膀胱移行细胞癌患者血液中血管内皮生长因子的研究

目的:探讨膀胱移行细胞癌患者血液中血管内皮生长因子(VEGF)的表达及意义。方法:采用双抗体夹心ELISA法对42例膀胱移行细胞癌患者及10例正常人血液中VEGF的检测,研究膀胱移行细胞癌患者在化疗或手术前、后血液中VEGF的表达,以及不同瘤级和不同浸润深度患者血液中VEGF的表达。结果:在术前、吡柔比星灌注化疗后、肿瘤切除后5-7d,病人血液中VEGF值明显高于正常人;在化疗或手术后,患者血液中VEGF的水平明显下降。随着瘤级的升高或浸润深度的增加,患者血液中VEGF的水平也增高。结论:检测膀胱癌患者血液中的VEGF的水平,监测它的变化,对预测肿瘤恶性潜能、以及了解肿瘤的治疗效果和肿瘤的发展情况,有重要的临床意义。     

基于光热效应和pH响应性的聚多巴胺膜靶向纳米粒子的制备及性能评价

目的 为构建高效、低毒、高肿瘤靶向性的乳腺癌给药系统,拟采用化疗与光疗相结合的治疗方法对乳腺癌进行治疗。方法 本文以盐酸吡柔比星和多西紫杉醇作为模型药物联合使用共同负载于介孔二氧化硅(MSNs)纳米粒内,利用盐酸多巴胺(PDA)碱性条件下自身氧化在介孔二氧化硅表面形成聚多巴胺薄膜,最后通过酰胺化反应将活化后的叶酸修饰于盐酸多巴胺表面,最终制得双载药叶酸修饰聚多巴胺膜包覆的介孔二氧化硅纳米粒(FA-PDA-THP-DTX-MSNs)。结果 通过单因素考察最终确定介孔二氧化硅载药条件：载药溶剂为25%乙醇水溶液、药物载体比为1∶1、载药时间为12 h;盐酸多巴胺包覆条件：盐酸多巴胺浓度为0.5 mg·mL^-1、搅拌时间为3 h。对双载药叶酸修饰聚多巴胺膜包覆的介孔二氧化硅纳米粒粒径、Zeta电位、傅立叶红外光谱等进行测定并与未进行修饰前介孔二氧化硅的数据进行比较,结果显示盐酸多巴胺和叶酸(FA)均成功修饰。测定最终成型的纳米粒,透射电镜下观察其形态为球形,大小均一,粒度分析仪测定结果显示,平均粒径为(201.4±21.7)nm, PDI指数为0.264,Zeta电位为...     

硼替佐米与吡喃阿霉素联合对T细胞淋巴瘤细胞系Hut-78细胞增殖和凋亡的影响

目的 探讨硼替佐米(BTZ)与吡喃阿霉素(THP)联合对人皮肤T细胞淋巴瘤细胞系Hut-78细胞的增殖抑制作用及其机制.方法 不同浓度的BTZ、THP单药或两药联合作用于Hut-78细胞48 h后,采用MTT法检测细胞增殖抑制率,应用联合指数分析两药是否存在协同效应,在此基础上应用流式细胞术分析细胞周期分布和细胞凋亡情况,利用Western blot法检测细胞周期抑制蛋白P21的变化.结果 BTZ与THP单药对Hut-78细胞增殖具有显著的抑制作用,呈时间和剂量依赖性,两药联合时,BTZ序贯THP组的细胞增殖抑制率显著高于BTZ与THP同时组及THP序贯BTZ组(P值均＜0.01),当细胞增殖抑制率＞50%时,THP序贯BTZ呈拮抗效应,而BTZ与THP同时及BTZ序贯THP则表现为协同效应,随着增殖抑制作用的增加,仅BTZ序贯THP的协同作用更为显著.BTZ与THP单药能有效诱导Hut-78细胞凋亡,呈剂量依赖性,且BTZ序贯THP的细胞凋亡诱导作用较单药显著增强.BTZ单药可使细胞明显阻滞于G2/M期,上调P21蛋白的表达水平,序贯应用THP可显著增强BTZ对细胞周期的阻滞作用.结论 BTZ序贯THP可协同抑制Hut-78细胞增殖并诱导其凋亡,协同机制可能与序贯应用THP增强BTZ介导的P21表达上调及G2/M期细胞阻滞有关,提示BTZ与THP联合可能成为治疗T细胞非霍奇金淋巴瘤的新选择.

Abstract：

Objective To investigate the in vitro effect of bortezomib (BTZ) alone and in combination with pirarubicin (THP) on the growth inhibition of human cutaneous T-cell lymphoma cell line Hut-78.Methods Hut-78 cells were cultured with different concentrations of BTZ or THP alone and the two drugs combination for 48 h. Cell proliferation, cell cycle and apoptosis were evaluated. The cell cycle inhibitor P21 was determined by Western blot. Results BTZ or THP alone significantly inhibited the growth of Hut-78 cells in a time- and dose-dependent manner. In the combination groups, the inhibitory effect of BTZ followed by THP was the highest ( P ＜ 0. 01 ). When the inhibition rate was more than 50%, the combination index analysis showed significant synergistic if treated with BTZ followed by THP or the two at the same time, but antagonistic if treated with THP followed by BTZ. With the inhibition rate increasing, only the synergistic effect of BTZ followed by THP was further increased. The apoptosis rate of BTZ followed by THP was higher than that of single agent each(P ＜0. 01 ). BTZ alone significantly increased the proportion of cells in G2/M phase ( P ＜0. 01 ) in a dose-dependent manner and up-regulated the expression level of P21. Sequential THP notably enhanced BTZ-induced cell cycle arrest and apoptosis. Conclusions BTZ alone effectively induces growth inhibition and apoptosis of Hut-78 cells in vitro. BTZ followed by THP can synergistically enhance this cytotoxic effect. The mechanism may be that THP enhances BTZ-induced G2/M arrest and P21 up-regulation.     

吡柔比星与丝裂霉素在浅表性膀胱癌术后治疗的应用价值研究

目的:探讨吡柔比星联合丝裂霉素在浅表性膀胱癌术后膀胱灌注治疗中的应用价值。方法:回顾性分析我院2007年4月-2011年4月术后采用吡柔比星与丝裂霉素交替灌注治疗的68例膀胱癌患者的临床资料,并以同期单纯采用丝裂霉素进行术后灌注治疗的68例膀胱癌患者为对照组。结果:观察组术后复发率明显低于对照组,组间比较差异具有统计学意义(P<0.05)。治疗期间观察组患者不良反应发生率低于对照组,组间比较差异具有统计学意义(P<0.05)。结论:采用吡柔比星与丝裂霉素进行交替膀胱灌注治疗可有效降低浅表性膀胱癌术后复发率。     

吡柔比星对膀胱原位癌定位诊断价值的初步探讨

目的 初步探讨吡柔比星(THP)对于伴随膀胱肿瘤的膀胱原位癌的定位诊断价值.方法 灌注前将50 mg THP溶解于50 ml 5%葡萄糖溶液,对上海交通大学泌尿外科研究所2007年12月至2008年6月收治的51例非肌层浸润性膀胱肿瘤患者和14例无痛性血尿患者行THP膀胱灌注,保留15 min后置入膀胱镜检查,观察肿瘤组织及周围膀胱黏膜染色情况.非肌层浸润性膀胱肿瘤患者检查后行经尿道膀胱肿瘤激光切除术.对肿瘤组织、THP染色区域全部进行组织学检查,肿瘤蒂旁2 cm处及膀胱其他部位非染色区域组织作为随机对照,分析比较染色结果.结果 共37例膀胱肿瘤患者的67块肿瘤周围膀胱黏膜THP染色阳性,其中11块病理证实为膀胱原位癌,分布在7例患者中.14例无痛性血尿患者中有2例膀胱黏膜呈现THP染色阳性,其中1例染色区病理证实为膀胱原位癌;另外12例未染色,组织学检查无阳性发现.膀胱原位癌细胞吸收THP的敏感度和特异度分别为92.3%(12/13)和86.7%(371/428).结论 THP对于伴随膀胱肿瘤的膀胱原位癌诊断操作简便、直观,有一定的定位诊断价值.     

经尿道等离子电切术联合吡柔比星灌注治疗膀胱黏膜白斑20例

目的探讨膀胱黏膜白斑临床特点及诊疗方法。方法经膀胱镜检查及病理活检确诊膀胱白斑20例,均采用经尿道等离子电切术治疗,术后辅以吡柔比星膀胱灌注治疗。结果术后患者尿路刺激、下腹不适症状明显改善,随访3个月～2年,未见复发及恶变者。结论经尿道等离子电切术联合吡柔比星膀胱灌注是治疗膀胱白斑和预防其恶变的有效方法。     

Double short-time exposure to pirarubicin produces higher cytotoxicity against T24 bladder cancer cells

This study was designed to determine the ideal manner (schedule and duration) of intravesical chemotherapy using pirarubicin (THP). At first, T-24 cancer cells were treated with 50, 100, 150, and 200 μg/ml THP for 10, 30 and 60 min. Following the first exposure, at various intervals (3, 6, 12, and 24 h), a second exposure to THP was performed under the same condition in vitro. The cell viability was measured by XTT assay. Further, the cells were scanned with a laser scanning cytometer (LSC) and DNA histograms were analyzed to evaluate the cell-cycle components. A single exposure of T-24 cells to THP resulted in significantly higher inhibition of cell growth for 30 min with 100 μg/ml and higher concentrations of THP; for example, the cell viability was reduced to 15, 2, and 0% by incubating cells with 100, 150, and 200 μg/ml of THP, respectively, whereas it was 49% with 50 μg/ml THP. Double exposure of T-24 cells to THP resulted in significantly higher inhibition of cell growth than single treatment at all intervals. LSC assay demonstrated a higher sub-G₁ peak after double treatment with THP when compared with that after a single treatment. Similar cytotoxic effects following double treatment with THP were observed on other bladder cancer cell lines (UMUC3, TCCSUP, 5637, and 253J cells) in vitro. In conclusion, the double short-term exposure to bladder cancer cells by THP has more remarkable cytotoxic effects than the single exposure in vitro.     

在肝癌治疗中吡柔比星碘油乳剂的应用

对62例肝癌患者使用以吡柔比星碘油乳剂动脉栓塞为主的联合化疗方案。其中9例单发巨块型肿瘤伴外周血象降低者单纯使用吡柔比星碘油乳剂栓塞，l例Ⅲ期肝癌、肝功ChildC级患者仅行导管化疗灌注，3例栓塞后手术切除肿瘤。结果显示近期有效率58％。8例出现胃肠道反应。2例较治疗前WBC明显降低。4例治疗后发生心律异常。9例单纯栓塞患者无ECG或外周血象改变。3例术后病理肿瘤细胞完全坏死。以吡柔比星碘油乳剂栓塞为主的方案毒副作用较低。对血象异常而血供较好的巨块型肝癌患者单纯采用吡柔比星碘油乳剂栓塞，疗效满意并避免了多种化疗药的毒副作用。     

高剂量吡喃阿霉素的CTOP方案治疗非霍奇金淋巴瘤

目的　观察高剂量吡喃阿霉素组成的CTOP方案治疗非霍奇金淋巴瘤的疗效及不良反应。方法　 60例初治非霍奇金淋巴瘤随机分为两组 ,分别接受常规剂量吡喃阿霉素的CTOP(THP 40mg/m2 )和高剂量吡喃阿霉素的CTOP(THP 60mg/m2 )方案化疗至少 2个疗程 ,观察疗效及不良反应。结果　高剂量吡喃阿霉素的CTOP与常规剂量吡喃阿霉素的CTOP方案相比完全缓解率有所提高(3 6 6%vs 2 0 % ) ,达到完全缓解的时间也缩短 ,但差异均无显著性 (P >0 0 5 )。提高吡喃阿霉素的剂量强度后并未增加心脏毒性、脱发及骨髓抑制等不良反应的发生 ,两组的不良反应的发生率及严重程度相仿 ,差异无显著性。结论　高剂量吡喃阿霉素组成的CTOP方案治疗非霍奇金淋巴瘤可提高疗效而不加重不良反应 ,高剂量吡喃阿霉素可安全使用。     

吡柔比星和阿霉素毒副反应的对比观察

 对含吡桑比星（THP）联合化疗方案施治的71例（183个治疗周期）和合阿霉素（ADM）联合化疗方案施治的106例（269个治疗周期）中晚期恶性肿瘤病人在毒副反应方面的资料进行了对比观察。结果表明，THP组的消化道副反应、脱发、心脏毒性较ADM组明显减轻；骨髓抑制、口腔炎、体温升高、肝肾功能损伤的毒副反应两药基本相当。综合判断，提示THP的毒副反应较ADM轻。