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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

21:45 EDT 19th August 2018 | BioPortfolio

Brief Title: Study To Determine Effectiveness Of GSK1120212 In BRAF Mutation-positive Melanoma Subjects Previously Treated With Or Without A BRAF Inhibitor PubMed articles on BioPortfolio. Our PubMed references draw on over 21 million records from the medical literature. Here you can see the latest Brief Title: Study To Determine Effectiveness Of GSK1120212 In BRAF Mutation-positive Melanoma Subjects Previously Treated With Or Without A BRAF Inhibitor articles that have been published worldwide.

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Showing "Brief Title Study Determine Effectiveness GSK1120212 BRAF Mutation" PubMed Articles 1–25 of 69,000+

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...

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...


A rare BRAF T599dup mutation conferring sensitivity to BRAF inhibitor in a patient with metastatic melanoma.

Treatment for patients with V600 mutation of the B-Raf protooncogene BRAF (BRAF-V600) and metastatic stage IV or unresectable stage III melanoma has greatly advanced with the introduction of selective BRAF inhibitors (BRAFi), such as vemurafenib and dabrafenib, combined with mitogen-activated protein kinase kinase inhibitors (MEKi), such as cobimetinib and trametinib, as first-line therapy [1,2]. Two mutations, V600E and V600K, are routinely searched in patients with stage IV and unresectable stage III canc...

Current insights of BRAF inhibitors in cancer.

Oncogenic BRAF kinase deregulates the ERK signaling pathway in a large number of human tumors. FDA-approved BRAF inhibitors for BRAFV600E/K tumors have provided impressive clinical responses extending survival of melanoma patients. However, these drugs display paradoxical activation in normal tissue with BRAFWT due to RAF transactivation and priming, acquired drug resistance, and limited clinical effectiveness in non-V600 BRAF-dependent tumors, underscoring the urgent need to develop improved BRAF inhibitor...

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...

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...

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...

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...

First-Line Cetuximab Monotherapy in KRAS/NRAS/BRAF Mutation-Negative Colorectal Cancer Patients.

Colorectal carcinomas (CRCs) are sensitive to treatment by anti-epidermal growth factor receptor (EGFR) antibodies only if they do not carry activating mutations in down-stream EGFR targets (KRAS/NRAS/BRAF). Most clinical trials for chemo-naive CRC patients involved combination of targeted agents and chemotherapy, while single-agent cetuximab or panitumumab studies included either heavily pretreated patients or subjects who were not selected on the basis of molecular tests. We hypothesized that anti-EGFR th...

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...

Heterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C.

Activating mutations in RAS genes are associated with approximately 20% of all human cancers. New targeted therapies show preclinical promise in inhibiting the KRAS G12C variant. However, concerns exist regarding the effectiveness of such therapies in vivo given the possibilities of existing intratumor heterogeneity or de novo mutation leading to treatment resistance. We performed deep sequencing of 27 KRAS G12-positive lung tumors to determine the prevalence of other oncogenic mutations within KRAS or with...

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.

Single-Agent Regorafenib in Metastatic Colorectal Cancer Patients with Any RAS or BRAF Mutation Previously Treated with FOLFOXIRI plus Bevacizumab (PREVIUM Trial).

RAS- or BRAF-mutated metastatic colorectal cancers (mCRCs) progressing after first-line treatment have a poor prognosis.European and U.S. guidelines include the multikinase inhibitor regorafenib as a standard option for second-line therapy and beyond, based on the results of the randomized phase III CORRECT trial demonstrating improvement in survival.Although stopped prematurely for failing to accrue, the PREVIUM trial, the first prospective interventional study exploring regorafenib as second-line treatmen...

Frequency of MAP2K1, TP53, and U2AF1 Mutations in BRAF-mutated Langerhans Cell Histiocytosis: Further Characterizing the Genomic Landscape of LCH.

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 pa...

MicroRNA Expression in KRAS- and BRAF-mutated Colorectal Cancers.

KRAS and BRAF are two genes commonly mutated in colorectal cancer (CRC). Even though BRAF is a downstream target of KRAS in the MAPK signalling pathway, KRAS- and BRAF-mutated CRCs are found to display several different clinical and histopathological features. We investigated whether a differential expression of microRNAs (miRNAs) could explain the clinicopathological differences seen between KRAS- and BRAF-mutated CRCs.

Early evolution of BRAFV600 status in the blood of melanoma patients correlates with clinical outcome and identifies patients refractory to therapy.

Serial analysis of BRAF mutations in circulating-free DNA (cfDNA) could be of prognostic value in melanoma patients. We collected blood samples from 63 advanced BRAFV600E/K melanoma patients and determined BRAFV600E/K status in cfDNA using a quantitative 5'-nuclease PCR-based assay. Levels of BRAF mutation in pre-cfDNAs were associated significantly with tumour burden, progression-free survival and overall survival. Changes in BRAF status in cfDNA after initiation of treatment (early-cfDNA) had a significan...


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