2011 Fiscal Year Final Research Report
Development of a gene mutation analysis system using photodynamic diagnosis for tumor cells exfoliated in the urine
| Project/Area Number |
21592057
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Nara Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HIRAO Yoshihiko 奈良県立医科大学, 医学部, 教授 (00133207)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 膀胱癌 / 光力学的診断 / 5-amminolevulinic acid / 尿細胞診 / 遺伝子 |
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| Research Abstract |
The specificity of conventional urine cytology for bladder cancer is high, whereas the sensitivity toward low-grade/low-stage tumors is unsatisfyingly low. In this study, we developed a fluorescence urine cytology system and a protoporphyrinIX(PpIX)-specific fluorescence positive cell detector based on the mechanism of photodynamic reaction of intracellularly accumulated PpIXthat is induced by 5-aminolevulinic acid exposure. Clinical feasibility of fluorescence cytology and the fluorescence positive cell detector was examined by using urine samples from bladder cancer patients and bladder cancer cell lines comparing with conventional cytology. Besides, we investigated significances of genetic alterations of chromosomes 9 and 17 and FGFR3 of tumor cells in urine specimens. Consequently, the PpIX-specific fluorescence positive cell detector, as well as fluorescence cytology, could detect fluorescence positive cells more sensitively in patients with low-grade/low-stage tumors when compared to conventional cytology. Meanwhile, the genetic alterations of shedding tumor cells in urine were highly detected and fluorescence positive tumors included chromosome 9 loss most frequently, p53 loss in high-grade tumors, and FGFR3 mutations in low-stage tumors in incidence order. Peptide nucleic acid real-time PCR clamping or pyrosequencing could detect the genetic alterations even in less shedding cells sensitively. We are currently promoting the system version-up by adopting micro-electro-mechanical systems for cell sorting and a micro-PCR plate for gene analysis to develop a more practical workstation utilizing the above high through-put micro-flow channel systems. The availability for other fluid samples such as ascites, sputum, or blood is also promising.
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[Journal Article] Heme oxygenase-1 promotes angiogenesis in urothelial carcinoma of the urinary bladder2011
Author(s)
Miyake M, Fujimoto K, Anai S, Ohnishi S, Kuwada M, Nakai Y, Inoue T, Matsumura Y, Tomioka A, Ikeda T, Tanaka N, Hirao Y
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Journal Title
Oncol Rep
Volume: 25
Pages: 653-660
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[Journal Article] Fibroblast growth factor receptor 3 mutation in voided urine is a useful diagnostic marker and significant indicator of tumor recurrence in non-muscle invasive bladder cancer2010
Author(s)
Miyake M, Sugano K, Sugino H, Imai K, Matsumoto E, Maeda K, Fukuzono S, Ichikawa H, Kawashima K, Hirabayashi K, Kodama T, Fujimoto H, Kakizoe T, Kanai Y, Fujimoto K, Hirao Y
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Journal Title
Cancer Sci
Volume: 101
Pages: 250-258
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[Journal Article] Clinical significance of heme oxygenase-1 expression in non-muscle-invasive bladder cancer2010
Author(s)
Miyake M, Fujimoto K, Anai S, Ohnishi S, Nakai Y, Inoue T, Matsumura Y, Tomioka A, Ikeda T, Tanaka N, Hirao Y
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Journal Title
Urol Int
Volume: 85
Pages: 355-363
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[Journal Article] Inhibition of heme oxygenase-1 enhances the cytotoxic effect of gemcitabine in urothelial cancer cells2010
Author(s)
Miyake M, Fujimoto K, Anai S, Ohnishi S, Nakai Y, Inoue T, Matsumura Y, Tomioka A, Ikeda T, Okajima E, Tanaka N, Hirao Y
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Journal Title
Anticancer Res
Volume: 30
Pages: 2145-2152
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[Journal Article] 1-tert-Butyl-3-[6-(3, 5-dimethoxy-phenyl)-2-(4-diethylamino-butylamino)-pyrido[2, 3-d] pyrimidin-7-yl]-urea(PD173074), a selective tyrosine kinase inhibitor of fibroblast growth factor receptor-3(FGFR3), inhibits cell proliferation of bladder cancer carrying the FGFR3 gene mutation along with up-regulation of p27/Kip 1 and G1/G0 arrest2010
Author(s)
Miyake M, Ishii M, Koyama N, Kawashima K, Kodama T, Anai S, Fujimoto K, Hirao Y, Sugano K
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Journal Title
J Pharmacol Exp Ther
Volume: 332
Pages: 795-802
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