanoma is a rare, deadly disease without effective treatment options in China. Vemurafenib is a selective inhibitor of oncogenic BRAFV600 kinase approved in more than 90 countries, based on results obtained primarily in Caucasian patients. Limited data are available regarding the efficacy and safety of vemurafenib in Asian patients. METHODS: This phase I study investigated the pharmacokinetics, efficacy, and tolerability of vemurafenib (960 mg twice daily) in Chinese patients with BRAFV600 mutation-positive unresectable or metastatic melanoma...
May 3, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29721378/a-phase-ii-study-of-combined-therapy-with-a-braf-inhibitor-vemurafenib-and-interleukin-2-aldesleukin-in-patients-with-metastatic-melanoma
#11
Meghan J Mooradian, Alexandre Reuben, Peter A Prieto, Mehlika Hazar-Rethinam, Dennie T Frederick, Brandon Nadres, Adriano Piris, Vikram Juneja, Zachary A Cooper, Arlene H Sharpe, Ryan B Corcoran, Keith T Flaherty, Donald P Lawrence, Jennifer A Wargo, Ryan J Sullivan
Background : Approximately 50% of melanomas harbor BRAF mutations. Treatment with BRAF +/- MEK inhibition is associated with favorable changes in the tumor microenvironment thus providing the rationale for combining targeted agents with immunotherapy. Methods : Patients with unresectable Stage III or IV BRAFV600E mutant melanoma were enrolled in a single-center prospective study (n = 6). Patients were eligible to receive two courses of HD-IL-2 and vemurafenib twice daily. The primary endpoint was progression-free survival (PFS) with secondary objectives including overall survival (OS), response rates (RR), and safety of combination therapy as compared to historical controls...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29717260/a-modified-gene-trap-approach-for-improved-high-throughput-cancer-drug-discovery
#12
Shelli M Morris, Andrew J Mhyre, Savanna S Carmack, Carrie H Myers, Connor Burns, Wenjuan Ye, Marc Ferrer, James M Olson, Richard A Klinghoffer
While advances in laboratory automation has dramatically increased throughout of compound screening efforts, development of robust cell-based assays in relevant disease models remain resource-intensive and time-consuming, presenting a bottleneck to drug discovery campaigns. To address this issue, we present a modified gene trap approach to efficiently generate pathway-specific reporters that result in a robust "on" signal when the pathway of interest is inhibited. In this proof-of-concept study, we used vemurafenib and trametinib to identify traps that specifically detect inhibition of the mitogen-activated protein kinase (MAPK) pathway in a model of BRAFV600E driven human malignant melanoma...
May 2, 2018: Oncogene
https://www.readbyqxmd.com/read/29708446/braf-mutant-colorectal-cancer-a-different-breed-evolving
#13
E Lai, A Pretta, V Impera, S Mariani, R Giampieri, L Casula, V Pusceddu, P Coni, D Fanni, M Puzzoni, L Demurtas, P Ziranu, G Faa, M Scartozzi
BRAF mutant colorectal cancer (BRAF MT CRC) is a unique category of colorectal tumour with peculiar molecular, pathological and clinical features and poor prognosis; despite recent research, BRAF mutation predictive value and standard treatment of BRAF MT CRC still have to be defined. In this review, we focused on this challenging topic. Areas Covered: The potential use of BRAF mutational status among recent additional prognostic and predictive indicators and current treatment strategy in use in these patients is discussed...
April 30, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29683947/encephalocraniocutaneous-lipomatosis
#14
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/29679497/ewsr1-patz1-gene-fusion-may-define-a-new-glioneuronal-tumor-entity
#15
Aurore Siegfried, Audrey Rousseau, Claude-Alain Maurage, Sarah Pericart, Yvan Nicaise, Frederic Escudie, David Grand, Alix Delrieu, Anne Gomez-Brouchet, Sophie Le Guellec, Camille Franchet, Sergio Boetto, Matthieu Vinchon, Jean-Christophe Sol, Franck-Emmanuel Roux, Valerie Rigau, Anne-Isabelle Bertozzi, David Tw Jones, Dominique Figarella-Branger, Emmanuelle Uro-Coste
We investigated the challenging diagnostic case of a ventricular cystic glioneuronal tumor with papillary features, by RNA sequencing using the Illumina TruSight RNA Fusion panel. We did not retrieve the SLC44A1-PRKCA fusion gene specific for papillary glioneuronal tumor, but an EWSR1-PATZ1 fusion transcript. RT-PCR followed by Sanger sequencing confirmed the EWSR1-PATZ1 fusion. It matched with canonic EWSR1 fusion oncogene, juxtaposing the entire N terminal transcriptional activation domain of EWSR1 gene and the C terminal DNA binding domain of a transcription factor gene, PATZ1...
April 21, 2018: Brain Pathology
https://www.readbyqxmd.com/read/29674508/combined-braf-and-hsp90-inhibition-in-patients-with-unresectable-braf-v600e-mutant-melanoma
#16
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/29666172/genetic-editing-of-colonic-organoids-provides-a-molecularly-distinct-and-orthotopic-preclinical-model-of-serrated-carcinogenesis
#17
Tamsin R M Lannagan, Young K Lee, Tongtong Wang, Jatin Roper, Mark L Bettington, Lochlan Fennell, Laura Vrbanac, Lisa Jonavicius, Roshini Somashekar, Krystyna Gieniec, Miao Yang, Jia Q Ng, Nobumi Suzuki, Mari Ichinose, Josephine A Wright, Hiroki Kobayashi, Tracey L Putoczki, Yoku Hayakawa, Simon J Leedham, Helen E Abud, Ömer H Yilmaz, Julie Marker, Sonja Klebe, Pratyaksha Wirapati, Siddhartha Mukherjee, Sabine Tejpar, Barbara A Leggett, Vicki L J Whitehall, Daniel L Worthley, Susan L Woods
OBJECTIVE: Serrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated kinase pathway gene, BRAF , and epigenetic modifications termed the CpG Island Methylator Phenotype, leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein...
April 17, 2018: Gut
https://www.readbyqxmd.com/read/29660527/the-association-between-mutations-in-braf-and-colorectal-cancer-specific-survival-depends-on-microsatellite-status-and-tumor-stage
#18
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/29649018/frequency-of-map2k1-tp53-and-u2af1-mutations-in-braf-mutated-langerhans-cell-histiocytosis-further-characterizing-the-genomic-landscape-of-lch
#19
Lisa M McGinnis, Grant Nybakken, Lisa Ma, Daniel A Arber
Langerhans cell histiocytosis is a proliferative disorder of neoplastic Langerhans cells with activating mutations in the Erk signaling pathway. TP53 and U2AF1 mutations have been implicated in other myelomonocytic malignancies and we hypothesized that mutations in these genes may cosegregate in LCH patients according to BRAF mutation status. Towards this end, we collected cases with a pathologic diagnosis of Langerhans cell histiocytosis from Stanford University Hospital. We analyzed the status of known pathogenic alleles in BRAF, ARAF, TP53, U2AF1, and MAP2K1 on formalin-fixed, paraffin-embedded tissue by direct sequencing...
April 11, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29645280/effect-of-vemurafenib-on-the-pharmacokinetics-of-a-single-dose-of-digoxin-in-patients-with-braf-v600-mutation-positive-metastatic-malignancy
#20
Weijiang Zhang, Christine McIntyre, Melissa Kuhn, Harper Forbes, Tae Min Kim, Jeeyun Lee, Lev Demidov, Dawn Colburn
The primary objective of this phase 1, open-label, multicenter, 3-period, fixed-sequence study was to evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of digoxin, a probe P-glycoprotein (P-gp) substrate, in patients with BRAFV600 mutation-positive metastatic malignancy. Following a 28-day screening period, patients received a single oral dose of digoxin 0.25 mg on day 1 in period A, oral vemurafenib 960 mg twice daily for 21 days in period B (days 8-28), and a single oral dose of digoxin 0...
April 12, 2018: Journal of Clinical Pharmacology
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