CYP19 catalyzes the conversion of androgens to estrogens and is a critical enzyme affecting the sex hormone milieu. In this study, we investigated the functions of CYP19A1 polymorphisms and their associations with prostate cancer risk and clinical outcome. This case-control study evaluated the effects of three single nucleotide polymorphisms (SNPs) in CYP19A1 on the risk of prostate cancer in 330 prostate cancer patients and 354 normal controls. The associations between each SNP and sex hormone levels were evaluated in 164 healthy male patients. The functions of the SNPs were determined by reporter gene assays in PC3 and DU145 cell lines. Prostate-specific antigen nadir was evaluated in 142 patients with metastatic prostate cancer treated with androgen deprivation therapy. Cancer-specific survival (CSS) was determined in 166 patients with metastatic prostate cancer, to evaluate the influence of the three SNPs. Each variant allele of the three SNPs significantly decreased the risk of prostate cancer. Haplotype analysis showed that the T-A-G haplotype (corresponding to rs2470152-rs10459592-rs4775936) increased the risk of prostate cancer, while the C-C-A haplotype decreased the risk. The estrone/ androstenedione ratio was significantly higher in men with the C allele of rs2470152, the C allele of rs10459592, and the A allele of rs4775936 in a gene-dosage-dependent manner. Patients with the variant allele at rs4775936 had significantly shorter CSS. These results indicate that CYP19A1 polymorphisms may influence prostate cancer risk and survival by modifying promoter activity, with subsequent effects on the sex hormone milieu.Sex hormones, especially androgens, appear to play an important role in the carcinogenesis and progression of prostate cancer. 1,2 Testosterone propionate was shown to induce prostate cancer in an Nb rat model, 3 and the 5-a reductase inhibitor, finasteride, inhibited carcinogenesis in rat prostate cancer induced by testosterone (TS) propionate and the carcinogen, 3,2 0 -dimethyl-4-aminobiphenyl. 4 In the clinical setting, Huggins et al. first reported that androgen deprivation therapy (ADT) caused tumor regression in patients with metastatic prostate cancer, 1 since when endocrine therapies became a key part of the treatment for patients with advanced prostate cancer. Abraterone, which inhibits CYP17 androgen-synthesis enzyme activity, was recently shown to be a powerful drug, even in patients with castration-resistant prostate cancer previously treated with chemotherapy. 5 The importance of androgens in prostate cancer means that the synthetic pathways for these hormones have been targets for intensive study. Androgens are synthesized by many enzymes, primarily in the testes and the adrenal gland, and to a lesser extent in peripheral organs including the prostate and skin. 2 Among the enzymes involved in sex hormone synthesis, CYP19, also known as aromatase and encoded by CYP19A1, catalyzes the conversions of androstenedione

To evaluate the efficacy and safety of anti-PD1 therapy (nivolumab) in advanced renal cell carcinoma (RCC) in a clinical setting. Between March 2013 and January 2018, 33 patients with RCC (27 men and 6 women) were treated with nivolumab. Before anti-PD1 treatment, 12, 9 and 12 patients received one, two, and three or more therapies, respectively. Objective response, survival rate, and clinical adverse events were evaluated by the revised RECIST criteria (version 1.1). The median patient age was 68 years (range: 37-79). In total, 14 (42%) patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 while 17 (52%) and two (6%) had an ECOG PS of 1 and 2 or higher, respectively. One (3%), 24 (73%) and eight (24%) were classified as having favorable, intermediate, and poor risk, respectively. The median follow-up duration after nivolumab initiation was 26 months (range: 1-131). The median progression-free and overall survival were 10.3 months and 45.9 months, respectively. Nivolumab was associated with a disease control rate of 58%, with an objective response of 24% (complete response, 1; partial response, 7; stable disease, 11; progressive disease, 10; not assessed, 4). A total of 15 (46%) patients experienced adverse events, of which six were severe (grade 3 or more) and 10 were immunotherapy-related. This study examined the initial experience of nivolumab administration in Japanese patients with advanced RCC. Our results suggest that nivolumab can achieve acceptable outcomes in a real clinical setting, with outcomes that are comparable to those of clinical trials. Patients and methods Eligibility criteria. The present study included patients who were diagnosed with advanced RCC and treated with nivolumab from two institutes between March 2013 and January 2018. All patients with histologically-proven mRCC, regardless of Eastern Cooperative Oncology Group (ECOG) performance status (PS), were eligible for inclusion. All patients received at least two cycles of nivolumab and were assessed for treatment efficacy and toxicity. This study was approved by both institutional review boards, The Research

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