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Demonstrates sexual dimorphism in serum leptin levels in puberty and childhood in Japan. Measurement of body weight and height in normal-weight Japanese children and adolescents; Correlation coefficient in weight of girls and boys; Correlation between serum leptin and percentage of overweight.

Talimogene laherparepvec (T-VEC) is approved for the treatment of unresectable melanoma in the USA, Europe, and Australia. This phase I, multicenter, open-label, dose de-escalation study evaluated the safety and efficacy of T-VEC in Japanese patients with unresectable stage IIIB-IV melanoma. Eligible adult patients had histologically confirmed stage IIIB-IVM1c cutaneous melanoma, may have received prior systemic anticancer therapy, must have had ≥1 injectable lesion, serum lactate dehydrogenase ≤1.5x upper limit of normal, ECOG performance status of 0 or 1, and adequate hematologic, hepatic, and renal function. T-VEC was injected intralesionally (first dose, ≤4.0 ml of 10 6  PFU/ml; after 3 weeks and then every 2 weeks thereafter, ≤4.0 ml of 10 8  PFU/ml). Primary endpoints were dose-limiting toxicities (DLTs) and durable response rate (DRR). Of 18 enrolled patients (72.2% female), 16 had received ≥1 prior line of therapy. Ten patients discontinued T-VEC due to disease progression. Median (range) follow-up was 20.0 (4-37) months. No DLTs were observed; 17 (94.4%) patients had treatment-emergent adverse events (AEs). Fourteen (77.8%) patients had treatment-related AEs; the most frequent were pyrexia (44.4%), malaise (16.7%), chills, decreased appetite, pruritus, and skin ulcer (11.1% each). The primary efficacy endpoint was met: 2 (11.1%) patients had a durable partial response ≥6 months. The DRR was consistent with that observed in a phase III trial of T-VEC in non-Asian patients. The safety profile was consistent with the patients' underlying disease and the known safety profile of T-VEC., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background & Aims: Patients with advanced chronic hepatitis C (CH-C) often are malnourished, but the effects of malnutrition on interferon (IFN) signaling and response to treatment have not been determined. We assessed the importance of the nutritional state of the liver on IFN signaling and treatment response., Methods: We studied data from 168 patients with CH-C who were treated with the combination of pegylated-IFN and ribavirin. Plasma concentrations of amino acids were measured by mass spectrometry. Liver gene expression profiles were obtained from 91 patients. Huh-7 cells were used to evaluate the IFN signaling pathway, mammalian target of rapamycin complex 1 (mTORC1), and forkhead box O (FoxO). Antiviral signaling induced by branched-chain amino acids (BCAAs) was determined using the in vitro hepatitis C virus replication system., Results: Multivariate logistic regression analysis showed that Fischer's ratio was associated significantly with nonresponders, independent of interleukin-28B polymorphisms or the histologic stage of the liver. Fischer's ratio was correlated inversely with the expression of BCAA transaminase 1, and was affected by hepatic mTORC1 signaling. IFN stimulation was impaired substantially in Huh-7 cells grown in medium that was low in amino acid concentration, through repressed mTORC1 signaling, and increased Socs3 expression, which was regulated by Foxo3a. BCAA could restore impaired IFN signaling and inhibit hepatitis C virus replication under conditions of malnutrition., Conclusions: Malnutrition impaired IFN signaling by inhibiting mTORC1 and activating Socs3 signaling through Foxo3a. Increasing BCAAs to up-regulate IFN signaling might be used as a new therapeutic approach for patients with advanced CH-C., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)