bcl-2/bax mRNA在三氧化二砷体外诱导人胆管癌细胞株凋亡中的表达

目的 观察bcl-2、bax mRNA在三氧化二砷(As2O3)诱导人类胆管癌株QBC939、RBE细胞凋亡中的表达.方法 Rhodamine123染色检测线粒体膜通透性变化;逆转录-聚合酶链反应(RT-PCR)检测bcl-2、bax mRNA的表达.结果 As2O3干预,实验组Rhodamine123荧光染色强度较对照组明显减弱;凝胶成像检测bcl-2/β-actin mRNA A比值,QBC939、RBE细胞对照组分别为0.41±0.03、0.84±0.03;24 h实验组为0.01±0.01、0.43±0.02.bax/GAPDHmRNAA比值QBC939、RBE细胞对照组分别为0.21±0.01、0.42±0.04;24 h实验组为1.44±0.16、1.15±0.21,对照组与实验组比较差异均有统计学意义(P＜0.01).结论 As2O3可能增加胆管癌细胞株线粒体膜的通透性,下调bcl-2mRNA表达,上调bax mRNA的表达,可能启动了线粒体凋亡信号传导途径.     

1,25二羟维生素D3对胆管癌细胞系QBC939增殖和凋亡的影响

目的 探讨1,25二羟维生素D3[1,25(OH)2 D3]对胆管癌细胞系QBC939的体外增殖及凋亡的影响.方法 将不同浓度的1,25(OH)2 D3与胆管癌细胞系QBC939共同培养,采用MTT法测定细胞增殖能力、显微镜观察细胞形态学的改变、流式细胞仪检测细胞周期与凋亡、免疫细胞化学观察bcl-2的表达.结果 0.1～0.5μmol/L的1,25(OH)2 D3对胆管癌细胞QBC939有抑制作用,呈剂量依赖性.经1,25(OH)2 D3作用72h后细胞G1期比例升高,S期比例下降,其中0.5μmol/L组细胞G1期由(50.3±1.0)%上升至(65.5±3.2)%,S期由(39.4±0.5)%下降至(23.6±0.7)%;并且可诱导细胞产生凋亡,0.5μmol/L组作用后细胞凋亡率由0.5%上升至24.6%;bcl-2的表达下调.结论 1,25(OH)2 D3能抑制胆管癌细胞系QBC939增殖并诱导细胞凋亡,其引起凋亡的机制可能与下调bcl-2的表达相关.     

法尼酯X受体激动剂GW4064对人胆管癌细胞株QBC939生长的影响

目的:研究法尼酯X受体(FXR)激动剂GW4064对人胆管癌细胞株QBC939增殖和凋亡的影响,并检测QBC939细胞株中FXR基因表达的改变。方法:用浓度为0.5、1.0和5.0μmol/L的法尼酯X受体(FXR)激动剂GW4064刺激人胆管癌细胞株QBC939,用四甲基偶氮唑蓝(MTT)比色法检测24、48 h后细胞活力的变化,以流式细胞仪技术检测药物刺激48 h后肿瘤细胞凋亡的变化,并以RT-PCR检测QBC939细胞株中FXR mRNA表达的改变。结果:浓度为1.0、5.0μmol/L的GW4064在作用24 h后即能显著抑制胆管癌细胞生长(P0.05);在药物作用48 h后,所有浓度的GW4064均能对肿瘤细胞生长起明显的抑制作用(P0.05)。流式细胞仪检测细胞凋亡的结果显示,药物刺激48 h后,对照组凋亡细胞占细胞总数的3.38%,加入0.5μmol/L浓度GW4064的细胞凋亡率为10.02%;而加入1.0和5.0μmol/L浓度的GW4064后,细胞凋亡率明显升高至23.74%和42.11%。RT-PCR结果显示,所有浓度的GW4064于刺激48 h后,QBC939细胞株中FXR基因表达增加,与对照组相比均有统计学差异(P0.05)。结论:GW4064能通过特异性激动FXR有效抑制胆管癌细胞株QBC939的细胞活力,并促进其凋亡,这一过程可能与其上调FXR的表达有关。     

三氧化二砷诱导人胃癌MKN45细胞凋亡及其分子机制的初步研究

目的研究三氧化二砷(As2O3)对人胃癌细胞的生物学效应及其作用机制。方法胃癌细胞经As2O3处理后,用台盼蓝方法检测As2O3的IC50,采用流式细胞仪、DAPI荧光染色、原位末端标记(TUNEL)及DNA电泳检测细胞凋亡。结果As2O3在一定浓度范围内以浓度依赖的方式抑制胃癌细胞生长,其IC50为(11.05±0.25)μmol/L。经1～10μmol/LAs2O3处理胃癌细胞后,流式细胞仪检测出凋亡峰,流式细胞光度计下可见明显的凋亡细胞形态特征,琼脂糖凝胶电泳出现DNA梯形条带。结论As2O3在体外可诱导胃癌细胞的凋亡,这是其对胃癌细胞产生生物学效应的基础。     

联合应用9-顺式维甲酸和化疗药物对人胆管癌细胞系QBC939的作用

目的 观察联合应用分化诱导剂9—cis RA和化疗药物对人胆管癌细胞QBC939细胞的作用，为临床诱导分化治疗胆管癌提供实验基础。方法 以10^-6mol／L的9—cis RA作用于培养的人胆管癌细胞系QBC939细胞1、2、3、5d后检测几种常用化疗药物对细胞的杀伤作用。并观察同时加入10^-6mol／L的9—cis RA和化疗药物对QBC939细胞的杀伤作用。结果 同时应用9—cis RA和化疗药物时，对QBC939细胞的杀伤作用与单用化疗药物时无明显差异。9—cis RA作用2d和3d时，化疗药物对QBC939细胞的杀伤作用强于9—cis RA作用前；9—cis RA作用5d时，化疗药物对QBC939细胞的作用较9—cis RA作用前强，但比3d时下降。结论 先用9—cis RA作用后可增强QBC939细胞对化疗药物的敏感性，此作用与9—cis RA作用时间有关。不同联合用药方法的效果不同。     

NS-398和DHA联合抑制β-eatenin、c-mye对胆管癌QBC939细胞凋亡的影响北大核心CSCD

目的研究选择性环氧合酶-2（cyclooxygenase-2,COX-2）抑制剂NS-398和二十二碳六烯酸（docosahexaenoic acid,DHA）联合对胆管癌细胞QBC939凋亡的影响及机制。方法体外培养胆管癌QBC939细胞,设立NS-398组、DHA组、联合组和空白组,将0,25,50,100,150,200μmol／L的NS-398和0,15,30,45,60,75μg／ml的DHA分别联合作用于QBC939细胞;应用CCK8法检测QBC939细胞的生长抑制率：采用流式细胞术检测细胞凋亡：应用实时荧光定量PCR、Western blot和ELISA检测细胞中β-catenin和c-myc的表达。结果NS-398和DHA在体外均能抑制QBC939细胞生长,NS-398为100pomol／L联合DHA为45μg／ml作用后,细胞生长抑制率达90％（F=5．85,P〈0．05）,二者联合能明显促进QBC939细胞凋亡（F=8．16,P〈0．01）。实时荧光定量PCR、Western blot和ELISA实验均显示联合能明显抑制β-catenin（F=7．61,P〈0．01）、（F=7．75,P〈0．01）、（F=8．17,P〈0．01）和c-myc（F=7．92,P〈0．01）、（F=8．76,P〈0．01）、（F=8．12,P〈0．01）表达。结论NS-398和DHA联合能明显抑制QBC939细胞生长,促进早期凋亡,二者联合对QBC939细胞生长的抑制作用可能是通过抑制β-catenin和c-myc的表达,促进细胞早期凋亡。     

5-氮-2-脱氧胞苷调控p53-baX凋亡通路DNA甲基化对胆管癌细胞生长的影响

目的 探讨甲基转移酶抑制剂5-氮-2-脱氧胞苷(DAC或5-aza-dc)对胆管癌细胞QBC939生长的影响及其机制.方法 应用噻唑蓝(MTT)比色法检测DAC在不同浓度(0.1、0.5、1.0、5.0、25.0、100.0μmol/L)及不同时间(24、48、72 h)下对胆管癌细胞QBC939存活率的影响,透射电镜观察细胞形态学改变,流式细胞仪观察细胞生长周期及凋亡率的变化;甲基化聚合酶链反应检测DAC作用前后p53-bax凋亡通路DNA甲基化变化.结果 DAC对QBC939细胞生长的抑制有浓度和时间依赖性,其半数抑制率(IC50)为72h 5μmol/L;经DAC作用后电镜下胆管癌细胞凋亡增加;胆管癌细胞凋亡发生率由DAC处理前的4.31%上升至处理后的43.04%;DAC作用前p53-bax凋亡通路中p14、DAPK抑癌基因甲基化,DAC作用后p14、DAPK抑癌基因脱甲基化.结论 DAC对胆管癌QBC939细胞的生长具有抑制作用,这一抑制作用是由于DAC脱甲基化造成的,DAC对胆管癌QBC939细胞p53-bax线粒体凋亡通路DNA甲基化的影响使细胞凋亡功能得以恢复.     

光动力抑制胆管癌QBC939细胞生长的实验研究

目的研究血卟啉衍生物介导的光动力（HPD-PDT）抑制胆管癌细胞生长状况及其机制。方法 MTT法用于评估人胆管癌细胞（QBC939）的生长状态;Hoechst33258染色和流式细胞术检测细胞凋亡;WesternBlotting法用于探测QBC939细胞中细胞色素C的释放情况;Caspases酶活性测定用于测定caspase-3、-8、-9的活化情况。结果 HPD-PDT在体外能够抑制胆管癌QBC939细胞生长,这一效应主要是通过诱导QBC939细胞线粒体凋亡达到的,在凋亡过程中,出现了细胞色素C释放,caspase-9和-3的活化。结论 HPD-PDT体外能够抑制胆管癌细胞生长,诱导胆管癌细胞凋亡。     

GABA对胆管癌细胞株QBC939增殖及凋亡的影响

目的观察γ-氨基丁酸(GABA)对胆管癌细胞QBC939增殖及凋亡的影响。方法采用MTT比色法观察GABA对人系胆管癌细胞QBC939增殖的作用,流式细胞术检测GABA对胆管癌细胞QBC939凋亡及其细胞周期的影响,放射免疫分析法检测cAMP含量。结果GABA抑制胆管癌细胞的增殖,呈剂量依赖性,流式细胞仪检测结果显示,随药物浓度增加,细胞凋亡率显著增加(4.8%增至28.03%,P<0.05),同时促进胆管癌细胞内cAMP含量的增加。结论GABA抑制胆管癌细胞QBC939增殖,诱导细胞凋亡,可能机制是通过受体后信息介导的。     

γ-氨基丁酸抑制胆管癌细胞株QBC939增殖及其机制的研究

目的 观察γ-氨基丁酸(GABA)对胆管癌细胞QBC939增殖、凋亡和端粒酶活性的影响.方法 采用MTT比色法观察GABA对人系胆管癌细胞QBC939增殖的作用,流式细胞术检测GABA对胆管癌细胞QBC939凋亡的影响,PCR-ELISA法观察其对QBC939细胞端粒酶活性的影响,放射免疫分析法检测cAMP含量.结果 GABA抑制胆管癌细胞的增殖(抑制率由2.6%增至26.8%,P<0.05),促进细胞凋亡(凋亡率由4.8%增至28.03%,P<0.05),并且抑制癌细胞中端粒酶的活性(0.82±0.048 vs 0.56±0.054,P<0.05),同时促进胆管癌细胞内cAMP含量的增加[(0.59±0.049)nmol/L vs (0.82±0.033)nmol/L,P<0.05].结论 GABA可能通过受体后信息介导途径,诱导细胞凋亡,并抑制癌细胞端粒酶活性,从而抑制胆管癌细胞的增殖.     

Sagittal plane analysis of the open and closed methods in children with displaced supracondylar fractures of the humerus (a radiological study)

OBJECTIVES: The aim of this study was to compare the radiological outcome of open and close reduction and osteosynthesis methods in the treatment of type II and III supracondylar humerus fractures in childhood with respect to the immediate post-operative reduction quality in sagittal plane. METHOD: One hundred and forty four-pediatric patients with type IIb and III supracondylar humerus fractures treated at two centers between 1995 and 2005 were evaluated radiologically within a retrospective study. Seventy-six patients (54 boys, 22 girls, mean age 7.6, range 2-12) were treated by closed reduction and cross percutaneous pinning while 68 (49 boys, 19 girls, mean age 7.3, range 2-13) were treated by open reduction. The reduction quality of the open and closed groups was compared on immediate post-operative lateral radiographs by measuring of lateral humerocapitellar angle, anterior humeral line and anterior coronoid line criteria. The reduction quality was classified excellent, good, fair and poor according to the achievement of three, two, one or none of the criteria, respectively. Reductions classified as excellent and good were introduced as acceptable results. RESULTS: At least one criterion was achieved in all the patients of both the groups. The mean humerocapitellar angle was 30.1 degrees in closed reduction group while the mean of it was 29.8 degrees in open reduced group. Radiograph of 48 (63.1%) patients with closed reduction were found to display the anterior humeral line intersecting the middle one-third of capitellum while this criteria was 45 (66%) in open reduction group. The anterior coronoid line was disturbed in three patients in each of both the groups. The reduction quality was evaluated to be excellent in 32 patients, good in 31, fair in 13 at the closed reduction group while these evaluations were 31, 20 and 17 in open reduction group, respectively. Successful reduction was achieved in 74.9% of the patients in closed reduction group and 75% of the patients in open reduction group. CONCLUSION: It is concluded that there was no significant difference between closed and open reductions of pediatric displaced supracondylar fractures with regard to the radiological criteria of reduction quality in sagittal plane.     

胆囊炎患者胆汁中内皮素浓度的意义

目的探讨胆囊炎患者胆汁中内皮素浓度及其意义。方法采用放射免疫分析法测定了４０４例单纯型、４８例化脓型和２７例坏疽型结石性胆囊炎患者胆汁中内皮素浓度。结果三型胆囊炎患者胆汁内皮素浓度分别为２７４±８３ｐｇ／ｍｌ,４２３±１１１ｐｇ／ｍｌ和６７５±１３８ｐｇ／ｍｌ,与对照组测值１９４±４７ｐｇ／ｍｌ比较,具有显著性差异（Ｐ＜０．０５～０．０１）。结论胆汁中内皮素参与了胆囊炎的病理过程,其作用机制尚需深入研究。     

Comprehensive review of post–organ transplant hematologic cancers

A higher risk for a variety of cancers is among the major complications of posttransplantation immunosuppression. In this part of a continuing series on cancers posttransplantation, this review focuses on the hematologic cancers after solid organ transplantation. Posttransplantation lymphoproliferative disorders (PTLDs), which comprise the great majority of hematologic cancers, represent a spectrum of conditions that include, but are not limited to, the Hodgkin and non‐Hodgkin lymphomas. The oncogenic Epstein‐Barr virus is a key pathogenic driver in many PTLD cases, through known and unknown mechanisms. The other hematologic cancers include leukemias and plasma cell neoplasms (multiple myeloma and plasmacytoma). Clinical features vary across malignancies and location. Preventive screening strategies have been attempted mainly for PTLDs. Treatments include the chemotherapy regimens for the specific cancers, but also include reduction of immunosuppression, rituximab, and other therapies.     

肾脏黏液样小管状和梭形细胞癌(附2例报道及文献复习)

目的 探讨肾脏黏液样小管状和梭形细胞癌(Mucinous tubular and spindle cell carcinoma,MTSCC)的临床及病理学特点.方法 对本院收治的2例肾脏黏液样小管状和梭形细胞癌患者临床及病理特点进行观察和讨论并结合相关文献复习.结果 2例患者术后诊断:肾脏黏液样小管状和梭形细胞癌.临床及病理特征符合相关文献对该型肾癌的报道,术后长期严密随访无复发.结论 MTSCC是罕见的肾癌分型,症状隐匿,具有独特的病理学特征,早期手术是最佳治疗方法,预后良好,罕见预后较差报道.     

胰腺素腺瘤和囊腺癌的诊治

目的 探讨胰腺囊性肿瘤的诊断和治疗。方法 对1978-1998年收治的均经手术和病理检查证实为胰腺囊性肿瘤的11例临床资料进行回顾性分析。结果 胰腺囊性肿瘤好发于中青年女性,临床表现为病程较长的上腹部肿物和胀痛。钡餐、B超、CT及ER-CP能协助诊断,本组11例中行胰十二指肠切除2例,胰体尾加脾切除6例,肿瘤单纯切除2例,囊肿-空肠袢式吻合1例,手术切除率为90.9%,术后1例死于腹内感染并峰主血症术后存活的10例均获随访（100%）。1例胰腺囊腺瘤手术后3个月死于心肌梗死,1例胰腺囊腺癌术后4年3个月死于癌转移,其余均健在,结论 凡中青年女性,上腹或左上腹出现较大肿块,且病程较长。结合B超和CT检查可对本病的诊断,胰腺囊腺瘤或囊腺癌,癌体虽较大,均有完整的包膜,而易于分离切除,首选手术方式为包括部分胰腺组织的全肿瘤切除术,疗效满意。     

Risk of lip cancer after solid organ transplantation in the United States

Solid organ transplant recipients have an increased risk of lip cancer, but the reasons are uncertain. Using data from the Transplant Cancer Match Study, we describe the epidemiology of lip cancer among 261 500 transplant recipients in the United States. Two hundred thirty‐one lip cancers were identified, corresponding to elevated risks for both invasive and in situ lip cancers (standardized incidence ratios of 15.3 and 26.2, respectively). Invasive lip cancer incidence was associated with male sex (adjusted incidence rate ratio [aIRR] 2.01, 95% CI 1.44‐2.82), transplanted organ (0.33, 0.20‐0.57, for liver transplants and 3.07, 1.96‐4.81, for lung transplants, compared with kidney transplants), and racial/ethnic groups other than non‐Hispanic whites (0.09, 0.04‐0.2). In addition, incidence increased with age and during the first 3 years following transplant, and was higher in recipients prescribed cyclosporine/azathioprine maintenance therapy (aIRR 1.79, 95% CI 1.09‐2.93, compared with use of tacrolimus/mycophenolate mofetil) and following a diagnosis of cutaneous squamous cell carcinoma (4.21, 2.69‐0.94). The elevation in lip cancer incidence is consistent with an effect of immunosuppression. Notably, the very strong associations with white race and history of prior skin cancer point to an important role for ultraviolet radiation exposure, and cyclosporine and azathioprine may contribute as photosensitizing or DNA damaging agents.     

胆石性重症胰腺炎的治疗对策及疗效分析

目的　探讨胆石性重症胰腺炎 (GSP)的合理治疗方法和疗效。方法　回顾性分析治疗的97例GSP临床资料。结果　 97例中 ,重症I级 5 4例 ,II级 43例 ;治愈 77例 ( 79.4% ) ,病死 2 0例( 2 0 .6% )。内镜治疗组 (EST)、延期手术组和早期手术组的并发率分别为 2 4.1% ,2 5 .0 %和 65 .5 % ;病死率分别为 10 .3 % ,13 .9%和 3 7.5 % ,前两组均明显低于早期手术组 (P <0 .0 5 )。结论　GSP治疗应根据“个体化方案” ,无胆石梗阻者应延期手术 ;有胆石嵌顿梗阻者应及早施行EST治疗或开腹手术 ,对重症II级患者首选EST治疗     

胆汁中氨肽酶N的分离、提纯及其促成核作用的初步研究

目的　观察氨肽酶N(APN )在胆石形成中的成核活性。方法　应用伴刀豆凝集素A亲和层析、羟基磷灰石柱层析及高压液相法从胆石症患者胆汁中分离、提纯胆汁中的APN ,并用模拟胆汁观察APN的成核活性。结果　最终APN纯化倍数达 2 94倍 ,酶的活性为12 .9nM·min-1·μg-1,分子量为 130kDa。随后在模拟胆汁观察到APN有明显的促成核活性。结论　APN在胆固醇结石形成中具有促成核作用。     

异搏定对急性胰腺炎大鼠磷脂酶A2影响的研究

目的探讨急性胰腺炎(AP)时胰组织磷脂酶A2(PLA2)的变化,以及钙通道阻滞剂异搏定对其的治疗作用.方法采用"十二指肠闭袢法”诱发AP大鼠模型,随机分组,观测AP组和异搏定治疗组PAL2活性变化,同期行胰腺组织进行光镜和电镜检查.结果诱发AP16h和24h,异搏定治疗组胰腺组织PLA2活性(32.34±3.87,35.26±4.52)较AP组(44.83±5.31,47.77±5.86)明显降低(P<0.01),病理改变明显减轻.结论大鼠AP时存在PLA2的活化,钙通道阻滞剂异搏定可通过抑制PLA2的活化而起到治疗AP的良好作用.     

Epidemiologic perspectives on immunosuppressed populations and the immunosurveillance and immunocontainment of cancer

The advent in the last several years of effective immunotherapy for cancer has renewed interest in the role of the immune system in controlling cancer. The idea that the immune system can help control cancer has a long history. Solid organ transplant recipients (SOTRs) as well as human immunodeficiency virus (HIV)–infected people are affected by cell‐mediated immune dysfunction. Epidemiologic studies of these populations reveal a pattern characterized by a strongly increased incidence of virus‐related cancers (eg, Kaposi sarcoma, non‐Hodgkin lymphoma, and anogenital cancers). In addition, recent epidemiologic studies have evaluated cancer‐specific mortality among SOTRs and HIV‐infected people following a cancer diagnosis. For a wider range of cancers—not limited to those caused by viruses, and including melanoma and cancers of the colorectum, lung, and breast— these immunosuppressed cancer patients have higher cancer‐specific mortality than other cancer patients. This latter group of cancers somewhat mirrors those for which immunotherapy with checkpoint inhibitors is approved. These epidemiologic observations suggest that there are 2 distinct immune selection processes in humans: immunosurveillance directed against premalignant cells before cancer diagnosis (most relevant for preventing virus‐related cancers), and “immunocontainment” directed against established cancers. These processes thus appear relevant for different groups of malignancies and may have different mechanisms.