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https://www.readbyqxmd.com/read/29140771/braf-v600e-status-alone-is-not-sufficient-as-a-prognostic-biomarker-in-pediatric-low-grade-glioma
#1
David T W Jones, Olaf Witt, Stefan M Pfister
No abstract text is available yet for this article.
November 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29138945/glioblastoma-in-neurofibromatosis-1-patients-without-idh1-braf-v600e-and-tert-promoter-mutations
#2
Ichiyo Shibahara, Yukihiko Sonoda, Hiroyoshi Suzuki, Akifumi Mayama, Masayuki Kanamori, Ryuta Saito, Yasuhiro Suzuki, Shoji Mashiyama, Hiroshi Uenohara, Mika Watanabe, Toshihiro Kumabe, Teiji Tominaga
Pilocytic astrocytomas and low-grade gliomas are more common compared with glioblastomas in patients with neurofibromatosis 1 (NF1). A recent genome-wide analysis has shown frequent NF1 gene alterations in the mesenchymal subtype of a glioblastoma; however, little is known about clinicopathological features of glioblastomas in NF1 patients (NF1 glioblastomas). We analyzed four NF1 glioblastomas. Radiographical and intraoperative findings showed well-circumscribed tumors from surrounding brain. Pathological analysis presented a paucity of processes with an eosinophilic cytoplasm, bizarre nuclei, xanthomatous-like appearance, multinucleated giant cells, and histiocytoid appearance...
November 14, 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/29137417/inhibition-of-retinoic-acid-receptor-%C3%AE-signaling-confers-glycolytic-dependence-and-sensitization-to-dichloroacetate-in-melanoma-cells
#3
Cecilie Abildgaard, Christina Dahl, Ahmad Abdul-Al, Annette Christensen, Per Guldberg
Dysregulation of metabolism during melanoma progression is tightly associated with the acquisition of genetic and epigenetic alterations in regulators of metabolic pathways. Retinoic acid receptor beta (RARβ) is epigenetically silenced in a large proportion of melanomas, but a link between RARβ and metabolic rewiring of melanoma has not been established. Here, we show that in primary human melanocytes, all-trans retinoic acid (a RARβ agonist) induced growth inhibition accompanied by a decrease in both glycolytic and oxidative metabolism, whereas selective inhibition of RARβ led to an increase in the basal glycolytic rate and increased sensitivity to inhibition of glycolysis...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29134959/targeting-ret-driven-cancers-lessons-from-evolving-preclinical-and-clinical-landscapes
#4
REVIEW
Alexander Drilon, Zishuo I Hu, Gillianne G Y Lai, Daniel S W Tan
The gene encoding the receptor-tyrosine kinase RET was first discovered more than three decades ago, and activating RET rearrangements and mutations have since been identified as actionable drivers of oncogenesis. Several multikinase inhibitors with activity against RET have been explored in the clinic, and confirmed responses to targeted therapy with these agents have been observed in patients with RET-rearranged lung cancers or RET-mutant thyroid cancers. Nevertheless, response rates to RET-directed therapy are modest compared with those achieved using targeted therapies matched to other oncogenic drivers of solid tumours, such as sensitizing EGFR or BRAF(V600E) mutations, or ALK or ROS1 rearrangements...
November 14, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29133617/response-and-resistance-to-paradox-breaking-braf-inhibitor-in-melanomas-in-vivo-and-ex-vivo
#5
Edward J Hartsough, Curtis H Kugel, Michael J Vido, Adam C Berger, Timothy J Purwin, Allison Goldberg, Michael A Davies, Matthew J Schiewer, Karen E Knudsen, Gideon Bollag, Andrew E Aplin
FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox breaking RAF inhibitor (PLX8394) has been designed. Here we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29132392/false-negative-braf-v600e-mutation-results-on-fine-needle-aspiration-cytology-of-papillary-thyroid-carcinoma
#6
Se Hyun Paek, Byung Seup Kim, Kyung Ho Kang, Hee Sung Kim
BACKGROUND: The BRAF V600E mutation is highly specific for papillary thyroid carcinoma (PTC). A test for this mutation can increase the diagnostic accuracy of fine-needle aspiration cytology (FNAC), but a considerably high false-negative rate for the BRAF V600E mutation on FNAC has been reported. In this study, we investigated the risk factors associated with false-negative BRAF V600E mutation results on FNAC. METHODS: BRAF V600E mutation results of 221 PTC nodules between December 2011 and June 2013 were retrospectively reviewed...
November 13, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29128931/universal-determination-of-microsatellite-instability-using-bat26-as-a-single-marker-in-an-argentine-colorectal-cancer-cohort
#7
María Laura González, Natalia Causada-Calo, Juan Pablo Santino, Mev Dominguez-Valentin, Fabiana Alejandra Ferro, Inés Sammartino, Pablo Germán Kalfayan, Maria Alicia Verzura, Tamara Alejandra Piñero, Andrea Romina Cajal, Walter Pavicic, Carlos Vaccaro
Microsatellite instability (MSI) is a hallmark tool for Lynch syndrome (LS) screening and a prognostic marker for sporadic colorectal cancer (CRC). In regions with limited resources and scarce CRC molecular characterization as South America, the implementation of universal MSI screening is under debate for both its purposes. We sought to estimate the frequency of BAT26 in colorectal adenocarcinomas and to determine associated clinical and histological features. Consecutive patients from a CRC registry were included...
November 11, 2017: Familial Cancer
https://www.readbyqxmd.com/read/29128185/correct-extent-of-thyroidectomy-is-poorly-predicted-preoperatively-by-the-guidelines-of-the-american-thyroid-association-for-low-and-intermediate-risk-thyroid-cancers
#8
Mashaal Dhir, Kelly L McCoy, N Paul Ohori, Cameron D Adkisson, Shane O LeBeau, Sally E Carty, Linwah Yip
BACKGROUND: Recent guidelines from the American Thyroid Association recommend thyroid lobectomy for intrathyroidal differentiated thyroid cancers <4 cm. Our aim was to examine histology from patients with cytologic results that were positive or suspicious for malignancy to assess the extent of initial thyroidectomy based on criteria from the 2015 American Thyroid Association guidelines. METHODS: We studied consecutive patients who had either a positive or suspicious for malignancy cytologic diagnosis and under prior American Thyroid Association guidelines underwent initial total thyroidectomy ± lymphadenectomy...
November 8, 2017: Surgery
https://www.readbyqxmd.com/read/29127628/immunohistochemistry-with-anti-braf-v600e-ve1-mouse-monoclonal-antibody-is-a-sensitive-method-for-detection-of-the-braf-v600e-mutation-in-colon-cancer-evaluation-of-120-cases-with-and-without-kras-mutation-and-literature-review
#9
Katerina Dvorak, Amanda Higgins, John Palting, Michael Cohen, Patrick Brunhoeber
The major aim of this study was to evaluate the performance of anti-BRAF V600E (VE1) antibody in colorectal tumors with and without KRAS mutation. KRAS and BRAF are two major oncogenic drivers of colorectal cancer (CRC) that have been frequently described as mutually exclusive, thus the BRAF V600E mutation is not expected to be present in the cases with KRAS mutation. In addition, a review of 25 studies comparing immunohistochemistry (IHC) using the anti-BRAF V600E (VE1) antibody with BRAF V600E molecular testing in 4041 patient samples was included...
November 10, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29127087/dabrafenib-plus-trametinib-is-active-in-braf-v600e-anaplastic-thyroid-cancer
#10
(no author information available yet)
Dual BRAF/MEK inhibition achieves responses in 69% of BRAFV(600E) anaplastic thyroid cancers (ATC).
November 10, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29120401/does-locoregional-chemotherapy-still-matter-in-the-treatment-of-advanced-pelvic-melanoma
#11
Stefano Guadagni, Giammaria Fiorentini, Marco Clementi, Giancarlo Palumbo, Paola Palumbo, Alessandro Chiominto, Stefano Baldoni, Francesco Masedu, Marco Valenti, Ambra Di Tommaso, Bianca Fabi, Camillo Aliberti, Donatella Sarti, Veronica Guadagni, Cristina Pellegrini
Pelvic Melanoma relapse occurs in 15% of patients with loco regional metastases, and 25% of cases do not respond to new target-therapy and/or immunotherapy. Melphalan hypoxic pelvic perfusion may, therefore, be an option for these non-responsive patients. Overall median survival time (MST), stratified for variables, including BRAF V600E mutation and eligibility for treatments with new immunotherapy drugs, was retrospectively assessed in 41 patients with pelvic melanoma loco regional metastases. They had received a total of 175 treatments with Melphalan hypoxic perfusion and cytoreductive excision...
November 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29119584/concordance-in-braf-v600e%C3%A2-status-over-time-in-malignant-melanoma-and-corresponding-metastases
#12
Line Bjerrehave Nielsen, Nina Dabrosin, Karen Sloth, Marie Louise Bønnelykke-Behrndtz, Torben Steiniche, Johanne Lade-Keller
AIMS: The present study analysed the usability of an immunohistochemical (IHC) analysis compared to a frequently used mutation detection analysis and examined the extent of intra- and inter-tumour heterogeneity of BRAF V600E in primary tumours and their corresponding metastases. In the development of inter-tumour heterogeneity between the primary tumour and the corresponding metastases, time as a factor was also investigated. METHODS: In total, 227 samples from 224 melanoma patients were analysed using both the Cobas(®) 4800 BRAF V600 Mutation test and IHC anti-BRAF V600E staining...
November 8, 2017: Histopathology
https://www.readbyqxmd.com/read/29118233/hairy-cell-leukemia-version-2-2018-nccn-clinical-practice-guidelines-in-oncology
#13
William G Wierda, John C Byrd, Jeremy S Abramson, Seema Bhat, Greg Bociek, Danielle Brander, Jennifer Brown, Asher Chanan-Khan, Steve E Coutre, Randall S Davis, Christopher D Fletcher, Brian Hill, Brad S Kahl, Manali Kamdar, Lawrence D Kaplan, Nadia Khan, Thomas J Kipps, Jeffrey Lancet, Shuo Ma, Sami Malek, Claudio Mosse, Mazyar Shadman, Tanya Siddiqi, Deborah Stephens, Nina Wagner, Andrew D Zelenetz, Mary A Dwyer, Hema Sundar
Hairy cell leukemia (HCL) is a rare type of indolent B-cell leukemia, characterized by symptoms of fatigue and weakness, organomegaly, pancytopenia, and recurrent opportunistic infections. Classic HCL should be considered a distinct clinical entity separate from HCLvariant (HCLv), which is associated with a more aggressive disease course and may not respond to standard HCL therapies. Somatic hypermutation in the IGHV gene is present in most patients with HCL. The BRAF V600E mutation has been reported in most patients with classic HCL but not in those with other B-cell leukemias or lymphomas...
November 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29117154/brafv600e-and-ret-ptc-promote-proliferation-and-migration-of-papillary-thyroid-carcinoma-cells-in-vitro-by-regulating-nuclear-factor-%C3%AE%C2%BAb
#14
Dehua Zhou, Zhou Li, Xuefeng Bai
BACKGROUND Papillary thyroid carcinoma (PTC) is associated with mutations of BRAFV600E and RET/PTC and high levels of expression of nuclear factor-κB (NF-κB). However, few studies have focused on the association between NF-κB expression and mutations in BRAFV600E and RET/PTC, especially regarding PTC cell proliferation and migration. The aim of this in vitro study was to investigate the effect of BRAFV600E or RET/PTC on NF-κB expression, cell proliferation and cell migration in four established PTC cell lines...
November 8, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29110361/hairy-cell-leukemia-2018-update-on-diagnosis-risk-stratification-and-treatment
#15
Xavier Troussard, Edouard Cornet
DISEASE OVERVIEW: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders, characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment. DIAGNOSIS: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation...
December 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29107542/imidazo-1-2-a-pyridin-6-yl-benzamide-analogs-as-potent-raf-inhibitors
#16
Aaron Smith, Zhi-Jie Ni, Daniel Poon, Zilin Huang, Zheng Chen, Qiong Zhang, Laura Tandeske, Hanne Merritt, Kevin Shoemaker, John Chan, Susan Kaufman, Kay Huh, Jeremy Murray, Brent A Appleton, Sandra W Cowan-Jacob, Clemens Scheufler, Takanori Kanazawa, Johanna M Jansen, Darrin Stuart, Cynthia M Shafer
A series of imidazo[1,2-a]pyridin-6-yl-benzamide analogs was designed as inhibitors of B-RAF(V600E). Medicinal chemistry techniques were employed to explore the SAR for this series and improve selectivity versus P38 and VEGFR2.
October 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29107340/langerhans-cell-histiocytosis-a-neoplastic-disorder-driven-by-ras-erk-pathway-mutations
#17
REVIEW
Gary Tran, Thy N Huynh, Amy S Paller
Langerhans cell histiocytosis (LCH) is a disorder of myeloid neoplasia of dendritic cells that affects 1 in 200,000 children <15 years of age and even fewer adults. LCH presents with a spectrum of clinical manifestations. High-risk stratification is reserved for infiltration of blood, spleen, liver, and lungs. After decades of debate on the disease pathogenesis, a neoplastic mechanism is now favored on the basis of LCH cell clonality, rare cases of familial clustering, and recent evidence of mutations involving the Ras/Raf/MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinase) pathway in lesional biopsy specimens...
October 26, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29105198/braf-v600e-tert-promoter-mutations-and-cdkn2a-b-homozygous-deletions-are-frequent-in-epithelioid-glioblastomas-a-histological-and-molecular-analysis-focusing-on-intratumoral-heterogeneity
#18
Nozomi Nakajima, Sumihito Nobusawa, Satoshi Nakata, Mitsutoshi Nakada, Tatsuya Yamazaki, Nozomi Matsumura, Kenichi Harada, Hadzki Matsuda, Nobuaki Funata, Shoichi Nagai, Hideo Nakamura, Atsushi Sasaki, Jiro Akimoto, Junko Hirato, Hideaki Yokoo
Epithelioid glioblastoma (E-GBM) is a rare aggressive variant of IDH-wildtype glioblastoma newly recognized in the 2016 World Health Organization classification, composed predominantly of monotonous, patternless sheets of round cells with laterally positioned nuclei and plump eosinophilic cytoplasm. Approximately 50% of E-GBM harbor BRAF V600E, which is much less frequently found in other types of glioblastomas. Most E-GBM are recognized as primary/de novo lesions; however, several E-GBM with co- or pre-existing lower-grade lesions have been reported...
November 4, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29103753/frequent-oncogenic-braf-v600e-mutation-in-odontogenic-keratocyst
#19
Yong Hoon Cha, Eunae Sandra Cho, Hee Eun Kang, Jaemin Ko, Woong Nam, Hyung Jun Kim, Nam Hee Kim, Hyun Sil Kim, In-Ho Cha, Jong In Yook
OBJECTIVES: Odontogenic keratocyst (OKC), also known as keratocystic odontogenic tumor (KCOT), has clinical significance due to its high incidence as well as high recurrence rate after surgical enucleation. Current clinical management for OCK is entirely dependent on surgical approach. While various genetic alterations, such as PTCH1 mutation and loss of heterozygosity in tumor suppressor genes, have been reported, the molecular background of OKC is not well-understood. Although recent identification of BRAF V600E mutation and subsequent activation of mitogen-activated protein kinase (MAPK) pathway in ameloblastoma and odontogenic tumors provide additional options with targeted therapeutics, the molecular background of OKC is not well understood...
November 2017: Oral Oncology
https://www.readbyqxmd.com/read/29100713/a-hrm-assay-for-identification-of-low-level-braf-v600e-and-v600k-mutations-using-the-cadma-principle-in-ffpe-specimens
#20
Claudia Huebner, Remeny Weber, Richard Lloydd
Melanoma patients with BRAF V600E and V600K mutations show complete or partial response to vemurafenib. Detection assays often scan for the common V600E mutation rather than the rare V600K variant, although this mutation can be found in a high proportion of melanoma patients in the South Pacific. Herein, we describe a BRAF high resolution melting (HRM) assay that can differentiate low level of V600E and V600K mutations using formalin fixed, paraffin embedded (FFPE) reference standards for assay validation. The assay is based on the competitive amplification of differentially melting amplicons (CADMA principle) and has a limit of detection of 0...
October 31, 2017: Pathology
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