Antivascular Therapy for Orthotopic Human Ovarian Carcinoma through Blockade of the Vascular Endothelial Growth Factor and Epidermal Growth Factor Receptors
| Autor: | Monique B. Nilsson, Kenji Yokoi, Rachel Tsan, Sun Jin Kim, Junqin He, Isaiah J. Fidler, Sertac Yazici, Anil K. Sood, Premal H. Thaker |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cancer Research medicine.medical_specialty Paclitaxel Blotting Western Mice Nude Drug Administration Schedule Cell Line Mice chemistry.chemical_compound Peritoneal cavity Growth factor receptor Epidermal growth factor Cell Line Tumor Proliferating Cell Nuclear Antigen Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans AEE788 Epidermal growth factor receptor Cell Proliferation Ovarian Neoplasms Dose-Response Relationship Drug biology business.industry Immunohistochemistry Survival Analysis Xenograft Model Antitumor Assays ErbB Receptors Mice Inbred C57BL Platelet Endothelial Cell Adhesion Molecule-1 Vascular endothelial growth factor Vascular endothelial growth factor A Treatment Outcome medicine.anatomical_structure Endocrinology Oncology chemistry Drug Resistance Neoplasm Purines Mice Inbred CBA Cancer research biology.protein Blood Vessels Female business |
| Zdroj: | Clinical Cancer Research. 11:4923-4933 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: We determined whether the administration of the tyrosine kinase inhibitor, AEE788, which targets the epidermal growth factor receptor and the vascular endothelial growth factor receptor, alone or in combination with paclitaxel, can inhibit progressive growth of human ovarian carcinoma in the peritoneal cavity of female nude mice. Experimental Design: Western blot analysis and immunohistochemical analysis identified the optimal dose and schedule of AEE788 therapy. In several different experiments, paclitaxel-sensitive and paclitaxel-resistant human ovarian carcinoma cells were injected into the peritoneal cavity of nude mice. Seven days later, treatment with saline (control), AEE788 alone, paclitaxel alone, or a combination of AEE788 and paclitaxel began and continued for 45 days when the mice were necropsied. In independent survival experiments, the mice were necropsied when they became moribund. Results: Oral administration of AEE788 inhibited phosphorylation of the epidermal growth factor receptor and vascular endothelial growth factor receptor for up to 48 hours. Treatment with AEE788 plus paclitaxel significantly reduced tumor weight and increased survival of mice implanted with paclitaxel-sensitive cell lines compared with control mice or mice treated with AEE788 alone or paclitaxel alone. In mice implanted with paclitaxel-resistant cells, the combination therapy also significantly reduced tumor weight but did not prolong survival. The combination therapy induced apoptosis of both tumor cells and tumor-associated endothelial cells. Conclusions: The administration of AEE788 and paclitaxel inhibits the progression of human ovarian carcinoma in the peritoneal cavity of female nude mice, in part, by inducing apoptosis of tumor-associated endothelial cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|