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 69,000+

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...

Improving classification of melanocytic nevi: BRAF V600E expression associated with distinct histomorphologic features.

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.

Concordance of somatic mutational profile in multiple primary melanomas.

This study aimed to determine the frequency and concordance of BRAF and NRAS mutation in tumours arising in patients with multiple primary melanoma (MPM). Patients with MPM managed at one of three tertiary referral centres in Melbourne, Australia from 2010-2015 were included. Incident and subsequent melanomas underwent mutation testing. Cohen's kappa (κ) coefficient assessed agreement between incident and subsequent primary melanomas for both BRAF and NRAS mutation status (mutant vs. wild-type). Mutation t...

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...

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...

A sibling pair with cardiofaciocutaneous syndrome (CFC) secondary to BRAF mutation with unaffected parents-the first cases of gonadal mosaicism in CFC?

Cardiofaciocutaneous (CFC) syndrome is a RASopathy characterized by intellectual disability, congenital heart defects, a characteristic facial appearance, gastro-intestinal complications, ectodermal abnormalities and growth failure. The RASopathies result from germline mutations in the Ras/Mitogen-activated-protein-kinase (MAPK) pathway. CFC is associated with mutations in BRAF, KRAS, MEK1 and MEK2. CFC has been considered a "sporadic" disorder, with minimal recurrence risk to siblings. In recent years, ver...

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...

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...

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.

BRAF-mutant colorectal cancer, a different breed evolving.

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 patie...

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...

Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAF mutation.

Diffuse lymphocytic infiltration (DLI) is frequently found with papillary thyroid cancer (PTC), so there has been long interest in how it affects the characteristics of PTC. This purpose of this study was to define the association between DLI and PTC aggressiveness according to thyroperoxidase antibody (TPOAb) and B-type Raf (BRAF) mutation positivity.

High incidence of BRAF V600 mutation in Indian patients with head and neck cancer.

In cancer cells, is frequently mutated at codon 600 () leading to the replacement of valine amino acid with other amino acids. The current study was performed to assess the prevalence of  mutation in Indian patients with head and neck squamous cell carcinoma (HNSCC). Among the patients, 27% were homozygous, and 71% were heterozygous for the mutation and only 2% showed a wild genotype. Since identification of  mutation in cancer patients is used for selection of the therapeutic agents, th...

Anticancer effects of combinational treatment with BRAF siRNA and PI3K pathway inhibitors in melanoma cell lines harboring BRAF.

In the present study, the anti-tumor effects of combination treatment with an siRNA targeting B-Raf proto-oncogene serine/threonine kinase (BRAF) and phosphoinositide 3-kinase (PI3K) signaling pathway inhibitors was investigated in melanoma cell lines harboring BRAF. Human melanoma A375 and WM115 cells were treated with siRNA targeting to BRAF or BRAF, combined with treatment with PI3K signaling pathway inhibitors. CCK-8 and EdU proliferation assays were performed to assess cell viability and proliferation,...

The Role of Title IX Coordinators on College and University Campuses.

The purpose of this study was to better understand the role of Title IX coordinators and their policies across four-year universities and two-year community colleges in the United States (U.S.). There is little information regarding Title IX coordinators' training, background, and policies on how they handle Title IX investigations regarding sexual violence. The data come from an online survey that included 692 Title IX coordinators across four-year (private and public) and two-year campuses and represented...

Targeted inhibition of the BRAF pathway in a patient with stage IV melanoma.

This article describes the use of vemurafenib, a BRAF inhibitor, to achieve disease regression in a woman with extensive metastatic melanoma and the BRAF V600 gene mutation. Given the improved survival rates seen in these patients, clinicians need to be aware of long-term patient management and adverse reactions to the drug.

Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes.

BRAF and NRAS mutations arise early in melanoma development but their associations with low-penetrance melanoma susceptibility loci remain unknown. In the Genes, Environment and Melanoma (GEM) Study, 1223 European-origin participants had their incident invasive primary melanomas screened for BRAF/NRAS mutations and germline DNA genotyped for 47 single-nucleotide polymorphisms (SNPs) identified as low-penetrant melanoma risk variants. We used multinomial logistic regression to simultaneously examine each SNP...

Thoracic involvement in Erdheim-Chester disease: computed tomography imaging findings and their association with the BRAF mutation.

To investigate the computed tomography (CT) thoracic findings in Erdheim-Chester disease (ECD) and evaluate the association of these findings with the BRAF mutation.

Metabolic Response to BRAF-MEK Combination Therapy in Cecal Neuroendocrine Carcinoma With BRAFV600E Mutation and Refractory Lactic Acidosis.

We report the results of serial F-FDG PET/CT investigations in a 49-year-old woman presenting with an advanced cecal high-grade neuroendocrine carcinoma harboring a somatic BRAF mutation. Patient was refractory to standard chemotherapy regimen showing life-threatening hyperlactatemia. Early after the beginning of BRAF-MEK therapy (dabrafenib and trametinib), impressive improvement in PET/CT imaging was achieved. The pathological F-FDG uptake in cecal primary tumor as well as in nodal, hepatic, and bone meta...

Significance of BRAF V600E Mutation and Cytomorphological Features for the Optimization of Papillary Thyroid Cancer Diagnostics in Cytologically Indeterminate Thyroid Nodules.

Ultrasound guided fine needle aspiration biopsy with cytologic analysis is an initial step in diagnostic of thyroid nodules. Unfortunately, up to 30% of biopsies are indeterminate and diagnostic surgery is required. The aim of this study was to estimate the diagnostic value of BRAF V600E mutation status combined with cytomorphological features for diagnosis of papillary thyroid cancer (PTC) in cytologically indeterminate thyroid nodules.

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