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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-8-19
pubmed:abstractText
Pancreatic cancer is the fifth leading cause of cancer death in the United States. Most patients have obvious metastases or locally advanced disease at the time of presentation. Surgical resection does not significantly change the clinical outcome. Combination chemotherapy induces a partial response but overall survival remains low. The aim of this study was to evaluate the feasibility of adenovirus-mediated suicide gene transduction as a therapeutic approach for pancreatic cancer. A cell line was established from a murine pancreatic ductal adenocarcinoma and intrahepatic tumors were generated by inoculation of pancreatic cancer cells into the left lateral liver lobe. Transduction efficiency was characterized in vitro and in vivo. Intrahepatic tumors were treated by intratumoral adenovirus injection in combination with intraperitoneal administration of ganciclovir. Adenovirus-mediated herpes simplex virus (HSV)-thymidine kinase (tk) gene expression followed by ganciclovir treatment was highly efficient in inhibiting pancreatic cancer cell proliferation in vitro. The proliferation of nontransduced cells was significantly reduced in the presence of HSV-tk expressing cells. Intrahepatic inoculation of pancreatic cancer cells leads to successful formation of solid adenocarcinomas in syngeneic recipients. Ad.RSV-tk injection of the tumor followed by intraperitoneal ganciclovir application caused highly significant tumor volume reduction and necrosis. These results indicate that transduction of the HSV-tk gene followed by ganciclovir is highly efficient for growth inhibition of hepatic metastases of pancreatic carcinoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0885-3177
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25-34
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9211489-Adenocarcinoma, pubmed-meshheading:9211489-Adenoviridae, pubmed-meshheading:9211489-Animals, pubmed-meshheading:9211489-Antiviral Agents, pubmed-meshheading:9211489-Avian Sarcoma Viruses, pubmed-meshheading:9211489-Defective Viruses, pubmed-meshheading:9211489-Female, pubmed-meshheading:9211489-Ganciclovir, pubmed-meshheading:9211489-Gene Therapy, pubmed-meshheading:9211489-Gene Transfer Techniques, pubmed-meshheading:9211489-Genetic Vectors, pubmed-meshheading:9211489-Liver Neoplasms, pubmed-meshheading:9211489-Mice, pubmed-meshheading:9211489-Mice, Inbred C57BL, pubmed-meshheading:9211489-Pancreatic Neoplasms, pubmed-meshheading:9211489-Simplexvirus, pubmed-meshheading:9211489-Thymidine Kinase, pubmed-meshheading:9211489-Tumor Cells, Cultured, pubmed-meshheading:9211489-Virus Replication
pubmed:year
1997
pubmed:articleTitle
Adenoviral-mediated herpes simplex virus thymidine kinase gene transfer: regression of hepatic metastasis of pancreatic tumors.
pubmed:affiliation
Howard Hughes Medical Institute, Department of Cell Biology, Baylor College of Medicine, Houston, Texas, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't