Metronomic doxifluridine chemotherapy combined with the anti-angiogenic agent TNP-470 inhibits the growth of human uterine carcinosarcoma xenografts
| Autor: | Batsuren Choijamts, Shigenori Ogata, Tatsuhiko Kawarabayashi, Shingo Miyamoto, Kyoko Shirota, Yasuko Naganuma, Kyoko Nakajima, Makoto Emoto |
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| Rok vydání: | 2011 |
| Předmět: |
Vascular Endothelial Growth Factor A
Pathology medicine.medical_specialty Cancer Research Angiogenesis medicine.medical_treatment Angiogenesis Inhibitors Thrombospondin 1 Mice Carcinosarcoma Cyclohexanes In vivo Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Neoplasm Tube formation Mice Inbred BALB C O-(Chloroacetylcarbamoyl)fumagillol Thymidine Phosphorylase Chemotherapy business.industry Endothelial Cells General Medicine medicine.disease Xenograft Model Antitumor Assays Metronomic Chemotherapy Radiation therapy Oncology Uterine Neoplasms Cancer research Female Floxuridine Vascular endothelial growth factor production business Sesquiterpenes |
| Zdroj: | Cancer Science. 102:Aug cover-Aug cover |
| ISSN: | 1347-9032 |
| DOI: | 10.1111/j.1349-7006.2011.01992.x |
| Popis: | Uterine carcinosarcoma is a highly aggressive gynecological neoplasm that responds poorly to conventional chemotherapy and radiotherapy. Metronomic chemotherapy is accepted as a new approach for cancer treatment, and its underlying mechanism seems to involve the suppression of angiogenesis. However, the efficacy of metronomic and anti-angiogenic therapies against uterine carcinosarcoma is unknown. The anti-angiogenic effect of doxifluridine was assessed in vitro using human umbilical vein endothelial cells (HUVEC) co-cultured with FU-MMT-1 human uterine carcinosarcoma cells. The antitumor and anti-angiogenic effects of metronomic doxifluridine (delivered via oral gavage) in combination with TNP-470 were evaluated in vivo. Tumor vascularity was assessed by contrast-enhanced color Doppler ultrasound, laser Doppler and microvessel density staining. Doxifluridine suppressed tube formation of HUVEC and vascular endothelial growth factor production by FU-MMT-1 cells. Metronomic doxifluridine alone significantly suppressed tumor growth compared with the untreated (control) group, while metronomic doxifluridine in combination with TNP-470 significantly inhibited tumor growth compared with each treatment alone. A significant reduction of intratumoral vascularity was observed in FU-MMT-1 xenografts following treatment with metronomic doxifluridine in combination with TNP-470, as compared with each treatment alone. Intestinal bleeding was only observed when the maximum tolerated dose of doxifluridine was administered in combination with TNP-470. Metronomic doxifluridine chemotherapy in combination with TNP-470 might be effective for uterine carcinosarcoma without marked toxicity, possibly acting via its potent anti-angiogenic effects. Clinical studies are needed to evaluate the safety and efficacy of this treatment in humans. |
| Databáze: | OpenAIRE |
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