Grant-in-Aid for Co-operative Research (A)
|Allocation Type||Single-year Grants|
|Research Institution||Faculty of Medicine, University of the Ryukyus|
OSAWA Akira University of the Ryukyus, Urology, Professor, 医学部泌尿器科, 教授 (70045251)
INOUE Masayasu Osaka City Medical School, Biochemistry, Professor, 医学部・第一生化, 教授 (80040278)
TAKEI Hiroshi University of the Ryukyus, Biochemistry, Professor, 医学部・第二生化, 教授 (70039501)
SAITO Yutaka Nagasaki University, Urology, Professor, 医学部・泌尿器科, 教授 (70039832)
KOISO Kenkichi University of Tsukuba, Urology, Professor, 臨床医学系・泌尿器科, 教授 (20010192)
KAWABE Kazuki University of Tokyo, Urology, Professor, 医学部・泌尿器科, 教授 (20124670)
津川 龍三 金沢医科大学, 泌尿器科, 教授 (80064509)
阿曽 佳郎 東京大学, 医学部泌尿器科, 教授 (00009961)
|Project Period (FY)
1992 – 1994
Completed(Fiscal Year 1994)
|Budget Amount *help
¥19,000,000 (Direct Cost : ¥19,000,000)
Fiscal Year 1994 : ¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1993 : ¥7,000,000 (Direct Cost : ¥7,000,000)
Fiscal Year 1992 : ¥9,000,000 (Direct Cost : ¥9,000,000)
|Keywords||Renal cysts / ACDK(Aquired cystic diseases of kidney) / Renal cancer / Cytokines / Growth factor / Cyst formation promoting activity / Renal tubulus / Oxygen toxicity / 多襄胞化萎縮腎(ACDK) / diphenylamine(DPA) / (EHEN) / ACDK / MDCK細胞 / HGF / グルタチオン(GSH) / 癌遺伝子 / mRNA|
1.Epidemioloy of renal cyst associated with RCC.
Patients exposed to iong-term hemodialysis tend to develop acquired renal cystic disease of the kidney (ACDK) in adults and are predisposed to form embryonal hyperpiasia of Bowman's capsular epithelium in cases of children. The incidence of renal carcinoma (RCC) in dialysis patients is 6.3 fold higher than in the general population. We collected 5,779 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 cysts. The incidence of multiple and/or bilateral tumors was higher in patients on hemodialysis than patients without hemodialysis. The percentage of low stage tumor was also higher in hemodialysis patients.
2.Pathogeneses of renal cyst and cancer.
Hyperplasia of the renal tubular epitheliums appears to be responsible for cyst formation which probably was regulated partially by several cytotokin
es, such as EGF,TGF-beta, IL-6 and so on. Their activities were estimated by measuring cyst formation promoting activity using MDCK cells. Epithelial hyperplasia and subsequent formation of cyst may induce and increase the risk of malingnacy. 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. The level of glutathione, which is well known as one of deoxidation coenzymes, in both cystic fluid and cyst wall, was significantly low, suggesting that active oxygen toxicity can potentially be induced in the cystic epithelium. Some antigenic substances on epithelial cells of the cyst wall differed from those on the surface of normal proximal or distal tubular epithelium. In addition, immunohistochemical analysis indicated that the cyst wall of ACDK showed precancerous predisposition. On the other hand, the volume of renal cysts in patients on maintenance hemo-dialyisis was found 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 on the therapy as compared with those in normal controls.
From the above findings.
Renal failure and its associated immunological alteration, together with formation of renal cysts, are major factors responsible for higher incidence of RCC in hemodialysis patients. Less