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Monoclonal antibodies directed against cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), such as ipilimumab, yield considerable clinical benefit for patients with metastatic melanoma by inhibiting immune checkpoint activity, but clinical predictors of response to these therapies remain incompletely characterized. To investigate the roles of(More)
Most patients with BRAF(V600)-mutant metastatic melanoma develop resistance to selective RAF kinase inhibitors. The spectrum of clinical genetic resistance mechanisms to RAF inhibitors and options for salvage therapy are incompletely understood. We performed whole-exome sequencing on formalin-fixed, paraffin-embedded tumors from 45 patients with(More)
BACKGROUND Recently, activating mutations in the TERT promoter were identified in cutaneous melanoma. We tested a cohort of ocular melanoma samples for similar mutations. METHODS The TERT promoter region was analysed by Sanger sequencing in 47 uveal (ciliary body or choroidal) melanomas and 38 conjunctival melanomas. RESULTS Mutations of the TERT(More)
OBJECTIVE Recent studies have suggested modifications of serotonin cerebral metabolism and of 5-HT(1A) receptors density in Alzheimer disease (AD). This study aims at exploring hippocampus 5-HT(1A) receptor density in patients at the amnesic mild cognitive impairment (aMCI) and mild AD dementia stages. METHODS With use of PET with a selective 5-HT(1A)(More)
To date, two positron emission tomography (PET) studies have explored 5-HT(1A) receptor density in the hippocampus of Alzheimer's disease (AD) patients. They showed early changes of 5-HT(1A) receptors in this brain region, known to have a dense serotonergic innervation. These studies only reported measurements in hippocampus. In the present PET study, we(More)
PURPOSE Up to 50% of patients with uveal melanoma (UM) develop metastatic disease with limited treatment options. The immunomodulating agent ipilimumab has shown an overall survival (OS) benefit in patients with cutaneous metastatic melanoma in two phase III trials. As patients with UM were excluded in these studies, the Dermatologic Cooperative Oncology(More)
Activating mutations in the TERT promoter were recently identified in up to 71% of cutaneous melanoma. Subsequent studies found TERT promoter mutations in a wide array of other major human cancers. TERT promoter mutations lead to increased expression of telomerase, which maintains telomere length and genomic stability, thereby allowing cancer cells to(More)
PURPOSE This phase I expansion study assessed safety, pharmacodynamic effects, and antitumor activity of RO4987655, a pure MEK inhibitor, in selected patients with advanced solid tumor. EXPERIMENTAL DESIGN We undertook a multicenter phase I two-part study (dose escalation and cohort expansion). Here, we present the part 2 expansion that included melanoma,(More)
BACKGROUND Melanoma is a deadly disease affecting people worldwide. Genetic studies have identified different melanoma subtypes characterized by specific recurrently mutated genes and led to the successful clinical introduction of targeted therapies. Hotspot mutations in SF3B1 were recently reported in uveal melanoma. Our aim was to see if these mutations(More)
Serotonin and its various receptors are involved in numerous brain functions and neuropsychiatric disorders. The 5-HT1A family is the best characterized subtype of the fourteen currently known 5-HT receptors. The 5-HT1A receptor is closely involved in the pathogenesis of anxiety, depression, epilepsy and eating disorders and therefore is an important target(More)