Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience.

Background: Uveal melanoma exhibits a high incidence of metastases; and, to date, there is no systemic therapy that clearly improves outcomes. The anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab is a standard of care for metastatic melanoma; however, the clinical activity of CTLA-4 inhibition in patients with metastatic uveal melanoma is poorly defined.

Methods: To assess ipilimumab in this setting, the authors performed a multicenter, retrospective analysis of 4 hospitals in the United States and Europe.

Prognosis of acral melanoma: a series of 281 patients.

Background: Acral melanoma (AM) is an unusual malignancy with poor survival. This study defines a cohort of patients, treated at a single institution, and the factors associated with survival and comparison with nonacral cutaneous melanoma (NACM).

Methods: All patients with AM presenting from 1995 to 2010 were identified from a prospectively maintained database.

Ipilimumab for patients with advanced mucosal melanoma.

The outcome of patients with mucosal melanoma treated with ipilimumab is not defined. To assess the efficacy and safety of ipilimumab in this melanoma subset, we performed a multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab. The clinical characteristics, treatments, toxicities, radiographic assessment of disease burden by central radiology review at each site, and mutational profiles of the patients' tumors were recorded.

Surveillance options for patients with uveal melanoma following definitive management.

Even though less than 1% of uveal melanoma patients are found to have radiographic or clinical evidence of distant disease at the time of treatment for their intraocular disease, they carry a lifetime risk of disease recurrence, with approximately 50% of patients ultimately developing fatal metastases. Despite this significant risk, there is no consensus within the ophthalmologic or oncologic community regarding the role of surveillance for detection of metastatic disease in these patients. The lack of consensus is due to the notable absence of clear data regarding the best radiologic or serum surveillance modalities, the optimal frequency of testing, or the ideal length of follow-up.

Metformin augments the levels of molecules that regulate the expression of the insulin-dependent glucose transporter GLUT4 in the endometria of hyperinsulinemic PCOS patients.

Study Question: Does treatment with the insulin sensitizer metformin modify the levels and activation of proteins related to the expression of the insulin-dependent glucose transporter (GLUT4), such as adenosine monophosphate-activated protein kinase (AMPK) and myocyte enhancer factor 2A (MEF2A), in endometria from hyperinsulinemic hyperandrogenemic polycystic ovary syndrome (PCOS h-Ins) patients?

Summary Answer: In PCOS h-Ins patients, metformin increases endometrial levels of GLUT4 mRNA and protein levels by normalizing the quantity and activation of molecules that regulate GLUT4 expression to healthy values. These changes could improve endometrial metabolic function.

What Is Already Known: PCOS is an endocrine-metabolic disorders closely associated with insulin resistance.

Physical activity and health-related quality of life among adult women in Cali, Colombia: a cross-sectional study.

Objectives: To examine the associations of leisure-time physical activity (LTPA) and walking for transportation (WT) with the physical and mental dimensions of health-related quality of life (HR-QOL) among women.

Methods: A cross-sectional study was carried out in 2009 among 1,263 women ages 18-59 years living in neighborhoods with low and middle-low socioeconomic status in the urban area of Cali. HR-QOL was assessed using the Short Form 8 (SF-8).

Phase II trial of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with BRAFV600E/K-mutated melanoma.

Purpose: Test the hypothesis that in BRAF-mutated melanomas, clinical responses to selumetinib, a MEK inhibitor, will be restricted to tumors in which the PI3K/AKT pathway is not activated.

Experimental Design: We conducted a phase II trial in patients with melanoma whose tumors harbored a BRAF mutation. Patients were stratified by phosphorylated-AKT (pAKT) expression (high vs.

Anti-programmed death-1 and anti-programmed death-ligand 1 antibodies in cancer therapy.

Introduction: Multiple agents targeting the immune "checkpoint" programmed death-1 (PD-1) pathway have demonstrated early evidence of durable clinical activity and an encouraging safety profile in patients with various tumor types, including some cancers, such as non-small-cell lung cancer, historically perceived as non-immunogenic and thus nonresponsive to immunotherapy.

Areas Covered: Functions of the PD-1 pathway in normal immune responses are reviewed, along with the significance of expression of PD-1 and its ligands in malignant settings. Rationale for the development of PD-1 pathway-targeted therapies and associated clinical data are presented.

Locoregional lymphadenectomy in the surgical management of anorectal melanoma.

Background: The effect of lymph node metastasis on local tumor control and distant failure in patients with anorectal melanoma has not been fully studied. Understanding the significance of lymphatic dissemination might assist in stratifying patients for either organ preservation or radical surgery.

Methods: A retrospective review of all patients with anorectal melanoma who underwent surgery at our institution between 1985 and 2010.

Managing obesity in primary care practice: a narrative review.

This narrative review examines randomized controlled trials of the management of obesity in primary care practice, in light of the Centers for Medicare and Medicaid Services' decision to support intensive behavioral weight loss counseling provided by physicians and related health professionals. Mean weight losses of 0.1-2.

Anal versus rectal melanoma: does site of origin predict outcome?

Background: Anatomic site is a predictive factor in subtypes of cutaneous and mucosal melanoma.

Objective: The aim of this study was to examine the clinical relevance of location of origin of anorectal melanoma as a prognostic factor.

Design: With the use of a prospectively maintained database, clinical characteristics, management, and outcomes were compared according to the site of origin.

A Nonrandomized, Phase II Study of Sequential Irinotecan and Flavopiridol in Patients With Advanced Hepatocellular Carcinoma.

Background: Flavopiridol, a Cdk inhibitor, potentiates irinotecan-induced apoptosis. In a phase I trial of sequential irinotecan and flavopiridol, 2 patients with advanced hepatocellular carcinoma (HCC) had stable disease (SD) for ≥14 months. We thus studied the sequential combination of irinotecan and flavopiridol in patients with HCC.

Immunologic responses to xenogeneic tyrosinase DNA vaccine administered by electroporation in patients with malignant melanoma.

Background: Prior studies show that intramuscular injection and particle-mediated epidermal delivery of xenogeneic melanosomal antigens (tyrosinase or Tyr, gp100) induce CD8(+) T cell responses to the syngeneic protein. To further define the optimal vaccination strategy, we conducted a phase I study of in vivo electroporation (EP) of a murine Tyr DNA vaccine (pINGmuTyr) in malignant melanoma patients.

Methods: Human leukocyte antigen (HLA)-A1, A2, A24 or B35 stage IIb-IV melanoma patients received up to five doses of the mouse tyrosinase DNA vaccine by EP every three weeks at dose levels of 0.

[Risk factors related to surgical site infection in orthopedic prosthesis surgery].

Objective: to identify the risk factors for surgical site infections (SSI) in patients with surgical management fractures with internal fixation or prosthetic material.

Materials And Methods: a cross-sectional study was conducted in a tertiary institution in Armenia-Colombia in 2008 and 2009 in 223 patients.

Results: The superficial incisional infection frequency was 9,4% (n: 21), and deep incisional infection was 7,6% (n: 17); there were no organ/space SSI.

Phase I/II study of pegylated arginine deiminase (ADI-PEG 20) in patients with advanced melanoma.

Background Arginine deiminase (ADI) is an enzyme that degrades arginine, an amino acid that is important for growth and development of normal and neoplastic cells. Melanoma cells are auxotrophic for arginine, because they lack argininosuccinatesynthetase (ASS), a key enzyme required for the synthesis of arginine. Patients and methods Patients with advanced melanoma were treated with 40, 80 or 160 IU/m(2) ADI-PEG 20 i.

Ipilimumab for metastatic melanoma.

Malignant melanoma is currently the fifth most common cancer in American men and the seventh most common in American women. Despite the advances made for early disease, the prognosis for metastatic melanoma is dismal, with an overall 5-year mortality rate of 90%. It is estimated that 8,000 Americans will die of melanoma in 2012.

Mucosal melanoma: pathogenesis, clinical behavior, and management.

Mucosal melanoma represents a rare subtype of melanoma with distinct biological, clinical, and management considerations. Knowledge regarding optimal treatment strategies for mucosal melanoma is limited and based primarily upon small case series and single-institution, retrospective analyses. Surgery remains the standard of care for loco-regional management, but the common presence of multifocal disease and the high rate of distant recurrence should be considered before pursuing aggressive surgical interventions associated with inherent significant morbidity.

Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors.

The purpose of this study was to determine the maximum-tolerated dose (MTD), pharmacokinetics and safety profile for two different dosing regimens of barasertib, a selective inhibitor of Aurora B Kinase. In this Phase I trial, patients with advanced solid malignancies were treated with escalating doses of barasertib, administered as either a 48-h continuous infusion or as two 2-h infusions on consecutive days, both every 14 days of a 28-day cycle. Thirty-five patients were treated.

Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.

Background: Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1.

Methods: We enrolled patients with advanced melanoma, non-small-cell lung cancer, castration-resistant prostate cancer, or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.

Atypical melanocytic proliferations and new primary melanomas in patients with advanced melanoma undergoing selective BRAF inhibition.

Purpose: Selective inhibition of mutant BRAF by using class I RAF inhibitors in patients with metastatic melanoma has resulted in impressive clinical activity. However, there is also evidence that RAF inhibitors might induce carcinogenesis or promote tumor progression via stimulation of MAPK signaling in RAF wild-type cells. We analyzed melanocytic lesions arising under class I RAF inhibitor treatment for dignity, specific genetic mutations, or expression of signal transduction molecules.

Ipilimumab-induced colitis on FDG PET/CT.

A 52-year-old woman with metastatic melanoma was treated with ipilimumab. After 2 cycles of treatment, she developed watery diarrhea, sweats, and chills. An FDG PET/CT study demonstrated new FDG-avid (maximum standardized uptake value 15.

Identification of unique MEK-dependent genes in GNAQ mutant uveal melanoma involved in cell growth, tumor cell invasion, and MEK resistance.

Purpose: Metastatic uveal melanoma represents the most common intraocular malignancy with very poor prognosis and no effective treatments. Oncogenic mutations in the G-protein α-subunit q and 11 have been described in about 85% of uveal melanomas and confer constitutive activation. Multiple signaling pathways are induced as a consequence of GNAQ/11 activation, which include the MEK/ERK kinase cascade.

Therapeutic implications of KIT in melanoma.

Melanoma is a heterogeneous disease representing distinct biologic and genetic subsets. Activating mutations in KIT have been discovered in a significant proportion of melanomas arising from acral, mucosal, and chronically sun-damaged sites and represent an important melanoma genetic subset. Initially, KIT was believed to function as a tumor suppressor, but additional research suggests that, in certain contexts, KIT functions as an oncogene.