紫杉醇膀胱灌注抑制大鼠膀胱癌生长的机制

目的探讨紫杉醇连续膀胱灌注对大鼠膀胱肿瘤生长的作用和机制。方法将40只雌性Wistar大鼠,随机分为对照组(n=20)和紫杉醇组(n=20),制作N-甲基亚硝基脲诱导大鼠原位膀胱癌模型,于第8周分别行生理盐水和紫杉醇制剂连续膀胱灌注,每周1次,共6次。于第14周进行病理观察、测量膀胱总重量,微血管密度(MVD)和凋亡指数(AI)。结果第14周时,对照组(n=16)和紫杉醇组(n=12)大鼠膀胱均可见明显肿物,光镜下可见癌组织侵入肌层。紫杉醇组大鼠膀胱的重量和肿瘤的MVD小于对照组(P<0.01);紫杉醇组大鼠膀胱肿瘤的AI大于对照组(P<0.01)。结论紫杉醇连续膀胱灌注可抑制大鼠膀胱肿瘤生长,可能与抑制肿瘤血管生长和诱导肿瘤细胞凋亡有关。     

草分枝杆菌死菌制剂治疗肺结核216例效果观察

目的：探讨草分枝杆菌死菌制剂(乌体林斯)对肺结核的治疗效果。方法：在正规抗结核治疗下，观察组加用乌体林斯免疫治疗。结果：初治治疗组在治疗2个月时痰菌阴转84例(97.7％)，治疗6个月时病灶明显吸收79例(91．9%)，空洞闭合43例(93.5%)，明显优于初治对照组，两者差异有显著性；耐多药肺结核治疗组在治疗6个月、9个月时痰菌阴转分别为18例(81．8％)，19型(86.4％)，病灶明显吸收17例(77.3%)，空洞闭合14例(73.7%)，与对照组比较差异有显著性。结论：乌体林斯免疫治疗肺结核，安全、有效，值得临床上推广应用。     

25 Hz和50 Hz电刺激对大鼠缺血心肌毛细血管新生的影响

目的: 观察10 Hz,15 Hz,25 Hz,50 Hz频率的阈下电刺激对缺血心肌血管新生的影响,寻找产生缺血心肌血管新生的有效阈下电刺激频率.方法: 将30只心肌缺血模型大鼠随机分为阈下电刺激频率10 Hz,15 Hz,25 Hz,50 Hz组与对照组,用免疫组织化学法检测缺血心肌中毛细血管内皮细胞数、毛细血管密度.结果: (1)与对照组比较,25 Hz组、50 Hz组大鼠缺血心肌中毛细血管内皮细胞数、毛细血管密度显著增加(P＜0.01);(2) 与对照组比较,10 Hz组、15 Hz组大鼠缺血心肌中毛细血管内皮细胞数、毛细血管密度差异无显著性.结论: 25 Hz,50 Hz频率的阈下电刺激可促进大鼠缺血心肌中毛细血管的新生.     

舒尼替尼靶向治疗裸鼠膀胱癌移植瘤的效果

目的观察舒尼替尼对裸鼠膀胱癌移植瘤的靶向治疗作用。方法建立裸鼠皮下人膀胱癌移植瘤模型,随机分为实验组和对照组(各6只),实验组裸鼠用舒尼替尼40 mg/kg灌胃,每天1次;对照组给予等体积蒸馏水灌胃。观察肿瘤的生长情况;用免疫组化法检测肿瘤CD34、Ki67的表达,计算肿瘤的微血管密度和增殖指数;用TUNEL法测肿瘤的凋亡指数。结果实验组裸鼠的肿瘤生长被明显抑制,抑瘤率为72.03%,肿瘤退缩率为43.42%。实验组微血管密度、肿瘤增殖指数明显低于对照组,凋亡指数高于对照组,差异均有显著性(t=10.222～18.700,P<0.05)。结论舒尼替尼可阻断裸鼠膀胱癌移植瘤血管的生成进程,使肿瘤体积退缩,对移植瘤起到了抑制作用。     

力达霉素对神经胶质瘤细胞血管生成拟态的抑制及对细胞凋亡的影响

目的 评价烯二炔类抗生素力达霉素对神经胶质瘤细胞血管生成拟态的抑制作用及对细胞凋亡的影响.方法 C6和U87细胞凋亡以Annexin V-FITC/PI法结合流式细胞仪法进行分析,小管形成实验分析药物对神经胶质瘤细胞血管拟态的影响.结果 0.1 nmol/L(12.7±0.6)、0.5nmol/L(9.0±1.7)和1 nmol/L(4.7±0.6)力达霉素处理的C6细胞血管生成拟态与对照(16.7±1.5)相比,差异有统计学意义(分别为P=0.013、P=0.005及P=0.0002);同样浓度的药物对U87细胞的血管生成拟态与对照(14.7±1.2)相比,差异有统计学意义(分别为P=0.025、P=0.005及P=0.0009).相同剂量的力达霉素处理C6和U87细胞后其凋亡率与相应对照组相比差异有统计学意义.力达霉素对神经胶质瘤细胞血管生成拟态和细胞凋亡的影响明显比新制癌菌素强.结论 力达霉素能够抑制神经胶质瘤细胞血管生成拟态并促进神经胶质瘤细胞凋亡,烯二炔类抗肿瘤抗生素治疗神经胶质瘤的研究值得进一步探讨.     

血管紧张素Ⅱ1型受体拮抗剂对裸鼠胰腺癌的抑制作用

目的：探讨选择性血管紧张素Ⅱ1型受体拮抗剂ZD7155对裸鼠胰腺癌的抑制作用及其作用机制。方法：60只裸鼠接种胰腺癌PaTu8988s细胞建立胰腺癌移植瘤模型,成瘤后随机分成对照组、低剂量（10mg·kg^-1·d^-1）ZD7155治疗组和高剂量（20mg·kg^-1·d^-1）ZD7155治疗组,每组20只。治疗10d后每组各处死10只裸鼠,测量肿瘤体积,称取瘤体质量,免疫组化检测移植瘤新生血管的CD31表达,透射电镜观察细胞凋亡;其余裸鼠共治疗30d,记录生存期并观察ZD7155的毒副作用等共49d。结果：（1）对照组和低、高剂量治疗组的实体瘤平均体积分别为（35．8±6．7）、（21．5±6．1）、（10．7±4．1）cm^3（P〈O．01）。（2）低剂量组以及高剂量组在治疗后10d的平均抑瘤率分别为22．7％和44．6％（P〈O．01）,与对照组相比均具有统计学意义（P〈O．01）。（3）对照组和低、高剂量组平均微血管数目分别为16．7±0．9、11．5±0．5、6．05±0．7（P〈0．01）。（4）对照组细胞未见凋亡改变,两治疗组均可见大量典型的处于不同阶段的凋亡细胞。（5）治疗组裸鼠生存期较对照组显著延长（P〈O．01）,而且高剂量组裸鼠生存期较低剂量组亦显著延长（P〉O．01）。（6）未见明显毒副作用。结论：选择性血管紧张素Ⅱ1型受体拮抗剂在体内能抑制胰腺癌细胞生长、抑制肿瘤血管生成、促进肿瘤细胞凋亡,可望成为治疗胰腺癌的安全有效药物。     

大鼠缺血后肢局部应用bFGF对血管新生的影响

目的 观察不同月龄大鼠缺血后肢肌肉内局部应用碱性成纤维细胞生长因子(bFGF)对血管新生的影响.方法 Wistar大鼠40只,按月龄分为A组(4个月)和B组(16个月),A组又分为A1、A2组,B组又分为B1、B2组,每组10只大鼠.40只大鼠均切断左股动脉,制作后肢缺血模型.成模后A1和B1组大鼠缺血后肢肌肉内多次注射重组牛bFGF蛋白;A2和B2组则给予等量生理盐水.术后4周,取各组大鼠内收肌组织行病理组织学检查,采用图像分析系统计算血管密度,免疫组化方法 检测内收肌中VEGF阳性表达的血管数.结果 各组大鼠缺血后肢肌内血管密度及VEGF阳性表达的血管数比较,A1组多于A2组,B1组多于B2组,差异均有显著意义(t=3.30～3.50,P<0.05);其他各组比较,差异无显著性(P>0.05).结论 在不同月龄大鼠缺血后肢肌肉内注射bFGF蛋白可促进肢体血管新生,改善肢体缺血状态,且与月龄无关.     

力达霉素对神经胶质瘤细胞血管生成拟态的抑制及对细胞凋亡的影响

Objective To evaluate the in vitro effects of lidamycin upon vasculogenic mimicry and apoptosis induction in glioma cells. Methods Tube formation assay was performed to estimate the inhibitory effects of lidamycin upon vasculogenic mimicry in C6 and U87 glioma cells. The vasculogenic mimicry of glioma cells was photographed and enumerated. Annexin V-FITC/PI was used for determination of glioma cell apoptosis with flow cytometry. Results Vasculogenic mimicry assay indicated that 0. 1 nmol/L, 0. 5 nmol/L and 1 nmol/L lidamycin showed significant inhibition of vasculogenic mimicry in C6 and U87 cells. Comparing with C6 control group (14. 7 ± 1.2), 0. 1 nmol/L (12. 7 ± 0. 6), 0. 5 nmol/L (9. 0 ± 1.7) and 1 nmol/L (4. 7 ± 0. 6) lidamycin inhibited vasculogenic mimicry in C6 cells with statistical significances (P = 0. 013, P = 0. 005 and P = 0. 0002 respectively). Comparing with U87 control group (14.7±1.2), the vasculogenic mimicry of 0.1 nmol/L (10.0±2.0), 0.5 nmol/L (8.3±1.5) and 1 nmol/L lidamycin (4. 3±0. 6) treated U87 cells showed statistical significances (P =0. 025, P =0. 005 and P =0. 0009 respectively). The apoptotic ratios of same dosages lidamycin treated C6 cells and U87 cells showed a similar tendency as vaaculogenic mimicry inhibition (P < 0. 001). Lidamycin was more potent than neocarzinostatin in vasculogenic mimicry inhibition and apoptosis induction of C6 cells and U87 cells. Conclusion Lidamycin can inhibit vasculogenic mimicry and promote apotosis of glioma cells. Thus it is a promising drug in glioma treatment. Further researches on the therapeutic efficacy of enediyne antibiotics in glioma are needed.     

力达霉素对神经胶质瘤细胞血管生成拟态的抑制及对细胞凋亡的影响

Objective To evaluate the in vitro effects of lidamycin upon vasculogenic mimicry and apoptosis induction in glioma cells. Methods Tube formation assay was performed to estimate the inhibitory effects of lidamycin upon vasculogenic mimicry in C6 and U87 glioma cells. The vasculogenic mimicry of glioma cells was photographed and enumerated. Annexin V-FITC/PI was used for determination of glioma cell apoptosis with flow cytometry. Results Vasculogenic mimicry assay indicated that 0. 1 nmol/L, 0. 5 nmol/L and 1 nmol/L lidamycin showed significant inhibition of vasculogenic mimicry in C6 and U87 cells. Comparing with C6 control group (14. 7 ± 1.2), 0. 1 nmol/L (12. 7 ± 0. 6), 0. 5 nmol/L (9. 0 ± 1.7) and 1 nmol/L (4. 7 ± 0. 6) lidamycin inhibited vasculogenic mimicry in C6 cells with statistical significances (P = 0. 013, P = 0. 005 and P = 0. 0002 respectively). Comparing with U87 control group (14.7±1.2), the vasculogenic mimicry of 0.1 nmol/L (10.0±2.0), 0.5 nmol/L (8.3±1.5) and 1 nmol/L lidamycin (4. 3±0. 6) treated U87 cells showed statistical significances (P =0. 025, P =0. 005 and P =0. 0009 respectively). The apoptotic ratios of same dosages lidamycin treated C6 cells and U87 cells showed a similar tendency as vaaculogenic mimicry inhibition (P < 0. 001). Lidamycin was more potent than neocarzinostatin in vasculogenic mimicry inhibition and apoptosis induction of C6 cells and U87 cells. Conclusion Lidamycin can inhibit vasculogenic mimicry and promote apotosis of glioma cells. Thus it is a promising drug in glioma treatment. Further researches on the therapeutic efficacy of enediyne antibiotics in glioma are needed.     

力达霉素对神经胶质瘤细胞血管生成拟态的抑制及对细胞凋亡的影响

Objective To evaluate the in vitro effects of lidamycin upon vasculogenic mimicry and apoptosis induction in glioma cells. Methods Tube formation assay was performed to estimate the inhibitory effects of lidamycin upon vasculogenic mimicry in C6 and U87 glioma cells. The vasculogenic mimicry of glioma cells was photographed and enumerated. Annexin V-FITC/PI was used for determination of glioma cell apoptosis with flow cytometry. Results Vasculogenic mimicry assay indicated that 0. 1 nmol/L, 0. 5 nmol/L and 1 nmol/L lidamycin showed significant inhibition of vasculogenic mimicry in C6 and U87 cells. Comparing with C6 control group (14. 7 ± 1.2), 0. 1 nmol/L (12. 7 ± 0. 6), 0. 5 nmol/L (9. 0 ± 1.7) and 1 nmol/L (4. 7 ± 0. 6) lidamycin inhibited vasculogenic mimicry in C6 cells with statistical significances (P = 0. 013, P = 0. 005 and P = 0. 0002 respectively). Comparing with U87 control group (14.7±1.2), the vasculogenic mimicry of 0.1 nmol/L (10.0±2.0), 0.5 nmol/L (8.3±1.5) and 1 nmol/L lidamycin (4. 3±0. 6) treated U87 cells showed statistical significances (P =0. 025, P =0. 005 and P =0. 0009 respectively). The apoptotic ratios of same dosages lidamycin treated C6 cells and U87 cells showed a similar tendency as vaaculogenic mimicry inhibition (P < 0. 001). Lidamycin was more potent than neocarzinostatin in vasculogenic mimicry inhibition and apoptosis induction of C6 cells and U87 cells. Conclusion Lidamycin can inhibit vasculogenic mimicry and promote apotosis of glioma cells. Thus it is a promising drug in glioma treatment. Further researches on the therapeutic efficacy of enediyne antibiotics in glioma are needed.     

Caspase-3在膀胱癌组织中的表达及意义

目的探讨caspase-3在膀胱癌发病过程中的作用及与细胞凋亡之间关系.方法应用免疫组织化学方法和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法,检测55例膀胱癌和12例正常膀胱组织中caspase-3和细胞凋亡的表达水平.结果膀胱癌中caspase-3阳性表达率为41.8%,显著低于正常膀胱组织的75.0%(P＜0.05).caspase-3表达与膀胱癌病理分级、临床分期和肿瘤复发之间无关(P＞0.05).膀胱癌中caspase-3阳性表达者的细胞凋亡指数为9.3±3.1显著高于阴性表达者的6.8±2.4(P＜0.001).结论 caspase-3表达下调导致细胞凋亡减少,可能在膀胱癌的发生发展过程中起重要作用.     

Apoptosis inducing effects of arsenic trioxide on human bladder cancer cell line BIU-87

Objective　To explore the apoptosis inducing effects of arsenic trioxide (As2O3) on human bladder cancer cells and elucidate possible mechanisms. Methods　After treatment with As2O3, the growth inhibition rates of human bladder cancer cell line BIU-87 were studied by MTT and cell counts methods. DNA synthesis rates were detected by 3　H-TdR assay. The morphological changes of cancer cells were observed by light and electronic microscopy and cell apoptosis rates were detected by TdT-mediated dUTP nick end labeling (TUNEL). bcl-2 gene expression of BIU-87 cells was observed by strept avidin-biotin complex (SABC) immunohistochemical method. Results　As2O3 could effectively inhibit the growth of BIU-87 (P&lt;0.05), which were time and concentration dependent. The inhibition rate of 4.0?μmol/L As2O3 for DNA synthesis of cancer cells was 55.64% (P&lt;0.01). Partial cancer cells presented the characteristic morphological changes of apoptosis which depended on the time of exposure to drug (P&lt;0.05). bcl-2 expression of BIU-87 cells was decreased significantly (P&lt;0.05). Conclusion　As2O3 can significantly induce apoptosis in bladder cancer cells by down-regulating the expression of the bcl-2 gene and inhibiting DNA synthesis. This provides a potentially effective method for prevention and cure of human bladder cancer.     

膀胱癌肿瘤血管生成与肿瘤细胞凋亡和增殖的关系

目的:探讨膀胱癌组织中微血管密度(MVD)与肿瘤细胞凋亡和增殖的关系.方法:应用S-P法对64例膀胱癌组织中血管内皮细胞的第Ⅷ因子抗原和ki-67抗原进行染色,计数肿瘤的微血管教及ki-67标记指数(LI);应用TUNEL法检测膀胱癌细胞凋亡状态.结果:MVD在不同病理分期和细胞学分级上有显著差异(P<0.05),且随着病理分期和组织学分级的增高而增高(P<0.05).MVD与凋亡指数(AI)呈负相关(P<0.001),与ki-67LI无关(P<0.05).结论:膀胱癌肿瘤血管生成与膀胱癌浸润、转移密切相关;血管生成可以抑制肿瘤细胞的凋亡,促进肿瘤的恶性进展.     

蝙蝠葛碱对人膀胱癌T-24细胞株生长增殖的抑制作用

目的 探讨中药北豆根提取物蝙蝠葛碱(dauricine,Dau)对人膀胱癌T-24细胞株的增殖抑制作用及其作用机制.方法 应用MTT法测定了蝙蝠葛碱对泌尿系肿瘤细胞增殖反应的影响;采用流式细胞技术、荧光染色法、琼脂糖凝胶电泳等技术测定和观察了蝙蝠葛碱对诱导肿瘤细胞凋亡的影响.结果 蝙蝠葛碱对膀胱癌T-24细胞株的增殖有较强的抑制作用,具有浓度依赖性特点.T-24细胞DNA琼脂糖凝胶电泳呈现凋亡特征性梯形条带.流式细胞分析,浓度为5～30μg/ml的蝙蝠葛碱具有诱导人膀胱癌细胞凋亡的作用,且随着药物作用时间延长凋亡率逐渐增加,随药物浓度的增高细胞周期被阻滞在G0/G1期.T-24细胞的bcl-2基因表达受抑,而bax基因的表达上调.结论 蝙蝠葛碱可有效抑制人膀胱癌T-24细胞株的生长增殖,阻滞细胞周期及诱导细胞凋亡可能起重要作用.     

Apoptin对人膀胱癌裸鼠皮下移植瘤的抑瘤作用研究

目的探讨Apoptin质粒对人膀胱癌裸鼠皮下移植瘤的抑瘤作用。方法皮下注射T24细胞,建立裸鼠移植瘤模型,于肿瘤直径0.5cm大小时,多点注射脂质体包裹质粒pApoptin-EGFP,设立空质粒组、生理盐水组作为对照组,观察裸鼠肿瘤生长情况;5周后处死,绘制肿瘤生长曲线,计算抑瘤率,肿瘤组织石蜡包埋,常规切片,TUNEL法检测移植瘤凋亡情况。结果成功建立移植瘤模型,注射脂质体包裹pApoptin-EGFP质粒能明显抑制移植瘤生长;TUNEL检测凋亡率为(23.24±6.12)%,与对照组相比,差异有统计学意义(P<0.01)。结论Apoptin通过诱导凋亡能明显抑制人膀胱癌裸鼠皮下移植瘤生长。     

X连锁凋亡抑制蛋白在膀胱癌的表达及其意义

目的:探讨X连锁的凋亡抑制蛋白(XIAP)在膀胱移行细胞癌(BTCC)的表达情况,以及XIAP与BTCC病理分级、临床分期的关系。方法:收集临床上经病理确诊的BTCC手术标本62例,应用免疫组织化学测定肿瘤组织中XIAP的表达情况,将结果进行相关分析。结果:XIAP在膀胱肿瘤中的阳性表达率为67.7%,在正常膀胱移行上皮阳性表达率为23.1%,两者差异有统计学意义(P<0.005);在Ⅰ、Ⅱ、Ⅲ级BTCC的阳性表达率分别是75.0%、57.9%和66.7%,在浅表性和浸润性BTCC的阳性表达率分别为63.9%和73.1%,阳性表达率各组之间无统计学意义(P>0.05)。结论:XIAP可能在BTCC的发生、发展中发挥重要作用。     

结核杆菌抗原对中性粒细胞自发性凋亡的抑制作用

目的: 探讨结核杆菌抗原(Mtb-Ag)对体外培养中性粒细胞自发性凋亡的影响。方法: 取健康成人外周血分离中性粒细胞,加Mtb-Ag培养24 h,或用Mek抑制剂PD98059预处理30 min后,Wright-Giemsa染色形态学方法和Annexin-V染色流式细胞术观察细胞凋亡。结果: 与中性粒细胞体外培养24 h后自发凋亡(55±10)%相比,加入Mtb-Ag (1.125 mg/ml)后,中性粒细胞自发凋亡率(31±3)%明显降低(P<0.01);Mek抑制剂PD98059(50μmol/L)可阻断Mtb-Ag的抑制凋亡作用(P<0.01)。结论: Mtb-Ag对中性粒细胞自发性凋亡有抑制作用,这一作用可能涉及Mek-Erk途径。     

Livin在膀胱癌中的研究进展

Livin作为凋亡抑制蛋白家族（ IAP）中的新成员,有抑制细胞凋亡的作用,在许多肿瘤组织中高表达,与肿瘤发病机制密切相关。近年来,许多研究证明Livin与膀胱癌的发生、发展及其复发有密切相关性,本文就Livin的抗凋亡机制及其在膀胱癌诊断和治疗中的研究进展作一综述。     

盐霉素对人膀胱癌5637细胞的生长抑制作用

目的：探讨盐霉素对人膀胱癌5637细胞生长、凋亡和侵袭力的影响,阐明其可能的作用机制。方法：取体外培养的对数生长期人膀胱癌5637细胞,分为空白对照组和不
同剂量（15、30和60 μmol?L-1）盐霉素组。MTT比色法检测各组人膀胱癌5637细胞的生长抑制率,流式细胞术检测各组人膀胱癌5637细胞的细胞凋亡率,Matrigel侵袭实验检测各组人膀胱癌5637细胞的侵袭能力,Western蛋白印迹实验检测各组人膀胱癌5637细胞中Wnt/β-catenin途径β-catenin蛋白表达水平。结果：与空白对照组比较,各剂量盐霉素组膀胱癌5637细胞的生长抑制率明显升高（P<0.05）,细胞凋亡率明显升高（P<0.05）,细胞穿膜数目减少（P<0.05）,β-catenin蛋白表达水平减少（P<0.05）。与低剂量(15 μmol?L-1)盐霉素组比较,高剂量(60 μmol?L-1)盐霉组人膀胱癌5637细胞生长抑制率升高（P<0.05）,细胞凋亡率升高（P<0.05）,细胞穿膜数目减少（P<0.05）,β-catenin蛋白表达量减少（P<0.05）。结论：盐霉素对人膀胱癌5637细胞的生长有较明显抑制作用,促进细胞凋亡,
降低细胞侵袭力,并且这种抑制作用可能是通过抑制Wnt/β-catenin信号传导途径来实现的。