阿霉素介入性化疗与热化疗对兔肝VX-2移植癌改良模型作用的比较研究

 目的　评价介入性热化疗对兔肝癌的抑瘤效果。方法　将VX 2瘤细胞接种于 6 0只新西兰白兔肝右叶 ,建立兔肝癌模型 ,随机分 4组 ,每组 15只。利用导管经肝动脉分别给生理盐水、37℃盐水 +阿霉素、6 0℃热生理盐水及ADM溶液 (6 0℃ )于不同组 ,1周后后观察各组肿瘤体积及血清AST水平 ,观察荷瘤兔的存活期。结果　ADM溶液 (6 0℃ )热灌注组生长率 (0 .5 3± 0 .2 1)与对照组 (3.4 8± 1.17)相比有显著性差异 (P <0 .0 1) ,与栓塞组 (1.13± 0 .2 3)、ADM溶液 (37℃ )灌注组 (1.0 9± 0 .2 6 ) )相比亦有显著性差异 (P<0 .0 5 )。ADM溶液 (6 0℃ )热灌注组存活期 (5 0 .0± 2 .0d)与对照组 (40 .5± 3.0d)相比差异有显著性 (P <0 .0 5 )。ADM溶液 (6 0℃ )热灌注组血清AST水平治疗前后变化与其它各组相比无显著性差异 (P >0 .0 5 ) ,与对照组相比有显著性差异 (P <0 .0 5 )。结论　ADM溶液 (6 0℃ )热灌注组可大大降低肿瘤生长率 ,延长...     

兔肝VX2瘤两种介入性热化疗方法的对比实验研究

目的:研究两种经动脉热灌注化疗方法对兔肝VX2移植瘤的热化疗的协同效率。方法:用新西兰大白兔建立肝VX2肿瘤模型,经股动脉插管,导管头置于兔肝动脉,DSA证实肿瘤供血动脉后,分3组(每组10只),分别给予常温100ml生理盐水+阿霉素(ADM)灌注、60℃热生理盐水100ml+阿霉素连续灌注、60℃热生理盐水100ml+阿霉素间歇性灌注。灌注过程中,测量两60℃热灌注化疗组肿瘤组织内43℃-45℃持续时间,灌注后即时检测各组肿瘤组织内阿霉素浓度。结果:灌注后肿瘤组织内阿霉素浓度(μg/ml):60℃间歇性热灌注化疗组为17.622±1.368,60℃连续热灌注化疗组12.013±2.237,常温灌注化疗组11.519±1.225。60℃间歇热灌注化疗组高于60℃连续热灌注化疗组(P<0.05),60℃连续热灌注化疗组高于常温灌注化疗组(P>0.05)。瘤体温度43℃-45℃持续时间(min):60℃间歇性热灌注化疗组为11.3±3.3,60℃连续热灌注化疗组4.1±2.7,60℃间歇性热灌注化疗组为60℃连续热灌化疗组近3倍。两60℃热灌注化疗组兔的呼吸、心率、体温变化无明显差异。结论:经动脉间歇性热灌注化疗方法是一种更有效的介入性热化疗方法。     

间歇和连续热灌注对兔 VX-2肿瘤内阿霉素浓度的影响

背景与目的:已证实阿霉素热化疗对体外兔 VX-2细胞的抑制作用比常温阿霉素的作用强,而热灌注对机体的生命体征有一定影响.本研究在兔 VX-2移 植瘤模型建立基础上,比较间歇性热灌注与连续性热灌注对兔呼吸、心率、体温及 VX-2肿瘤内阿霉素浓度的影响,验证间歇性热灌注的有效性和安全性,以寻找更安全有效的灌注方式.方法:在 30只新西兰大白兔后腿上建立 VX-2肿瘤模型,并随机分为常温灌注组、 60℃连续灌注组和 60℃间歇灌注组(每组 10只).经股动脉插管、 DSA证实为肿瘤供血动脉后,分别给予常温 100 ml盐水加阿霉素 (ADM)灌注、 60℃热盐水 100 ml加阿霉素连续灌注、 60℃热盐水 100 ml加阿霉素间歇性灌注.灌注过程中,测量 60℃热灌注组与 60℃间歇灌注组肿瘤组织内 43℃～ 45℃持续时间;灌注后即时检测各组兔呼吸(次 /分)、心率(次 /分)、体温(℃)及肿瘤组织内阿霉素浓度.结果:常温灌注组阿霉素浓度为( 7.115± 2.180)μ g/ml, 60℃连续灌注组为( 17.213± 1.657)μ g/ml, 60℃间歇性灌注组为( 16.545± 3.426)μ g/ml;60℃间歇灌注组阿霉素浓度与 60℃连续灌注组无显著性差异( P >0.05), 60℃连续组、间歇组阿霉素浓度与常温灌注组均有显著性差异( P< 0.05). 60℃间歇性灌注组 43℃～ 45℃持续时间为( 24.31± 2.45) min, 60℃连续灌注组为( 22.53± 1.44) min,两组之间无显著性差异( P >0.05).连续灌注组与常温灌注组兔的呼吸、心率、体温变化有显著性差异( P< 0.05),而间歇灌注组与常温灌注组兔的呼吸、心率、体温变化无显著性差异( P >0.05).结论:常温灌注组与连续灌注组的药物浓度无显著性差异;与连续性热灌注相比,经动脉间歇性热灌注化疗方法更安全.     

热碘油栓塞阻断兔肝VX2肿瘤血供的研究

[目的]应用多普勒超声观察热碘油栓塞阻断兔肝VX2肿瘤血供的效果及其对肝脏血流动力学指标的影响.[方法]30只载瘤兔,随机分为3组.分别采用37℃生理盐水(对照)、37℃碘油及60℃热碘油经兔肝动脉灌注治疗,1周后多普勒超声观察肿瘤血供、肝动脉最大血流速度(Vmax)、阻力指数(RI)、门静脉平均血流速度(Ⅴ)、门静脉血管内径的变化.[结果]治疗前,所有病灶能量及彩色多普勒均可检测出瘤内及瘤周较丰富血流信号,治疗后显示60℃热碘油组瘤内及瘤周血流信号均明显减弱,部分消失.治疗后60℃热碘油组肝动脉血流速度与37℃碘油组比明显降低(P=0.004),与对照组比阻力指数增大(P=0.021),门静脉血流速度及内径与其他两组比尤明显变化(P均＞0.05);60℃热碘油组存活期41.0±3.0d与对照组31.5±3.0d相比有显著差异(P=0.006).[结论]热碘油栓塞可更有效地阻断兔肝VX2肿瘤供血,延长荷瘤兔生存期.     

介入性热化疗对兔肝VX-2肿瘤血管渗透性的影响

背景及目的:研究表明,加热对兔VX-2细胞阿霉素化疗有增敏作用,加热可提高细胞内阿霉素的含量。本研究探讨介入性热化疗对正常肝组织及肿瘤肝组织血管渗透性的影响。方法:建立可供实验用的兔VX-2移植性肝癌模型30只,随机分为3组:非灌注组(插管后只注射1%伊文思蓝),常温灌注组(灌注液为25℃生理盐水)。热灌注组(灌注液为60℃生理盐水)。使用标准曲线和分光光度法测量各组组织中伊文思蓝含量(作为血管渗透性的指标)。结果:肿瘤组织与肝组织的EB含量在3组中均有差别(P<0.05);正常灌注组与非灌注组肝组织的EB含量、肿瘤组织的EB含量无明显差别(P>0.05);热灌注组与非灌注组、正常灌注组肝组织的EB含量、肿瘤组织的EB含量有明显差别(P<0.05)。结论:介入性热化疗可以增加肝组织及肿瘤组织的血管渗透性。     

犬肝动脉不同温度热灌注对肝肾功能的影响

目的：以犬为研究对象,研究不同温度（45℃,50℃,55℃,60℃,65℃）的热灌注液经肝动脉灌注对犬肝内温度、肝组织学及肝、肾功能的动态影响,为介入性热化疗的临床应用提供实验依据。方法：经犬肝动脉分别灌注入45℃、50℃、55℃、60℃、65℃生理盐水180 ml,持续30 min。观察并比较热灌注前后肝脏穿刺活检及肝、肾功能的动态变化情况。结果：1.45℃、50℃、55℃、60℃、65℃肝动脉热灌注时,肝内中心测得的温度分别为(37.9±0.5)℃、(38.6±0.3)℃、(40.5±0.3)℃、(42.1±0.5)℃和(45.8±0.6)℃,谷丙转氨酶（alanine aminotransferase,ALT）、谷草转氨酶（aspartate transaminase,AST）于60℃灌注后24 h开始升高,72 h达到高峰（P< 0.01）,168 h后逐渐下降,216 h后恢复正常;总胆红素（total bilirubin,T-BIL）、白蛋白（albumin,ALB）、γ－谷氨酰基转移酶（γ-glutamyltransferase,γ-GT）无明显变化（P< 0.05）。2.肝组织可见一过性淋巴细胞浸润、肝细胞混浊肿胀,168h后恢复正常。3.尿素氮（blood urea nitrogen,BUN）、肌酐（creatinine,Cr）无显著性变化（P< 0.05）,尿酸（uric acid,UA）呈一过性增高（P< 0.05）。4.45～55℃热灌注对肝肾功能无显著影响,65℃热灌注后肝肾功能恢     

热盐水灌注对兔肝VX2肿瘤血管内皮细胞的影响

目的：研究将60℃生理盐水经肝动脉灌注兔肝VX2肿瘤对肿瘤血管内皮细胞及通透性的影响。方法：20只VX2肝荷瘤兔,随机分为2组,分别经兔肝动脉灌注37℃生理盐水60ml（对照组）、60℃生理盐水60ml（治疗组）。灌注后再经导管推注1% Evans Blue （EB）,2ml/kg。24小时后处死荷瘤兔,取小块瘤组织,称重后,放入1ml甲酰胺液中,置于50℃恒温水浴箱60h,提取液用722型光栅分光光度计测出620nm下的OD值,从标准曲线上测出相应的伊文思蓝含量,以反映该组织血管的通透性。切取肿瘤边缘血管组织包埋,行电镜检查观察肿瘤血管内皮细胞形态变化。结果：60℃生理盐水灌注组肿瘤组织EB含量［（10.71±0.84）μg/100mg］与37℃灌注组［（3.42±0.87）μg/100mg］相比有差异（P〈0.01）。电镜观察热灌注组肿瘤血管内皮细胞,细胞间隙增大。结论：60℃灌注可增大肿瘤内皮细胞间隙从而增加肝肿瘤组织的血管通透性。     

VX2活细胞数与兔肝癌模型成功率及成瘤时间的关系

目的探讨接种不同数量的VX2瘤株活细胞的成瘤率、成瘤时间。方法制备VX2细胞匀浆,并计数活细胞浓度。将新西兰大兔分为三组(每组10只):A组(低细胞数组):活细胞数1×104;B组(中细胞数组):活细胞数为1×105;C组(多细胞数组):活细胞数1×106。分别于接种后5d、10d、14d、21d、28d做B超观察成瘤情况及瘤体的大小、形态、转移等情况。结果A组:于接种后5d、10d、14d、21d、28d分别作腹部B超未见肝内肿瘤生长(0/10);B组:于接种后第10d(1/10)和第14d(8/10),B超显示肝内接种部位可见体积(0.53±0.02)cm3低回声区,有声晕,血供丰富;1只于接种后5d、10d、14d、21d、28d分别作腹部B超未见肝内肿瘤生长(1/10)。平均成瘤时间为(13.5±0.18)天。成瘤率为90%。C组:于接种后第5d(1/10)、第10d(9/10),B超显示肝内接种部位可见体积为(0.67±0.03)cm3低回声区,血供丰富,成瘤率为100%,平均成瘤时间为(9.5±1.33)天。A与B组及A与C组的成瘤率在统计学上有显著差异(χ12=16.36,P1<0.05;χ22=20.0,P2<0.05),B与C组的成瘤率在统计学上无显著性差异(χ2=1.046,P>.0.05)。B组与C组成瘤后体积及肿瘤生长情况无显著差异。结论VX2细胞株是制作兔移植性肝癌模型较好的瘤株,创建模型的成功率及成瘤时间与接种的活细胞数有关,接种活细胞数>1×105则其成瘤率可达90%~100%。VX2活细胞多比活细胞少的成瘤时间早,一般成瘤时间在9天以上。     

高强度聚焦超声消融兔腹主动脉旁肝肿瘤的安全性和有效性

  目的  观察高强度聚焦超声消融兔腹主动脉旁肝肿瘤后肝肿瘤剂量学、磁共振图像、病理学及生存期影响, 评价HIFU消融兔腹主动脉旁肝肿瘤安全性和有效性。  方法  分别于HIFU组(32只)和对照组(20只)实验兔建立腹主动脉旁的VX2肝肿瘤模型, HIFU组瘤兔于MR引导的高强度聚焦超声消融肿瘤, 分析腹主动脉旁肿瘤消融剂量学, MR观察消融前后肿瘤影像学变化, 病理学观察肿瘤消融后坏死情况, 对比观察HIFU组与对照组瘤兔生存期。  结果  MRI和病理学均表明MR引导下HIFU能完全消融兔腹主动脉旁VX2肝肿瘤, EEF为25.72±11.40 J/mm3 HIFU组的生存期明显高于对照组, 差异具有统计学意义(P < 0.05)。  结论  HIFU能安全有效消融兔腹主动脉旁VX2肝肿瘤并且能明显提高存活期。      

硫普罗宁防治恶性肿瘤化疗致肝损害临床疗效的初步观察

将恶性肿瘤患者分为化疗加硫普罗宁组 3 3例 (观察组 )和单纯化疗组 3 7例 (对照组 ) ,均于化疗前后分别测定肝功能。结果肝功异常观察组 1例 ( 3 0 % )、对照组 8例 ( 2 1 6% ) ,2组相比差异有显著性 (P <0 0 5 )。硫普罗宁 (凯西莱 )可以防治阿霉素 (ADM )为主化疗引起的药物性肝损害。     

Adriamycin Thermotherapy through the Hepatic Artery Using VX2 Carcinoma in Rabbit liver as a Model

OBJECTIVE It has been reported that heating can enhance sensitivity of rabbit VX2 cells to adriamycin and increase the intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effect of interventional hyperthermia and interventional thermochemotherapy on VX2 carcinoma in rabbit liver. METHODS VX2 carcinoma cells were surgically implanted into the right liver lobe of 60 male New Zealand white rabbits, which were randomly divided into 4 groups (15 per group). The 4 groups (designated as 1, 2, 3, 4 respectively) were injected with 10 ml of the following via the hepatic artery: physiological saline (37℃); adriamycin (37℃); physiological saline (60℃); adriamycin (60℃). One week later, the tumor volume, serum level of aspartate transaminase (AST) and the survival of the rabbits bearing VX2 were observed and compared among the different treated groups. RESULTS The tumor growth rate in group 4 (ADM 60℃) (0.53±0.21)% was significantly lower than that in group 1 (3.48±1.17)%, in group 2 (1.09±0.26)% and group 3 (3.32±1.28)% (P<0.05, P<0.05, P<0.01, respectively). The days of survival days for group 4 (87.0±2.0) were significantly more than that in group 1 (40.0±3.0). Group 4 showed a significantly higher increase in serum AST compared to group 1 (P<0.05), but without significant differences compared to the other groups (P>0.05). CONCLUSION Adriamycin treatment at 60℃ significantly deceased the tumor growth, prolonged the survival period and resulted in reversible liver damage.     

Hyperthermic liver toxicity: a role for oxidative stress

Rat livers were perfused at 37 degrees C, 41 degrees C, 42 degrees C, 42.5 degrees C, and 43 degrees C for 2 hr. Among perfusate constituents analyzed were urea, total amino acids, N-acetyl-beta-glucosaminidase (NAG), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malonaldehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), allantoin, potassium, phosphate, and glucose. After perfusion, livers were homogenized and analyzed for xanthine oxidase (XO) activity, GSH content, and lysosomal lability. Perfusate AST, LDH, NAG, potassium, glucose, and phosphate increased significantly with time, and there were significant differences in the final values between 37 degrees C and 42 degrees C, 42.5 degrees C and 43 degrees C (P less than .05). GSH levels increased significantly at all temperatures after 90 and 120 min, whereas GSSG levels differed significantly at 60, 90, and 120 min for 37 degrees C vs. 42 degrees C, 42.5 degrees C, and 43 degrees C (P less than .05). Mean MDA levels at 37 degrees C differed from those at 41 degrees C and 43 degrees C (P less than .05) at each temperature. Allantoin levels increased significantly with time of perfusion; mean levels at 37 degrees C were significantly different from mean levels at each temperature at 60, 90, and 120 min. GSH liver tissue levels decreased with perfusion at hyperthermic temperatures; mean values at 41 degrees C, 42 degrees C, and 42.5 degrees C, and 43 degrees C differed from 37 degrees C mean values (P less than .01). Type O XO increased after 120 min perfusion from 6.4% +/- 2.0% at 37 degrees C to 55% +/- 30%, 43% +/- 27%, and 63% +/- 29% at 42 degrees C, 42.5 degrees C, and 43 degrees C, respectively. Lysosomal lability increased after perfusion at 42.5 degrees C. There was a significant increase in nonsedimentable NAG activity at 42.5 degrees C (P less than .05). These data support the premise that hyperthermic toxicity to the liver may be a consequence of oxidative stress brought about by enhanced adenosine triphosphate (ATP) consumption and conversion of XO to type O. Such conversion results in superoxide formation and subsequent depletion of cellular GSH, labilization of the lysosomes, and plasma membrane damage.     

兔VX2肝癌介入治疗后早期发生凋亡的流式细胞术检测

目的研究经肝动脉插管灌注碘油抗癌药乳液化疗栓塞和单纯灌注化疗后的早期兔肝VX2肿瘤发生凋亡。方法27只新西兰大白兔瘤组织块种植肝VX2肿瘤,A组(n=9)经肝动脉灌注碘油抗癌药乳液,B组(n=9)肝动脉灌注化疗,C组(n=9)肝动脉灌注生理盐水,每组分别在处理后第24h、72h、120h处死实验兔各3只,采用FITC-AnnexinV/PI流式细胞术分析介入处理后早期的肿瘤细胞凋亡。结果肿瘤边缘部的凋亡早期细胞百分率(PapE)与凋亡晚期细胞百分率(PapL)及峰值时间点分别为:A组(9.48±4.58)%、(33.46±8.81)%、24h、72h,B组(4.46±1.47)%、(11.65±3.51)%、24h、24h,C组(2.50±1.39)%、(5.99±1.22)%。肿瘤中心部的PapE、PapL与峰值时间点分别为:A组(16.48±6.32)%、(43.56±18.51)%、24h、72h,B组(7.50±3.10)%、(18.53±14.04)%、24h、24h,C组(5.61±1.92)%、(14.63±12.23)%。结论Lp-THACE诱导肝癌肿瘤细胞早期大量凋亡是其有效的主要作用机制,...     

经皮介入微波热凝治疗实验性VX2肺癌的有效性与安全性

背景与目的:经皮微波热凝治疗(percutaneous microwave coagulation therapy,PMCT)是一种重要的实体肿瘤微创介入治疗方法.本研究评价新型国产微波肿瘤治疗仪及气冷循环微波刀经皮穿刺介入治疗肺VX2移植肿瘤的安全性及有效性.方法:用组织块悬液注射法在30只新西兰大白兔中建立实验性VX2肺癌模型,随机分为对照组、治疗A组(40 W×120 s)、B组(80 W×60 s).在CT引导下经皮穿刺,并按预设参数进行微波热凝治疗;对照组予以假性治疗.观察实验兔术后一般状况,定期CT检查观察肿瘤进展情况,在治疗后第0、1、7天每组随机解剖1只实验兔观察局部组织学改变.结果:肿瘤细胞种植成功率100%.肺癌模型制作成功率为86.7%(26/30).对照组、治疗A组和B组的生存期分别为(39.7±5.3)天、(62.2±4.4)天和(61.7±4.5)天(P＜0.01).气胸的发生情况分别为33.3%(2/6)、55.6%(5/9)和33.3%(3/9)(P＞0.10).结论:PMCT是一种安全、有效、微创的治疗方法,可为肺癌的介入治疗提供一种新的选择.     

放射性125I粒子组织间植入治疗肝移植癌的实验研究

目的：研究瘤体内植入125I粒子治疗兔VX2肝移植癌的疗效及其病理变化,探讨125I粒子组织间植入治疗肝癌的可行性.方法：建立荷瘤兔肝移植癌动物模型.对照组（A组）植入空白剂量（OmCi）125I粒子,B组植入1.0mCi125I粒子,C组植入0.7mCi125I粒子,D组植入0.4mCi125I粒子.观察植入前后各组肿瘤体积并计算抑瘤率,切除肿瘤组织进行常规病理检查.结果：各治疗组肿瘤大小在治疗前后比较具有显著差异（P〈0.01）,均小于同期对照组（P〈0.01）.在不同观察时期抑瘤率差别均有统计学意义（P〈0.05）,治疗1周后抑瘤率变化显著;各个组间抑瘤率差异在治疗后2周最为明显（P〈0.01）,以后减小,但均高于D组（P〈0.01）.病理切片显示靠近125I粒子处肿瘤细胞坏死,但远离粒子处仍可见存活肿瘤细胞.1.0mCi粒子对正常肝组织损伤较大.结论：125I粒子组织间植入治疗肝癌有效,单个粒子活度以0.7mCi左右较为适宜.     

Clinical application of chemotherapy via the portal vein with liposome-encapsulated adriamycin in inoperable metastatic liver cancer

We studied the effects of liposome-entrapped adriamycin (L-ADM) administered via the portal vein and the clinical application of this treatment in the therapy and inhibition of liver metastasis, experimentally and clinically. Liposomes composed of egg phosphatidylcholine (cholesterol 50 mol%) were used as drug carriers. We examined the distribution in tissues and antitumor effect of freeze-dried L-ADM administered via the portal vein to rabbits bearing VX2 tumors. The liver concentration of ADM increased after delivery and cardiac uptake decreased compared with free drug treatment. The life span was prolonged by L-ADM treatment compared with the control group and the free ADM group. This L-ADM administration was confirmed to be safe and revealed a decrease in the heart toxicities compared with free adriamycin. Nineteen cases were studied from Jan. 1986 to May 1991 via the portal vein and the clinical effects were evaluated. From Mar. 1988 to date, 10 cases were treated with L-ADM (20-30 mg every 2 weeks/body) in patients with inoperable cases using subcutaneously implanted reservoir. The median survival was 450 days; 275 days for colon cancer, 492 days for gastric cancer, and 1,052 days for uterine cancer (range: 136-1,152 days), compared with 141 days (range: 52-253 days) in 9 cases of historical control treated with free-ADM via the portal vein. These results suggest that chemotherapy via the portal vein with L-ADM for metastatic liver cancer may increase survival time.