Inhibition of tumor angiogenesis through chondromodulin-I gene transfer
| Project/Area Number |
16591295
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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 | Chiba University |
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Principal Investigator |
OHTSUKA Masayuki Chiba University, Hospital, Research Associate, 医学部附属病院, 助手 (90334185)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Masaru Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (70166156)
ITO Hiroshi Chiba University, Graduate School of Medicine, Associate professor, 大学院・医学研究院, 助教授 (00232463)
SHIMIZU Hiroaki Chiba University, Graduate School of Medicine, Assistant professor, 大学院・医学研究院, 講師 (80272318)
KATO Atsushi Chiba University, Hospital, Research Associate, 医学部附属病院, 助手 (70344984)
KUROSAWA Hisashi Chiba University, Hospital, Senior Resident, 医学部附属病院, 医員 (10375678)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | chondromodulin-I / angiogenesis / gene transfer / mTOR / rapamycin / lymphangiogenesis |
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| Research Abstract |
In our first study, we examined whether insertion of chondoromodulin-I gene into the cancer tissue could inhibit tumor growth through the prevention of tumor angiogenesis. Chondoromodulin-I was identified as an angiogenesis inhibitor derived from extracts of fetal epiphyseal cartilage, which is normally devoided of capillary network. At present, although chondoromodulin-I protein was detected in vitro after transfection, the efficiency was not high after chondormodulin-I gene transfer with several vectors, especially in vivo. Therefore, inhibition of tumor growth and reduction of microvessel density were not significant. We are now developing a new vector to provide for efficient gene transfer.
In our second study, we investigated the effect of rapamycin (inhibitor of mammalian target of rapamycin (mTOR)) on the proliferation activity of several cell lines including cancer cells and the expression of angiogenesis-related molecules such as vascular endothelial growth factor (VEGF) family, angiopoietin family. Tumor growth was also evaluated in vivo after administration of rapamycin. In vitro, the levels of VEGF-A mRNA and protein expressions were significantly decreased after treatment of rapamycin with even relatively low dose. In addition, the expression level of VEGF-C, which is a strong promoter of lymphangiogenesis, was also found to be down-regulated. In vivo, tumor growth was significantly inhibited. These results suggest that rapamycin could inhibit not only angiogenesis but also lymphangiogenesis. Based on these results, we are now investigating whether rapamycin could prevent lymph node metastasis by inhibiting cancer lymphangiogenesis.
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Report
(3 results)
Research Products
(11 results)
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[Journal Article] Relationship between pancreatic secretory trypsin inhibitor and early recurrence of intrahepatic cholangiocarcinoma following surgical resection.
Author(s)
Tonouchi A, Ohtsuka M, Ito H, Kimura F, Shimizu H, Kato M, Nimura Y, Iwase K, Hiwasa T, Seki N, Takiguchi M, Miyazaki M.
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Journal Title
Am J Gastroenterol (in press)
Description
「研究成果報告書概要(欧文)」より
Related Report
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