Wnt信号通路与肾细胞癌

Wnt信号是一种跨膜信号,参与细胞的分化和运动,是近年来研究的热点,针对肿瘤的许多新的分子靶向治疗亦是以Wnt信号通路为靶点的.本文就Wnt信号通路及其在肾细胞癌(RCC)中的变化、肾细胞癌中针对Wnt信号的靶向治疗作一综述.     

肾细胞癌免疫治疗的历史与研究进展

由于肾癌具有对放、化疗的高度不敏感性,使得免疫疗法在转移性肾癌患者的治疗中尤为重要.一些研究报告了在基于免疫治疗的基础上,诸多学者尝试利用抗原、细胞因子、树突细胞等不同方法进行大量的临床试验,安全性有目共睹,但长期的临床疗效无法在多数人群中体现.本文旨在对细胞介导的肿瘤免疫疗法作出整体描述,并探讨近年来有关肾细胞癌在临床试验中的免疫治疗进展.     

遗传性肾细胞癌的研究进展

肾癌有遗传和散发两种形式,对肾癌发病机制的理解相当一部分来自对遗传性肾癌的研究.本文对von Hippel Lindau病、遗传性乳头状肾癌、Birt Hogg Dubé综合征、遗传性平滑肌瘤病肾细胞癌等遗传性肾细胞癌的研究进行了综述.     

肾细胞癌佐剂治疗研究进展

随着检测手段的不断完善,越来越多的肾细胞癌患者被临床发现．而传统的外科手术治疗并不能使所有患者取得良好疗效,化疗、放疗对其也不敏感,然而佐剂治疗作为一种新的治疗方法为肾细胞癌患者带来了新的希望。     

树突状细胞与肾细胞癌治疗的进展

树突状细胞(DC)是一类具有典型树突状形态、膜表面高表达MHC-Ⅱ类分子、能移行至淋巴器官和刺激初始型T细胞增殖活化的细胞.本文就DC的分类、生物学作用及其机理、肾细胞癌患者DC的变化、肾细胞癌的DC治疗进展作一综述.     

骨髓干细胞促进肾细胞癌生长的研究进展

BMSCs是新生血管内皮祖细胞的来源,BMSCs中的EPC募集到瘤灶中参与新生血管和转移微环境的形成促进肿瘤的生长转移,SDF-1/CXCR4是EPC被募集迁徙的主要机制;同理推测,肾癌组织中的CD133+祖细胞可能来源于BMSCs或者是血管的内皮祖细胞(EPC).肾癌中CD133+祖细胞与骨髓中VEGFR1+和VEGFR2+BMSCs可能是用不同表面标志鉴别的相同亚群.肾细胞癌HIF的高表达可能是肾癌富含血管和生长转移的主要始动原因.这些推测有待于进一步的实验证实.     

肾细胞癌靶向治疗预后相关因素研究进展

肾细胞癌（RCC）是泌尿系统常见的恶性肿瘤之一。分子靶向治疗是通过干预肿瘤细胞信号传导通路,抑制肿瘤的生长。相比于传统的细胞冈子治疗手段．肾癌靶向治疗效果更好。但是目前对肾癌靶向治疗的预后仍缺乏有效判断手段,本文结合最新研究综述了RCC靶向治疗预后密切相关的影响冈素研究现状及进展。     

舒尼替尼治疗转移性肾细胞癌的研究进展

在过去20年,非特异性免疫治疗被认为是晚期肾细胞癌治疗标准.近年来,随着对肾癌生物学和分子发病机制的加深理解,分子靶向治疗已成为肿瘤治疗的研究热点,相继有多种分子靶向治疗药物问世.在转移性肾癌治疗中取得了令人瞩目的 成果.2006年1月美国食品和药品管理局(FDA)正式批准了舒尼替尼(sunitinib)用于治疗转移性肾细胞癌(mRCC).本文就舒尼替尼治疗转移性肾细胞癌的研究进展作一综述.     

缺氧诱导因子与肾细胞癌

肾细胞癌的缺氧适应与缺氧诱导因子(HIF)有关.HIF是由两个亚单位组成的二聚体,通过作用于靶基因的缺氧反应元件(HRE)调控相关基因的表达,在肾细胞癌血管生成方面起重要作用,进而影响肾细胞癌的增殖和转移.研究HIF与肾细胞癌的关系可为其治疗提供新的思路.     

慢性内脏痛及其信号转导通路的研究进展

背景 慢性内脏痛是功能性胃肠病(functional gastrointestinal disorders,FGID)和慢性胰腺炎(chronic pancreatitis,CP)的主要症状,这种疼痛不但降低患者的生活质量也是其寻求医疗帮助的主要原因,但目前有关内脏痛的确切机制仍不清楚,因而其治疗效果不佳. 目的 就当前慢性内脏痛及其信号转导通路的研究进展进行综述. 内容 介绍内脏痛及其信号转导通路、神经胶质细胞特别是脊髓小胶质细胞在慢性内脏痛中的作用. 趋向 脊髓小胶质细胞可能是未来慢性内脏痛治疗的新靶点.     

3号染色体抑癌基因突变在肾细胞癌发生中的研究进展

【摘要】肾细胞癌是一种多基因相关的泌尿系统恶性肿瘤,发病机制复杂,基因研究对阐明其发生及发展的生物分子学机制显得极其重要。近年发现,人类3号染色体上存在多个与肾细胞癌密切相关的抑癌基因,本文对VHL、PBRM1、BAP1、SETD2及其他3号染色体抑癌基因在肾细胞癌发生发展中的研究进展作一综述。     

周细胞在肾间质纤维化中的研究进展

周细胞是与内皮细胞接触并部分包埋于血管基底膜的间充质细胞.周细胞具有分化能力,其表面标志物根据不同组织、不同发育阶段、不同病理生理环境而发生变化.研究表明,周细胞是肾脏肌成纤维细胞的主要来源,多种信号通路参与了周细胞/成纤维细胞转分化为肌成纤维细胞的过程.本文综述了周细胞在肾间质纤维化发病机制中的研究进展,提出了周细胞...     

MAPK途径与巨噬细胞介导的肾损伤

在巨噬细胞介导的肾损伤机制中，有丝分裂原激活蛋白激酶（Mitogen—Actived Plotein Kinase，MAPK）信号传导通路是近年来的研究热点之一，它不但参与多种趋化因子和粘附分子的表达，促进巨噬细胞在肾小球及肾间质内的浸润，还直接参与巨噬细胞的活化过程，促进巨噬细胞分泌促炎症因子和活性氧自由基等组织损伤效应因子。MAPK途径是巨噬细胞介导的’肾损伤过程中一条重要的信号传导通路。     

骨代谢信号通路的研究进展

骨代谢包括骨形成及骨吸收两方面,受到多种因素的调控,其分子机制涉及遗传基因、信号通路、激素及旁分泌因子等多方面作用,而信号通路在其中起到了重要的调控作用。在目前的骨代谢信号通路研究中,BMP/Smads、Wnt/β-catenin及OPG/RANKL/RANK等3条通路已经得到较为深入的研究,并且公认为在骨代谢中起到了关键的信号调节作用,其中BMP/Smads及、Wnt/β-catenin通路主要影响骨形成,而OPG/RANKL/RANK则主要影响骨吸收。最新的研究表明,低氧/低氧诱导因子-la通路、PDGF、TGF-beta和FGF通路、AKt2选择通路、G蛋白信号通路、硫酸已酰肝素和硫酸软骨素通路、黏着斑激酶及胞外信号调节激酶通路等同样对成骨细胞及破骨细胞的分化增殖起到调节作用,并且发现BMP/Smads通路和Wnt/β-catenin通路之间存在着相互调节作用。对骨代谢信号通路的深入研究,可为骨代谢疾病尤其是骨质疏松症提供潜在的以细胞为基础的治疗新途径。     

Recent advances in targeted therapy for renal cell carcinoma

PURPOSE OF REVIEW: To provide an overview and summary of the recent developments in the use of targeted therapy in the management of advanced kidney cancer. The focus is on publications within the last year. RECENT FINDINGS: The last year has seen several exciting developments in the targeted approach to managing advanced renal cell carcinoma. The benefits of small-molecule tyrosine kinase inhibitors have been demonstrated in two large-scale, phase III prospective, randomized controlled trials. There is growing evidence, some not yet published, that mammalian target of rapamycin inhibitors are effective in this disease and the roles of therapies directed at the receptor for vascular endothelial growth factor continue to be refined. SUMMARY: Recent published trials offer substantial hope for those patients with advanced kidney cancer, where before the outlook was often bleak. There is an expanding menu of potential agents in this disease, so-called targeted therapies, that are grounded in a growing understanding of the biology of kidney cancer. Many challenges and questions still remain, but there are encouraging signs of progress and hope for the future.     

Recent advances in the treatment of metastatic renal cell carcinoma

In the past 5 years, the treatment of patients with metastatic renal cell carcinoma has changed dramatically from being largely cytokine‐based with the emergence of targeted therapy. Following the elucidation of various molecular pathways in renal cell carcinoma, targeted agents (particularly vascular endothelial growth factor‐targeting antiangiogenic agents) now form the backbone of most therapeutic strategies for patients with metastatic renal cell carcinoma and the outcome of treatment has improved. However, many tumors eventually develop resistance to targeted therapy due to secondary mutation of the target protein or compensatory changes within the target pathway that bypass the site of inhibition. On the other hand, there are new forms of immunotherapy that hold the promise of improving the outcome for patients with metastatic renal cell carcinoma. In this article, we describe some of these new therapies, including the anti‐vascular endothelial growth factor monoclonal antibody bevacizumab, several receptor tyrosine kinase inhibitors (sorafenib, sunitinib, pazopanib, axitinib, and tivozanib), the mammalian target of rapamycin inhibitors temsirolimus and everolimus, and new immunotherapy modalities, such as anti‐cytotoxic T‐lymphocyte‐associated antigen 4 antibody and anti‐programmed cell death 1/programmed cell death‐ligand 1 antibody. We also discuss their role in the current management of patients with metastatic renal cell carcinoma.     

破骨细胞分化过程中的信号通路及信号因子的研究进展

破骨细胞（osteoclast,OC）来源于骨髓,在生长发育过程中,起着骨吸收的重要功能,其增多或减少会引起骨质疏松或骨质硬化等相关的骨代谢性疾病。本文将从OC分化过程中所涉及的信号通路（NF-κB、Src-PI3K-Akt、MAPK、CN/NFAT、IDO/Tryptophan通路等）及相关信号因子（PU 1、 Lhx2、TNF-α、 M-CSF、TGF-β等）方面,对OC分化的信号通路及相关信号因子的研究进展进行简要综述,以期能为相关骨代谢性疾病的治疗提供新的思路。     

转移性肾细胞癌免疫治疗的研究进展

转移性肾细胞癌为化疗和激素治疗抵抗性肿瘤,目前仍缺乏有效的治疗手段.经过20多年的发展,随着分子免疫机制的研究深入,新型免疫治疗方法不断推陈出新,过继免疫疗法、树突状细胞疫苗、免疫基因治疗等治疗方法研究发展迅速,部分已经应用于临床治疗.相信在不久将来,免疫治疗将获得突破性进展,终将成为临床治疗进展期肾细胞癌的主要手段.本文就近年来转移性肾细胞癌免疫治疗最新进展作一综述.     

Puerarin attenuates renal fibrosis by reducing oxidative stress induced-epithelial cell apoptosis via MAPK signal pathways in vivo and in vitro

Puerarin (PR) is an isoflavonoid isolated from the root of the plant Pueraria lobata and has been widely used in traditional Chinese herbal medicine for the treatment of various diseases. Oxidative stress and epithelial cell apoptosis play important roles in the renal fibrotic process. The present study aimed to determine whether or not PR inhibits renal fibrosis by reducing oxidative stress induced-epithelial cell apoptosis. In vivo, unilateral ureteral obstruction (UUO) induced renal fibrosis, and epithelial cell apoptosis. A total of 24 mice were randomly assigned to four experimental groups: sham, UUO alone, UUO +50?mg/kg PR, and UUO +100?mg/kg PR. In vitro, 200?μM hydrogen peroxide (H₂O₂) induced epithelial cell apoptosis. The experiments were dived into four groups: control, H₂O₂ alone, H₂O₂+50?μM PR, and H₂O₂+100?μM PR. Tubular injury was measured in the renal cortex of the mice through periodic acid-Schiff (PAS) staining, and the extracellular matrix (ECM) was measured through Sirius red (SR), immunohistochemistry (IHC) staining, and Western blot. Renal epithelial cell apoptosis was measured through terminal deoxynucleotidyl transferase-mediated dUTP Nick-End labeling (TUNEL), flow cytometry (FCM), and Hoechst assays. The protein expression of NOX4, caspase3, ERK, P38, and JNK was assessed through Western blot. PAS staining showed that PR decreased renal tubular injury in UUO mice. SR and IHC staining demonstrated that PR decreased the accumulation of ECM. PR treatment significantly inhibited epithelial cell apoptosis according to the results of TUNEL, FCM, Hoechst, and Western blot. Furthermore, NOX4 increased in UUO mice and decreased with PR treatment. H₂O₂-derived oxidative stress activated epithelial apoptosis and mitogen-activated protein kinases (MAPK), and PR treatment significantly reversed it. These results suggest that PR treatment ameliorates renal fibrosis by inhibiting oxidative stress induced-epithelial cell apoptosis through MAPK signaling.