Vascular endothelial growth factor trap combined with paclitaxel strikingly inhibits tumor and ascites, prolonging survival in a human ovarian cancer model
| Autor: | Judith Hofmann, George D. Yancopoulos, Anil K. Sood, Robert B. Jaffe, Jocelyn Holash, Limin Hu |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cancer Research medicine.medical_specialty Time Factors Combination therapy Paclitaxel Mice Nude Apoptosis Cachexia Metastasis chemistry.chemical_compound Mice Necrosis In vivo Internal medicine Cell Line Tumor Ascites Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Neoplasm Metastasis Ovarian Neoplasms Analysis of Variance business.industry medicine.disease Antineoplastic Agents Phytogenic Vascular endothelial growth factor Disease Models Animal Endocrinology Treatment Outcome Oncology chemistry Cancer research Female medicine.symptom business Ovarian cancer Neoplasm Transplantation |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 11(19 Pt 1) |
| ISSN: | 1078-0432 |
| Popis: | Ovarian cancer is characterized by i.p. carcinomatosis and massive ascites. Vascular endothelial growth factor (VEGF) plays a pivotal role in tumor angiogenesis and vascular leakage leading to ascites. We assessed the efficacy of a soluble decoy receptor (VEGF Trap) combined with paclitaxel, in a mouse model of human ovarian cancer. Tumor burden after VEGF Trap plus paclitaxel was reduced by ∼98% versus controls. No measurable ascites developed in the treated group. Morphologic studies showed that most residual tumor had degenerative changes. Diaphragmatic and hepatic tumors were not found in the VEGF Trap plus paclitaxel group in contrast to controls, indicating lack of metastasis. In vivo FITC-lectin tumor vessel imaging showed sparse, short, straight vessels in treated mice as compared to controls, in which vessels were numerous, irregular, tortuous, and leaky. In a survival study, all controls underwent euthanasia between 29 and 58 days after tumor cell inoculation (cachexia, extensive ascites, and tumor masses). In the VEGF Trap plus paclitaxel group, mice were ambulating and eating normally with no signs of disease for at least 81 days after tumor cell inoculation, and survival occurred for 129.9 ± 38.88 days with no further treatment. We conclude that combination therapy with VEGF Trap plus paclitaxel may provide a novel, long-lasting therapeutic strategy for treatment of patients with ovarian cancer associated with ascites. |
| Databáze: | OpenAIRE |
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