| Project/Area Number |
11671551
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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 | Shiga University of Medical Science |
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Principal Investigator |
OKAMOTO Keisei Department of Urology, Shiga University of Medical Science, Research Assistant, 医学部, 助手 (50303780)
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| Co-Investigator(Kenkyū-buntansha) |
KIM Chol Jang Department of Urology, Shiga University of Medical Science, Research Assistant, 医学部, 助手 (10204968)
YOSHIKI Tatuhiro Department of Urology, Shiga University of Medical Science, Assistant Professor, 医学部, 助教授 (80230704)
OKADA Yusaku Department of Urology, Shiga University of Medical Science, Professor, 医学部, 教授 (20127062)
KATAOKA Akira Department of Urology, Shiga University of Medical Science, Research Assistant, 医学部, 助手 (80293835)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | renal cell carcinoma / rapid growing / LOH / tumor suppressor gene / マイクロサテライトマーカー |
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| Research Abstract |
Renal cell carcinoma (RCC) is known to be frequently associated with paraneoplastic inflammatory syndrome (PIS), including episodes of fever, increased serum acute phase protein levels, and body weight loss. Elevated inflammatory parameters have been observed in patients with and without distant metastasis. These inflammatory markers are recognized to be poor prognostic signs and predictive of poor response to cytokine therapy. The molecular mechanisms responsible for the symptoms of PIS in RCC remains poorly understood although previous reports suggest that endogenous IL-6 production in RCC may play a key role. We retrospectively studied 72 surgically collected RCC cases. Of those, 18 cases of dear cell RCC (CRCC) demonstrated elevated pretreatment serum C-reactive protein (Group A). We also selected 49 cases of CRCC with normal pretreatment C-reactive protein (Group B). Group B was further divided into stage I or II cRCCs (Group B1 ; 32 cases) and stage III or IV cRCCs (Group B2 ; 17 cases). Using 22 microsatellite markers, we compared the incidence of LOH at 3p, 4q, 6q, 7q, 8p, 9p, 14q, and 17p between the Group A and B and between Group A and B2. LOH at 3p was common in Group A (89 %), Group B1 (91 %), and B2 (94 %). The frequency of 14q LOH was higher in Group A (16 of 18 [89%]) than Group B (4 of 49 [8 %]) (p < 000l) and higher in Group A than Group B2 (2 of 17 [12 %]) (p < 0001). LOH at chromosomes 3p and 14q are characteristics of CRCC with elevated acute phase reactants, including PIS, regardless of the presence of metastasis. On the contrary, 14q LOH is a rare genomic alternation in advanced stage CRCC without PIS. Our results imply that disruption of a 14q gene(s) may result in not only aggressive tumor growth, but also in inflammatory manifestations in the tumor host. Isolation of the gene(s) on 14q will be an important goal in the treatment of PIS-associated RCC.
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