| Project/Area Number |
15591403
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Osaka University |
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Principal Investigator |
KITAGAWA Toru Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40314322)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Toshinori Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 寄附講座教授 (20231152)
NISHIDA Toshiro Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (40263264)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Pancreatic Cancer / Liver Metastasis / Liposome / Chondroitin sulfate / TRX-20 / ポリエチレングリコール・リポソーム |
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| Research Abstract |
Pancreatic cancer is one of the most refractory cancers, because liver metastasis that is discovered at the same time of diagnosis of pancreatic cancer or at post operative period is lethal factor for cure.
So the novel strategy is required to control metastasis of pancreatic cancer.
Significant increases in CS were reported in a variety of neoplasms including pancreatic cancer. Indeed, the expression of CS in pancreatic cancer clinically respected in our institute was significantly higher than normal pancreas and gastric cancer.
In previous study, CS expressed on highly metastatic tumor cells was used as a target for the selective delivery of anti-cancer drugs by polyethylene glycol-coated liposomes containing new cationic lipid (TRX-20). Cisplatin-loaded TRX-20 liposomes significantly suppressed the local growth and liver metastasis of CS-expressing tumor cells comparing with cisplatin-loaded plain liposomes or free cisplatin in vivo.
We investigated the effectiveness of Gemcitabine-load
… More
ed TRX-20 liposomes (TRX-20L-Gem) on human pancreatic cancer cells. TRX-20L-Gem killed the CS-expressing tumor cells (CFPAC-1) in vitro cytotoxicity assay under the experimental conditions of co-culturing with drugs, whereas TRX(-)-Gem were totally ineffective. Therapeutic experiments in mice bearing CFPAC-1 tumor revealed that TRX-20L-Gem were significantly more effective in reducing the local tumor growth than free Gemcitabine or TRX(-)-Gem. Moreover TRX-20L-Gem prevents liver metastasis in mice within 30 days after tumor inoculation, however mice treated with saline, free Gemcitabine, and TRX(-)-Gem suffered from liver metastasis of CFPAC-1 on day30. These data suggest that the CS-targeted delivery of Gemcitabine by our liposomes represents a potentially useful strategy to prevent the local growth and liver metastasis of human pancreatic cancer cells that have enhanced expression of CS.
These data suggest that the CS-targeted delivery of Gemcitabine by our liposomes represents a potentially useful strategy to prevent the liver metastasis of human pancreatic cancer cells that have enhanced expression of CS. Less
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