The cystic degeneration and carcinogenesis of the kidney

肾脏囊性变和癌变

• 批准号: 02304047
• 负责人: OSAWA Akira
• 金额: $ 12.99万
• 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: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02304047/
• 关键词: 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) /

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

1.囊肿和肾细胞癌的流行病学。长期接受血液透析的患者在成人中明显有患获得性肾囊肿病(ACDK)的倾向，而在儿童中则易形成包膜上皮胚胎性增生。透析患者的肾细胞癌 (RCC) 发生率是普通人群的预期发生率的 6.3 倍。我们收集了 5779 例 RCC 病例。 385个诊所，其中223例（3.9%）伴有肾囊肿，在这223例中，32%伴有单纯性囊肿，28%伴有ACDK，9%伴有多房性囊肿。血液透析患者双侧肿瘤发生率高于未接受血液透析治疗的患者，低期肿瘤比例也较高。 2．肾囊肿和癌症。肾小管上皮的增生似乎是囊肿形成的原因，囊肿的形成可能部分受到几种细胞因子的调节，例如EGF、TGF-β、IL-6等，通过测量它们的活性来估计。在实验性药物诱导的肾囊性疾病中，上皮增生和随后的囊肿形成可能会增加恶性肿瘤的风险。 C-myc 基因在肾小管组织中被短暂识别，而谷胱甘肽是众所周知的脱氧辅酶之一，在囊液和囊壁中都显着降低，表明可能在囊肿中诱导活性氧毒性。囊壁上皮细胞的一些抗原性与正常近端或远端肾小管上皮表面的抗原性不同。另一方面，维持性血液透析患者的肾囊肿数量在肾移植后随着时间的推移而减少，并且 PBL 产生的细胞因子显着受到抑制。与正常对照组相比，治疗开始后 5 年内接受维持性血液透析的患者。从上述研究结果来看。肾衰竭及其相关的免疫学改变，以及肾囊肿的形成，是主要因素血液透析患者肾细胞癌发生率较高的机制较少。

项目成果

Small Misfolded Tau Species Are Internalized via Bulk Endocytosis and Anterogradely and Retrogradely Transported in Neurons*

错误折叠的小 Tau 蛋白通过大量内吞作用内化，并在神经元中顺行和逆行运输*

• DOI: 10.1074/jbc.m112.394528
• 发表时间: 2012-11-27
• 期刊: The Journal of Biological Chemistry
• 作者: Jessica W. Wu;Mathieu Herman;Li Liu;Sabrina Simoes;C. Acker;H. Figueroa;Joshua I. Steinberg;M. Margittai;R. Kayed;C. Zurzolo;G. Di Paolo;K. Duff
• 通讯作者: K. Duff

STING an Endoplasmic Reticulum Adaptor that Facilitates Innate Immune Signaling

STING 是一种促进先天免疫信号传导的内质网适配器

• DOI: 10.1038/nature07317
• 发表时间: 2008-10-02
• 期刊: Nature
• 影响因子: 64.8
• 作者: Ishikawa, Hiroki;Barber, Glen N.
• 通讯作者: Barber, Glen N.