儿童视网膜母细胞瘤发生发展密切相关的可疑新基因位点研究

背景：近年来研究表明视网膜母细胞瘤(retinoblastoma，RB)的发生和病变的进展除了与已知的Rb1基因有相关性外，可能还有其他抑癌基因的参与。目的：探讨其他可能参与RB发生发展的基因存在的位点，并试图寻找和确定具有监测及预后价值的杂合性缺失(LOH)检测指标。设计：以RB患者为研究对象的病例分析。单位：一所军医大学医院的基因诊断治疗中心。对象：本研究在第三军医大学西南医院基因诊断治疗中心完成，研究对象为1998-05／2001-10在本校三所附属医院门诊就诊的RB患者16例。纳入标准：符合RB诊断标准的年龄小于3岁的患儿；排除标准：有家族遗传史者。其中男10例，女6例；累及双眼者12例，累及单眼者4例。方法：在患者的RB肿瘤及外周血标本中运用荧光聚合酶链反应(PCR)分别扩增13号染色体上14个微卫星DNA标记，分析测定各位点LOH发生率；同时通过家系分析确定位点缺失的遗传学来源。主要观察指标：患者13号染色体上LOH发生频率。结果：16例RB患者中，12例在13号染色体上1个或1个以上位点发生LOH。其中3个位点D13S265、D13S263和D13S153(位于Rb1基因内)LOH发生机率最高。12个LOH阳性标本中有10个位点的缺失被确定发生在父系来源的染色体中。LOH阳性及阴性组RB的确诊时间分别为504和1086d，两组相比差异具有显著性意义(t=2．357，P&;lt;0．05)。结论：LOH阳性组的患者RB确诊时间早于LOH阴性组。除已确定的Rb1基因外，D13S263(13q14．1—14．2)和D13S265(13q31—32)两个位点的LOH现象也可能对RB患者的早期干预和功能监测具有一定提示作用。     

视网膜母细胞瘤中DLC-1启动子甲基化异常

目的探讨肝癌缺失基因1(deleted in liver cancer-1,DLC-1)启动子在视网膜母细胞瘤(retinoblastoma,RB)中的甲基化情况及与临床参数的关系。方法收集37例RB石蜡切片,4例正常眼部组织标本和2株RB细胞系(WERI-Rb1及Y79)。用甲基化敏感性高分辨率熔解(MS-HRM)法定量检测DLC-1甲基化情况,用亚硫酸氢盐测序对其进行验证,并用RT-PCR检测WERI-Rb1和Y79细胞系中DLC-1 mRNA的表达。结果 35.1%的RB中存在DLC-1启动子甲基化,而在正常眼部组织中未发现甲基化;WERI-Rb1和Y79检测出DLC-1 mRNA表达。DLC-1启动子甲基化与肿瘤分化、伴随其他肿瘤和家族史均无显著关系,但单侧RB患者中的DLC-1甲基化率明显高于双侧患者(P<0.05)。结论 RB患者DLC-1启动子存在一定程度的甲基化,DLC-1甲基化在RB的发生、发展中具有一定的作用。     

视网膜母细胞瘤易感基因在人肺癌中的缺失和突变研究

目的研究视网膜母细胞瘤易感基因(Rb基因)在人肺癌中的缺失和突变情况。方法采用PCR和限制性内切酶分析技术,对20例人肺癌组织DNA样品和3例正常人肺组织DNA样品Rb基因外显子14~16、22~23区域进行分析。结果2例样品存在外显子14~16区域的缺失。结论Rb基因在人肺癌,特别是小细胞肺癌中存在缺失,此为肺癌发病机制的研究积累了资料。     

视网膜母细胞瘤的护理体会

视网膜母细胞瘤的护理体会６４６０００泸州医学院附属医院鲁晓霞，梁克丽，程文惠视网膜母细胞瘤是以视网膜内颗粒层，细胞层和外颗粒层为起源的胚胎性恶性肿瘤，是常染色体显性遗传病，大多数见于３岁以下儿童，年龄越小．预后愈差。我科从１９９３年１月～１９９５年７...     

视网膜母细胞瘤患儿的护理

目的 探讨视网膜母细胞瘤患儿的护理方法.方法 术前进行健康教育和心理护理,术后密切观察术眼情况,预防并发症,同时做好用药护理,保证有效治疗及检查,出院时正确指导保养义眼片及护理义眼,提供遗传咨询.结果 经过及时正确的治疗和护理,加强遗传咨询,患儿均未发生并发症,康复情况良好,生活质量提高.结论 加强健康教育和心理护理,提高患儿及家属的依从性,密切观察病情,精心护理,加强出院指导,是促进患儿康复,减少并发症,提高生活质量的重要保证.     

视网膜母细胞瘤误诊报告

【病例】男性，６岁。左眼发现白瞳１０余日，于１９９７年６月１５入院。无外伤史。查体：右眼正常。左眼视力光感，眼位正常，无突眼；球结膜轻度充血，瞳孔下方有白色反光；眼前节无炎症；玻璃体混浊，少量积血；眼底于颞下方可见网膜呈灰黄色隆起，其上有血管爬行，视...     

视网膜母细胞瘤中survivin的表达

目的 探讨survivin在视网膜母细胞瘤中的表达情况.方法 对20例视网膜母细胞瘤组织和8例正常视网膜组织采用免疫组织化学方法分析,采用Mann-Whitney U法分析组间差异.结果 视网膜母细胞瘤组中有14例suvivin表达阳性,正常组无1例阳性,两组间存在统计学差异(P＜0.01).结论 视网膜母细胞瘤组织中snrvivin表达上调,可能与肿瘤的发生和发展相关.     

视网膜母细胞瘤的生存率和预后因素研究

目的研究视网膜母细胞瘤(Rb)的生存率及预后因素。方法随访1997～2001年102例Rb患者的生存状况,进行Rb的生存率和相关预后因素分析。结果随访102例Rb患者,平均随访时间为45.2个月。81例存活(79.4%),21例死亡(20.6%);1、3、5年的生存率分别为87.25%、81.37%和78.79%。单眼、双眼患者生存率分别为84.52%和54.55%,差异有统计学意义(P<0.01);病程≤6个月的生存率为85.36%,病程>6个月的生存率为58.33%,两者差异有统计学意义(P<0.01);12例眶组织侵犯,存活5例,死亡7例,生存率为41.67%,眶组织未受侵犯组生存率为83.78%,两者差异有统计学意义(P<0.01);10例进行眼球保守治疗,5例成功;93例Ⅰ期行眼球摘除术的患者中,84例行Ⅰ期义眼座植入术,其中73例(86.9%)存活,11例(13.1%)死亡。结论 102例Rb患者42个月后生存率达到78.72%。双眼患者、病程>6个月和眶组织侵犯者预后较差,生存率低。Rb患者有一定的保守治疗成功率,Rb患者行眼球摘除术时,可选择联合行Ⅰ期义眼座植入。     

视网膜母细胞瘤患儿主要照顾者照顾负担及影响因素分析

目的：探讨视网膜母细胞瘤（RB）患儿主要照顾者的照顾负担水平及其影响因素。方法：采用一般资料调查表、Zarit照顾者负担量表（ZBI）及社会支持评定量表（SSRS）对180例视网膜母细胞瘤患儿的主要照顾者进行调查。结果：视网膜母细胞瘤患儿主要照顾者的照顾负担总分为（44.37±14.27）分,社会支持总分为（36.62±7.69）分。回归分析结果显示,患儿年龄、疾病治疗时间、主要照顾者的照顾时长、工作状况、费用支付方式、社会支持是影响患儿主要照顾者照顾负担的主要因素,解释照顾负担变异的45.3%。结论：视网膜母细胞瘤患儿主要照顾者的照顾负担处于重度水平,建议护理人员采取积极的应对方式,帮助减轻照顾负担,从而提高照顾质量。     

80年代末与90年代末躁狂发作患者治疗比较

目的 :了解躁狂发作患者的治疗现状。方法 :对 1998年和 1999年与 1988年和 1989年躁狂发作患者服药人数及剂量作回顾性分析 ,调查服用碳酸锂人数及服用剂量 ,以及氯氮平 ,氯丙嗪等应用情况。结果 :1998、1999年与 1988、1989年比较碳酸锂的使用率和使用量均减少 (均P <0 .0 1) ,碳酸锂合并氯丙嗪或氟哌啶醇、或ECT的治疗率降低 (P <0 .0 1) ,碳酸锂合并氯氮平的治疗率增高 (P <0 .0 1)。结论 :躁狂发作应用碳酸锂尚欠规范 ,碳酸锂合并氯氮平已成为治疗躁狂发作的主流。     

围产期脑损伤小儿康复治疗的效果及相关因素

目的：了解围产期脑损伤小儿康复治疗效果及相关影响因素。方法：总结了123例新生儿期曾住院治疗，在随访中发现运动功能异常，接受康复治疗的疗效，分别用单因素和Logistic多元逐步回归法分析了可能影响疗效的生物学因素。结果：本组小儿接受康复治疗的起始时间：生后4个月内占81．3％，5—6个月13．01％，)6个月5．69％。纳入阶段性总结77例，完全恢复正常者63例(81．82％)，治疗至1岁半仍不正常，完全恢复较困难者14例(18．18％)。影响小儿康复治疗效果的相关生物学因素是出生时的成熟程度、脑损伤的严重程度、新生儿期后是否遗留脑部病变以及整体智能发育水平，其中以小儿的孕周、严重的脑损伤、智能水平与治疗效果关系更为密切。结论：康复治疗对存在运动异常的小儿是有效的途径。     

Agrin expression is correlated with tumor development and poor prognosis in cholangiocarcinoma

ObjectiveThis study examined the role of agrin in the development of cholangiocarcinoma (CCA).MethodsWestern blotting was performed to detect the expression of target genes. The correlation between agrin expression and prognosis was analyzed using the Kaplan–Meier method. Proliferation, migration, invasion, and tumorigenesis were examined in CCA cells and tissues using the Cell Counting Kit-8 assay, cell cycle analysis, transwell migration assay, and nude mouse tumorigenicity assay in vivo, respectively.ResultsAgrin expression was significantly upregulated in CCA tissues compared with that in adjacent non-tumor tissues, and agrin expression was correlated with poorer tumor characteristics such as portal vein tumor thrombus, intrahepatic metastasis, and worse survival. Forced agrin expression in CCA cells apparently promoted proliferation, colony formation, migration, invasion, and cell cycle progression, but agrin depletion had the opposite effects. Furthermore, agrin-depleted CCA cells developed fewer and smaller tumors than control cells in vivo. Mechanistic analyses indicated that agrin activated the Hippo signaling pathway and induced the translocation of YAP to the nucleus.ConclusionsAgrin promoted CCA progression by activating the Hippo signaling pathway, suggesting its promise as a target for CCA therapy.     

儿童常见外眼肿瘤与视网膜母细胞瘤诊疗进展

儿童眼部肿瘤以先天性和胚胎性肿瘤为主,其中恶性肿瘤主要为原发性肉瘤和胚胎性肿瘤,横纹肌肉瘤和神经母细胞瘤多见;良性肿瘤主要为上皮来源、血管源性和神经源性良性肿瘤,以皮样囊肿、脂肪瘤、角膜皮样瘤多见。     

肝病患者血清肿瘤标记物含量及肿瘤坏死因子相关凋亡诱导配体受体表达在癌变中的临床意义

目的 探讨血浆透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型胶原(ⅢC)、Ⅳ型胶原(ⅣC)、甲胎蛋白(AFP)和肿瘤坏死因子相关凋亡诱导配体(TRAIL)受体-2(DR5)、诱捕受体-1(DcR1)的表达与肝纤维化及肝癌变的关系.方法 用ELISA方法测定正常对照组(A 组)、肝炎组(B 组)及肝硬化并发肝癌组(C 组)的HA、ⅢC、ⅣC 及LN 和AFP 的含量,用WesternBlotting 检测肝癌手术的癌组织、癌旁组织AFP、DR5 和DcR1 的表达.结果 HA、LN、ⅢC、ⅣC 和AFP 的血清含量由高到低:C 组＞B 组＞A 组;(1)ⅢC、ⅣC、LN 的相关性:A、B、C 组ⅢC、ⅣC、LN 表达呈正相关,r 分别为0.623、0.651、0.714 (P 均＜0.05).(2)C 组的各个观察指标均高于B 组和A 组,特别是血清AFP 和HA 含量,在A 组和B 组之间尽管也有统计学的意义(P ＜0.05),但是C 和A、B 组比较,这两者的含量显著性升高(P ＜0.001).(3)Western Blotting 分析显示,癌旁组织的AFP 和DcR1 表达明显低于癌组织(P 均＜0.05);而DR5 在癌旁组织表达则明显高于癌组织(P 均＜0.05).结论 由肝炎到肝硬化、肝癌的过程中HA 的累聚以及LN、ⅢC、ⅣC 和AFP 的表达是一个渐进的基因激活过程;AFP、DR5 和DcR1 在肝癌组织的表达变化预示癌细胞耐受凋亡诱导.     

Butyrylcholinesterase: association with the metabolic syndrome and identification of 2 gene loci affecting activity

BACKGROUND: Plasma cholinesterase activity is known to be correlated with plasma triglycerides, HDL- and LDL-cholesterol, and other features of the metabolic syndrome. A role in triglyceride metabolism has been proposed. Genetic variants that decrease activity have been studied extensively, but the factors contributing to overall variation in the population are poorly understood. We studied plasma cholinesterase activity in a sample of 2200 adult twins to assess covariation with cardiovascular risk factors and components of the metabolic syndrome, to determine the degree of genetic effects on enzyme activity, and to search for quantitative trait loci affecting activity. METHODS AND RESULTS: Cholinesterase activity was lower in women than in men before the age of 50, but increased to activity values similar to those in males after that age. There were highly significant correlations with variables associated with the metabolic syndrome: plasma triglyceride, HDL- and LDL-cholesterol, apolipoprotein B and E, urate, and insulin concentrations; gamma-glutamyltransferase and aspartate and alanine aminotransferase activities; body mass index; and blood pressure. The heritability of plasma cholinesterase activity was 65%. Linkage analysis with data from the dizygotic twin pairs showed suggestive linkage on chromosome 3 at the location of the cholinesterase (BCHE) gene and also on chromosome 5. CONCLUSIONS: Our results confirm and extend the connection between cholinesterase, cardiovascular risk factors, and metabolic syndrome. They establish a substantial heritability for plasma cholinesterase activity that might be attributable to variation near the structural gene and at an independent locus.     

Head injury in children and teenagers; functional recovery correlated with the duration of coma.

Residual impairments and mortality were assessed in 48 patients under 20 years of age at least two years after a traumatic head injury had caused coma lasting more than seven days. In this study the duration of coma was defined as the period of time when it is impossible to establish intellectual contact with the patient. A classification of functional levels 1 to 8 was used to identify the residual impairment and relate this impairment to the duration of coma for each patient. Of 30 patients who remained in coma less than three month, only one did not have independent ambulation with or without equipment at the time of his last follow-up evaluation. This was one parameter among others to show that the prognosis for recovery in this age group is much better than expected following severe head injury. These follow-up data, correlated with the duration of coma, can assist rehabilitation personnel in the prognostic planning for younger people with severe head injuries. Rehabilitation medicine needs to be involved in patient care during the period of coma to prevent contractures and other complications which often interfere with and delay later rehabilitation programs, making them more costly and less successful.     

Understanding pRb: toward the necessary development of targeted treatments for retinoblastoma

Retinoblastoma is a pediatric retinal tumor initiated by biallelic inactivation of the retinoblastoma gene (RB1). RB1 was the first identified tumor suppressor gene and has defined roles in the regulation of cell cycle progression, DNA replication, and terminal differentiation. However, despite the abundance of work demonstrating the molecular function and identifying binding partners of pRb, the challenge facing molecular biologists and clinical oncologists is how to integrate this vast body of molecular knowledge into the development of targeted therapies for treatment of retinoblastoma. We propose that a more thorough genetic understanding of retinoblastoma would inform targeted treatment decisions and could improve outcomes and quality of life in children affected by this disease.