Objective Use of adenoviral mediated delivery of the herpes simplex virus thymidine kinase (HSV-TK) gene as a gene therapy strategy for carcinoma of the pancreas. Summary Background Data Expression of HSV-TK selectively sensitizes cells to the nucleoside analog ganciclovir (GCV). This strategy has been used to treat other compartmentalized tumor models. Therefore, the containment of pancreatic carcinoma makes it amenable to this gene therapy approach. Methods A recombinant adenoviral vector encoding the HSV-TK gene was used to induce GCV sensitivity and test the potential bystander effect in established pancreatic carcinoma cell lines and patient-derived tumor material. Additionally, Balb/C nude mice were injected intraperitoneally with human pancreatic carcinoma cells and treated with GCV (50 mg/kg per day) for 14 days. Results Expression of the HSV-TK gene elicited a significant bystander effect in the presence of GCV. Pancreatic tumor cells injected intraperitoneally into nude mice resulted in significant tumor formation. Treatment of animals with AdCMVHSV-TK and GCV induced a dramatic decrease in overall tumor burden for up to 8 weeks post-GCV treatment. Conclusions Pancreatic carcinoma cells are highly susceptible to transduction with recombinant adenoviral vectors and elicit a potent bystander effect on neighboring tumor cells. Additionally, in vivo treatment of tumor-bearing animals results in dramatic reduction of overall tumor burden, thus providing the rationale for molecular chemotherapy of pancreatic carcinoma.
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BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709
ELION, GB
FURMAN, PA
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BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709
FURMAN, PA
FYFE, JA
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BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709
FYFE, JA
DEMIRANDA, P
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BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709
DEMIRANDA, P
BEAUCHAMP, L
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BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709
BEAUCHAMP, L
SCHAEFFER, HJ
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BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709
机构:
BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709
ELION, GB
FURMAN, PA
论文数: 0引用数: 0
h-index: 0
机构:
BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709
FURMAN, PA
FYFE, JA
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h-index: 0
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BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709
FYFE, JA
DEMIRANDA, P
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h-index: 0
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BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709
DEMIRANDA, P
BEAUCHAMP, L
论文数: 0引用数: 0
h-index: 0
机构:
BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709
BEAUCHAMP, L
SCHAEFFER, HJ
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h-index: 0
机构:
BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709BURROUGHS WELLCOME CO,WELLCOME RES LABS,DEPT ORGAN CHEM,RES TRIANGLE PK,NC 27709