Cytopathic effects and local immune responses in repeated neoadjuvant HSV-tk + ganciclovir gene therapy for prostate cancer

Autor: Nobuyuki Yanagisawa, Takefumi Satoh, Ken-ichi Tabata, Hideyasu Tsumura, Yasutomo Nasu, Masami Watanabe, Timothy C. Thompson, Isao Okayasu, Yoshiki Murakumo, Shiro Baba, Masatsugu Iwamura
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Asian Journal of Urology, Vol 8, Iss 3, Pp 280-288 (2021)
Druh dokumentu: article
ISSN: 2214-3882
DOI: 10.1016/j.ajur.2020.06.004
Popis: Objective: Cytopathic effects and local immune response were analyzed histologically in prostatic cancer (PCa) with in situ herpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) gene therapy (GT). Methods: Four high-risk PCa patients who received HSV-tk/GCV GT were investigated. After two cycles of intraprostatic injection of HSV-tk and administration of GCV, radical prostatectomy was performed. Formalin-fixed, paraffin-embedded sections were evaluated using immunohistochemistry. PCa with hormone therapy (HT, n=3) or without neoadjuvant therapy (NT, n=4) that were equivalent in terms of risk were also examined as reference. Immunoreactively-positive cells were counted in at least three areas in cancer tissue. Labeling indices (LI) were calculated as percentage values. Results: ssDNA LI in GT increased, indicating apoptosis, as well as tumor-infiltrating lymphocytes and CD68-positive macrophages, compared with their biopsies. GT cases showed significantly higher numbers of single-stranded DNA (ssDNA) LI, CD4/CD8-positive T cells and CD68-positive macrophages including M1/M2 macrophages than HT or NT cases. However, there was no significant difference in CD20-positive B cells among the types of case. There were strong correlations between CD8+ T cells and CD68+ macrophages (ρ=0.656, p
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