miRNA在肾脏疾病发生发展及诊断治疗中的作用研究进展

miRNA是一类小的非编码RNA分子,参与了细胞生长、增殖、发育及多种疾病的发生发展过程。miRNA在不同肾脏疾病中具有特异性的表达谱,在多种肾脏相关疾病包括IgA肾病、糖尿病肾病及肾脏肿瘤等发挥重要的作用。特异、敏感地检测循环miRNA的表达差异,使得miRNA成为了一种非常有潜力的非侵袭性的生物标志物。基于miRNA的靶向治疗也为肾脏相关疾病的治疗带来新的希望。     

miRNA在胰腺癌诊断中的意义

胰腺癌是一种恶性程度高、预后不良的消化道恶性肿瘤。据统计,美国1996～2004年胰腺癌病人总的5年生存率为5%,在所有癌症中最低[1]。手术根治是胰腺癌病人获得长期生存的唯一途径,手术达到R0切除并给以辅助化疗的胰腺癌病人的5年生存率可达到4%～26%[2-3]。但仅有10%～30%的胰腺癌病人在诊断时有手术根治的机会,其中也只有一半的病人可达到手术切除[4]由于胰腺的特殊解剖位     

miRNA在肿瘤治疗中的研究进展

恶性肿瘤已成为人类死亡的第一位死因,每年全世界约有800万人死于癌症,且癌症的发病率还在逐年升高[1]。目前常规治疗方法(手术、放疗和化疗)具有一定局限性,不能完全根除或彻底杀灭肿瘤细胞。寻找一种新的治疗方法迫在眉睫,而MicroRNA(miRNA)作为近年来发现的内源性非编码RNA,其表达与个体发育、增殖、分化以及恶性肿瘤发生密切相关。新近研究发现了若干在各种人类肿瘤中具有治疗潜能的miRNA。同时,随着对miRNA靶基因及其对肿瘤细胞影响的深入了解,调节miRNA的表达或可为癌症治[2]     

miRNA在肾脏纤维化中的研究进展

小RNA（microRNA,miRNA）是一类普遍存在的参与转录后水平基因表达调控的小分子RNA,近年来关于miRNA在细胞增殖、分化和凋亡等方面研究很多,本文主要对miRNA研究中涉及肾脏纤维化的机制进行简要概述。     

Micro-RNA在骨关节炎中的研究进展

骨关节炎(osteoarthritis,OA)是由全身易感因素和局部机械性因素相互作用导致的一种以关节软骨退变为主的常见老年性骨与关节退行性疾病[1].其主要的临床表现为:受累关节的疼痛、肿胀、畸形、活动受限,影像学的主要表现为:受累关节的关节间隙变窄、软骨下骨周围骨赘形成[2].美国大约有2700万OA患者,每年需要施行60万例关节置换术治疗晚期OA[3].OA也是中国中老年人群中的常见病和疑难病,据估计中国OA患者有超5000万之多.随着中国人口的老龄化进程,由0A带来的医疗负担及因劳动力丧失所带来的社会生产力损失给国家背上了沉重的包袱.正是由于OA的发病率高、致残率高、治疗周期长的特点,大大增加了医疗资源消耗,引起国际社会的高度关注.1999年,世界卫生组织(WHO)将OA与心血管疾病和癌症列为三大严重影响健康的疾病;联合国把2000～2010年定为“骨与关节十年”,以期重视OA的基础研究、预防和治疗,从根本上征服OA.     

miRNA与前列腺癌的研究进展

前列腺癌足男性泌尿系统最常见的恶性肿瘤之一。miRNA在转录后水平对基因表达进行调控,在生命活动中发挥重要作用,并可通过类似痈基因、抑癌基因或其他方式调控肿瘤的发生、发展和转归过程。最近研究表明一些miRNA在前列腺癌组织中异常表达,miRNA在前列腺癌发生、发展的分子机制中起着重要作用。本文对miRNA的特点、与细胞凋亡、雄激素信号通路间的关系以及前列腺癌预后的最新研究进展作一综述。     

miRNA在乳腺癌中的作用及中医药治疗的研究进展

<正>乳腺癌是女性最常见的恶性肿瘤,其发病率呈逐年升高的趋势,且预后较差,严重影响了女性的身心健康^[1]。现代医学多采用局部手术、常规化疗、精确放疗、内分泌治疗和单克隆抗体等实施对症治疗,尽管这些手段的应用对乳腺癌患者的预后有显著的益处,但仍有很多患者面临复发和死亡的威胁。乳腺癌的预后与患者的临床表型、病理与病变组织的分子特征有关^[2]。     

乳头溢液中miRNA作为潜在肿瘤标志物的研究进展

乳头溢液是乳腺疾病的常见症状之一.对于不伴有乳腺肿块的乳头溢液患者,临床上诊断比较棘手.通过对乳头溢液中成分的检测分析来鉴别良恶性乳头溢液,是临床工作的需求.乳头溢液中糖蛋白类肿瘤标志物的检测展现出较好的临床应用价值.microRNA在恶性肿瘤中异常表达,在肿瘤发生发展中发挥重要作用,提示其有成为肿瘤标志物的潜力.最近...     

-80℃低温保藏对结直肠癌血浆miRNA标志物的影响

目的 探讨在非溶血和溶血状态下,低温保藏时间对结直肠癌患者血浆miRNA标志物质量的影响。方法 随机抽取中山大学附属第三医院生物样本资源库2014年至2021年间在-80℃低温环境下保藏不同时间的结直肠癌血浆标本,采用分光光度计检测评估血浆溶血程度,并分为溶血组和非溶血组。miRNA提取后采用实时荧光定量PCR对潜在的结直肠癌miRNA标志物miR-92a-3p和miR-378a-5p进行丰度分析和比较。结果 在-80℃低温储存环境下,非溶血组保藏8年以及溶血组保藏3年的血浆中miR-92a-3p和miR-378a-5p丰度无明显变化,溶血组保藏1、3年的血浆中miR-92a-3p的丰度显著高于同期非溶血组（均P<0.01）,而两组同期保藏1、3年miR-378a-5p的丰度差异无统计学意义（P=0.931、0.339）。结论 血浆初始溶血状态会影响循环miRNA的丰度,但低温保藏时间不影响血浆中miRNA的丰度,能较好地保持血浆样本中miRNA的稳定,用于后续研究。     

miRNA在骨质疏松症中的作用及中医药干预研究进展

骨质疏松症(osteoporosis, OP)是一种全身性代谢性骨骼疾病,目前公认的发病机制主要为骨吸收大于骨形成所引起的骨重塑失衡。微小核糖核酸(MicroRNA,miRNA)在参与调控骨重塑的基因表观遗传机制中扮演重要角色,可通过靶向上游关键调控因子(Runx2、RANKL等)及相关信号通路(Wnt/β-catenin通路、PI3K/Akt通路等)调控骨髓间充质干细胞成骨分化、成骨细胞分化及破骨细胞分化等细胞代谢进而影响骨重塑。中医药防治OP历史悠久,确有疗效,具有多通路、多靶点协同的特点。随着分子生物学研究的不断深入,中医药可通过干预多种miRNA表达参与调控成骨及破骨分化,进而改善骨代谢防治OP。该文通过总结多种miRNA调控相关因子影响成骨及破骨分化的靶向作用机制及中医药干预miRNA防治OP的研究成果,为探索miRNA在OP中的作用机制及中医药防治OP提供理论依据。     

食管癌新辅助放化疗疗效预测分子标志物

局部晚期食管癌单纯手术治疗预后较差,新辅助放化疗并手术治疗的方案可明显延长食管癌患者的总体生存时间.目前,该治疗方案已成为欧美国家及我国对局部晚期食管癌进行规范化治疗的指南.然而,由于只有经新辅助放化疗后获得病理缓解的患者可从中获益,治疗无反应的患者预后可能比单纯手术更差.因此,预测食管癌新辅助放化疗的疗效,区分优势人群和耐受人群,从而实现个体化的治疗极为重要.分子标记物用于预测食管癌新辅助放化疗的疗效研究前景广阔,有望广泛应用于临床实践,指导局部晚期食管癌个体化治疗方案的决策.     

From cancer genomics to thoracic oncology: discovery of new biomarkers and therapeutic targets for lung and esophageal carcinoma

Over the last decade, many genetic and epigenetic alterations involved in the development and progression of lung and esophageal cancers have been reported, but their precise molecular mechanisms have remained unclear. Although novel drugs targeting some of these molecular targets have been developed, they provide limited survival benefits to only a small subset of cancer patients, and only a small number of practically useful biomarkers are presently available. To identify the molecules involved in lung and esophageal carcinogenesis and those applicable as novel tumor biomarkers and for the development of new molecular therapies, we performed gene expression profile analysis of 101 archived lung cancers and 19 esophageal squamous cell carcinomas whose tumor cells were purified by laser microdissection. Through a subsequent systematic approach using tissue microarray, RNA interference, and high throughput enzyme-linked immunosorbent assay techniques as well as bioinformatics, we have identified a set of molecules that fall into the category of oncoantigens. These molecules are potentially promising candidates for the development of novel diagnostic biomarkers, therapeutic drugs, and/or immunotherapy; there is also a small subset of biomarkers for predicting the presence of lymph node metastasis in surgically treated patients. In this article, we introduce our sophisticated and integrated cancer genomics strategy for improving the treatment of cancer patients. This review was submitted at the invitation of the editorial committee.     

食管癌患者生命质量测评的现状

生命质量（QOL）测评应用于临床治疗方法或方案选择、临床新药筛选、卫生资源投入的效益评价和建议、探讨癌症患者QOL的影响因素与防治重点，为改进社会卫生服务等功能提供更客观的依据和预测患者预后等。对食管癌患者QOL的研究较少，绝大多数局限于身体功能的研究，其最大原因是没有一个统一的信度、效率高，又具有鉴别能力的食管癌专用量表。欧洲癌症研究与治疗组织（EORTC）QLQ－OES24是在EORTC QLQ－C30量表基础上发展的食管癌专用量表，已进行了Ⅱ期临床试验，与EORTC QLQ－C30联合应用，具有较高的信度、效度和鉴别能力，但其尚未汉化。FACT食管子量表（FACT－E）是癌症治疗功能评价系统（FACT）的子量表，刚开始用于食管癌患者QOL测评，其信度、效度未见报道。     

MUC1在食管癌成瘤中的作用

目的:研究黏蛋白1(mucin1,MUC1)在食管癌发生中的作用,寻找食管癌发病的新机制。方法 :采用MUC1-siRNA和CTL-siRNA质粒转染Ec1.71细胞获得MUC1稳定沉默细胞系,分别通过MTT法、软琼脂克隆形成实验和裸小鼠移植瘤模型检测下调MUC1对鳞状上皮细胞食管癌细胞生长、克隆形成能力和体内成瘤能力的影响。结果:建立Ec1.71/MUC1-siRNA-A/B稳定沉默MUC1细胞系和Ec1.71/CTL-siRNA-A/B对照组细胞系各两株。与对照组Ec1.71/CTL-siRNA-A/B细胞系相比,MUC1沉默组Ec1.71/MUC1-siRNA-A/B细胞的生长速度显著减慢,软琼脂克隆数目明显减少,移植瘤的生长速度明显减慢、肿瘤体积更小。结论:MUC1与食管癌的形成密切相关,抑制其表达,可显著降低食管癌细胞的恶性程度。本研究为食管癌的发病机制研究和临床治疗提供了重要参考。     

Ivor Lewis esophagogastrectomy for esophageal cancer

Background. To examine the efficacy of the Ivor Lewis esophagogastrectomy for esophageal carcinoma prior to the widespread use of preoperative chemotherapy and irradiation, we reviewed our experience.

Methods. We reexamined the cases of 220 consecutive patients who underwent an Ivor Lewis esophagogastrectomy for esophageal cancer from January 1992 through December 1995.

Results. There were 196 men (89.1%) and 24 women. Median age was 65 years (range, 29 to 85 years). The results of pathological study showed adenocarcinoma in 188 patients (85.5%), squamous cell carcinoma in 31 (14.1%), and leiomyosarcoma in 1 patient (0.5%). Postsurgical staging was as follows: stage 0 in 10 patients, stage I in 19, stage IIa in 38, stage IIb in 28, stage III in 111, and stage IV in 14. The operative mortality rate was 1.4% (3 patients), and complications occurred in 83 patients (37.7%). Follow-up was 98.6% complete. Median survival for operative survivors was 1.9 years (range, 32 days to 8.7 years). The overall 5-year survival rate was 25.2%; it was 80% for patients in stage 0, 94.4% for those in stage I, 36.0% for those in stage IIa, 14.3% for patients in stage IIb, 10% for those in stage III and 0% for patients in stage IV.

Conclusions. Ivor Lewis esophagogastrectomy for esophageal cancer is a safe operation. Long-term survival is stage dependent. The low survival associated with advanced cancers should stimulate the search for effective neoadjuvant therapy.     

细胞自噬在食管癌研究中的进展

细胞自噬(autophagy)是一个在各种外界因素影响下,真核细胞通过溶酶体降解其内部受损的细胞器、错误折叠的蛋白质和侵入其内的病原体并产生可以重新参与生命活动的物质和能量的生物学过程,在维持机体内环境稳定等方面发挥着重要的作用。目前,我国食管癌患者的发病率和病死率均远高于世界平均水平,放化疗联合靶向药物治疗已逐渐应用于食管癌的临床治疗,而这些新兴治疗措施与细胞自噬有着一定的关系。该文就细胞自噬在食管癌发生发展中的作用和调控机制进行综述。     

An experimental study of regional chemotherapy using CDDP-loaded microspheres for esophageal cancer

Purpose. The purpose of this study was to assess the antitumor effects of cisplatin-loaded microspheres (CDDP-MS) and the efficacy of the administration of CDDP-MS into the mediastinum. Methods. To evaluate the antitumor effect, we first performed a paratumoral injection of CDDP-MS to FF6 tumor-bearing DA rats to compare its effect with that of the intraperitoneal injection of a CDDP solution at different doses. Results. In the CDDP-MS groups the tumor growth was effectively delayed in proportion to the dosage of CDDP-MS. All rats treated with the CDDP solution at a dose of 10 mg/kg died within 1 week, while no rats treated with CDDP-MS even at a CDDP dose of 20 mg/kg were lost. In the second experiment, which was designed to determine the delivery of the microspheres-released CDDP to various organs, CDDP-MS was injected directly into the mediastinum via the diaphragm in male Wistar rats. In the CDDP-MS group, the plasma CDDP concentration stayed significantly lower than that in the CDDP solution (intravenous) group while the tissue CDDP concentration in the paratracheal lymph nodes was higher. Moreover, the lymph node-to-kidney platinum ratio was eight times higher in the rats given CDDP-MS intramediastinally than in those given the CDDP solution intravenously. Conclusion. These results demonstrate that a high dose of CDDP can be administered with less systemic side effects by means of encapsulation in the microspheres, and that the administration of CDDP-MS into the mediastinum is more effective for delivering CDDP to the paratracheal lymph nodes. As a regional chemotherapy after esophageal cancer operation, the injection of CDDP-MS into the mediastinum for targeting of the lymph nodes thus promises to be an effective treatment. Received: February 16, 2001 / Accepted: September 11, 2001     

Laparoscopic transhiatal esophagectomy for esophageal cancer

BACKGROUND: Traditional esophagectomy may be associated with mortality, considerable morbidity, and lengthy recovery. It is often performed in cancer patients who are typically older, have associated comorbidities, and are often malnourished, all factors that increase surgical risk. Minimally invasive esophagectomy has the potential advantages of being a less traumatic procedure with an easier postoperative recovery and fewer wound and pulmonary complications. METHODS: A retrospective analysis of patients who underwent laparoscopic transhiatal esophagectomy was performed. Assessed parameters included patient demographics and operative data, pathology results, and long-term follow-up of at least 12 months. RESULTS: Twenty-two patients underwent laparoscopic transhiatal esophagectomy; 19 had esophageal cancer. Two patients were operated on for Barrett esophagus, and 1 patient had achalasia. The majority of patients were men (82%), and the mean age was 59 years (range 15 to 74 years); 1 patient (4.5%) was converted to open surgery. The average operative time was 380 minutes (range 285 to 525 minutes), and the average blood loss was 220 mL; only 3 patients required transfusion. The median hospital stay was 8 days (range 5 to 46 days). Postoperative mortality occurred in 1 patient (4.5%), and postoperative complications developed in 6 patients (27.2%). In the 19 cancer patients, the average number of harvested nodes was 14.3 (range 10 to 19). The average follow-up was 30 months (range 12 to 48 months). The overall survival for cancer patients was 61% (11 of 19), and disease-free survival was 39% (7/19). CONCLUSIONS: Esophagectomy is a major surgery with considerable morbidity and potential mortality. Minimally invasive esophagectomy is a feasible approach that can be safely performed by surgeons with extensive experience in that field. Advantages include less intraoperative blood loss, a smaller incision, and a potentially faster postoperative recovery. In cancer patients, immediate oncologic goals of adequate margins and lymph node dissection can be achieved, and long-term outcome appears to be similar to that found with open approaches.     

Preclinical study of adenoviral p53 gene therapy for esophageal cancer

An alteration of the p53 gene function is a major factor in the development of esophageal cancer. Recently, p53 gene therapy has been applied for clinical studies in lung cancer and head and neck cancer. However, no preclinical studies have yet demonstrated an anticancer effect of adenoviral-mediated wild-type p53 gene therapy on esophageal cancer. We herein evaluated the effect of p53 adenoviral gene therapy on human esophageal squamous cell carcinoma to test the ability of clinical application. A normal esophageal epithelial cell line (EN53F) and two human esophageal cancer cell lines (ECGI-10 and T.Tn) with a p53 alteration were used. The transduction efficiency, p53 protein expression, p21 protein expression, the induction of apoptosis, and growth suppression were assessed by using the recombinant adenoviral vector Ad5CMV-p53. The transduction efficiency was 60%–80% at 100 plaque-forming units (PFU)/cell and 80%–100% at 300 PFU/cell. A significant growth suppression following an Ad5CMV-p53 infection was observed in both cancer cell lines. A Western blot analysis confirmed the presence of both exogenous p53 protein expression and p21 protein induction. Apoptotic cell death was observed with TUNEL staining. T.Tn xenografts in nude mice transduced with Ad5CMV-p53 demonstrated significant growth suppression. These data suggest that Ad5CMV-p53 may thus be a potentially effective therapeutic agent for locally advanced esophageal cancer. Received: July 19, 2000 / Accepted: January 9, 2001