2001 Fiscal Year Final Research Report Summary
Establishment of a new gene therapy for cancer using antisense ODG and atelocollagen
| Project/Area Number |
12670132
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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 |
Pathological medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KUBOTA Shunichiro Graduate School of Medicine, The University of Tokyo, Assistant Professor, 大学院・医学系研究科, 助教授 (00260480)
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| Project Period (FY) |
2000 – 2001
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| Keywords | cancer / antisense / ODC / atelocollagen / gene therapy |
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| Research Abstract |
Background and Aims: Substantial evidence supports a direct role of ornitine decarboxylase (ODC) in the development and maintenance of human tumors. Although antisenseoligonucleotide therapy targeting various genes are useful for cancer treatment, one of the major limitations is the problem of delivery. We describe here a novel antisense oligonucleotide delivery method which allows prolonged sustainment and release of ODC antisense oligonucleotides in vivo using atelocollagen. Methods: The effect of ODC antisense oligonucleotides in the atelocollagen on cell growth of gastrointestinal cancer (MKN 45 and COLO201), and rhabdomyosarcoma (RD) was studied in vitro using MTT assay. In vivo, the effect of intratumoral, intramuscular and intraperitoneal single administration of ODC antisense oligonucleotides in the atelocollagen on tumor growth of MKN45, COLO201 and RD cells was examined. ODC activity and polyamine contents were measured. Results: In vitro, ODC antisense oligonucleotides in the atelocollagen remarkably suppressed MKN45, COLO201 and RD cell growth. A single administration of antisense oligonucleotides in the atelocollagen via three routes remarkably suppressed the growth of MKN45, COLO201 and RD tumor over a period of 3542 days. Conclusion: As various human cancers significantly express ODC, the results strongly suggest that this new antisense method may be of considerable value for treatment of human cancers.
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Research Products
(8 results)
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[Publications] Takei, Y., Kadomatsu, K., Matsuo, S., Nakazawa, K., Kubota, S., Muramatsu, T.: "Antisense oligonucleotides targetted to midkine, a heparin-binding growth factor, suppresses tumorigenicity of mouse rectal carcinoma cells"Cancer Res.. 61. 8486-8491 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Takei, Y., Kadomatsu, K., Matsuo, S., Nakazawa, K., Kubota, S. and Muramatsu, T.: "Antisense oligonucleotides targetted to midkine, a heparin-binding growth factor, suppresses tumorigenicity of mouse rectal carcinoma cells."Cancer Res.. 61. 8486-8491 (2001)
Description
「研究成果報告書概要(欧文)」より
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