2007 Fiscal Year Final Research Report Summary
Establishment of anti-angiogenesis therapy combined with Ultrasound irradiation for human cancer
| Project/Area Number |
17300178
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical systems
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| Research Institution | Fukuoka University |
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Principal Investigator |
EMOTO Makoto Fukuoka University, Faculty of Medicine, Assistant Professor (80258540)
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| Co-Investigator(Kenkyū-buntansha) |
TACHIBANA Katsuro Fukuoka University, Faculty of Medicine, Professor (40271605)
HORIUCHI Shinji Fukuoka University, Faculty of Medicine, Assistant Professor (70360302)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Angiogenesis / anti-angiogenesis therapy / cancer therapy / ultrasound / ultrasound therapy / molecular target therapy / sarcoma / drug delivery system |
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| Research Abstract |
The microvascular endothelial cells, which are recruited by tumors, have become an important target in cancer therapy. This study firstly examined the antitumor effect of angiogenesis inhibitor combined with ultrasound (US) irradiation for human cancer in vivo and evaluated its vascularity by color Doppler US in real time using a microbubble US contrast agent. A human uterine sarcoma cell line, FU-MMT-1, was used in vivo because this tumor is one of the most malignant neoplasm of the human solid tumors and it also has a poor response to any of the chemotherapeutic agents currently used as well as to radiotherapy. In angiogenic inhibitors, TNP-470 was selected to use in an in vivo study, because this agent showed a higher inhibitory effect in tube formation assay in vitro, than that of FR118487, or thalidomide. The FU-MMT-1 xenografts in nude mice were treated by US at a low-intensity (2.0 w/cm^2, 1MHZ) for 4 min three times per week each after the subcutaneous injection of TNP-470 (30 mg/kg), an angiogenesis inhibitor, and this treatment was continued for eight weeks. Either treatment of US alone or TNP-470 alone showed a suppression of tumor growth, in comparison to the non-treatment group (control), and a significantly enhanced effect was obtained by the combined treatment. A reduction in the intratumoral vascularity, which was evaluated by both color Doppler and immunohistochemistry, was significantly demonstrated by the combined treatment, in comparison to each treatment alone, and the control. No side effect was observed in any mice in the combined treatment group. These results suggest that anti-tumor effect of TNP-470 for uterine sarcoma was accelerated by US irradiation in vivo and this combination might be a potentially effective for new cancer therapy.
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