The cystic degeneration and carcinogenesis of the kidney

肾脏囊性变和癌变

• 批准号: 04304043
• 负责人: OSAWA Akira
• 金额: $ 12.16万
• 依托单位: Faculty of Medicine, University of the Ryukyus
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Co-operative Research (A)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04304043/
• 关键词: 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

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 … More 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

1.与RCC相关的肾囊肿的流行病学：暴露于长期血液透析的患者在成人中倾向于发展肾脏的获得性肾囊肿病（ACDK），并且在儿童病例中倾向于形成Bowman囊上皮的胚胎性增生。透析患者中肾癌（RCC）的发病率是普通人群的6.3倍。我们从385个诊所收集了5，779例RCC，其中223例（3.9%）与肾囊肿相关。在这223例病例中，32%与单纯囊肿相关，28%与ACDK相关，9%与多房囊肿相关。血液透析患者的多发性和/或双侧肿瘤发生率高于非血液透析患者。肾囊肿和肾癌的发病机制肾小管上皮细胞的增生是肾囊肿形成的主要原因，可能与多种细胞因子有关 ...更多信息 通过测定MDCK细胞促囊肿形成活性来评价它们的活性。上皮增生及囊肿的形成可诱发及增加恶变的风险。在这项研究中获得了一些支持性证据。在实验性药物性肾囊肿中，C-myc基因在肾小管组织中被瞬时识别。在囊液和囊壁中，谷胱甘肽（众所周知的脱氧辅酶之一）的水平显著较低，表明活性氧毒性可能在囊上皮中诱导。囊壁上皮细胞表面的抗原物质与正常近端或远端肾小管上皮细胞表面的抗原物质不同。此外，免疫组化分析表明ACDK的囊壁具有癌前病变的倾向。另一方面，维持性血液透析患者的肾囊肿体积在肾移植后随着时间的推移而减少。在维持性血液透析患者中，与正常对照组相比，在5年内，淋巴细胞介导的细胞毒性和PBL产生的细胞因子被显著抑制。从上述结果可以看出，肾功能衰竭及其相关的免疫学改变，以及肾囊肿的形成，是血液透析患者中RCC发病率较高的主要因素。少

项目成果

Inoue, M.: "Superoxide dismuatase with prolonged in vivo half life inhibits intravascular hemolysis and renal injury in burned rats." Am.J.Emergency Med. 11. 355-359 (1993)

Inoue, M.：“超氧化物歧化酶具有延长的体内半衰期，可抑制烧伤大鼠的血管内溶血和肾损伤。”

Inoue, M.: "Effect of adrenomedullin on hepatic stellate cells of the rat." FEBS Lett. 356. 109-113 (1994)

Inoue, M.：“肾上腺髓质素对大鼠肝星状细胞的影响。”

Inoue,M.: "Albumin binding superoxide dismutase with a prologed half-life reduces reperfusion brain injury." Am.J.Physiol.264. H1708-1716 (1993)

Inoue,M.：“白蛋白结合超氧化物歧化酶的半衰期延长，可减少再灌注脑损伤。”

奴田原 紀久雄: "腎嚢胞性疾患" 医学書院(東京)、「今日の診断指針第3版」亀山正邦、亀田治男、高久歴麿、阿部令彦編。, 1415-1417 (1992)

Kikuo Nutahara：《肾脏囊性病》Igaku Shoin（东京），《今日诊断指南第 3 版》，作者：Masakuni Kameyama、Haruo Kameda、Rekimaro Takaku 和 Reihiko Abe。

斉藤 泰: "腎の嚢胞性疾患と透析" 腎と透析. 36. 1091-1092 (1994)

Yasushi Saito：“囊性肾病和透析”《肾脏和透析》36。1091-1092（1994）。