| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
|
|---|
| Research Abstract |
We immunohistochemically examined the expression of cyclin A, B1, D1 and E, cyclin dependent kinase (CDK), and p27 proteins in esophageal squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC) of the urinary tract. to determine their significance for the tumor behavior and patient prognosis. The prevalence of cases exhibiting cyclin A, B1 or D1 were higher in the progressive tumors than in the other types of tumors in esophageal SCCs. In TCC cases, cyclin A or E were higher in the progressive tumors than in the other types of tumors. Patients whose SCCs overexpressed these cyclin-overexpresion had a significantly poorer prognosis than those expressing neither of these cyclins. Interestingly, our findings also suggest that in esophageal SCC, cyclin D1 and cyclin E and their functional partners, CDK4 and CDK2, often exhibit dysregulated overexpression in many cases. We also examined the relationships between immunohistochemically-detected expression of p27 and clinicopatholo
… More
gical factors in SCC. In contrast to the evidence supporting a tumor-suppressive function of p27, the present study suggests that expression of p27 may be associated with the progression of SCC.
Maintenance of genetic stability supported by mismatch repair plays ah important role in the avoidance of cancer. We studied hMSH2 expression in bladder TCCs by immunohistochemistry and demonstrated that reduced hMSH2 expression in tumor cells is associated with recurrence of TCCs. In addition, We examined genomic DNA from TCCs for mutations in hMSH6 gene by polymerase chain reaction and direct sequencing analysis. mutational status of p53 gene was also studied as a potential target of genetic instability secondary to hMSH6 dysfunction. A total of 3 cases displayed hMSH6 mutations. p53 gene mutations were detected in 22 cases. No tumors with p53 mutation had any hMSH6 missense mutations. Compared to the cases without hMSH6 alterations, the three patients with hMSH6 alterations ,had more frequent additional primary cancer. These findings provide the first in vivo evidence ,for the type of alterations and frequency of possible involvement of the hMSH6 mutations in sporadic type urothelial TCCs. We will next try to determine the involvement of hMLH1 promoter methylation or mutation in urothelial carcinogenesis. Less
|
