兔肝VX2肿瘤模型的建立及影像学研究现状

VX2肿瘤细胞株是一种可移植的肿瘤细胞株,可接种到兔的肝脏、肾脏等部位,建立原位肿瘤动物模型。兔VX2肝癌模型是目前较常用的实验性动物肝癌模型,本文就兔肝VX2肿瘤模型的建立和影像学表现进行综述。     

经肝动脉As2O3碘化油化疗栓塞 对兔肝移植瘤生长及转移的影响

目的观察As2O3与碘油联合经肝动脉化疗栓塞术后对兔VX2肝移植瘤生长及转移的作用.方法 40只家兔肝内肿瘤种植后2周,随机分为5组,经肝动脉插管分别给予不同处理,实验设生理盐水灌注组、As2O3灌注组、单纯碘油栓塞组、阿霉素碘油栓塞及As2O3碘油栓塞组,As2O3的用量为2 mg/kg.肿瘤种植后5周,测量动物体重,所有动物均处死,取出肝脏及双肺标本,测定肝脏的重量,计算肝移植瘤的体积、坏死面积,观察肝内、双肺及其他器官肿瘤转移的发生率.结果肿瘤植入后5周,各处理组动物体重均有明显的下降,肝脏重量增加,计算的肝指数各组分别为9.8±2.2、9.7±2.1、8.5±2.0、8.4±2.1、6.4±1.2;肿瘤体积分别为(35.5±7.6) cm3、(32.2±9.7) cm3、(21.2±8.5) cm3、(20.9±11.3) cm3、(11.8±4.0) cm3,栓塞治疗组与非栓塞治疗组间差异有统计学意义,As2O3碘油栓塞治疗组与其他组相比差异有统计学意义.平均坏死率各组间差异无明显的统计学意义.双肺转移结节的数目各组分别为52.4±32.2、51.8±26.3、54.8±29.2、53.5±30.7、19.6±17.0;转移结节的直径各组分别为(3.8±1.2) mm、(3.6±1.1) mm、(3.9±1.3) mm、(3.5±1.6) mm、(2.2±0.7) mm.As2O3碘油栓塞治疗组与其他各组相比差异有统计学意义(P<0.05).结论 As2O3与碘油联合经肝动脉栓塞治疗,可抑制肝移植瘤的生长及肺转移.     

Stimulation of tumor growthin vitro andin vivo by suramin on the VX2 model

Suramin is an antitrypanosomal compound with confirmed efficacy against several human malignancies. It is generally assumed that its mechanism of action includes the interaction with different growth factors, unlike most of the anticancer drugs. Its anticancer activity has not been testedin vivo against squamous cell carcinoma. The purpose of this study was to assess the efficacy and toxicity of suraminin vivo andin vitro on the VX2 tumor model at therapeutic monitored plasma concentrations. We determined the pharmacokinetics of suramin in rabbits, and modelized its administration in order to obtain plasma concentrations between 150 and 300 μg/ml throughout the treatment course of 3 weeks. Under these conditions, antitumor effects of suramin were evaluatedin vivo by comparing liver tumor involvement in suramin-treated and control rabbits. Liver involvement was quantified by image analysis andin vitro effects were also determined at the same concentrations.In vivo, suramin promoted liver tumor growth significantly (p<0.05), compared to untreated controls.In vitro, suramin significantly stimulated tumor cell growth at concentrations above 200 μg/ml (p<0.01). Suramin may have stimulatory effects on tumor growth in squamous cell carcinoma at relevant plasma drug concentrations. Caution should be taken in further trials in patients with squamous cell carcinomas.     

兔VX2肝癌MRI征象与病理对照研究

目的探讨新西兰兔VX2肝癌MRI征象的病理学基础。方法移植法建立新西兰兔VX2肝癌模型20只共32个瘤灶。模型建立后2~4周,全部兔肝癌模型行肝脏MRI平扫,10只兔肝癌模型(包括15个瘤灶)加做MRI增强扫描。MRI检查完成后,留取肿瘤最大横截面标本,行VX2肝癌MRI征象与病理学对照研究。结果种植瘤成活率为100%。T2WI 6个瘤灶呈均匀稍高信号,其余26个瘤灶显示特征性瘤内异常信号,其中"结中结征"5个瘤灶、"靶环征"7个瘤灶、"点彩征"14个瘤灶。对照研究证实此种瘤内异常信号病理基础为不同结构类型的坏死肿瘤组织。增强后肿瘤环形强化,轻微强化6个瘤灶,中等程度强化7个瘤灶,明显强化2个瘤灶,光镜下轻微强化者强化肿瘤组织有大量点状坏死区,明显强化者瘤内血窦明显扩张。结论MRT2WI可评价坏死肿瘤组织结构类型,兔VX2肝癌肿瘤强化程度与肿瘤内血窦扩张程度及瘤内点状坏死数量有关。     

一个新的可逆性胆硷酯酶抑制剂——二甲氨基甲酸-3-叔丁基-4-〔2-(1-哌啶基)乙氧基〕苯酯

本文报告了我所自己合成的可逆性胆硷酯酶抑制剂——二甲氨基甲酸-3-叔丁基-4-〔2-(1-哌啶基)乙氧基〕苯酯(代号"8294")与生理对抗剂或胆硷酯酶重活化剂伍用,对不同神经性毒剂中毒的预防效价、安全系数、有效时间以及与催醒宁("705")比较等所进行的观察.结果显示,"8294"比"705"的毒性小,安全系数大,效价高,有效时间长.     

全肝容积灌注CT成像评估兔肝血流灌注及体积对肿瘤坏死率的影响

目的 探讨全肝容积灌注CT成像（VPCT）评估兔肝血流灌注及体积对肿瘤坏死率的影响。方法 采用兔肝VX2移植瘤作为实验组,并设立对照组。实验组及假手术对照组在术后14 d通过全肝VPCT并获得相应的灌注参数,测量并计算实验组肿瘤体积（TV）、肿瘤坏死率（TNR）。检查完后对所有实验组肿瘤标本进行病理学观察。结果 实验组癌组织与对照组肝组织灌注血流量（BF）、灌注血容量（BV）、动脉灌注量（ALP）、门静脉灌注量（PVP）、动脉灌注指数（HPI）比较,差异均有统计学意义（P <0.05）,实验组癌旁组织与对照组肝组织BF、BV、ALP、PVP、HPI比较,差异均无统计学意义（P >0.05）。Pearson相关性分析显示,TNR与ALP、HPI呈负相关（r =-0.410和-0.356,均P <0.05）,TNR与BF、BV、PVP无相关性（r =-0.016、-0.155和0.256,均P >0.05）;TV与BF、BV、PVP、ALP、HPI无相关性（r =0.062、0.292、0.140、0.142和0.014,均P >0.05）;肝VX2移植瘤TNR与TV无相关性（r =-0.098,P >0.05）。HE染色发现肿瘤边缘区为富含血管的环形癌组织,中央为坏死区。结论 兔肝VX2移植瘤TNR与全肝VPCT反映的肿瘤动脉灌注高低有关,与TV无明显关联。     

经动脉化疗栓塞兔VX2肝癌后早期肿瘤细胞凋亡

目的　研究介入治疗兔VX2肝癌肿瘤细胞凋亡的早期动态改变 .方法　建立 2 7只新西兰大白兔VX2肝癌模型 ,随机分成肝动脉化疗栓塞组 (Transarterialchemoembolization ,TACE)、灌注化疗组 (Transarterialinfusion ,TAI)、灌注肝素生理盐水组 (对照组 ,Control) ,每组各 9只 .介入治疗后每组再随机分成 3个亚组 ,每亚组 3只 .在治疗后第2 4、72、12 0小时分别处死 3组中一亚组 ,取材肿瘤生长活跃的外带组织用流式细胞仪AnnexinV和PI双标记法定量检测细胞凋亡 ,组织病理切片苏木精 -伊红染色 (HE染色 )和甲基绿 -派洛宁染色 (MG -P染色 )光镜下形态学方法观察不同时间肿瘤细胞的凋亡变化 .结果　TACE、TAI、Control组在治疗后 2 4、72、12 0小时流式细胞仪法定量检测肿瘤细胞凋亡比率分别为 11.4 4± 2 .15、10 .99± 1.74、6 .0 0± 0 .5 8,5 .84± 0 .6 8、4 .6 5± 0 .11、2 .88± 1.2 3和 2 .80± 0 .15、2 .19± 1.6 9、2 .5 1± 2 .13.TACE、TAI、Control组凋亡在各时间点均有显著差异 (p <0 .0 1) ,TACE组 2 4、72小时的凋亡明显高于 12 0小时 (p <0 .0 5 ) .TACE组诱导的肿瘤细胞凋亡比率明显高于TAI、Control组 ;TACE组诱导的肿瘤细胞早期凋亡比率随时间呈下降趋势 ,在 12 0小时凋亡仍明显高于其     

碘佛醇对兔VX2肾癌超声血流显像影响的研究

目的评价碘佛醇在兔VX2肾癌超声血流显像中的作用。方法24只实验兔建立肾VX2肿瘤模型，随机分3批，每批8只，分别于种植后第7、14、21天，静脉注射碘佛醇，观察注射前后肿瘤彩色血流信号的变化情况。结果注射碘佛醇后肿瘤内彩色血流信号较注射前增多、增强。其中第7天，肿瘤的CDFl分级变化无显著统计学意义，第14天和第21天差异有显著统计学意义。注射碘佛醇后连续观察20min，血流信号增强仍保持在高峰状态。结论碘佛醇对兔VX2肾癌的彩色多普勒血流显像起增强作用。     

Reactivating and protective effects of pyridinium compounds in human erythrocyte acetylcholinesterase inhibition by organophosphates in vitro

The reactivation of human erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7) inhibited by O-ethyl-S-2-di-isopropylaminoethyl methylphosphonothioate (VX) and the protection against AChE inhibition by O-1,2,2-trimethylpropyl methylphosphonofluoridate (Soman) was studied with sixteen quaternized pyridinium compounds. TMB-4 which is known as a good reactivator of AChE inhibited by organophosphates proved to be the most effective reactivator. Of the tested newly synthetised compounds 3 were fairly good reactivators of methylethoxyphosphonylated AChE. These compounds have 2 pyridinium rings connected by a dimethylether link and a hydroxiiminomethyl group in position 2 of one pyridinium ring, while the radicals of the other pyridinium ring are benzoylcarbonyl, cyclohexylcarbonyl or amidocarbonyl residue.The rate of reactivation with these compounds followed a two-phase pattern, being fast at the beginning and then slowing down to an equilibrium. Kinetic treatment of the first-phase reaction course yielded the second-order rate constants of reactivation. All 3 compounds had similar reactivating efficiency (k _r values range from 0.8×10³ to 3.6×10³ M^–1 min^–1) and in effective concentrations (1 to 100 M) they also inhibited AChE (K _i(app) values range from 0.11 to 0.19 mM). Their reactivating properties were not better than those revealed by TMB-4 (k _r= 19.4×10³ M^–1 min^–1) which was tested as a reference compound.HGG-12, HGG-42 and HI-6 were also found to exert a good protective effect against AChE inhibition by Soman; no protection was obtained with TMB-4.     

人红细胞-兔VX2肿瘤细胞融合疫苗的制备及其对兔VX2肿瘤复发转移的影响

目的:制备一种新型肿瘤疫苗,观察其抗肿瘤效应.方法:PEG法制备人红细胞-兔VX2细胞融合疫苗,MTT法检测疫苗体外刺激兔单核细胞增殖的作用,观察疫苗治疗对兔VX2肿瘤复发转移的影响.结果:融合疫苗体外显著刺激单核细胞增殖,后者能特异性杀伤VX2靶细胞,疫苗治疗能显著降低VX2肿瘤的复发转移率.结论:人红细胞-兔VX2细胞融合疫苗体内外均可诱导特异性抗肿瘤免疫效应,该疫苗为研究人肿瘤细胞融合疫苗提供了支持.