| Project/Area Number |
10470276
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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 | The University of Tokushima |
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Principal Investigator |
MONDEN Yasumasa MD, PhD, Professor, Second Department of Surgery, School of Medicine, The University of Tokushima, 医学部, 教授 (60028628)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Kazuya MD, PhD, Assistant Professor, Second Department of Surgery, School of Medicine, The University of Tokushima, 医学部, 講師 (10263815)
三好 孝典 徳島大学, 医学部附属病院, 医員(臨床)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1999: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1998: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | Chromate lung cancer / Microsatellite instability / loss of heterozygosity / Mismatch repair gene / hMLH1 hMSH2 |
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| Research Abstract |
Our previous study for human lung cancer from chromate-exposure workers have revealed that chromate exposure induce the particular mutation pattern in the p53 gene of human lung cancer (Biochem Biophys Res Com 139, 95-100, 1997). In this study, we examined the genomic instability in 40 Lung cancers from 33 chromate-exposure workers and 29 lung cancers patients without chromate exposure (control samples) using 6 microsatellite markers. Thirty (75.0%) of the 40 tumors with chromate exposure showed RER+. On the other hand, only 4 (13.3%) of the 29 tumors without chromate exposure showed the replication error-positive phenotype (RER+). The frequency of RER+ in tumors with chromate exposure was higher than that in tumors without chromate exposure (p<0.0001). Moreover, the duration of chromate exposure but not Brinkman index may be associated with numbers of MSI positive.
To clarify the relationship between RER+ and the abnormality of mismatch repair gene, we examined the expressions of hMLH1 and hMSH2 protein in 28 chromate lung cancers and 28 non-chromate lung cancers by immunohistochemistry. All 28 non-chromate lung cancers strongly expressed both hMLH1 and hMSH proteins. On the other hand, 14 (50%) of 28 chromate lung cancers moderately or weakly expressed hMLH protein. Eight (29%) of 28 chromate lung cancers moderately or weakly expressed hMSH protein. It is possible that RER+ in chromate lung cancer may be due to the abnormality of mismatch repair genes.
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