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https://www.readbyqxmd.com/read/27900869/-evaluation-of-five-years-of-treatment-of-erdheim-chester-disease-with-anakinra-case-report-and-overview-of-literature
#1
Zdeněk Adam, Hana Petrášová, Zdeněk Řehák, Renata Koukalová, Marta Krejčí, Luděk Pour, Eva Vetešníková, Aleš Čermák, Sabina Ševčíková, Petr Szturz, Zdeněk Král, Jiří Mayer
: Erdheim-Chester disease is a histiocytic neoplasm of diseases from the group of non-Langerhans-cell histiocytoses, formed by infiltrates of foamy histiocytes. These pathological histiocytes produce pro-inflammatory cytokines. Therefore Erdheim-Chester disease is called inflammatory histiocytary neoplasm. The disease is accompanied by clinical symptoms of systemic inflammatory response, i.e. B symptoms. Imaging examinations detect typical osteosclerotic changes affecting diaphyses and metaphyses of the lower long bones and fibrotic changes which affect the aorta wall and the vessels leading from it...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27898473/histopathological-and-clinical-findings-in-cutaneous-manifestation-of-erdheim-chester-disease-and-langerhans-cell-histiocytosis-overlap-syndrome-associated-with-the-brafv600e-mutation
#2
Julia Liersch, J Andrew Carlson, Jörg Schaller
The overlap of Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) is more common than it was generally accepted. Both diseases seem to be linked by a mutation in oncogenic BRAFV600E, probably an early event which occurs in bone marrow progenitor cells. In this article are described the clinical and histological findings in 2 cases of ECD-LCH overlap syndrome bearing the BRAFV600E mutation in both ECD and LCH lesions in bone and skin. In one case, lesions of ECD and LCH were situated directly site-to-site in the same bone section leading to the assumption of a common myeloid precursor cell for these diseases...
November 23, 2016: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/27883956/efficacy-of-braf-inhibitors-in-asian-metastatic-melanoma-patients-potential-implications-of-genomic-sequencing-in-braf-mutated-melanoma
#3
Hee Kyung Kim, Sunyoung Lee, Kyung Kim, Mi Hwa Heo, Hansang Lee, Jinhyun Cho, Nayoung K D Kim, Woongyang Park, Su Jin Lee, Jung Han Kim, Kee-Taek Jang, Sang-Hee Choi, Jeeyun Lee
BACKGROUND: The BRAF inhibitors vemurafenib and dabrafenib are currently the standard treatment for metastatic melanoma with BRAF V600 mutations. However, given the rarity of noncutaneous melanoma, including acral and mucosal subtypes, the efficacy of BRAF inhibitors for this subset of patients has not been extensively investigated. Acquired resistance generally appears 6 to 8 months after treatment with a BRAF inhibitor, and the mechanism of resistance is not well established. METHODS: We examined treatment outcomes for patients diagnosed with metastatic melanoma and treated with BRAF inhibitors at Samsung Medical Center between April 2013 and December 2015...
November 21, 2016: Translational Oncology
https://www.readbyqxmd.com/read/27881018/a-different-prognostic-value-of-brafv600e-mutation-positivity-in-different-age-groups-of-patients-with-papillary-thyroid-cancer
#4
E Takacsova, R Kralik, I Waczulikova, K Zavodna, J Kausitz
The aim of retrospective single-center study was to assess the prognostic value of BRAFV600E mutation positivity (BRAFV600E+) on disease persistence/recurrence in patients with papillary thyroid cancer (PTC). A total of 199 patients having had initial surgery with neck dissection in our hospital between 6/2009-6/2012 were included in the cohort. Excluded were patients with unifocal microcarcinoma ≤1cm. BRAFV600E mutation was tested from formalin-fixed paraffin-embedded surgicaly removed tumors. All included patients were postoperatively treated with radioiodine...
November 24, 2016: Neoplasma
https://www.readbyqxmd.com/read/27863426/quantification-of-tumor-derived-cell-free-dna-cfdna-by-digital-pcr-digpcr-in-cerebrospinal-fluid-of-patients-with-brafv600-mutated-malignancies
#5
Parisa Momtaz, Elena Pentsova, Omar Abdel-Wahab, Eli Diamond, David Hyman, Taha Merghoub, Daoqi You, Billel Gasmi, Agnes Viale, Paul B Chapman
Tumor-derived cell free DNA (cfDNA) can be detected in plasma. We hypothesized that mutated BRAF V600 cfDNA could be quantified in the cerebrospinal fluid (CSF) of patients with central nervous system (CNS) metastases. We collected CSF from patients with BRAF V600E or K-mutated melanoma (N=8) or BRAF V600E mutated Erdheim-Chester Disease (ECD) (N=3) with suspected central nervous system (CNS) involvement on the basis of neurological symptoms (10/11), MRI imaging (8/11), or both. Tumor-derived cfDNA was quantified by digital PCR in the CSF of 6/11 patients (range from 0...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27846237/integrated-genomics-identifies-mir-32-mcl-1-pathway-as-a-critical-driver-of-melanomagenesis-implications-for-mir-replacement-and-combination-therapy
#6
Prasun J Mishra, Pravin J Mishra, Glenn Merlino
AIMS: Cutaneous malignant melanoma is among the deadliest human cancers, broadly resistant to most clinical therapies. A majority of patients with BRAFV600E melanomas respond well to inhibitors such as vemurafenib, but all ultimately relapse. Moreover, there are no viable treatment options available for other non-BRAF melanoma subtypes in the clinic. A key to improving treatment options lies in a better understanding of mechanisms underlying melanoma progression, which are complex and heterogeneous...
2016: PloS One
https://www.readbyqxmd.com/read/27846054/sequencing-treatment-in-brafv600-mutant-melanoma-anti-pd-1-before-and-after-braf-inhibition
#7
Douglas B Johnson, Eirini Pectasides, Emily Feld, Fei Ye, Shilin Zhao, Romany Johnpulle, Ryan Merritt, David F McDermott, Igor Puzanov, Donald Lawrence, Jeffrey A Sosman, Elizabeth Buchbinder, Ryan J Sullivan
Novel agents targeting immune checkpoint molecules or mutated BRAF are active therapeutic options for patients with BRAF-mutant melanoma. However, the most effective first-line treatment and the optimal sequencing of these agents have not been well characterized. To explore this, we retrospectively assessed 114 patients from 4 centers with advanced, BRAF-mutant melanoma who received anti-programmed cell death-1 (PD-1)/PD-L1 antibodies. We evaluated clinical outcomes, including objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) to initial and subsequent therapies in patients that received anti-PD-1 first (n=56) versus those that received BRAF±MEK inhibitors (BRAFi) first (n=58)...
January 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27835901/mutational-activation-of-braf-confers-sensitivity-to-transforming-growth-factor-beta-inhibitors-in-human-cancer-cells
#8
Lindsay C Spender, G John Ferguson, Sijia Liu, Chao Cui, Maria Romina Girotti, Gary Sibbet, Ellen B Higgs, Morven K Shuttleworth, Tom Hamilton, Paul Lorigan, Michael Weller, David F Vincent, Owen J Sansom, Margaret Frame, Peter Ten Dijke, Richard Marais, Gareth J Inman
Recent data implicate elevated transforming growth factor-β (TGFβ) signalling in BRAF inhibitor drug-resistance mechanisms, but the potential for targeting TGFβ signalling in cases of advanced melanoma has not been investigated. We show that mutant BRAFV600E confers an intrinsic dependence on TGFβ/TGFβ receptor 1 (TGFBR1) signalling for clonogenicity of murine melanocytes. Pharmacological inhibition of the TGFBR1 blocked the clonogenicity of human mutant BRAF melanoma cells through SMAD4-independent inhibition of mitosis, and also inhibited metastasis in xenografted zebrafish...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27834723/evolution-of-papillary-thyroid-carcinoma-into-tall-cell-variant-and-tenis-syndrome
#9
REVIEW
Avik Chakraborty, S V Kane, Yogita Pawer, Sandip Basu
We herein report an unusual case of a 55-y-old woman with papillary carcinoma of the thyroid, who presented with multiple recurrences, with its subsequent evolution to tall cell variant and thyroglobulin-elevated negative iodine scintigraphy (TENIS) syndrome. During the course of the disease the lesions became non-iodine-concentrating with an increased proportion of tall cells and evidence of local and distant metastasis. Molecular analysis of the tissue specimen demonstrated BRAF(V600E) and I582 M mutations along with upregulation of tumor markers in metastatic tissue...
December 2016: Journal of Nuclear Medicine Technology
https://www.readbyqxmd.com/read/27834461/clinicopathological-significance-of-loss-of-p27kip1-expression-in-papillary-thyroid-carcinoma
#10
Nae Yu Kim, Jin Hwa Kim, Jung-Soo Pyo, Won Jin Cho
INTRODUCTION: A meta-analysis was done to investigate the clinicopathological significance of the loss of p27kip1 expression in papillary thyroid carcinoma (PTC). METHODS: The meta-analysis involving 17 studies included 1,652 PTC and 328 benign cases. The rate of p27kip1 expression loss in PTC and benign lesions, and the correlations between p27kip1 expression loss and clinicopathological characteristics of PTC were determined. RESULTS: The estimated rate of p27kip1 expression loss was 0...
November 5, 2016: International Journal of Biological Markers
https://www.readbyqxmd.com/read/27824297/single-point-mutations-in-pediatric-differentiated-thyroid-cancer
#11
Ali S Alzahrani, Avaniyapuram Kannan Murugan, Ebtesam Qasem, Meshael Alswailem, Hindi Nassir Al-Hindi, Yufei Shi
PURPOSE: Differentiated Thyroid Cancer (DTC) is rare in children. Previous studies suggested that it has different clinicopathological features and mutation profiles compared with adult DTC. However, those studies focused on single or a limited number of gene mutations. We comprehensively studied a large series of pediatric DTC for single point mutations in BRAF, HRAS, KRAS, NRAS, PIK3CA, PTEN and TERT. We also analyzed associations between clinicopathological features and the BRAFV600Emutation...
November 8, 2016: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/27802204/knockdown-of-s100a4-blocks-growth-and-metastasis-of-anaplastic-thyroid-cancer-cells-in-vitro-and-in-vivo
#12
Kejun Zhang, Meiqin Yu, Fengyun Hao, Anbing Dong, Dong Chen
Anaplastic thyroid cancer (ATC) is a locally aggressive type of thyroid tumor with high rate of distant metastases. It is often incurable because it does not respond to radioiodine, radiotherapy, or chemotherapy. With conventional treatment, the median survival is about 6 months; therefore, new treatment options are needed. S100A4 is a calcium-binding protein related to the metastatic potential of carcinoma. Previous study has found S100A4 was overexpressed in human papillary thyroid carcinomas (PTC) tissues, and overexpression of S100A4 is associated with thyroid tumour invasion and metastasis...
September 26, 2016: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27791984/droplet-digital-pcr-is-a-powerful-technique-to-demonstrate-frequent-fgfr1-duplication-in-dysembryoplastic-neuroepithelial-tumors
#13
Frédéric Fina, Doriane Barets, Carole Colin, Corinne Bouvier, Laëtitia Padovani, Isabelle Nanni-Metellus, L'Houcine Ouafik, Didier Scavarda, Andrey Korshunov, David T W Jones, Dominique Figarella-Branger
Dysembryoplastic neuroepithelial tumors (DNT) share V600E mutation in the BRAF gene with other low grade neuroepithelial tumors (LGNTs). FGFR1 internal tandem duplication of the tyrosine-kinase domain (FGFR1-ITD), another genetic alteration that also leads to MAP kinase pathway alteration, has been previously reported in LGNTs by whole-genome sequencing. In the present study we searched for FGFR1-ITD by droplet digital PCR (DDPCR™) and for FGFR1 point mutations by HRM-sequencing in a series of formalin-fixed paraffin-embedded (FFPE) LGNTs including 12 DNT, 2 oligodendrogliomas lacking IDH mutation and 1p/19q co- deletion (pediatric-type oligodendrogliomas; PTOs), 3 pediatric diffuse astrocytomas (PDAs), 14 gangliogliomas (GGs) and 5 pilocytic astrocytomas (PAs)...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27781490/dabrafenib-in-brafv600-mutated-anaplastic-pleomorphic-xanthoastrocytoma
#14
Nicholas F Brown, Thomas Carter, Paul Mulholland
Pleomorphic xanthoastrocytoma (PXA) is a rare brain tumor. Anaplastic features are found in 20-30% of cases of PXA and are associated with poor outcomes. Typical treatment is with gross total resection, followed by radiation therapy and cytotoxic chemotherapy at relapse. BRAFV600 mutations have been identified in 38-60% of patients with PXA. Several case reports and small case series have identified clinical benefit with BRAF inhibition in patients with BRAFV600-mutated PXA. We report the second published case of successful treatment with the BRAF inhibitor dabrafenib in a female patient with relapsed anaplastic PXA with a BRAFV600 mutation, and the first published case of dabrafinib treatment following intolerance to vemurafenib...
October 26, 2016: CNS Oncology
https://www.readbyqxmd.com/read/27779705/diphenhydramine-induces-melanoma-cell-apoptosis-by-suppressing-stat3-mcl-1-survival-signaling-and-retards-b16-f10-melanoma-growth-in-vivo
#15
Chi-Hung R Or, Hong-Lin Su, Wee-Chyan Lee, Shu-Yi Yang, Cheesang Ho, Chia-Che Chang
Melanoma is the most aggressive skin malignancy with a high rate of mortality and is frequently refractory to many therapeutics, thus demanding the discovery of novel effective anti-melanoma agents. Diphenhydramine (DPH) is an H1 histamine receptor antagonist and a relatively safe drug. Previous studies have revealed the in vitro cytotoxicity of DPH against melanoma cells, but the mechanisms involved concerning its cytotoxicity and the in vivo anti-melanoma effect remain unknown. We herein present the first evidence supporting that DPH is selectively proapoptotic for a panel of melanoma cell lines irrespective of BRAFV600E status while sparing normal melanocytes...
October 25, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27765849/mutant-braf-upregulates-mcl-1-to-confer-apoptosis-resistance-that-is-reversed-by-mcl-1-antagonism-and-cobimetinib-in-colorectal-cancer
#16
Hisato Kawakami, Shengbing Huang, Krishnendu Pal, Shamit K Dutta, Debabrata Mukhopadhyay, Frank A Sinicrope
Oncogenic BRAF(V600E) mutations activate MAPK signaling and are associated with treatment resistance and poor prognosis in patients with colorectal cancer. In BRAF(V600E)-mutant colorectal cancers, treatment failure may be related to BRAF(V600E)-mediated apoptosis resistance that occurs by an as yet undefined mechanism. We found that BRAF(V600E) can upregulate anti-apoptotic MCL-1 in a gene dose-dependent manner using colorectal cancer cell lines isogenic for BRAF BRAF(V600E)-induced MCL-1 upregulation was confirmed by ectopic BRAF(V600E) expression that activated MEK/ERK signaling to phosphorylate (MCL-1(Thr163)) and stabilize MCL-1...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27748799/growth-arrest-by-activated-braf-and-mek-inhibition-in-human-anaplastic-thyroid-cancer-cells
#17
Kento Kurata, Naoyoshi Onoda, Satoru Noda, Shinichiro Kashiwagi, Yuka Asano, Kosei Hirakawa, Masaichi Ohira
Anaplastic thyroid cancer (ATC) is a rare malignancy that progresses extremely aggressively and often results in dismal prognosis. We investigated the efficacy of inhibiting the activated RAS/RAF/MEK pathway in ATC cells aiming to clarify the mechanism of effect and resistance. Four human ATC cell lines (ACT-1, OCUT-2, OCUT-4 and OCUT-6) were used. OCUT-4 had a BRAF mutation. OCUT-2 had both BRAF and PI3KCA mutations. ACT-1 and OCUT-6 had wild-type BRAF and NRAS mutations. The effects of dabrafenib, a selective inhibitor of the BRAFV600E kinase, and trametinib, a reversible inhibitor of MEK activity, were investigated...
October 7, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27738305/somatic-mutations-in-solid-tumors-a-spectrum-at-the-service-of-diagnostic-armamentarium-or-an%C3%A2-indecipherable-puzzle-the-morphological-eyes-looking-for-braf-and-somatic-molecular-detections-on-cyto-histological-samples
#18
Esther Diana Rossi, Maurizio Martini, Tommaso Bizzarro, Fernando Schmitt, Adhemar Longatto-Filho, Luigi Maria Larocca
This review article deals with the analysis and the detection of the morphological features associated with somatic mutations, mostly BRAFV600E mutation, on both cytological and histological samples of carcinomas. Few authors demonstrated that some architectural and specific cellular findings (i.e. polygonal eosinophilic cells defined as "plump cells" and sickle-shaped nuclei) are able to predict BRAF V600E mutation in both cytological and histological samples of papillary thyroid carcinoma (PTC) as well as in other carcinomas...
October 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27729313/phase-ib-study-of-vemurafenib-in-combination-with-irinotecan-and-cetuximab-in-patients-with-metastatic-colorectal-cancer-with-brafv600e-mutation
#19
David S Hong, Van K Morris, Badi El Osta, Alexey V Sorokin, Filip Janku, Siqing Fu, Michael J Overman, Sarina Piha-Paul, Vivek Subbiah, Bryan Kee, Apostolia M Tsimberidou, David Fogelman, Jorge Bellido, Imad Shureiqi, Helen Huang, Johnique Atkins, Gabi Tarcic, Nicolas Sommer, Richard Lanman, Funda Meric-Bernstam, Scott Kopetz
: In vitro, EGFR inhibition, combined with the BRAF inhibitor vemurafenib, causes synergistic cytotoxicity for BRAF(V600E) metastatic colorectal cancer, further augmented by irinotecan. The safety and efficacy of vemurafenib, irinotecan, and cetuximab in BRAF-mutated malignancies are not defined. In this 3+3 phase I study, patients with BRAF(V600E)-advanced solid cancers received cetuximab and irinotecan with escalating doses of vemurafenib. Nineteen patients (18 with metastatic colorectal cancer and 1 with appendiceal cancer) were enrolled...
December 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27713119/concurrent-mek-targeted-therapy-prevents-mapk-pathway-reactivation-during-brafv600e-targeted-inhibition-in-a-novel-syngeneic-murine-glioma-model
#20
Stefan Grossauer, Katharina Koeck, Nicole E Murphy, Ian D Meyers, Mathieu Daynac, Nathalene Truffaux, Albert Y Truong, Theodore P Nicolaides, Martin McMahon, Mitchel S Berger, Joanna J Phillips, C David James, Claudia K Petritsch
Inhibitors of BRAFV600E kinase are currently under investigations in preclinical and clinical studies involving BRAFV600E glioma. Studies demonstrated clinical response to such individualized therapy in the majority of patients whereas in some patients tumors continue to grow despite treatment. To study resistance mechanisms, which include feedback activation of mitogen-activated protein kinase (MAPK) signaling in melanoma, we developed a luciferase-modified cell line (2341luc) from a BrafV600E mutant and Cdkn2a- deficient murine high-grade glioma, and analyzed its molecular responses to BRAFV600E- and MAPK kinase (MEK)-targeted inhibition...
October 3, 2016: Oncotarget
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