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1.
目的 探讨脂质体型奥沙利铂经动脉灌注给药对兔VX2肝移植瘤的影响.方法 25只兔VX2肝移植瘤模型建立14 d后均分为五组:空白对照(A)组;游离型奥沙利铂静脉注射(B)组和动脉灌注(C)组;脂质体型奥沙利铂静脉注射(D)组和动脉灌注(E)组.均一次性给予奥沙利铂10 mg/kg.用高效液相色谱法检测给药后2、24、48h肿瘤组织中奥沙利铂浓度;CT扫描计算治疗前1d、治疗后7d肿瘤体积、增长体积及增长率;检测各组治疗前1d及治疗后1、3、7d肝肾功能.结果 25只兔VX2肝移植瘤模型均成功建立.E组移植瘤奥沙利铂浓度显著高于其他各组(P<0.05).治疗后7d,五组肿瘤体积均较治疗前增大;但E组肿瘤体积、增长体积及增长率均小于其他各组(P<0.05).治疗后1、3d,B、C、D、E组ALT、AST、BUN、Cr值均升高(P<0.05),治疗后7d,各组肝肾功能均恢复至治疗前水平.结论 脂质体型奥沙利铂经动脉灌注治疗兔VX2肝移植瘤有效、安全. 相似文献
2.
目的研究托瑞米芬及联合长春瑞滨对兔VX2肿瘤模型影响,为肿瘤化疗提供新的途径及方法。方法 32只健康日本大耳白兔VX2肿瘤细胞的传代建立移植瘤动物模型后随机分成VX2肿瘤组织皮下移植瘤模型托瑞米芬干预组(A组)、VX2肿瘤组织皮下移植瘤模型长春瑞滨干预组(B组)、VX2肿瘤组织皮下移植瘤模型长春瑞滨联合托瑞米芬干预组(C组)、VX2肿瘤组织皮下移植瘤模型对照组(D组)4组,每组8只。分别于给药后2、3、4周计算瘤体体积及瘤体生长率。自接种肿瘤细胞当天计至30d后处死白兔并进行病理取样,甲醛固定、石蜡包埋、切片、HE染色,观察肿瘤组织病理结果。结果联合用药组移植瘤生长率第2周与各组比较差异有统计学意义(均P<0.01),第3、4周较对照组差异有统计学意义(P<0.01),与托瑞米芬组比较差异有统计学意义(P<0.05),与长春瑞滨组比较差异无统计学意义(P>0.05)。结论联合用药组、长春瑞滨组及托瑞米芬组对接种肿瘤细胞的生长均有不同程度的抑制作用,其中联合用药组对肿瘤细胞的作用明显,托瑞米芬对长春瑞滨有明显的协同作用。 相似文献
3.
目的观察VX2兔肝癌的超声检查影像学及病理学特征。方法采用超声引导下穿刺组织块接种法建立VX2肝癌兔模型20只,分别于接种后14d、21d行超声检查,并于检查后处死动物,行病理学检查。结果20只VX2肝癌兔模型均建立成功。超声影像学表现:在肿瘤种植后14d,20只中超声检查检出瘤灶18只,肿瘤直径8.6~11.8mm,平均(10.15±0.67)mm;在肿瘤种植21d时,超声检出瘤灶20只,瘤灶直径13.2—18.3mm,平均(16.13±1.98)mm。二维超声影像表现为圆形或类圆形的均匀低回声病灶,无包膜回声,其周边血供丰富,中央血供稀少。病理学大体检查见肿瘤呈结节状,无包膜,肿瘤切面呈灰白色,鱼肉样;光镜下癌细胞呈巢状分布,体积大,呈不规则排列,胞核大而深染,胞质量少。结论兔VX2肝癌病灶呈结节状,光镜下癌细胞呈巢状分布,异型性明显;超声检查是一种监测肝癌模型的有效手段。 相似文献
4.
目的观察热疗联合阿霉素碘油化疗栓塞对兔VX2肝种植瘤生长及血管生成的影响。方法用日本大耳白兔建立VX2肝种植瘤模型,随机分为5组,每组8只,分别为生理盐水组(A组)、碘油组(B组)、热疗组(C组)、阿霉素加碘油组(D组)、热疗联合阿霉素加碘油组(E组)。治疗后1周CT扫描观察各组肿瘤体积;血清生化检测AST、ALT水平;免疫组化检测残存肿瘤区微血管密度(MVD)、血管内皮生长因子(VEGF)表达情况。结果治疗后1周,各治疗组肿瘤生长均受到限制,E组肿瘤体积及生长率与其他组相比有显著差异(P<0.05)。E组血清AST、ALT水平与B、D组相比无显著差异(P>0.05),与A、C组比较有显著差异(P<0.05)。E组残存肿瘤区MVD、VEGF表达最低,明显低于其他组各组(P<0.05)。结论热疗联合阿霉素碘油栓塞兔VX2肝种植瘤可明显抑制肿瘤生长并抑制残存肿瘤区血管生成。 相似文献
5.
目的评估二巯基丁二酸修饰的Fe3O4(DSMA-Fe3O4)纳米磁液联合碘油动脉栓塞热疗治疗兔VX2肝癌的疗效。方法 25只开腹肝左叶种植VX2瘤的实验兔,随机等分为五组:对照组(A组)、碘油栓塞组(B组)、DSMA-Fe3O4纳米磁液+碘油栓塞组(C组)、DSMA-Fe3O4纳米磁液+热疗组(D组)、DSMA-Fe3O4纳米磁液+碘油栓塞+热疗组(E组)。成瘤2周后各组行CT扫描并测量,随后行肝动脉栓塞,D、E组栓塞后诱导热疗。分别在术后7、14d行CT检查,计算肿瘤生长比率、肿瘤增长体积。14dCT扫描结束后每组处死部分实验兔,取完整的肝、肾、脾及肺作病理检查。各组分别在术前1d,术后1、3、7d经兔耳缘静脉采血测ALT和AST。结果所有肝癌模型均建立成功。五组术前肿瘤体积、术前1d、术后7dALT、AST水平均无统计学差异(P>0.05)。术后14d,E组肿瘤体积平均缩小26.7%,而B、C、D三组肿瘤体积分别平均增大了200.7%、209.4%和422.5%。结论 DSMA-Fe3O4纳米磁液联合碘油动脉栓塞热疗兔VX2肝癌有效、安全。 相似文献
6.
目的探讨甘氨双唑钠(CMNa)对兔VX2肺移植瘤三维适形放疗(3-DCRT)的增敏作用。方法建立24只兔VX2肺移植瘤模型,按随机数字表法分为单纯放疗组、CMNa+放疗组及对照组,18F-脱氧葡萄糖(FDG)PET/CT监测治疗前后肺部肿瘤组织与对侧脊柱旁肌肉组织对18F-FDG最大标准摄取值(SUVmax)的比值(T/M)及肿瘤的体积变化,免疫组化法检测肿瘤组织血管内皮生长因子(VEGF)表达。对治疗前后T/M变化百分数(M%)、肿瘤体积生长率(V%)和VEGF阳性率(VEGF%)进行统计学分析。结果治疗24 h后,CMNa+放疗组和单纯放疗组T/M比值较治疗前减低,对照组明显升高,CMNa+放疗组M%(34.3±12.4)减少幅度高于单纯放疗组(17.6±13.3),组间差异有统计学意义(P<0.05);3组荷瘤兔肺部肿瘤体积较治疗前均有增长,其中CMNa+放疗组V%和VEGF%均为最低,与其余两组相比差异均有统计学意义(P<0.05)。各组VEGF%与M%、V%均呈正相关关系(r=0.847、0.745,P<0.05)。结论 CMNa可增加VX2肺移植瘤乏氧细胞对三维适形放疗的敏感性,其与放疗联合应用较单纯放疗能明显抑制肿瘤血管生成。 相似文献
7.
目的 研究经导管肝动脉化疗栓塞(TACE)联合选择性门静脉栓塞(SPVE)治疗兔VX2肝癌对残癌组织新生血管生成的影响。方法 42只实验兔,采用随机数表法分为实验组(A组)和对照组(B组),每组21只。A组行TACE联合SPVE治疗,B组单纯行TACE治疗。A、B两组于第14、21天,行CT平扫+增强扫描,第15天行TACE治疗,第18天分别行SPVE和门静脉数字减影血管造影(DSA)检查,第22天开腹行直接穿刺肝动脉和门静脉DSA检查并处死,取肿瘤周边残癌组织,检测血管内皮细胞生长因子(VEGF)及微血管密度(MVD)的表达情况。结果 A组VEGF、MVD值分别为(120.7±10.99)、(58.9±9.05),B组VEGF、MVD值分别为(136.5±15.45)、(71.8±12.06),两组差异均有统计学意义(P<0.05)。结论 门静脉对周边的肝癌组织具有部分血供,且TACE联合SPVE能够提高肿瘤的坏死程度,抑制新生血管的生成。 相似文献
8.
VX2乳腺癌兔的阿霉素致心脏毒性模型的建立 总被引:1,自引:0,他引:1
目的建立VX2乳腺癌兔的阿霉素致的心脏毒性模型。方法先建立兔VX2乳腺癌模型。2周后,将接种VX2乳腺癌成功模型兔随机分为阿霉素(ADR)组和对照组,阿霉素组10只,雌雄各5只,对照组8只,雌雄各4只。ADR组,每周1次于兔耳缘静脉注射ADR(用生理盐水配制成1mg/ml)2mg/kg,共6次。对照组,每周1次于耳缘静脉推注生理盐水每次2ml/kg,共6次。比较左心室射血分数的变化,并作心脏和肿块的病理切片,观察其组织学变化,记录动物的生存时间。结果模型成功率为90%,两组左心室射血分数(LVEF)差异有统计学意义(P〈0.05),阿霉素组的心脏经病理检查证实为有心肌病变,病理学结果证实符合心肌病样改变,肿块经病理检验证实为鳞状细胞癌。结论成功建立了VX2乳腺癌兔的阿霉素致心脏毒性模型,它将为临床研究提供的理想动物模型 相似文献
9.
目的 探讨交变磁场介导的二巯基丁二酸(DMSA)-Fe3O4纳米磁流体热疗治疗兔VX2肿瘤的疗效.方法 建立20只兔后肢VX2软组织肿瘤模型,随机分为4组:A组(对照组)、B组(磁流体局部注射组十热疗)、C组(磁流体动脉灌注组十热疗)、D组(磁流体静脉注射组十热疗),每组5只.成瘤2周后CT测量肿瘤大小.结果 B组和C组的肿瘤中心区[(46.01±1.97)℃和(40.38±1.50)℃]和肿瘤边缘区[(40.35±1.36)℃和(42.57±1.80)℃]的温度显著高于正常肌肉组织[(35.73±1.32)℃和(35.37±1.55)℃]和直肠[(35.69±1.05)℃和(35.25±1.15)℃](P<0.05);A组及D组肿瘤区域温度无明显增高.治疗后14 d,B组和C组肿瘤生长率分别为(441.04±29.61)%和(354.81±59.51)%,明显低于A组的(1119.90±179.40)%和D组的(1099.90±215.11)% (P<0.05).结论 交变磁场介导的DSMA-Fe3O4纳米磁流体热疗能明显抑制兔VX2肿瘤生长. 相似文献
10.
《Nanotoxicology》2013,7(4):459-468
AbstractThere is a paucity of data regarding the safety of administering solid gold nanoparticles (AuNPs) in large animal tumor models. We assessed the acute toxicity and biodistribution of 5 nm and 25 nm solid AuNPs in New Zealand White rabbits (n = 6 in each) with implanted liver Vx2 tumors 24 h after intravenous injection. Gold concentration was determined by inductively coupled plasma atomic emission spectrometry (ICP) and imaged with transmission electron microscopy (TEM). There was no clinico-pathologic evidence of renal, hepatic, pulmonary, or other organ dysfunction. After 25 nm AuNP administration, the concentration of white blood cells increased after treatment (p = 0.001). Most other blood studies were unchanged. AuNPs were distributed to the spleen, liver, and Vx2 tumors, but not to other tissues. The urinary excretion of AuNPs was bimodal as measured by ICP. 25 nm AuNPs were more evenly distributed throughout tissues and may be better tools for medical therapy. 相似文献
11.
目的 利用转移淋巴结放疗动物模型,研究扩散加权成像(DWI)评估早期疗效的价值.方法 建立新西兰大白兔VX2移植瘤转移淋巴结模型,并随机分为放疗组(10只)和对照组(7只),分别于放疗前、放疗后第1、3、7天行MRI常规及DWI检查,测量淋巴结的大小及ADC值.结果 两组各时间点转移淋巴结体积变化未见明显差异(P>0.05).放疗组放疗后第3和第7天的ADC值分别为1.267±0.200和1.688±0.330,明显高于放疗前的1.054±0.120和放疗后第1天的1.040±0.170(P<0.01).结论 与传统方法比较,DWI能更早反应实验动物转移淋巴结放疗后的变化. 相似文献
12.
目的探讨肝动脉栓塞化疗(TACE)恩度联合应用对兔VX2肝移植瘤生长及血管生成的影响。方法建立兔VX2肝移植瘤模型,并随机分为对照组、TACE组和抗血管生成组(TACE+恩度),二维超声监测肿瘤的生长情况,HE染色、免疫组化法检测CD31、PCNA的表达,Western bolt检测血管内皮生长因子(vascular endothelial growth factor,VEGF)表达。对微血管密度(microvessel density,MVD)、VEGF与肿瘤体积生长率(volume growth rate,VGR)间进行相关性分析。结果治疗后7、14 d,抗血管生成组肿瘤体积生长率与对照组比较,差异具有统计学意义(P<0.05)。治疗后14 d,抗血管生成组细胞增殖指数(proliferation index,PI)(62.83±7.82)明显低于TACE组(85.36±10.37)和对照组(82.67±11.25)(P<0.05);抗血管生成组MVD值(31.55±6.71)最低,与其余两组相比差异具有统计学意义(P<0.05)。TACE组VEGF的相对表达水平(1.29±0.11)高于抗血管生成组(0.60±0.05)和对照组(0.85±0.06),差异具有统计学意义(P<0.05),抗血管生成组与对照组相比,差异也具有统计学意义(P<0.05)。各组肿瘤VEGF表达与MVD、VGR均呈正相关性(r=0.933,r=0.563,P<0.05)。结论 TACE与恩度联合应用与单纯应用TACE相比可明显抑制兔VX2肝移植瘤的生长及肝癌组织细胞增殖,下调VEGF的表达,抑制肿瘤的血管生成。 相似文献
13.
Luis H. Ramirez Morbize Juliéron Marc Bonnay Serge Koscielny Zhongxin Zhao Alain Gouyette Jean-Nicolas Munck 《Investigational new drugs》1995,13(1):51-53
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. 相似文献
14.
《江苏医药》2012,38(12)
目的 评估超声引导下微波消融联合乙醇注射治疗兔肝VX2瘤的可行性和安全性.方法 30只新西兰大白兔于肝脏上移植VX2瘤,2周后经超声造影确认肿瘤移植成功后,MW组(15只)和MP组(15只)分别接受超声引导下微波消融治疗和微波消融联合无水乙醇注射治疗.治疗结束后1周,将动物处死,取出肝脏观察消融范围.结果 种植VX2瘤后2周,MW组和MP组分别有13只和14只兔子成瘤.两组兔子均耐受治疗,MP组消融范围明显大于MW组(P<0.01).消融后大体标本显示,MP组形态欠规则.HE染色显示,两组病理组织无明显差异.结论 微波消融联合乙醇注射治疗兔肝VX2瘤安全、有效. 相似文献
15.
目的评估超声引导下微波消融联合乙醇注射治疗兔肝VX2瘤的可行性和安全性。方法 30只新西兰大白兔于肝脏上移植VX2瘤,2周后经超声造影确认肿瘤移植成功后,MW组(15只)和MP组(15只)分别接受超声引导下微波消融治疗和微波消融联合无水乙醇注射治疗。治疗结束后1周,将动物处死,取出肝脏观察消融范围。结果种植VX2瘤后2周,MW组和MP组分别有13只和14只兔子成瘤。两组兔子均耐受治疗,MP组消融范围明显大于MW组(P<0.01)。消融后大体标本显示,MP组形态欠规则。HE染色显示,两组病理组织无明显差异。结论微波消融联合乙醇注射治疗兔肝VX2瘤安全、有效。 相似文献
16.
Comparative neurotoxicity of oxaliplatin, cisplatin, and ormaplatin in a Wistar rat model. 总被引:9,自引:0,他引:9
J Holmes J Stanko M Varchenko H Ding V J Madden C R Bagnell S D Wyrick S G Chaney 《Toxicological sciences》1998,46(2):342-351
Oxaliplatin (4 mg/kg), cisplatin (2 mg/kg with 20 mg/kg mannitol) and ormaplatin (2 mg/kg) were administered i.p. twice weekly for 4.5 weeks. Lactose injections (0.9%) were used as a control for oxaliplatin and 0.9% saline injections were used as a control for cisplatin and ormaplatin. Morphometric changes to dorsal root ganglia L4-L6 were quantitated as a measure of neurotoxicity. Drug treatment resulted in a decrease in cell and nuclear area and an increase in the percentage of cells with eccentric nucleoli for neuronal cell bodies in the DRG. Immediately following treatment the order of morphometric changes was ormaplatin > cisplatin > or = oxaliplatin. The accumulation of platinum in the DRG was measured by inductively coupled plasma mass spectrometry. The order of accumulation was cisplatin > oxaliplatin > ormaplatin. Following an 8-week recovery period the order of morphometric changes to the DRG was ormaplatin approximately equal to oxaliplatin > cisplatin. This correlated with a greater retention of platinum by the DRG for ormaplatin and oxaliplatin than for cisplatin. The results suggest that ormaplatin is uniquely neurotoxic immediately following treatment in the Wistar rat model. However, following an 8-week recovery period both ormaplatin and oxaliplatin are more neurotoxic than cisplatin and this neurotoxicity correlates with a greater retention of platinum by the DRG. 相似文献
17.
Heudi O Mercier-Jobard S Cailleux A Allain P 《Biopharmaceutics & drug disposition》1999,20(2):107-116
The activity of platinum compounds is dependent on nucleophile substitution reactions. In this paper, we study the reactivity of L-met with carboplatin, oxaliplatin and cisplatin by following with HPLC-UV the concentration of L-met and by characterizing the resulting adducts with LC-MS. In the absence of NaCl, in water, the initial rate at which L-met concentration decreases with cisplatin, oxaliplatin and carboplatin is 0.25 +/- 0.007, 0.057 +/- 0.01 and 0.17 +/- 0.02 mM h(-1), respectively. In phosphate buffer this rate is 0.056 +/- 0.009 for cisplatin, 0.019 +/- 0.001 and 0.13 +/- 0.02 for carboplatin and oxaliplatin, respectively. Reactions of L-met with cisplatin occurred via its conversion into monoaqua species in water and into phosphato-derivatives (AP) in phosphate buffer but finally the same methionine-platinum adducts M2 [(NH3)2(met)]Pt, M4 and M5 [(met)2]Pt were characterized. Reaction of carboplatin with L-met occurred via the formation of M0 [(NH3)2(met)(CBDCA)]Pt whose structure is consistent with the direct interaction of L-met with carboplatin. However, the same final products as those found with cisplatin were characterized. The reaction of oxaliplatin with L-met proceeded through a mechanism similar to that of carboplatin to give M7 [(met)(DACH)]Pt. In the presence of NaCl, cisplatin directly reacted with L-met to yield at least five methionine-platinum adducts. The reaction of carboplatin gave the same adducts suggesting its transformation into cisplatin. The reaction of oxaliplatin with L-met occurred via the formation of aquated species A [(OH)(Cl)(DACH)]Pt which readily underwent reaction with L-met to form M6 [(met)(Cl)(DACH)]Pt and M7. This study shows that the reactivity of cisplatin, carboplatin and oxaliplatin is dependent on the media in which they occur. The discrepancy between their reactions with L-met could partly explain their therapeutic differences. 相似文献
18.
STUDY OBJECTIVES: To compare the relative bioavailability of enfuvirtide, a human immunodeficiency virus type 1 (HIV-1) fusion inhibitor, injected with the Biojector 2000 (B2000) needle-free device versus a 27-gauge half-inch needle-syringe; and to assess safety, tolerability, and patient preference for the two devices. DESIGN: Open-label, randomized, two-period crossover bioequivalence evaluation. SETTING: Clinical research center. PATIENTS: Twenty-seven adults with HIV-1 viral loads below 1000 copies/ml. INTERVENTION: Each patient received enfuvirtide 90 mg subcutaneously with the B2000 and with the needle-syringe, with a 1-week washout between treatments. MEASUREMENTS AND MAIN RESULTS: Twenty-six and 27 patients were included in the bioequivalence and safety analyses, respectively. Plasma enfuvirtide concentrations were measured at baseline and at several intervals after each injection. The B2000:needle-syringe ratios of maximum concentration (C(max)), area under the concentration-time curve from time zero extrapolated to infinity (AUC(0-infinity)), and AUC from time zero to tau (dosing interval) (AUC(0-tau)) served as criteria for bioequivalence determination. The two drug delivery systems were considered bioequivalent if the 90% confidence intervals (CIs) for the ratios were within 0.8-1.25. Safety and tolerability were evaluated based on documentation of adverse events, graded laboratory toxicities, and local injection-site reactions. Patient surveys provided feedback on device preference. Ratios of C(max), AUC(0-infinity), and AUC(0-tau) were 0.95 (90% CI 0.84-1.09), 0.99 (90% CI 0.93-1.05), and 0.99 (90% CI 0.93-1.05), respectively. The frequency of injection-site reactions was low, and severity was generally mild for both devices. Survey results showed 18 patients (69%) had a positive overall impression of the B2000 and 14 (54%) felt safer injecting with this device. Overall, 17 patients (65%) preferred the B2000 over the needle-syringe. CONCLUSION: Bioavailability of enfuvirtide with the B2000 and needle-syringe was equivalent based on C(max), AUC(0-tau), and AUC(0-infinity). Safety profiles and injection-site reactions were comparable between the devices, but patients preferred the B2000. Delivery of enfuvirtide with the B2000 is a feasible alternative to standard needle administration and warrants further evaluation. 相似文献
19.
Nicholas D. Barber Ullrich K. Hoffmeyer 《The International journal of pharmacy practice》1993,2(1):15-17
Heparin is commonly administered for prophylaxis of thromboembolism in a dose of 5,000iu in 0.2ml subcutaneously twice or three times daily. The presentation may be as a prefilled syringe or as an ampoule. The effect of the presentation on nursing time and the true costs involved has been studied in two London hospitals. Thirty-eight administrations from prefilled syringes and 27 from ampoules were recorded. The mean times to prepare and administer the dose and dispose of the equipment were 67.6 seconds for a prefilled syringe and 128.5 seconds for an ampoule; the mean time saving per dose (95 per cent confidence intervals) was 60.9 (40.8, 80.9) seconds. The total cost per dose using a prefilled syringe was 104p; using an ampoule it was 113p. A generic cost model was created. The use of prefilled syringes saved approximately one minute of time and 9p (8 per cent) in cost per administration. 相似文献