Angiogenesis inhibition with TNP-470, 2-methoxyestradiol, and paclitaxel in experimental pancreatic carcinoma.
BACKGROUND
Inhibition of tumor angiogenesis is a novel therapeutic modality for various malignancies.


OBJECTIVE
To investigate the effect of different antiangiogenic agents (TNP-470, 2-methoxyestradiol, and paclitaxel) on growth and neovascularization of experimental pancreatic cancer.


METHODS
In 25 male Lewis rats, tumor induction was achieved by orthotopic and subcutaneous tumor fragment implantation of ductlike pancreatic cancer DSL6A. Four weeks after tumor implantation, the animals were randomly treated with TNP-470, 2-methoxyestradiol, or paclitaxel. After 2 weeks of antiangiogenic therapy, total tumor volume, vital tumor surface, vascular density, and apoptosis were measured.


RESULTS
Total tumor volume and vital tumor surface were not significantly different in any of the treatment groups. Similarly, vascular density and apoptosis were not altered by treatment with the various angiogenesis inhibitors at the specific doses used.


CONCLUSIONS
We conclude that in contrast to many earlier studies, angiogenesis inhibition by a single-drug application and by the doses used in the present model did not reveal a favorable therapeutic effect on pancreatic cancer DSL6A. The combination of different angiogenesis inhibitors or higher doses might be more effective.
Ryschich
E
E
Department of Surgery, University of Heidelberg, Heidelberg, Germany.
Werner
J
J
Gebhard
M M
MM
Klar
E
E
Schmidt
J
J
D000077584:2-Methoxyestradiol; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003510:Cyclohexanes; D004958:Estradiol / Q000031:analogs & derivatives / Q000627:therapeutic use; D008297:Male; D009368:Neoplasm Transplantation; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D017239:Paclitaxel / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D012717:Sesquiterpenes / Q000627:therapeutic use; D013997:Time Factors; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D004958:Estradiol; D000077584:2-Methoxyestradiol; D017239:Paclitaxel; D000077609:O-(Chloroacetylcarbamoyl)fumagillol