| Project/Area Number |
11470276
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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 |
Thoracic surgery
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| Research Institution | NAGOYA CITY UNIVERSITY |
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Principal Investigator |
FUJII Yoshitaka Nagoya City University, Medical School, Professor, 医学部, 教授 (40156831)
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| Co-Investigator(Kenkyū-buntansha) |
KAJI Masahiro Nagoya City University, Medical School, Research Associate, 医学部, 助手 (30326144)
KIRIYAMA Masanobu Nagoya City University, Medical School, Assistant Professor, 医学部, 講師 (30244552)
YAMAKAWA Yosuke Nagoya City University, Medical School, Associate Professor, 医学部, 助教授 (40148284)
YANO Motoki Nagoya City University, Medical School, Research Fellow, 医学部, 研究員 (40315883)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥17,200,000 (Direct Cost: ¥17,200,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥14,800,000 (Direct Cost: ¥14,800,000)
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| Keywords | endostatin / transfection / nonviral vector / lung metastases model / antiangiogenic factor / アンジオスタチン |
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| Research Abstract |
Inhibition of angiogenesis by production of antiangiogenic factors should be a viable approach for cancer gene therapy. Recently, nonviral vectors have been suggested as an alternative to viruses. In this study, we investigated whether intravenous administration of endostatin gene complexed with GL67/DOPE or PEI22K could inhibit the development of lung metastatic lesions in murine models. The biological activity of the expressed endostatin was also determined by its ability to prevent the growth of lung metastases using stable transfectants from murine NFSa Y83 fibrosarcoma cells expressing endostatin. RT-PCR analysis in various organs of mice after intravenous injection of endostatin gene complexed with GL67/DOPE or PEI22K showed that the highest levels of mRNA expression were found in the lung, followed by heart, spleen, kidney and liver. In addition, immunohistochemistry of whole lungs after intravenous injection of the complexes showed that transfected cells were localized in a variety of cell types, including respiratory cells. Single intravenous injection of endostatin gene complexed either GL67/DOPE or PEI22K at the time of 3 days or 7 days from fibrosarcoma cells implantation resulted in striking inhibition of formation of lung metastases after 2 weeks (compared to empty plasmid complexed each vector, 87-98% reduction in the number of lung metastases and 53-59% reduction in lung weight). These results demonstrated the potential usefulness of intravenous delivery of an antiangiogenic gene, using cationic vector-mediated gene transfer, for treatment of disseminated cancers in lung.
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