| Project/Area Number |
05404047
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Chiba University School of Medicine |
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Principal Investigator |
YAMAGUCHI Yutaka Institute of Pulmonary Cancer Research, Professor Chiba University School of Medicine, 医学部, 教授 (80009448)
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| Co-Investigator(Kenkyū-buntansha) |
MITSUNUGA Shinichiro Chiba University Hospital Assistant, 医学部・附属病院, 助手 (50272331)
SUITO Yukio Chiba University Hospital Assistant, 医学部・附属病院, 助手 (60261905)
SHIBA Mitutoshi Chiba University Hospital Associate Professor, 医学部・附属病院, 講師 (20162620)
BABA Masayuki Chiba University Hospital Associate Professor, 医学部・附属病院, 講師 (00143305)
IIZASA Toshihiko Institute of Pulmonary Cancer Research, Assistant Chiba University School of Med, 医学部, 助手 (10272303)
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| Project Period (FY) |
1993 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥29,600,000 (Direct Cost: ¥29,600,000)
Fiscal Year 1996: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1995: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1994: ¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 1993: ¥9,700,000 (Direct Cost: ¥9,700,000)
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| Keywords | Lung Cancer / Metastasis / Genes associated with Metastasis / Matrix Metalloproteinase / Type IV Collagenase / Gene Therapy / アンチセンスDNA / IV型コラゲナーゼ / アンチセンスオリゴヌクレオチド |
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| Research Abstract |
We planed to examine expression of metastasis relating genes and those proteins and to clone a new gene related to metastasis in lung carcinoma. We thought to be able to clarify a mechanism of metastasis of lung carcinoma and help to diagnose and treat metastasis of lung carcinoma in this study.
In an experiment of expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) which are thought to express cancer tissue and corelate with metastasis of lung carcinoma, we could demonstrate that MMP-2 was more expressed in both cell lines and tissues of lung carcinoma than MMP-9. MMP-2 plays an important role in invasion and metastasis of lung carcinoma. On the other hand, many cases were positively stained in immunohistochemistry of TIMP-2. TIMP-2 was thought not to regulate MMPs suppressively but to work as a growth factor to tumor cells.
We have investigated lavels of MMPs and TIMPs in sera of patients with and without lung carcinoma in order to
… More
find out the relation to clinical features. The titers of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1 and TIMP-2 of patients of lung carcinoma, benign diseases of the lung and volunteers were measured with an ELISA system in which anti-those monoclonal antibodies were utilized. We could not show any relation among MMPs, TIMPs levels and clinical stage and histological type statistically, whereas many cases of lung cancer advanced and metastasized showed high levels of MMPs and TIMPs. Our results suggest that MMP-1, MMP-9, TIMP-1 and TIMP-2 derived from lung cancer are released into sera, might be useful markers for invasion and metastasis.
We could not clone a gene relating to metastasis in this study, but we are still checking some libraries which subtracted cDNA of metastatic lesion from primary lesion. It is a topic to clarify a mechanism of metastasis of cancer cells in recent years, but we could not get enough clones to explain it. We will try to get a new gene relating to metastasis.
In the future, elucidation of regulation for MMPs and TIMPs, relation between levels of MMPs and TIMPs in sera and metastasis, and discovery of a new gene for invasion and metastasis are issues for us to study. Less
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