University of Turin

About: University of Turin is a education organization based out in Turin, Piemonte, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 29607 authors who have published 77952 publications receiving 2480900 citations. The organization is also known as: Universita degli Studi di Torino & Università degli Studi di Torino.

Pembrolizumab Cutaneous Adverse Events and Their Association With Disease Progression

Abstract: Importance Immunomodulatory anticancer drugs, such as the anti–programmed death-1 drug pembrolizumab, have shown promising results in trials, and more patients will receive such treatments. Little is known about cutaneous adverse events (AEs) caused by these drugs and their possible correlation with treatment response. Objective To describe the frequency and spectrum of cutaneous AEs linked with pembrolizumab and their possible correlation with treatment response. Design, Setting, and Participants A single-institution, retrospective medical record review was conducted of patients with cancer who were treated with pembrolizumab from March 1, 2011, to May 28, 2014. The review comprised 83 consecutive patients who were enrolled in 2 clinical trials, received at least 1 dose of pembrolizumab, and had at least 1 follow-up visit. Patients were grouped according to the following therapeutic regimen for pembrolizumab: 43 received 10 mg/kg every 3 weeks, 24 received 10 mg/kg every 2 weeks, and 16 received 2 mg/kg every 3 weeks. Sixty-six patients were treated for melanoma, 15 patients for lung cancer, 1 patient for prostate cancer, and 1 patient for Merkel cell carcinoma. Median follow-up was 15 weeks (range, 2-105 weeks). The analysis was conducted from March 1 to September 30, 2014. Main Outcomes and Measures Occurrence, severity, and type of cutaneous AEs, as well as disease progression and response to pembrolizumab treatment. Results Thirty-five patients (42%) developed cutaneous AEs attributed to pembrolizumab. The most common cutaneous AEs were macular papular eruption (24 [29%]), pruritus (10 [12%]), and hypopigmentation (7 [8%]). All 7 patients who developed hypopigmentation were treated for melanoma. Survival analyses showed that patients who developed cutaneous AEs had significantly longer progression-free intervals in all 3 groups (pembrolizumab, 10 mg/kg, every 3 weeks,P = .001; pembrolizumab, 10 mg/kg, every 2 weeks,P = .003; pembrolizumab, 2 mg/kg, every 3 weeks,P = .009) compared with patients who did not develop cutaneous AEs. Conclusions and Relevance Pembrolizumab therapy was associated with cutaneous AEs in 42% of patients. The development of cutaneous AEs, especially of hypopigmentation in patients with melanoma, could point toward better treatment response.

Non-Acylated Ghrelin Counteracts the Metabolic But Not the Neuroendocrine Response to Acylated Ghrelin in Humans

Abstract: Ghrelin possesses strong GH-releasing activity but also other endocrine activities including stimulation of PRL and ACTH secretion, modulation of insulin secretion and glucose metabolism. It is assumed that the GH secretagogue (GHS) receptor (GHS-R) 1a mediates ghrelin actins provided its acylation in Serine 3; in fact, acylated ghrelin only is able to exert endocrine activities. Acylated ghrelin (AG) is present in serum at a 2.5 fold lower concentration than unacylated ghrelin (UAG). UAG, however, is not biologically inactive; it shares with AG some non-endocrine actions like cardiovascular effects, modulation of cell proliferation and even some influence on adipogenesis. Thus, these actions are likely to be mediated by GHS-R subtypes able to bind ghrelin independently of its acylation. In order to further clarify whether UAG is really devoid of any endocrine action, we studied the interaction of the combined administration of AG and UAG (1.0 μg/kg iv) in 6 normal young volunteers (age [mean ± SE]: 25.4 ...