| Project/Area Number |
12470268
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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 | TOHOKU UNIVERSITY |
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Principal Investigator |
MATSUMURA YUJI (2002) TOHOKU UNIVERSITY HOSPITAL, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (80281997)
佐藤 雅美 (2000-2001) 東北大学, 加齢医学研究所, 助教授 (30250830)
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| Co-Investigator(Kenkyū-buntansha) |
ENDO CHIAKI TOHOKU UNIVERSITY HOSPITAL, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (80333813)
OKADA YOSHINORI TOHOKU UNIVERSITY INSTITUTE OF DEVELOPMENT, AGING AND CANCER, RESEARCH ASSOCIATE, 加齢医学研究所, 助手 (90323104)
KONDO TAKASHI TOHOKU UNIVERSITY INSTITUTE OF DEVELOPMENT, AGING AND CANCER, PROFESSOR, 加齢医学研究所, 教授 (10195901)
HOSHIKAWA YASUSHI TOHOKU UNIVERSITY HOSPITAL, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (90333814)
松村 輔二 東北大学, 医学部・付属病院, 助手 (80281997)
谷田 達男 東北大学, 加齢医学研究所, 助教授 (20217144)
佐川 元保 東北大学, 医学部・附属病院, 講師 (70292274)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | SQUAMOUS CELL LUNG CANCER / P53 GENE / GENE ALTERATION / IMMUNOHISTOCHEMISTRY / hnRNP B1 / TUMOR ANGIOGENESIS / MATRIX METALLOPROTEINASE / 発癌 / マトリックスメタロプロアーゼ / 肺癌 / 自然史 / over diagnosis bias |
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| Research Abstract |
We investigated the natural course of patents diagnosed to have roentgenographically occult squamous cell carcinoma (ROSCC) of the lung but were medically inoperable or refused treatments. Most of the patients showed development of tumor on chest roentgenogram and some of these cases died from lung cancer. However, one third of patients with ROSCC had complained no symptom and showed no abnormal findings in chest roentgenogram for years.
We analyzed the status of p53 gene in patients with advanced squamous cell carcinoma and in patients with ROSCC. By determining the sequence of exon 5-8 of p53 gene, we found that miss-sense mutations were frequently occurred in advanced squamous cell carcinoma as reported, and interestingly, non-sense mutations were occurred in one third of ROSCCs. These findings might be one of the reasons that some patients with ROSCC showed better prognosis. To clarify the difference of the status of other biomarkers in advanced squamous cell carcinoma and in ROSCC, we screened hnRNP B1, MDM2, WAF1, PD-ECGF, Bc12, and Bax by immunohistochemical method. Only hnRNP B1 protein expressed both in advanced squamous cell carcinoma and in ROSCC, in addition, hnRNP B1 protein was expressed in precanoerous lesion of ROSCC. Furthermore, the suruvival curve of the patients with hnRNP B1 overexpression showed a better prognosis compared with that of the patients without hnRNP B1 expression. Subsequently, we examined the expression pattern of the matrix metalloproteinase (MMP) family and its inhibitor (TIMP-2), which are known to play important roles in tumor angiogenesis. TIMP-2 frequently expressed in tumor cells, while MMP-2, MMP-3 and MMP-9 showed low expression level. Our genetic and immunohistochemical examination revealed that some different mechanisms involve in carcinogenesis of squamouc cell carcinoma of the lung, and they might determine the prognosis of the patients.
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