2004 Fiscal Year Final Research Report Summary
Possibility of new treatment modality by inhibition of anti-apoptotic molecule XIAP
| Project/Area Number |
14370506
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Yamagata University Faculty of Medicine |
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Principal Investigator |
TOMITA Yoshihiko Yamagata University, Faculty of Medicine, Professor, 医学部, 教授 (90237123)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Tomoyuki Yamagata University, Faculty of Medicine, Assistant, 医学部, 講師
OJI Hiroshi Yamagata University, Faculty of Medicine, Assistant, 医学部, 助手 (30302293)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Urological cancer / apoptosis / renal cell cancer / XIAP / FAs / urinary bladder cancer / Bcl-2 |
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| Research Abstract |
Detailed study of inter-molecular mechanism in apoptotic machinery of tumor cells may contribute to invention of new modality of cancer therapy. In the present study, a putative anti-apoptotic molecule, XIAP, was investigated in terms its expression and action for new modality of treatment. < design and examination of its action of short interference (si) RNA to XIAP> Previous study revealed insufficient inhibition of XIAP tempted us to use siRNA instead. Three sequences were used to siRNA and cloned into a plasmid vector good for siRNA. One of the three siRNA was most potent to knock down XIAP expression. <stable transfectant> Ten to twelve clones each were isolated from transfection of the vector to Caki-1 or LNCap, and under investigation of its function. <XIAP expression and its relation to CRP, interleukin (IL)-6 and tumor necrosis factor(TNF) pathway> Statistically significant correlation between XIAP expression and serum CRP was noticed in renal cell cancer patients. Among cultured cell lines, some of them secreted high titer of IL-6 and TNF-alpha, and frequently expressed XIAP. This indicates that possibility of double inhibition of XIAP expression itself and TNF pathway render more complete inhibition of XIAP leading to more susceptible to apoptotic stimuli. Further examination was being performed.
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