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

作　　者：Nobuyuki Yanagisawa Takefumi Satoh Ken-ichi Tabata Hideyasu Tsumura Yasutomo Nasu Masami Watanabe Timothy C.Thompson Isao Okayasu Yoshiki Murakumo Shiro Baba Masatsugu Iwamura 

机构地区：[1]Department of Pathology,St.Marianna University School of Medicine Yokohama-City Seibu Hospital,Yokohama,Kanagawa,Japan [2]Department of Pathology,Kitasato University School of Medicine,Sagamihara,Kanagawa,Japan [3]Department of Urology,Kitasato University School of Medicine,Sagamihara,Kanagawa,Japan [4]Takefumi Satoh Prostate Clinic,Machida,Tokyo,Japan [5]Department of Urology,Okayama University,Okayama,Japan [6]Center for Innovative Clinical Medicine,Okayama University Hospital,Okayama,Japan [7]Department of Genitourinary Medical Oncology-Research,Division of Cancer Medicine,The University of Texas MD Anderson Cancer Center,Houston,TX,USA [8]Division of Nutrition,School of Health Care,Kiryu University,Midori-City Gunma,Japan

出　　处：《Asian Journal of Urology》2021年第3期280-288,共9页亚洲泌尿外科杂志（英文）

基　　金：supported by Grants-in-Aid for Scientific Research(JSPS KAKENHI)grant(number 21592060).

摘　　要：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<0.0001)as well as CD4+T cells and CD20+B cells(ρ=0.644,p<0.0001)in PCa with GT.Conclusions:Enhanced cytopathic effect and local immune response might be indicated in PCa patients with HSV-tk/GCV gene therapy.

关 键 词：Suicide genetherapy Prostatecarcinoma HSV-TK GANCICLOVIR Immuno histochemistry 

分 类 号：R737.25[医药卫生—肿瘤]