2001 Fiscal Year Final Research Report Summary
Development and standardization of new molecular diagnostic methods for genito-urinary cancers
| Project/Area Number |
12307033
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kagawa Medical University (2001)
Kyoto University (2000) |
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Principal Investigator |
KAKEHI Yoshiyuki Kagawa Medical University, Urology, Professor, 医学部, 教授 (20214273)
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| Co-Investigator(Kenkyū-buntansha) |
NAITO Seiji Kyusyu University, Urology, Professor, 医学研究科, 教授 (40164107)
KAGAWA Susumu The University of Tokushima School of Medicine, Urology, Professor, 医学部, 教授 (40035738)
KAMIDONO Sadao Kobe University School of Medicine, Urology, Professor, 医学部, 教授 (30030935)
KUWATA Yoshihiro Kagawa Medical University, Urology, Lecturer, 医学部, 助手 (30294763)
TAKETA Sigeo Kagawa Medical University, Urology, assistant professor, 医学部・附属病院, 講師 (10227027)
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| Project Period (FY) |
2000 – 2001
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| Keywords | gento-urinary tumor / standardization of molecular diagnosis / p53 function analysis / uroplakin / MMP-9 / TIMP / CD44 / multidrug resistance-associated genes |
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| Research Abstract |
The aim of this study was to develop new molecular diagnostic methods for genito-urinary cancers in terms of early detection, prediction of disease progression, and selection of proper patients who will respond to chemotherapy. Standardization of the developed method was also an important goal. As to early detection, we found that the mRNA ratio of CD44v8-10 to standard from of CD44 in urine was a useful marker for early detection of bladder cancer. We also found that MMP-9 and TIMP-2 expression in superficial bladder cancer were respectively independent predictors for intravesical recurrence. As to prediction of prognosis, invasiveness of bladder cancer was correlated with the ratio of CD44v8-10 to standard form of CD44 and plasminogen activator expression. By the gene profiling analysis using microarray, we found a novel gene set that can predict prognosis of kidney cancer patients. We also identified that serum concentration of VEGF, HGF, and endostatin was useful prognostic marker for kidney cancer. We developed and standardized a method of nested RT-PCR for uroplakin II mRNA in peripheral blood of urothelial cancer patients. The method was assumed to be promising as to detection of micrometastasis. As to prediction of good responders to chemotherapy in ladder cancer patients, aberration of p53 function evaluated by the yeast functional assay was correlated with elevated expression of MRP1 (a member of multi-drug resistance genes). Expression of MDR1 and MRP1, 2, 3 genes was increased after cisplatin-based combination chemotherapy in bladder cancer patient. Moreover, resistance to adriamycin was correlated with MDR1 and MRP1 and in bladder cancer tissues.
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