Publication: Suicide gene therapy with Herpes
simplex virus thymidine kinase and
ganciclovir is enhanced with connexins
to improve gap junctions and bystander effects
Authors
Nicholas, T.W. ; Read, S.B. ; Burrows, F.J. ; Kruse, C.A.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Connexins are proteins that form gap
junctions between cells in various mammalian tissues.
Because of their role in intercellular communication,
connexins are important in the bystander cell death seen
in Herpes simplex virus-thymidine kinase (HSV-TK)
gene therapy for brain tumors. A selective review of
connexin transduction/transfection studies with
particular emphasis to central nervous system tumor
cells is presented. In addition, specific references to
studies with cell types that demonstrate low gap junction
intercellular communication are presented. Data are
included with the HT-29 colorectal tumor cell line to
support the concept that enhancing gap junction protein
expression in otherwise low gap junction communicating
HT-29 cells increases bystander cell death and reduces
tumor burden beyond what might be expected from
HSV-TK and ganciclovir (GCV) treatment alone.
Maximum in vitro bystander cell death was always
produced when GCV treated co-cultures of TKtransduced
and non-TK-transduced HT-29 cell lines
were also transduced with connexin-43. When connexin
was present in only one group of cells in the co-culture,
there was more bystander cell death observed with
connexin transduced into the non- TK-transduced cells,
rather than the TK-transduced cells. The data presented
reinforces conclusions made from earlier findings from
cell line mixing experiments in which the non- TKtransduced
cell population determined the level of
bystander cell death (Burrows et al., 2002).
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