PubMed Journals Articles About "Brief Title: Study To Determine Effectiveness Of GSK1120212 In BRAF Mutation-positive Melanoma Subjects Previously Treated With Or Without A BRAF Inhibitor" RSS

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Showing "Brief Title Study Determine Effectiveness GSK1120212 BRAF Mutation" PubMed Articles 1–25 of 68,000+

BRAF Inhibition in BRAF-Mutant Gliomas: Results From the VE-BASKET Study.

BRAF mutations are frequently found in several glioma subtypes, including pleomorphic xanthoastrocytoma (PXA) and ganglioglioma and much less commonly in glioblastoma. We sought to determine the activity of vemurafenib, a selective inhibitor of BRAF, in patients with gliomas that harbor this mutation.

BRAF mutation: A promising target in colorectal neuroendocrine carcinoma.

To determine the role of BRAF mutation and MAPK signaling as well as the effects of BRAF and MEK directed therapy in gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN), with a focus on highly aggressive gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC). Using Sanger sequencing of BRAF exon 15 we determined the frequency of BRAF mutations in 71 primary GEP-NENs. MEK phosphorylation was examined by immunohistochemistry in corresponding tissue samples. To evaluate the biological relevance of BRA...

Clinical Validation of Newly Developed Multiplex Kit Using Luminex xMAP Technology for Detecting Simultaneous RAS and BRAF Mutations in Colorectal Cancer: Results of the RASKET-B Study.

Detection of RAS and BRAF mutations is essential to determine the optimal treatment strategy for metastatic colorectal cancer (CRC). We prospectively evaluated the MEBGEN RASKET-B KIT (RASKET-B), a novel multiplex kit, simultaneously detecting 48 types of RAS mutations and the BRAF V600E mutation using Luminex xMAP technology. The aim was to obtain market approval for RASKET-B as an in vitro diagnostic (IVD) option in Japan. Genomic DNA was extracted from 302 formalin-fixed paraffin-embedded tissues obtaine...

BRAF V600E Gene Mutation Is Associated With Bilateral Malignancy of Papillary Thyroid Cancer.

Papillary thyroid cancer (PTC) is the most prevalent type of thyroid cancer, which is the most common type of endocrine malignancy. Stratification and personalized surgical management of PTC patients are the major challenges for thyroid surgeons. Though BRAF V600E gene mutation presents in 50-70% of PTCs, it is unclear whether BRAF V600E testing could contribute to clinical practice. Therefore, this study investigated the association between BRAF V600E mutation and clinicopathologic features of PTC to evalu...

The Mutational Profile of Unicystic Ameloblastoma.

BRAF V600E is the most common mutation in conventional ameloblastoma (AM) of the mandible. In contrast, maxillary AMs appear to harbor more frequently RAS, FGFR2, or SMO mutations. Unicystic ameloblastoma (UAM) is considered a less aggressive variant of ameloblastoma, amenable to more conservative treatment, and classified as a distinct entity. The aim of this study was to characterize the mutation profile of UAM ( n = 39) and to compare it to conventional AM ( n = 39). The associations between muta...

Desmoplastic non- infantile astrocytoma/Ganglioglioma: rare low-grade tumor with frequent BRAF V600E mutation.

Desmoplastic Infantile Astrocytoma/Ganglioglioma (DIA/DIG) are rare primary glioneuronal tumors that comprise 0.5-1.0% of all intracranial tumors. While BRAF mutation is found in up to 50% of pediatric gangliogliomas, data for DIA/DIGs is limited. This study was carried out to evaluate the frequency of BRAF V600E mutation in DIA/DIG. All cases of DIA/DIGs diagnosed over 7years (2010-2016) were reviewed retrospectively. The clinical, radiological and histopathological characteristics of these patients were e...

Synergistic inhibition of MEK/ERK and BRAF V600E with PD98059 and PLX4032 induces sodium/iodide symporter (NIS) expression and radioiodine uptake in BRAF mutated papillary thyroid cancer cells.

The activating mutation BRAF is a frequent genetic event in papillary thyroid carcinomas (PTC). Mutation BRAF is associated with the loss of a sodium/iodine symporter (NIS), and subsequent radioiodide-refractory (RAI) metastatic disease. Use of BRAF V600E inhibitors could partly restore NIS expression and Iodide uptake by inhibition of mitogen-activated protein kinase (MAPK) pathway. Previous study has reported that the BRAF V600E inhibitors could re-activate MAPK signals. In the present study, we investiga...

BRAF Splice Variant Resistance to RAF Inhibitor Requires Enhanced MEK Association.

Expression of aberrantly spliced BRAF V600E isoforms (BRAF V600E ΔEx) mediates resistance in 13%-30% of melanoma patients progressing on RAF inhibitors. BRAF V600E ΔEx confers resistance, in part, through enhanced dimerization. Here, we uncoupled BRAF V600E ΔEx dimerization from maintenance of MEK-ERK1/2 signaling. Furthermore, we show BRAF V600E ΔEx association with its substrate, MEK, is enhanced and required for RAF inhibitor resistance. RAF inhibitor treatment increased phosphorylation at serine 729...

BRAF mutation: Current and future clinical pathological applications in colorectal carcinoma.

The aims are to review the relevance of the BRAF mutations in the clinical settings of colorectal carcinoma. All the literature concerning BRAF mutations and colorectal carcinoma published in PubMed from 2010 to 2018 was reviewed. Multiple variants of BRAF mutations exist in colorectal cancer, the most common type being V600E. The mutation is found in 5 to 15% of colorectal carcinomas and is less common in Asian populations. BRAF mutations are linked with older age, female gender, cigarette smoking and are ...

The interaction between BRAF mutation and microsatellite instability (MSI) status in determining survival outcomes after adjuvant 5FU based chemotherapy in stage III colon cancer.

The predictive role of biomarkers in colon cancer is still being defined. The aim of this study is to determine the interaction between BRAF mutation and microsatellite instability (MSI) status in determining survival benefit after adjuvant 5-FU based chemotherapy in stage III colon cancer.

Utility of including BRAF mutation analysis with ultrasonographic and cytological diagnoses in ultrasonography-guided fine-needle aspiration of thyroid nodules.

This study investigated the role of BRAF mutation analysis in thyroid fine-needle aspiration (FNA) samples compared to ultrasonographic and cytological diagnoses. A total 316 patients underwent ultrasonography (US)-guided FNA with BRAFV600E mutation analysis to diagnose thyroid nodules. One hundred sixteen patients with insufficient US images (n = 6), follow-up loss (n = 43), or unknown final diagnosis (n = 67) were excluded from the study. Comparisons between US diagnoses, cytological diagnoses, and BRAF m...

Diagnostic value of the BRAF variant V595E in urine samples, smears and biopsies from canine transitional cell carcinoma.

Transitional cell carcinoma (TCC) is the most common malignant tumour of the canine urinary tract. Previously, the mutation of the BRAF gene V595E was identified in approximately 85 % of canine TCC cases by DNA sequencing of TCC tumour cells, both in frozen and paraffin-embedded tissue sections, as well as in urine. The objective of this study was to establish these methods in cytological smears and to investigate the prevalence of BRAF mutation V595E in canine TCC in our cohort of patients.

An open-label, multicentre safety study of vemurafenib in patients with BRAF-mutant metastatic melanoma: final analysis and a validated prognostic scoring system.

The oncogenic BRAF inhibitor vemurafenib improves outcomes for patients with advanced BRAF mutation-positive melanoma compared with cytotoxic chemotherapy. Vemurafenib is now approved for use in this patient population.

MicroRNA-150-5p affects cell proliferation, apoptosis, and EMT by regulation of the BRAF mutation in papillary thyroid cancer cells.

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. Studies have confirmed an association between microRNA (miRNA) and the BRAF mutation in various cellular biological processes of PTC. This study aimed to clarify the potential relationship between miR-150-5p and the BRAF mutation in PTC. Human PTC cell lines B-CPAP and TPC-1 were transfected with the miR-150-5p mimic, an inhibitor, and the corresponding controls. Then, cell proliferation, viability, and apoptosis were detected by bromod...

Cutaneous adverse event associated with vemurafenib in a 3-year-old pediatric patient with BRAF mutation-positive metastatic melanoma and factor X deficiency.

Malignant melanoma is very rare in childhood. The approach to diagnosis and treatment in children has been adopted from adult guidelines. Vemurafenib is indicated in adults with BRAF V600 mutation-positive stage IIIc/IV melanoma and causes cutaneous adverse events. We report on a 3-year-old child with recurrent, metastatic (bone) BRAF mutation-positive melanoma. He also had severe factor X deficiency. Four days after vemurafenib treatment, bilateral palpebral edema and violet-colored hyperpigmentation were ...

Dabrafenib plus trametinib in BRAF K601E-mutant melanoma.

About 40 - 50% of cutaneous melanomas have activating BRAF mutations that are reachable with targeted therapy and combined BRAF-MEK inhibition improves clinical outcomes in advanced BRAF V600E/K-mutant melanoma. Three combinations are FDA-approved for this indication: dabrafenib-trametinib, vemurafenib-cobimetinib and encorafenib-binimetinib. The K601E mutation comprises approximately 3% of BRAF mutations in patients with melanoma. This article is protected by copyright. All rights reserved.

BRAF alterations in primary brain tumors.

Primary brain tumors can harbor v-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene alterations. BRAF is a serine/threonine kinase protein and is a downstream effector of the Ras-Raf-MEK extracellular signal-regulated kinase (ERK) signaling pathway, which is responsible for cell division and differentiation. BRAF-V600E mutations are most commonly found in pleomorphic xanthoastrocytoma, ganglioglioma, epithelioid glioblastoma, and gliomas diagnosed at a younger age; BRAF-KIAA1549 fusion is the most co...

A Clinical Rule for Preoperative Prediction of BRAF Mutation Status in Craniopharyngiomas.

Papillary craniopharyngiomas are characterized by BRAFV600E mutations. Targeted therapy can elicit a dramatic radiographic regression of these tumors. Therefore, prediction of BRAF mutation status before definitive surgery could enable neoadjuvant treatment strategies.

Development of ultra-short PCR assay to reveal BRAF V600 mutation status in Thai colorectal cancer tissues.

The protein kinase BRAF is one of the key players in regulating cellular responses to extracellular signals. Somatic mutations of the BRAF gene, causing constitutive activation of BRAF, have been found in various types of human cancers such as malignant melanoma, and colorectal cancer. BRAF V600E and V600K, most commonly observed mutations in these cancers, may predict response to targeted therapies. Many techniques suffer from a lack of diagnostic sensitivity in mutation analysis in clinical samples with a...

Unusually long-term responses to vemurafenib in BRAF V600E mutated colon and thyroid cancers followed by the development of rare RAS activating mutations.

V600E BRAF mutation is an established driver mutation in a variety of tumors. Vemurafenib is a selective inhibitor of the BRAF V600E kinase, known to be highly effective in BRAF V600E-positive metastatic melanoma. As a single agent, vemurafenib is relatively ineffective in other V600E-positive malignancies. Case 1: A 72 year old man with metastatic CRC who failed several previous lines of chemotherapy. Genetic analysis of 315 cancer-related genes (Foundation Medicine, FMI) revealed a BRAF V600E mutation. Th...

The BRAFV600E mutation in papillary thyroid microcarcinoma with intermediate-risk to high-risk features: does the mutation have an effect on clinical response to radioiodine therapy?

Preclinical studies showed that BRAF mutation significantly reduced radioiodine uptake and decreased the sensitivity to radioactive iodine (RAI) therapy. However, clinical data regarding its role in therapeutic decision making with respect to RAI therapy are currently insufficient. Thus, this study aimed to evaluate the effect of BRAF mutation on the clinical response to RAI therapy for papillary thyroid microcarcinoma (PTMC) with intermediate-risk to high-risk features.

Phase 1 study of the combination of vemurafenib, carboplatin, and paclitaxel in patients With BRAF-mutated melanoma and other advanced malignancies.

BRAF inhibitors are effective against selected BRAF -mutated tumors. Preclinical data suggest that BRAF inhibition in conjunction with chemotherapy has increased therapeutic activity.

Signal transducer and activator of transcription 3 inhibition enhances vemurafenib sensitivity in colon cancers harboring the BRAF mutation.

The BRAF inhibitor vemurafenib is widely used to treat melanomas harboring the activated BRAF mutation; however, vemurafenib showed poor efficacy in colon cancer, which impeded its clinical application for colon cancer patients with this mutation. The specific mechanism of vemurafenib resistance is not clear in colon cancer. In this study, we demonstrated that signal transducer and activator of transcription 3 (STAT3) activation influenced vemurafenib sensitivity in BRAF mutant colon cancer cells. When vemu...

Congenital self-healing reticulohistiocytosis with BRAF V600E mutation in an infant.

Congenital self-healing reticulohistiocytosis (CSHR) is a rare disorder characterized by benign skin lesions with a tendency to self-heal. Multiple skin lesions are usually present in CSHR. It is very difficult to distinguish between CSHR and an invasive Langerhans cell histiocytosis. We present a case of a 5-month-old infant girl who had hypopigmented skin lesions distributed over her neck, thorax and torso. The skin lesions regressed spontaneously 2 months after the diagnosis of CSHR and the child has re...

Computational modeling reveals MAP3K8 as mediator of resistance to vemurafenib in thyroid cancer stem cells.

Val600Glu (V600E) mutation is the most common BRAF mutation detected in thyroid cancer. Hence, recent research efforts have been performed trying to explore several inhibitors of the V600E mutation-containing BRAF kinase as potential therapeutic options in thyroid cancer refractory to standard interventions. Among them, vemurafenib is a selective BRAF inhibitor approved by FDA for clinical practice. Unfortunately, vemurafenib often displays limited efficacy in poorly differentiated and anaplastic thyroid ca...

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