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

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Asian Journal of Urology 2021年第3期8卷 280-288页

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 Department of Pathology St.Marianna University School of Medicine Yokohama-City Seibu HospitalYokohamaKanagawaJapan Department of Pathology Kitasato University School of MedicineSagamiharaKanagawaJapan Department of Urology Kitasato University School of MedicineSagamiharaKanagawaJapan takefumi satoh prostate clinic MachidaTokyoJapan Department of Urology Okayama UniversityOkayamaJapan Center for Innovative clinical Medicine Okayama University HospitalOkayamaJapan Department of Genitourinary Medical Oncology-Research Division of Cancer MedicineThe University of Texas MD Anderson Cancer CenterHoustonTXUSA Division of Nutrition School of Health CareKiryu UniversityMidori-City GunmaJapan

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 *** two cycles of intraprostatic injection of HSV-tk and administration of GCV,radical prostatectomy was ***-fixed,paraffin-embedded sections were evaluated using *** with hormone therapy(HT,n=3)or without neoadjuvant therapy(NT,n=4)that were equivalent in terms of risk were also examined as ***-positive cells were counted in at least three areas in cancer *** indices(LI)were calculated as percentage ***:ssDNA LI in GT increased,indicating apoptosis,as well as tumor-infiltrating lymphocytes and CD68-positive macrophages,compared with their *** 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 ***,there was no significant difference in CD20-positive B cells among the types of *** 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 ***: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

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