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Herpes simplex virus thymidine kinase/ganciclovir-mediated apoptotic death of bystander cells.
Hamel, W; Magnelli, L; Chiarugi, V P; Israel, M A.
Afiliação
  • Hamel W; Preuss Laboratory Molecular Neuro-oncology, Brain Tumor Research Center, University of California, USA.
Cancer Res ; 56(12): 2697-702, 1996 Jun 15.
Article em En | MEDLINE | ID: mdl-8665496
An emerging strategy for cancer gene therapy involves the transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene into tumor cells, rendering them susceptible to the cytotoxic effects of ganciclovir. The observation that HSV-tk-expressing cells can also induce cell death in neighboring cells, which do not express HSV-tk, has been called the bystander effect. Gap junction-mediated transfer of cytotoxic molecules to bystander cells may be an important mechanism of bystander cell death, although others have suggested a role for phagocytosis. In this study, we evaluated the mode of cell death in bystander cells. We detected apoptosis in bystander cells and found that bystander cell death could be inhibited by BCL2 expression. We determined that ganciclovir incubations for 10 h were sufficient to induce cell death in most bystander cells cocultured with HSV-tk-expressing cells. During this period, no phagocytosis was detected, although it was obvious at later stages.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Fagocitose / Timidina Quinase / Proteínas Virais / Ganciclovir / Apoptose / Simplexvirus / Técnicas de Transferência de Genes / Genes Virais Limite: Animals / Humans Idioma: En Revista: Cancer Res Ano de publicação: 1996 Tipo de documento: Article País de afiliação: Estados Unidos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Fagocitose / Timidina Quinase / Proteínas Virais / Ganciclovir / Apoptose / Simplexvirus / Técnicas de Transferência de Genes / Genes Virais Limite: Animals / Humans Idioma: En Revista: Cancer Res Ano de publicação: 1996 Tipo de documento: Article País de afiliação: Estados Unidos