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Adenovirus-mediated gene transfer in the treatment of pancreatic cancer.

AbstractINTRODUCTION:
Suicide gene therapy is a new experimental form of cancer chemotherapy that is currently being evaluated in human trials.
AIM:
To evaluate the killing effects of the cytosine deaminase (CD) gene mediated by an adenovirus vector on human pancreatic carcinoma in vitro and in vivo.
METHODOLOGY:
The CD gene was cloned into pAdTrack-CMV-CD, pAdTrack-CMV-CD, and pAdEasy-1, which underwent recombination in bacteria BJ5183. The newly recombinant Ad-CD containing green fluorescent protein was propagated in 293 cells and purified by cesium chloride gradient centrifugation. The human pancreatic carcinoma cell line PaTu8988/SW1990 was infected with this virus, and then 5-fluorocytosine (5-FC) was added; XTT assay was used to estimate relative numbers of viable cells. An in vivo model of pancreatic cancer was established by injecting 1.0 x 10(7) PaTu8988/SW1990 cells subcutaneously in Balb/c nude mice. When tumors were palpable, Ad-CD was injected into each tumor, and 5-FC was administered. The positive clones were selected by endonuclease digestion of the combinations, and the concentration of viral liquids containing the CD gene was 2 x 10(11) pfu/mL.
RESULTS:
It was found that significant cytotoxic activities were possessed by 5-FC for CD gene-transduced PaTu8988/SW1990 cells, but there was little effect on the nontransduced pancreatic carcinoma cells. The antitumor effect was observed in PaTu8988/SW1990 xenografts from nude mice with in situ CD gene transduction.
CONCLUSION:
These results indicate that the CD gene mediated by adenovirus has a high level of infectivity and is efficient for gene therapy for pancreatic carcinoma.
AuthorsXue Pan, Zhao-Shen Li, Guo-Ming Xu, Long Cui, Zhen-Xing Tu
JournalPancreas (Pancreas) Vol. 26 Issue 3 Pg. 274-8 (Apr 2003) ISSN: 1536-4828 [Electronic] United States
PMID12657954 (Publication Type: Journal Article)
Chemical References
  • Cytosine Deaminase
Topics
  • Adenoviridae (genetics)
  • Animals
  • Bystander Effect
  • Carcinoma (therapy)
  • Cell Line, Tumor
  • Cytosine Deaminase (genetics)
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Pancreatic Neoplasms (therapy)
  • Transduction, Genetic

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