Improvement of gene therapy for ovarian cancer by using acyclovir instead of ganciclovir in adenovirus mediated thymidine kinase gene therapy.

Abstract:

:Adenovirus(ADV) mediated thymidine kinase(TK) gene therapy followed by ganciclovir(GCV) administration is widely used in different types of cancer. ACV shares the same mechanism of selective cell killing in ADV/TK positive cells as GCV and can be used at 4.5 times higher doses in patients without significant side effects. An increased dose of TK substrate is associated with improved bystander effect and more efficient cell killing. Toxicity and cell killing efficacy were assessed using a 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide(MTT) based assay in three ovarian cancer cell lines with different proliferation patterns. At the same concentration, equal or higher cell killing efficacy and bystander effect were observed using ACV rather than GCV. 2.5 and 5 times (25 micrograms/ml and 50 micrograms/ml) higher concentrations of ACV always resulted in more effective cell killing than GCV (10 micrograms/ml, P < 0.01). Our data indicate that replacing GCV with ACV in the ADV-TK gene therapy may increase the treatment effect without increasing toxicity.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Tong XW,Engehausen DG,Kaufman RH,Agoulnik I,Contant C,Freund CT,Oehler MK,Kim TE,Hasenburg A,Woo SL,Kieback DG

subject

Has Abstract

pub_date

1998-03-01 00:00:00

pages

713-8

issue

2A

eissn

0250-7005

issn

1791-7530

journal_volume

18

pub_type

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