Cytopathic effect of in situ gene therapy in prostate cancer

Gustavo Ayala, Thomas M. Wheeler, Moshe Shalev, Timothy C. Thompson, Brian J. Miles, Estuardo Aguilar-Cordova, Subhendu Chakraborty, Dov Kadmon

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

This is a morphologic study of in sire gene therapy effects in patients with prostate cancer using the Herpes Simplex Virus-Thymidine Kinase gene (HSV-tk) followed by ganciclovir. Prostatectomy specimens from the first 4 patients showed the following morphologic changes: (1) various degrees of necrosis were seen in cancer foci; (2) cytopathic changes were seen across the whole spectrum of Gleason grades; (3) the normal prostate was rarely affected by necrosis, but contained an intense mononuclear infiltrate; (4) loss of nuclear detail was a common finding. Volumetric studies showed that only portions of the tumor show morphologic effects as well as an inverse relationship between percentage of affected tumor and prostate and tumor size. An inflammatory response was observed, with predominance of CD20- positive cells in normal prostate tissue, CD8 (cytotoxic T cells) in the tumor, and macrophages in all areas of the treated prostates. We believe that these changes represent the cytopathic effect of our in situ gene therapy on prostate cancer, and that they trigger a local immune response. (C) 2000 by W.B. Saunders Company.

Original languageEnglish (US)
Pages (from-to)866-870
Number of pages5
JournalHuman Pathology
Volume31
Issue number7
DOIs
StatePublished - 2000

Keywords

  • Gene therapy
  • Morphology
  • Prostate cancer

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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