2014 Fiscal Year Final Research Report
Distribution analysis of intraperitoneally administrated nanomicellar drugsin peritoneal metastasis
| Project/Area Number |
24390310
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KITAYAMA Joji 東京大学, 医学部附属病院, 准教授 (20251308)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 腹腔内化学療法 / NK105 / ナノ化抗癌剤 / 繊維化 / 血管新生阻害 |
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| Outline of Final Research Achievements |
Intraperitoneal (IP) administration of nanomicellar PTX (NK105) significantly reduced peritoneal tumors than conventional PTX formulation with similar systemic toxic effects, suggesting the clinical usefulness of IP-NK105. Peritoneal nodules are covered with fibrous capsule containing many CD31(+) microvessels both in human and mice. After IP-PTX, however, the peripheral vessels were greatly reduced in number with luminal obstruction. These findings strongly suggest that the remarkable efficacy of IP-PTX is partly dependent on the destruction of peripheral tumor vessels. CD90(+) cells in human peritoneum vigorously grew in culture and express CAF characteristics by TGF-b, and IP co-injection with MKN45 significantly enhanced peritoneal metastasis in nude mice. The CD90(+) cells were engrafted in metastatic nodules mainly at the fibrous area. Oral administration of Dasatinib significantly inhibited the development of peritoneal metastasis of MKN45 with reduced fibrillar formation.
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| Free Research Field |
腫瘍外科学
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