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RISS 인기검색어
- 검색키워드
- 저자 : Kazutoshi Fujita (검색결과 3 건)
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Role of Androgen Receptor in Prostate Cancer: A Review
Kazutoshi Fujita,Norio Nonomura 대한남성과학회 2019 The World Journal of Men's Health Vol.37 No.3
Androgen receptor (AR) is a steroid receptor transcriptional factor for testosterone and dihydrotestosterone consisting of four main domains, the N-terminal domain, DNA-binding domain, hinge region, and ligand-binding domain. AR plays pivotal roles in prostate cancer, especially castration-resistant prostate cancer (CRPC). Androgen deprivation therapy can suppress hormone-naïve prostate cancer, but prostate cancer changes AR and adapts to survive under castration levels of androgen. These mechanisms include AR point mutations, AR overexpression, changes of androgen biosynthesis, constitutively active AR splice variants without ligand binding, and changes of androgen cofactors. Studies of AR in CRPC revealed that AR was still active in CRPC, and it remains as a potential target to treat CRPC. Enzalutamide is a second-generation antiandrogen effective in patients with CRPC before and after taxane-based chemotherapy. However, CRPC is still incurable and can develop drug resistance. Understanding the mechanisms of this resistance can enable new-generation therapies for CRPC. Several promising new AR-targeted therapies have been developed. Apalutamide is a new Food and Drug Administration-approved androgen agonist binding to the ligand-binding domain, and clinical trials of other new AR-targeted agents binding to the ligand-binding domain or N-terminal domain are underway. This review focuses on the functions of AR in prostate cancer and the development of CRPC and promising new agents against CRPC.
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Firmicutes in Gut Microbiota Correlate with Blood Testosterone Levels in Elderly Men
Matsushita Makoto,Fujita Kazutoshi,Motooka Daisuke,Hatano Koji,Hata Junya,Nishimoto Mitsuhisa,Banno Eri,Takezawa Kentaro,Fukuhara Shinichiro,Kiuchi Hiroshi,Pan Yue,Takao Toshifumi,Tsujimura Akira,Yach 대한남성과학회 2022 The World Journal of Men's Health Vol.40 No.3
Purpose: In males, testosterone levels have been implicated in various diseases. Recently, the influence of gut microbialderived compounds on host metabolism has become evident, and it has been suggested that some gut bacteria may be involved in testosterone metabolism. In the present study, we examined the relationship between testosterone levels and gut microbiota in elderly Japanese men. Materials and Methods: We collected samples from Japanese male subjects suspected of having prostate cancer and underwent prostate biopsies and excluded patients with positive biopsies to avoid the effect of prostate cancer on the gut microbiota. In total, 54 Japanese males with negative biopsy results were included in our study. The gut microbiota was analyzed by 16S rRNA gene sequencing of bacterial DNA extracted from rectal swabs. Gut microbiota compositions were compared between the two groups according to the level of serum testosterone (above or below 3.5 ng /mL). Results: The median age of the cohort was 71 years, and the quartile range was 67 to 73 years. We observed no significant difference in alpha or beta diversity, but some bacteria belonging to the phylum Firmicutes (Clostridiales, Turicibacter, and Gemella) were increased in the high testosterone group. Serum testosterone levels positively correlated with the relative amount of Firmicutes (rS=0.3323, p=0.0141), and the amount of Firmicutes affected serum testosterone levels independent of host factors (age, body mass index, triglyceride, and total cholesterol; β=0.770, p=0.0396). Conclusions: Some intestinal bacteria belonging to the phylum Firmicutes were associated with testosterone levels in elderly males. Therefore, the gut microbiota could affect testosterone metabolism in elderly males.
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Erectile Dysfunction in Germ Cell Tumor Survivors
Okada Koichi,Fujita Kazutoshi,Fukuhara Shinichiro,Kiuchi Hiroshi,Uemura Motohide,Imamura Ryoichi,Nonomura Norio 대한남성과학회 2021 The World Journal of Men's Health Vol.39 No.3
Purpose: Germ cell tumors (GCTs) are the most common malignant neoplasms in adolescents and young adults, and most patients with these tumors can be completely cured. Therefore, maintaining quality of life (QOL) is important. Erectile dysfunction (ED) is one factor that reduces the QOL of GCT survivors. We aimed to clarify the relationship between ED and age, follow-up period, serum levels of hormones, and treatment methods for GCT survivors. Materials and Methods: We evaluated ED using the Sexual Health Inventory for Men questionnaire (SHIM) and measured serum levels of hormones in survivors after GCT treatment. The relationships between the SHIM score responses and age, serum levels of hormones, follow-up period, and treatment methods were assessed using a logistic analysis. Results: Fifty-two GCT survivors were enrolled and 46 survivors completed the SHIM. The median age, follow-up period, and SHIM score were 38 years, 35 months, and 18, respectively. Regarding the SHIM scores, 85% had scores <22 and 46% had scores <17. The percentage of SHIM scores <17 was 69% in patients with under 2 years of follow-up. It significantly improved to 33% in patients with over 2 years of follow-up. The multivariate analysis identified the follow-up period as an independent factor for SHIM scores <17. Age, serum levels of hormone, and treatment method were not significant factors for SHIM scores <17. Conclusions: Improvement of SHIM score can be expected after GCT treatment regardless of age, serum levels of hormone, and treatment method.
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