人胰腺癌干细胞差异性基因的表达

目的 分选、鉴定人胰腺癌干细胞,运用基因芯片技术分析其差异性基因的表达.方法 运用流式分选技术分选胰腺癌干细胞(CD24+CD44+ESA+),NOD/SCID鼠移植瘤试验进行肿瘤干细胞特性鉴定.采用Affymetrix U133 plus2.0人类全基因组表达谱芯片对胰腺癌干细胞和非干细胞进行差异基因筛选.结果 分选得到人胰腺癌CD24+CD44+ESA+亚群细胞,占所有细胞的0.8%;5×103个CD24+CD44+ESA+细胞就能成瘤(2/4),而阴性细胞1×105才能成瘤(1/4);CD24+CD44+ESA+具有一定的自我更新和分化能力.基因芯片杂交获得6553(11.99%)条差异基因,胰腺癌干细胞中5255(9.61%)条上调表达,1298(2.37%)条下调表达.其中差异基因涉及细胞凋亡、细胞周期、代谢、细胞线粒体结构和耐药等多个方面.结论 胰腺癌于细胞具有自身特征性基因表达谱,为进一步从干细胞层面研究胰腺癌发病机制及靶向治疗奠定基础.     

Gating modifier peptides as probes of pancreatic beta-cell physiology.

Pancreatic beta-cells depolarize in response to glucose and fire calcium-dependent actions potentials that trigger insulin secretion. The major current responsible for action potential repolarization in these cells is a delayed rectifier and Kv2.1 subunits are thought be a major contributor of the delayed rectifier channels. Hence, blockers of Kv2.1 channels might prolong action potentials and enhance calcium influx and insulin secretion. However, the lack of specific small molecule Kv2.1 inhibitors has hindered the testing of this mechanism. Importantly, several gating modifier peptides inhibit Kv2.1 channels in a relatively specific fashion. Hanatoxin (HaTX) and guangxitoxin-1 (GxTX-1) are examples that have been used to probe the role of Kv2.1 channels in beta-cell physiology. Both HaTX and GxTX-1 strongly inhibit the Kv current of beta-cells from various species, arguing that Kv2.1 subunits contribute significantly to the beta-cell delayed rectifier. GxTX-1 prolongs glucose-triggered action potentials, enhances glucose-dependent intracellular calcium elevations and augments glucose-dependent insulin secretion. Taken together, these data suggest that blockers of Kv2.1 channels may be a useful approach to the design of novel therapeutic agents for the treatment of type 2 diabetes. These studies highlight the utility of gating modifier peptides in the study of physiological systems.     

胰腺癌微血管壁通透性的形态学研究

目的 观察胰腺癌微血管壁的通透性相关结构,为胰腺癌药物治疗靶向性的提高提供参考.方法 选取我院切除的中分化胰腺癌10例,对肿瘤中心、边缘、瘤旁、正常/远隔胰腺4个部位进行透射电镜检测.结果 胰腺癌微血管数量和内皮窗孔数量明显少于正常胰腺组织(P<0.05),且内皮间隙和窗孔的内径并不超过正常胰腺组织.胰腺癌微血管内皮间隙内径中位数为12.8～13.2 nm,5～95百分位数为0～24.4 nm,内皮间隙存在局部扩张的现象,最宽处可以达到60.3～76.4 nm.胰腺癌微血管窗孔的内径在40.0nm左右.瘤旁组织破口较多,破口内径平均516.3 mm左右.结论 与正常胰腺组织比较,胰腺癌具有一定的微血管异质性,体现为血供较少和微血管壁通透性较低等特点.     

联合门静脉和/或肠系膜上静脉切除的扩大胰十二指肠切除术

目的探讨胰头癌侵犯门静脉和／或肠系膜上静脉（PV／SMV）时的根治切除的可行性。方法回顾分析包括受侵PV／SMV在内的扩大胰头十二指肠切除术16例的临床资料。16例均行胰头十二指肠切除术，其中9例行血管壁部分切除，5例行血管节段性切除及对端吻合，2例行受侵血管切除＋自体静脉移植。结果全组患者术后均未发生血管栓塞、肠坏死、肝衰竭等并发症。除1例并发多器官衰竭于术后2d死亡外，均康复出院。15例均随访。存活超过3年者3例，超过5年者1例，存活3～26个月4例。结论对单纯侵犯PV／SMV的胰头癌施行联合PV／SMV住内的胰头癌扩大根治术是可行的。     

β-catenin和cyclinD1基因在胰腺癌中的表达及意义

目的探讨-βcatenin和cyclinD1基因在胰腺癌中的表达及意义。方法采用免疫组织化学SP法测定胰腺癌45例和正常组织10例中-βcatenin和cyclinD1的表达。同时,检测胰腺癌增殖细胞核抗原(PCNA)作为胰腺癌增殖状态的指标。结果-βcatenin在癌细胞胞浆的表达明显高于正常胰腺组织者。其表达与胰腺癌的大小、分化程度、增殖、发病年龄无关(P>0.05),而与胰腺癌的浸润、转移相关(P<0.05)。cyclinD1在胰腺癌中的表达与胰腺癌的大小、分化程度及发病年龄无关(P>0.05),而与胰腺癌的增殖、浸润和转移呈显著的相关性。cyclinD1和-βcatenin在胰腺癌中的表达显著相关。结论cyclinD1是与胰腺癌浸润、增殖相关的调节基因之一。-βcatenin的异常表达激活cyclinD1,是调节cyclinD1的上游基因。     

Assessment of the quality of life in chronic pancreatitis using Sf-12 and EORTC Qlq-C30 questionnaires

BACKGROUND: SF-12 Health Survey, and European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30 are the two main questionnaires proposed and validated for assessing the quality of life in chronic pancreatitis. AIMS: To evaluate the role of the information furnished by both the SF-12 Health Survey and European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30 questionnaires, and to determine which of these two questionnaires may be considered more efficacious, in clinical practice, in describing the quality of life of patients with chronic pancreatitis. PATIENTS: We studied 163 consecutive patients with proven chronic pancreatitis. METHODS: The Italian version of the SF-12 Health Survey and the Italian neutral version of the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30 Version 3.0 questionnaires were administered. RESULTS: Pancreatic pain was the only clinical variable able to significantly impair the SF-12 Health Survey component summaries as well as all domains of the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30, while body mass index was positively related to the physical component summary-12 and to the domains of the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30. A high level of reliability of the domains/scores of the two questionnaires in evaluating the quality of life in patients with chronic pancreatitis was found and two main factors were identified. These two factors were mainly related to the two SF-12 Health Survey summary components. CONCLUSIONS: From a practical point of view, the SF-12 Health Survey is more reliable and easier to use in routine clinical practice than the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30.     

胰腺假性囊肿的外科治疗：附89例报告

目的：探讨胰腺假性囊肿的治疗策略。方法：回顾性分析近5年湘雅医院普通外科收治的89例胰腺假性囊肿临床资料，根据囊肿部位、形成时间及囊壁厚度，采用非手术治疗20例，经皮囊肿穿刺引流7例，开腹手术62例（外引流8例、内引流45例、囊肿切除9例）。结果： 全组无死亡病例，手术后并发症发生率15.9%，随访3个月至5年，复发率5.6%。结论：胰腺假性囊肿的治疗宜根据情况采用不同方式，非手术治疗适于无并发症者;急诊手术应选择外引流;囊壁成熟者，选择内引流术疗效好。     

The expression of β-adrenoceptors in human pancreatic cancer cell lines and their roles in cell invasiveness

Objective To investigate the effect and mechanism of β-adrenoceptors on norepi-nephrine-induced invasiveness of pancreatic cancer cell lines. Methods The expression of β-adrenocep-tors mRNA in human pancreatic cancer cell lines MiaPaCa-2 and BxPC3 was detected by using RT-PCR. The cells were randomly divided into control group.10 mol/L NE intervention group, 1 mol/L propranolol intervention group and NE + propranolol intervention group. After 48 h , transwell invasiveness test was used to examine the changes in invasive ability of MiaPaCa-2. The expression of MMP-2, MMP-9 and VEGF mRNA was measured by semi-quantitative RT-PCR. The levels of MMP-2 , MMP-9 and VECF proteins were assayed by immunocytochemistry. Results Both MiaPaCa-2 and BxPC3 expressed β1-and β2-adrenocep-tors. The absorbance ( A) values of invasive cells in NE, NE + propranolol, propranolol and control groups were 0.78±0.02 ,0.32±0.03 ,0.26±0.01 and 0.28±0.02 , respectively, and those in NE intervention group were significantly higher than in control and NE + propranolol groups ( P <0.05) . There was no sig-nificant difference in the number of invasive cells between propranolol and control groups ( P > 0. 05) . In NE group , the expression index of MMP-2 , MMP-9 and VEGF mRNA was 0. 87±0.02 , 1.04±0.02 and 0. 92±0. 01 , and the gray value of the protein expression was 131.20±2.34,105.32±7.21 and 115.60 ±5. 03 , respectively, which were higher than those in control and NE + propranolol groups ( P<0.05). There was no significant difference in the expression levels of MMP-2 , MMP-9 and VEGF mRNA and pro-tein between propranolol and control groups ( P>0.05 ) . Conclusion β-adrenoceptors play an important role in the process of norepinephrine-induced invasiveness of pancreatic cancer cells. NE can promote the invasiveness of MiaPaCa-2 through up-regulating the expression of MMP-2 , MMP-9 and VEGF via β-adre-noceptors.     

肺耐药蛋白在胰腺癌细胞中的表达及意义

目的探讨肺耐药蛋白(lungresistanceprotein,LRP)在胰腺癌细胞株中的表达及意义。方法采用反转录多聚酶链反应(RT-PCR)和免疫细胞化学方法检测8株胰腺癌细胞株(SW1990、PCT-2、PCT-3、PCT-4、Aspc-1、Capan-1、Mia-PaCa-2及Panc-1)中LRP在基因水平和蛋白水平的表达。结果RT-PCR结果显示,在胰腺癌细胞株PCT-2中未检测到LRPmRNA的表达,在PCT-4、Aspc-1和Panc-1中,LRPmRNA表达条带较强;在SW1990、PCT-3、Capan-1和Mia-PaCa-2中LRPmRNA表达条带较弱;半定量平均表达水平为0.56±0.33。免疫细胞化学结果证实,在PCT-2细胞中无LRP蛋白表达,PCT-3细胞中LRP蛋白弱表达,SW1990、Aspc-1和Capan-1细胞中LRP蛋白中度表达,而在PCT-4、Mia-PaCa-2和Panc-1细胞中可见LRP蛋白的过度表达。结论在胰腺癌细胞中存在LRP的先天性表达,LRP过表达可能是介导胰腺癌细胞先天性耐药的重要机理之一。     

假性胰腺囊肿的内窥镜治疗

目的 探讨假性胰腺囊肿内窥镜治疗的适应证、手术效果、并发症及优缺点。方法 对假性胰腺囊肿内窥镜治疗的相关文献进行综述。结果 内窥镜技术具有创伤小、操作方便、可反复进行等特点，其适应证正不断扩大．除内窥镜治疗失败、囊肿合并并发症和多发性囊肿时考虑外科手术外，其他情况下假性胰腺囊肿的治疗可考虑内窥镜优先的策略。结论 假性胰腺囊肿的治疗应根据囊肿大小、数量、解剖学部位及有无并发症等综合因素实行个体化原则。