PI3K/Akt通路与肿瘤治疗

磷酸肌醇3激酶/蛋白激酶B (phosphoinositide 3kinase /protein kinase B,PI3K/Akt)信号通路参与很多重要生物学过程的调控，但其过度激活可导致肿瘤的发生。在正常组织中PI3K/Akt信号转导途径处于活化状态，但是该通路如果被过度激活则可通过下调肿瘤抑制蛋白p53、刺激蛋     

西罗莫司在慢性移植肾肾病患者中的转换治疗应用

概述新型免疫抑制剂不断改进并应用于移植临床,但却未能阻止慢性移植肾肾病(CAN)的发展,CAN依然是晚期移植肾失功的主要原因。2007年6月西班牙第9届国际移植病理Banff会议上,美国移植病理学家Cortese建议在移植领域Banff分类中继续使用CAN的术语,提示有关CAN术语应用仍有争论;笔者在本文中将继续引用CAN这一术语。移植临床更为关注的是分清CAN的引发原因,制定适宜的防治策略。     

冠状动脉药物涂层支架治疗急性心肌梗死

20世纪80年代以来的研究表明，在冠状动脉粥样硬化斑块破裂的基础上血栓形成，使冠状动脉急性闭塞，是导致ST段抬高的急性心肌梗死的原因。常用的血运重建方法是溶栓治疗和直接冠脉介入术（percutaneous coroanry intervention，PCI）。溶栓治疗与安慰剂对比可明显降低病死率。直接PCI可使梗死相关血管再通率高，达到心肌梗死溶栓试验（TIMI）3级血流者明显多，再闭塞率低。缺血复发少，且出血（尤其脑出血）的危险性低。Keeley等比较了两种方法的23个随机临床对照试验。直接PCI无论是短期死亡、非致死性心肌梗死、卒中．还是联合终点，都好于溶栓治疗。2004年的美国心脏学会／美国心脏协会在治疗急性心肌梗死指南中建议的对早期急性心肌梗死患者中梗塞相关血管的早期支架植入术已成为标准的治疗方案之一。     

04026 西罗莫司药物洗脱支架用于冠脉复杂病变的效果依然喜人

第17届经导管心血管治疗（TCT）年会上公布的两项研究结果进一步证明，西罗奠司（sirolimus）药物洗脱支架Cypher用于冠脉复杂病变的效果好。PRISON Ⅱ研究显示，与裸金属支架相比，西罗莫司药物洗脱支架可更有效预防慢性完全闭塞病变的支架内再狭窄。SISR研究显示，与放射治疗相比，西罗莫司药物洗脱支架用于裸金属支架支架内再狭窄的靶血管血运重建的失败率低。     

两组免疫抑制方案用于肾移植的对比研究

目的通过两组免疫抑制方案在肾移植中的临床应用,评估新型免疫抑制剂雷帕霉素预防急性排斥反应(AR)的疗效和安全性。方法回顾分析肾移植患者的临床资料,按术后免疫抑制方案的不同,随机分为两组:采用雷帕霉素(RPM,首次剂量6.0 mL,维持剂量2.0 mL/d)+环孢素A(CsA,5~6 mg.kg-1.d-1)+泼尼松(Pred)25例为SRL组,采用霉酚酸酯(MMF)+CsA(6~8 mg.kg-1.d-1)+Pred 35例为MMF组。比较两组用药后的血肌酐(SCr)、AR发生率及药物的不良反应。结果在SCr水平、AR发生率方面,MMF组与SRL组无统计学意义(P>0.05);两组在随访期间均未见严重感染发生;除SRL组高脂血症的发生率明显升高外,两组药物不良反应无统计学意义。结论SRL组抗排斥反应的疗效及安全性与MMF组相似,可作为肾移植抗排斥反应治疗方案推广使用。     

雷帕霉素纳米粒滴眼液联合环孢素A缓释膜治疗兔高危角膜移植术后免疫排斥反应的研究

Objective To evaluate the combined effect of topical rapamycin (RAPA) eye drop in nanometer vector and poly (lactic acid) (PLA) wafers of cyclospoirne A(CsA) in the prevention of acute allograft rejection after rabbit corneal transplantation. Methods It was an experimental study. RAPA was incorporated into the nanometer particles and CsA was incorporated into PLA wafers. A was syngeneic control whose both donor and recipient are New Zealand rabbit. Gray donor corneas were implanted into the 102 recipients of New Zealand albino rabbits with corneal neovascularization who were randomly divided into B, C, D, E, F, G 6 groups to receive the different types of therapy: B was no therapy control; C was eye drop of nanometer vector but no RAPA twice a day,28 days; D was PLA wafers in the anterior chamber of rabbit eyes but no drugs; E was 0.5% RAPA eye drop of nanometer vector twice a day,28 days; F was PLA wafers of CsA in the anterior chamber of rabbit eyes; G was PLA wafers of CsA in the anterior chamber of rabbit eyes and 0.5% RAPA eye drop of nanometer vector eye drop twice a day for 28 days together. Postoperative evaluation included slit-lamp biomicroscopy, histopathology and immunohistoiogy, Cytokines related with neovascularization and immunosuppression in the corneal tissue by RT-PCR. The graft survival was assessed by One-Way ANOVA and q test. Results Corneal allograft survival time: A (100.00±0.00), B ( 8.44±1.24), C (8.89±2.57), D (8.56±2.30), E (43.11±5.58), F (43.67±9.54), G (72.00±15.34)d. Group G led to a statistically significant prolongation of transplant survival and was superior than group E and F which was a statistical prolongation compared with group B, C and D (qGE=11.42, qGF=11.24,qEB=13.64, qEC=13.38, q<=13.46, qFB=13. 82, qFC=13.56, qFD=13.64; P<0.01). Immunohistopathologically, the grafts were subjected to an immune response contained a dense infiltrate of neutorphils,CD4+ and CD8+ T lymphocytes in the group B ,C and D. This cellular infiltrate was a significant reduction in group E,F,G. RT-PCR showed that the gene expression of IL-2 was inhibited earlier (3 days) in group F, G and VEGF gene expression being suppressed later (14 days) in group E, G. Conclusions Combined therapy with topical application of RAPA eye drop of nanometer vector and CsA PLA wafers can significantly prolong the survival of allograft at high-risk. Moreover, topical combined treatment of them is more effective, lower dosage, less side-effects and cheaper than the treatment with topical individual immunosuppressive drug.     

在非裔美国人中用1％吡美莫司软膏治疗伴色素减退的脂溢性皮炎的先导性试验

背景:非裔美国人发生脂溢性皮炎时可伴色素减退。治疗通常应用皮质激素和抗真菌药,然而长期使用皮质激素可导致皮肤萎缩,眼内压增高,或加重色素减退。吡美莫司已被成功用于治疗一些脂溢性皮炎患者。目的:此开放性预试验用于评估吡美莫司治疗非裔美国人中伴色素减退的脂溢性皮炎     

既往深部静脉血栓形成部位出现局限性移植后Kaposi肉瘤：停用西罗莫司后的突发皮损

K aposi肉瘤(K S)是一种与人疱疹病毒8感染相关的血管增殖性肿瘤。H H V-8引发K aposi肉瘤的机制是通过分泌血管内皮生长因子(V EG F)及上调内皮细胞中VEG F受体———K DR,而致病。作者报道了一例72岁接受肾移植发生K S的男性患者,其使用了西罗莫司、麦考酚酸莫酯、他克莫司及     

西罗莫司的研究进展

从最近研究结果看西罗莫司对器官移植排斥反应、支架植入后预防再狭窄以及抗肿瘤等方面都有良好作用,而且与6-巯基嘌呤、环孢菌素A(CsA)等合用有协同作用,是目前临床用途较广的,且较安全的新免疫抑制剂.最近发现西罗莫司还具有抗肿瘤作用.     

冠状动脉药物涂层支架的晚期血栓

药物涂层支架（drug—eluting stent，DES）被认为是冠心病介入治疗的又一个里程碑，它能够显著降低再狭窄率和再次血管重建率，使过去经皮冠脉腔内成形术（percutaneous transluminal coronary angioplastv．PTCA）最困扰的再狭窄问题得到很大的改善．根除再狭窄终于有了希望。自从美国食品药品监督管理局（Food and Drug Administration，FDA）批准使用两种冠状动脉药物支架（西罗莫司涂层支架，Sirolimus—eluting stents，SES，