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Adenoviral mediated suicide gene transfer in the treatment of pancreatic cancer / 中华医学杂志(英文版)
Chinese Medical Journal ; (24): 1205-1208, 2002.
Article in English | WPRIM | ID: wpr-340356
ABSTRACT
<p><b>OBJECTIVE</b>To determine the efficacy of adenovirus mediated suicide gene transduction combined with prodrug 5-fluorocytosine (5FC) as a therapeutic protocol for pancreatic cancer.</p><p><b>METHODS</b>Cytosine Deaminase(CD) gene was cloned into pAdTrack-CMV-CD, pAdTrack-CMV-CD and pAdEasy-1 were recombined in bacteria. The newly recombined adenovirus (Ad)-CD containing green fluorescent protein (GFP) were packaged and propagated in 293 cells and purified by cesium chloride gradient centrifugation. Human pancreatic carcinoma cell line-Patu8988 was infected with this virus, then 5FC was added. XTT assay was used to estimate relative numbers of viable cells. In vivo model of pancreatic cancer was established by injecting 1.0 x 10(7) Patu8988 cells subcutaneously in Balb/c nude mice. When tumors were palpable, Ad-CD was injected into each tumor and 5FC was administered.</p><p><b>RESULTS</b>Positive clones were selected using endonuclease to digest the recombinants and the concentration of viral liquids containing the CD gene was 2 x 10(11) pfu /ml. Significant cytotoxic activity as shown for 5FC in the CD gene transduced 8988 cell line, while little effect was found in the nontransduced pancreatic carcinoma cells. Antitumor effect was observed in Patu8988 xenograft nude mice with in situ CD gene transduction.</p><p><b>CONCLUSIONS</b>CD gene mediated by adenovirus has high infectivity and may be useful for gene therapy in pancreatic carcinoma. These data demonstrate the use of an enzyme prodrug strategy in experimental pancreatic cancer.</p>
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Pancreatic Neoplasms / Therapeutics / Genetic Therapy / Adenoviridae / Gene Transfer Techniques / Cytosine Deaminase / Genetic Vectors / Genetics / Mice, Inbred BALB C / Nucleoside Deaminases Type of study: Practice guideline Limits: Animals / Humans Language: English Journal: Chinese Medical Journal Year: 2002 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pancreatic Neoplasms / Therapeutics / Genetic Therapy / Adenoviridae / Gene Transfer Techniques / Cytosine Deaminase / Genetic Vectors / Genetics / Mice, Inbred BALB C / Nucleoside Deaminases Type of study: Practice guideline Limits: Animals / Humans Language: English Journal: Chinese Medical Journal Year: 2002 Type: Article