| Project/Area Number |
02304047
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | Faculty of Medicine, University of the Ryukyus |
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Principal Investigator |
OSAWA Akira University of the Ryukyus, Urology, Professor, 医学部・泌尿器科, 教授 (70045251)
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| Co-Investigator(Kenkyū-buntansha) |
HIDAI Hideo St. Mariana University, Urology, Instructor, 泌尿器科, 兼任講師 (30046007)
ISHIKAWA Isao Kanazawa Medical University, Nephrology, Professor, 腎臓内科, 教授 (30097414)
KOISO Kenkichi University of Tsukuba, Urology, Professor, 臨床医学系・泌尿器科, 教授 (20010192)
SAITO Yutaka Nagasaki University, Urology, Professor, 医学部・泌尿器科, 教授 (70039832)
ASO Yoshio University of Tokyo, Urology, Professor, 医学部・泌尿器科, 教授 (00009961)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥20,300,000 (Direct Cost: ¥20,300,000)
Fiscal Year 1991: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1990: ¥14,200,000 (Direct Cost: ¥14,200,000)
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| Keywords | Renal cysts / ACDK (Aquired renal diseases of kidney) / Renal cancer / Cytokines / Growth factor / Cyst formation promoting activity / Renal tubes / Oxygentoxicity / 上皮成長因子(EGF) / トランスフォ-ミング増殖因子(TGF) / グルタチオン(GSH) / 上皮膜抗原(EMA) / BSAー11 / インタ-ロイキン1(ILー1) / 糸球体性嚢胞 |
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| Research Abstract |
1. Epidemiology on cyst and RCC.
Patients exposed to long-term hemodialysis has definite tendency to develop the acquired renal cystic disease of kidney (ACDK) in adults and are predisposed to form of embryonal hyperplasia of bowman's capsular epithelium if they are children. Incidence of renal cell carcinoma (RCC) in dialysis patients is 6.3 fold the expected rates in the general population. We collected 5779 cases of RCC from 385 clinics, out of which 223 cases (3.9%) were associated with renal cysts. On these 223 cases, 32% of them were associated with a simple cyst, 28% with ACDK and 9% with multilocular cyst. The incidence of multiple and/or bilateral tumors was higher in patients on hemodialysis than patients without having hemodialysis treatment. The percentage of low stage tumor was also higher in hemodialysis patients.
2. Pathogeneses of renal cyst and cancer.
Hyperplasia of renal tubular epithelium appeared to be responsible for cyst formation which probably was regulated partia
… More
lly by several cytokines, such as EGF, TGF-beta, IL-6 and so on. Their activity was estimated by measuring cyst formation promoting activity using MDCK cells. The epithelial hyperplasia and subsequent formation of cyst may induce an increased risk for malignancy. Several supporting evidences were obtained in this study. In experimental drug-induced renal cystic disease, C-myc gene was transiently recognized in renal tubular tissues. Level of glutathione, which is well known as one of deoxidation coenzymes, in both cystic fluid and cyst wall, was significantly low suggesting the possibility that active oxygen toxicity can be induced in the cystic epithelium. Some of the antigenicities on epithelial cells of the cyst wall differed from that on the surface of normal proximal or distal tubular epithelium. In addition, immunohistochemical analysis indicated that the cyst wall of ACDK showed a kind of precancerous predisposition. On the other hand, number of the renal cysts in patients on maintenance hemodialysis was founded to decrease with time after renal transplantation. Lymphocyte-mediated cytotoxicity and cytokine production by PBL were significantly suppressed in some patients on maintenance hemodialysis within 5 years of the therapy initiation as compared to those in normal controls.
From above findings.
Renal failure and its associated immunological alteration, together with formation of renal cysts, are major factors containing responsible mechanisms for higher frequency of development of RCC in hemodialysis patients. Less
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