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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 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

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Experimental infection with Yersinia pseudotuberculosis in European brown hare(Lepus europaeus,Pallas)

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Asian Pacific Journal of Tropical Medicine 2017年第3期10卷 269-274页

作者： Filippo Fratini Ranieri Verin Valentina V.Ebani Cecilia Ambrogi Fabrizio Bertelloni Barbara Turchi Alessandro Poli Domenico Cerri Dipartimento di Scienze Veterinarie Universita di PisaPisa Italy Department of Veterinary Pathology and Public Health Institute of Veterinary ScienceUniversity of LiverpoolUK Corpo Forestale dello Stato Azienda Faunistica di MontefalconePisaItaly

Objective:To investigate clinicopathological,bacteriological and pathological aspects of an experimental infection with Yersinia pseudotuberculosis(Y.pseudotuberculosis)in hares in order to verify the efficacy of serology for the in vivo diagnosis.Moreover,the pathogenicity of two Y.pseudotuberculosis strains was investigated in order to detect potential differences.Methods:Twelve European brown hares(Lepus europaeus,Pallas)were experimentally infected per os and via conjunctival mucosae with Y.pseudotuberculosis:six subjects were infected with a strain isolated from a naturally infected hare(YpH)and six subjects with a strain isolated from a naturally infected rabbit(YpR).Two hares were used as negative controls.All animals were subjected to clinical,bacteriological and serological examinations during 9 weeks following the infection and,at the end of the control period,subjects still alive were euthanized and submitted to a complete post mortem examination.Results:All faecal samples collected during the control period were positive for bacteriological examinations and to a PCR for the inv gene of Y.pseudotuberculosis,while only one Yp H-infected hare showed a positive haemocultures.From the 2nd to the 9th week post infection(pi),serological analysis revealed specific antibodies with titers ranging from 1:10 to 1:160 in all YpH-infected and two YpR-infected subjects.All the Yp H-infected and two Yp R-infected hares scored positive for Y.pseudotuberculosis by means of bacteriological investigations.Grossly,suppurative multifocal lesions were detected in liver,spleen,kidney and sub-mandibular lymph nodes in both YpH-and YpR-infected hares and confirmed with histopathology.Pulmonary lesions were observed only in Yp H-infected subjects.immunohistochemistry confirmed the presence of bacterial antigen in all infected animals.Conclusion:Results of this study revealed that YpH strain is more pathogenic for hares than the YpR strain;moreover the serological test performed in this study could be used for the diagnosis of p

关键词： Yersinia pseudotuberculosis Hare Bacteriology Serology Histopathology immuno histochemistry

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