{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:24:15Z","timestamp":1760189055276},"reference-count":26,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1995,10]]},"abstract":"<jats:p content-type=\"fine-print\">\u2713 Retrovirus-mediated herpes simplex virus\u2014thymidine kinase (HSV-tk) gene therapy is a promising approach in the treatment of brain tumors. Previous <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> studies have demonstrated a bystander effect in which nonmodified tumor cells in proximity to HSV-tk\u2014modified tumor cells are killed with the modified cells in the presence of ganciclovir. In the present study the authors assessed the contribution of infectious HSV-tk retrovirus made by producer cells to the bystander cytocidal effect in tissue culture using Walker 256 rat breast carcinosarcoma cells, which represent an established model for carcinomatous meningitis. The authors observed ganciclovir-dependent growth inhibition even when only one HSV-tk\u2014positive Walker cell was mixed with 1000 HSV-tk\u2014negative Walker cells and showed that the bystander cytocidal effect is not mediated by toxic cell lysis products. Walker cells engineered to produce HSV-tk retrovirus with titers ranging from 10<jats:sup>3<\/jats:sup> to 10<jats:sup>5<\/jats:sup> colony-forming units\/ml exert no greater cytocidal effect than nonviral producer HSV-tk\u2014positive Walker cells <jats:italic>in vitro<\/jats:italic>. Murine fibroblast\u2014producer cells with viral titers ranging from 10<jats:sup>6<\/jats:sup> to 10<jats:sup>7<\/jats:sup> colony-forming units\/ml exerted a stronger cytocidal effect than nonviral producer HSV-tk\u2014positive murine fibroblasts. Despite the high viral titers of fibroblast producer cells, HSV-tk\u2014modified Walker cells performed better than fibroblast producer cells in their cytotoxic effect on wild\u2014type Walker tumor cells. Given that HSV-tk\u2014modified tumor cells can become ganciclovir resistant, we tested \u03b3-irradiation as a means to overcome resistance. Lethal \u03b3-irradiation of the HSV-tk\u2014positive Walker cells did not abolish their bystander effect on Walker HSV-tk\u2014negative cells. One can infer from these results that HSV-tk\u2014modified tumor cells, irradiated or not, may be a better alternative to murine fibroblast producer cells in the treatment of central nervous system neoplasia.<\/jats:p>","DOI":"10.3171\/jns.1995.83.4.0698","type":"journal-article","created":{"date-parts":[[2009,6,2]],"date-time":"2009-06-02T16:58:27Z","timestamp":1243961907000},"page":"698-704","source":"Crossref","is-referenced-by-count":12,"title":["A more potent bystander cytocidal effect elicited by tumor cells expressing the herpes simplex virus\u2014thymidine kinase gene than by fibroblast virus\u2014producer cells in vitro"],"prefix":"10.3171","volume":"83","author":[{"given":"Fotios D.","family":"Vrionis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian 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