MISC

2011年8月

Metronomic doxifluridine chemotherapy combined with the anti-angiogenic agent TNP-470 inhibits the growth of human uterine carcinosarcoma xenografts

CANCER SCIENCE
  • Yasuko Naganuma
  • ,
  • Batsuren Choijamts
  • ,
  • Kyoko Shirota
  • ,
  • Kyoko Nakajima
  • ,
  • Shigenori Ogata
  • ,
  • Shingo Miyamoto
  • ,
  • Tatsuhiko Kawarabayashi
  • ,
  • Makoto Emoto

102
8
開始ページ
1545
終了ページ
1552
記述言語
英語
掲載種別
DOI
10.1111/j.1349-7006.2011.01998.x
出版者・発行元
WILEY-BLACKWELL

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. (Cancer Sci 2011; 102: 1545-1552)

リンク情報
DOI
https://doi.org/10.1111/j.1349-7006.2011.01998.x
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000292863700016&DestApp=WOS_CPL
ID情報
  • DOI : 10.1111/j.1349-7006.2011.01998.x
  • ISSN : 1347-9032
  • Web of Science ID : WOS:000292863700016

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