| Co-Investigator(Kenkyū-buntansha) |
KUWANO Hiroyuki GUNMA UNIVERSITY, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (90186560)
ASAO Takayuki GUNMA UNIVERSITY, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (40212469)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
RASSF1A is frequently inactivated by promoter methylation in human cancers. To understand the involvement of the RASSF1A gene in esophageal squamous cell cancer (ESCC), we investigated the methylation of the RASSF1A gene in primary ESOC to define the frequency of this epigenetic aberration and the clinicopathological significance. Methylation-specific polymerase chain reaction (MSP) was used to detect RASSF1A gene methylation in DNA from 55 cases of ESCC. Methylation of the RASSF1A gene was found in 13 of 55 (24%) cases of primary ESOC. No association was found between the promoter methylation of the RASSF1A gene in primary ESCO and age, gender, localization, invasion depth, or tumor stage. Association was found with tumor differentiation. There was no correlation with its prognosis. In conclusion, it was suggested that an inactivation of the RASSF1A gene due to promoter methylation was associated with de-differentiation of the tumor in ESCC.
Tissue inhibitor of metalloproteinase-3 (TII
… More
MP-3) inhibits the activity of matrix metalloproteinase, which may play an important role in carcinoma invasion and metastasis. We have investigated the relationship between TIMP-3 reduction and clinicopathological factors in ESCC. We examined tissue specimens that had been removed from 90 patients with thoracic esophageal cancer who had undergone surgery between 1983 and 2001. Immunohistochemical staining was performed by the standard streptavidin-biotin method. Immunostaining of TIMIP-3 was seen in the cytoplasm of cancer cells and normal esophageal epithelial cells, particularly in cells located in shallow areas of the tumour. TIMP-3 preserved (+), moderate (+/-), and reduced (-) cases accounted for 30, 27, and 33 of the 90 patients, respectively (33, 30, 37%). Significant correlations were observed between TIMP-3 expression and depth of tumour invasion (P=0.001), number of lymph node metastases (P=0.003), infiltrative growth pattern (P=0.003), and disease stage (P=0.005). The survival rates of patients with TIMP-3 (-) cancer were significantly lower than those of patients with TIMP-3 (+) and TIMP-3 (+/-) cancer (P=0.0003). The mean 5-year survival rates of patients with TIMP-3 (+), (+/-), and (-) were 50, 58, and 21%, respectively. In conclusion, decreased expression of TIMP-3 protein correlates with invasive activity and metastasis. This makes the prognosis for patients with cancer that has lost TIMP-3 significantly less favorable than that for patients with cancer that has maintained TIMP-3. Less
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