Search results for "BRAF"
showing 10 items of 253 documents
Cetuximab plus FOLFOX-4 in untreated patients with advanced colorectal cancer: a Gruppo Oncologico dell'Italia Meridionale Multicenter phase II study.
2010
<i>Objectives:</i> FOLFOX-4 and FOLFIRI are considered equivalent in terms of activity and efficacy as first-line chemotherapy in metastatic colorectal cancer (mCRC). The monoclonal antibody (mAb) cetuximab showed intrinsic activity as a single agent in mCRC and was approved in combination with CPT-11 for patients who failed previous CPT-11-based treatment. The purpose of this phase II study was to evaluate the activity and safety of FOLFOX-4 plus cetuximab in untreated mCRC patients. <i>Methods:</i> Untreated patients with measurable metastatic disease and expressing epidermal growth factor receptor (EGFR) received cetuximab at a loading dose of 400 mg/m<sup>2…
The association between dermoscopic features and BRAF mutational status in cutaneous melanoma: Significance of the blue-white veil.
2018
Background: The genetic basis of melanoma affects its clinicopathologic characteristics and increasingly influences its management. B-Raf proto-oncogene, serine/threonine kinase gene (BRAF)-mutated melanoma may present with specific dermoscopic features. Objectives: To identify the dermoscopic features associated with BRAF mutation in cutaneous melanoma and to evaluate a model capable of predicting BRAF mutations on the basis of dermoscopic and clinicopathologic features that are easily accessible in normal clinical practice. Methods: A prospective, cross-sectional, observational, and descriptive study was performed. A total of 93 cutaneous melanomas with dermoscopic images from 93 patients…
Acquired BRAF inhibitor resistance: A multicenter meta-analysis of the spectrum and frequencies, clinical behaviour, and phenotypic associations of r…
2015
BackgroundAcquired resistance to BRAF inhibitors (BRAFi) is a near-universal phenomenon caused by numerous genetic and non-genetic alterations. In this study, we evaluated the spectrum, onset, pattern of progression, and subsequent clinical outcomes associated with specific mechanisms of resistance.MethodsWe compiled clinical and genetic data from 100 patients with 132 tissue samples obtained at progression on BRAFi therapy from 3 large, previously published studies of BRAFi resistance. These samples were subjected to whole-exome sequencing and/or polymerase chain reaction-based genetic testing.ResultsAmong 132 samples, putative resistance mechanisms were identified in 58%, including NRAS o…
Radiotherapy with BRAF inhibitor therapy for melanoma: progress and possibilities.
2015
The introduction of small molecule BRAFV600 kinase inhibitors represents a milestone in the targeted therapy of patients with metastatic melanoma by a significant increase in therapeutic efficacy in terms of overall and progression-free survival compared with conventional chemotherapy. Beside BRAFV600 inhibitor treatment, radiotherapy is a further mainstay for the therapy of metastatic melanoma and thus a concomitant or sequential application of BRAFV600 inhibitors and radiotherapy is inevitable. Recent reports show a significant radiosensitization of the irradiated healthy tissue in patients with melanoma after the combination of radiotherapy and BRAFV600 inhibitors, evoking concern in cl…
1122P Real-world analysis of dabrafenib plus trametinib in patients with BRAFV600-mutated melanoma brain metastases
2020
Targeted Therapies in Melanoma
2015
The standard approach for malignant melanoma is represented by surgical excision. In most cases, distant metastases develop. Until few years ago, the main strategies to treat metastatic melanoma were chemotherapy and cytokines with subsequent low efficacy and poor tolerability profile. In the last few years, a new biological therapy has become available for metastatic melanoma. It includes targeted therapy, such as BRAF inhibitors (vemurafenib and dabrafenib) and MEK inhibitors (trametinib), and immunotherapy, such as the monoclonal antibodies anti-CTLA-4 (ipilimumab) and anti-PD-1 (nivolumab and lambrolizumab). The different mechanisms of action of these new drugs imply a variability of ou…
An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes
2015
Item does not contain fulltext Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequen…
The neuropeptide Pth2 modulates social behavior and anxiety in zebrafish
2021
SummaryAnimal behavior is strongly context-dependent and behavioral performance is often modulated by internal state. In particular, different social contexts can alter anxiety levels and modulate social behavior. The vertebrate-specific neuropeptide parathyroid hormone 2 (pth2) is directly regulated by the presence or absence of conspecifics in zebrafish. As its cognate receptor, the parathyroid hormone 2 receptor (pth2r), is widely expressed across the brain, we tested fish lacking the functional Pth2 peptide in several anxiety-related and social paradigms. Rodents lacking PTH2 display increased anxiety-related behavior. Here we show that the propensity to react to sudden stimuli with an …
The metabolism of phenol and substituted phenols in zebra fish.
1987
1. The metabolism of five phenols in zebra fish was studied after uptake from the medium. The results showed no qualitative differences to other Cyprinid fish species, only the oxidation rate seemed to be lower. 2. Phenyl glucuronide, phenyl sulphate, and quinol sulphate were identified as metabolites of phenol. 3. Identified metabolites of 2-cresol were 2-cresyl glucuronide, 2-cresyl sulphate, and 2-hydroxybenzoic acid in trace amounts. 4. Only the glucuronide and sulphate conjugates were detected as metabolites of 4-nitrophenol, 4-chlorophenol, and pentachlorophenol.
Toxicokinetics of xenobiotics in zebrafish—Comparison between tap and river water
1991
Abstract 1. 1. Uptake and elimination of lindane, 3,4-dichloroaniline, phenol and 4-nitrophenol by the zebrafish Brachydanio rerio were investigated in tap water and in water of the river Rhine. 2. 2. The differences in bioconcentration of chemicals between the two water types did not exceed a factor of 2.5. 3. 3. Elimination kinetics were comparable in tap and river water. 4. 4. It can be concluded that water of the river Rhine does not influence the kinetics of the investigated xenobiotics.