| Co-Investigator(Kenkyū-buntansha) |
OKAYASU Isao Kitasato University, Pathology, professor, 医学部, 教授 (20014342)
SATO Yuichi Kitasato University, Allied Health Science, Molecular Diagnostics, Associate Professor, 医療衛生学部, 助教授 (30178793)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
hASH1 mRNA expression was investigated by in situ hybridization in 238 surgically resected lung carcinomas, and the correlations between hASH1 expression and general neuroendocrine marker and peptide hormone expression as well as clinical outcome were analyzed. hASH1 expression was restricted to tumors with neuroendocrine phenotypes. However, not all neuroendocrine tumors expressed hASH1 and hASH1 expression correlated closely with chromogranin A, gastrin-releasing peptide and calcitonin (P<0.0001, r=0.852), but was not related to neural cell adhesion expression (P=0.8892), suggesting that hASH1 expression, at least in lung cancer, is associated with endocrine phenotype expression other than 'neuroendocrine differentiation' in a broad sense. That hASH1 was virtually absent in almost fully differentiated typical carcinoids (TC), but was expressed in most, if not all, less differentiated atypical carcinoids (ATC) as well as large-cell neuroendocrine carcinoma (LCNEC) and small cell lung
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carcinoma (SCLC), suggests that hASH1 expression in lung cancer imitates its early and transient expression in fetal development, and that hASH1 is instrumental in the establishment, but not in the maintenance, of a cellular endocrine phenotype. Finally, hASH1 expression correlated with a significantly shortened survival in SCLC patients (P=0.041).
Dysregulated cyclin B1 expression and disruption of the Rb/p16/cyclin D1 pathway (Rb pathway) were also studied, and the results were correlated with tumor proliferation activity and clinical outcome. Both cyclin B1-associated G2/M arrest and Rb-mediated G1 arrest are consistently compromised in high-grade LCNEC and SCLC, but are generally intact or occasionally altered in TC/ATC ; and the mechanisms involved in Rb pathway aberration among the tumor categories are different. Cyclin B1 expression closely correlated with the Ki-67 labeling index in each tumor category (P<0.0001, r=0.742), suggesting a key role for cyclin B1 in regulating cell proliferation. Neither cyclins B1 and D1, Rb, p16, nor Ki-67 correlated with patient survival in individual tumor categories. Less
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