异种抗原对荷S180肉瘤小鼠肿瘤内T淋巴细胞亚群的影响

目的:评价对于小鼠为异种抗原的人A型红细胞膜免疫后序贯瘤内注射对荷S180肉瘤小鼠肿瘤生长的抑制作用及时肿瘤内T淋巴细胞亚群的影响.方法:24只荷S180肉瘤小鼠分为实验组、抗原对照组、免疫对照组及空白对照组.实验组荷瘤小鼠成瘤前应用A型人红细胞膜悬液腹腔免疫,成瘤后瘤内注射5 mg/mL A型人红细胞膜,连续注射5 d.抗原对照组,不预先免疫,瘤内注射A型人红细胞膜.免疫对照组,成瘤前预先免疫,瘤内注射生理盐水,连续注射5 d.空白对照组,不预先免疫,瘤内注射生理盐水.注射第14天处死小鼠,测量瘤重,检测肿瘤内浸润Th、CTL、Treg细胞亚群数量及IL-2的含量.结果:实验组小鼠肿瘤平均重量低于免疫对照组及空白对照组(P<0.05,P<0.01).实验组肿瘤内IL-2含量高于空白对照组(P<0.01).实验组Th细胞的比例高于其他3组(P<0.01).实验组CTL细胞比例高于免疫对照组及空白对照组(P<0.01).而Treg细胞的比例低于免疫对照组及空白对照组(P<0.01).结论:人A型红细胞膜免疫后序贯瘤内注射可抑制荷S180肉瘤小鼠肿瘤生长,并使肿瘤内部Treg细胞数量降低,Th细胞及CTL细胞数量增多,IL-2含量增加.     

中药复方I号对荷瘤鼠肿瘤生长抑制作用的实验研究

目的 研究中药复方I号对移植性肿瘤的抑制作用。方法 运用人工形成的肿瘤模型，观察中药复方I号单用、联用其它化疗药物后的抗癌效果及其相互作用。结果 中药复方I号7．5、15、30g／kg灌胃给药，对S180、H22荷瘤小鼠和大鼠W256肉瘤有抑制作用，瘤重抑制率分别达26％～47％、18％～47％、13％～43％。对大剂量环磷酰胺引起白细胞减少的毒副作用有对抗效果，用药后能使外周血白细胞和骨髓有核细胞显著回升。此外、中药复方I号与环磷酰胺、顺铂等化疗药配伍用于小鼠移植性肿瘤的试验性治疗，有增效、减毒的功效。结论 中药复方I号能抑制多种肿瘤细胞的生长，与环磷酰胺、顺铂等化疗药配伍有协同作用。     

TIL细胞联合IL-2瘤内注射对荷瘤小鼠作用的观察

目的用TILIL－2对荷瘤小鼠进行瘤体内注射，使肿瘤生长受到抑制。方法将荷瘤小鼠分为两组，腹腔注射组和瘤内注射组，每鼠给药量TIL0.5×107＋IL－2500U／次，每隔3～4天注射一次，共6次。测量肿瘤大小，病理切片进行分析。结果瘤内注射者肿瘤生长明显受到抑制，在病理切片中可见肿瘤周围组织中有大量淋巴细胞浸润而全身给药者治疗结果不及前者。结论瘤体内给药提高了肿瘤局部的免疫力，同时可以合理的安排杀伤细胞到达肿瘤部位的有效浓度，从而抑制了肿瘤细胞的增殖，也避免了全身用药所产生的毒副作用，是一种很有潜力的治疗手段。     

中药复方Ⅰ号对荷瘤鼠肿瘤生长抑制作用的实验研究

目的　研究中药复方Ⅰ号对移植性肿瘤的抑制作用。方法　运用人工形成的肿瘤模型 ,观察中药复方Ⅰ号单用、联用其它化疗药物后的抗癌效果及其相互作用。结果　中药复方Ⅰ号 7 5、15、3 0g/kg灌胃给药 ,对S1 80 、H2 2 荷瘤小鼠和大鼠W2 56 肉瘤有抑制作用 ,瘤重抑制率分别达 2 6%～ 47%、18%～ 47%、13 %～ 43 %。对大剂量环磷酰胺引起白细胞减少的毒副作用有对抗效果 ,用药后能使外周血白细胞和骨髓有核细胞显著回升。此外 ,中药复方Ⅰ号与环磷酰胺、顺铂等化疗药配伍用于小鼠移植性肿瘤的试验性治疗 ,有增效、减毒的功效。结论　中药复方Ⅰ号能抑制多种肿瘤细胞的生长 ,与环磷酰胺、顺铂等化疗药配伍有协同作用     

苦参碱对S180肉瘤小鼠肿瘤血管形成抑制作用的研究

目的：探讨苦参碱抗肿瘤的作用机制。方法：40只Balb／c小鼠接种S180肉瘤细胞后，随机分成4组，即单纯肿瘤组（对照组），苦参碱组，环磷酰胺组．苦参碱组＋环磷酰胺组，连续10日施加处理因素，停药后次日断颈处死小鼠。采用计算抑瘤率；光镜下观察瘤体内血管数目的影响；免疫组化法检测瘤体内微血管密度（MVD）、血管内皮生长因子（VEGF）表达。结果：苦参碱具有明显的抑制S180肉瘤小鼠作用．其抑瘤率为34．7%；免疫组化显示瘤体内微血管密度、血管内皮生长因子（VEGF）阳性表达均明显低干对照组（p〈0.05）；血管内皮生长因子表达与微血管密度呈正相关。结论：苦参碱对S180肉瘤小鼠有一定的抑制作用，对S180内瘤小鼠血管形成有明显的抑制作用，降低VEGF表达可能是其抑制肿瘤血管形成的主要机制之一。     

氢氧化钠溶液肿瘤瘤内注射的实验研究

目的 研究氢氧化钠溶液瘤内注射溶液组织特点，初步探讨其作用为瘤内用药的可行性。方法 Ｗｉｓｔａｒ大鼠８只，腋下种植Ｗａｒｋｅｒ－２５６癌肉瘤。大鼠分２组，直视下瘤内分别注射我水忆醇或氢氧化钠溶液。无水乙醇剂量：０．１－０．３ｍｌ，１０％氢氧化钠溶液剂量：０．１ｍｌ。治疗后饲养３天，取肿瘤、肝脏、肾脏标本行病理检查。家兔５只，在清醒或麻醉情况下，先后行氢氧化钠小剂量（１０％０．０３ｍｌ）皮下注射、静     

甘草黄酮对S180、H22荷瘤小鼠红细胞膜和肿瘤细胞膜Na^＋，K^＋-ATPase及Ca^2＋，Mg^2＋-ATPase活性的影响

目的观察甘草黄酮对S180、H22荷瘤小鼠红细胞膜和肿瘤细胞膜Na^ ，K^ -ATPse及Ca^2 ，Mg^2 -ATPase活性的影响。方法荷瘤小鼠分为治疗组(高剂量、中剂量、低剂量)和对照组(生理盐水组、环磷酰胺组)，分别测定各组红细胞膜和肿瘤细胞膜的Na^ ，K^ -ATPase及Ca^2 ，Mg^2 -ATPase活性。结果甘草黄酮可明显恢复红细胞膜Na^ ，K^ -ATPase及Ca^2 ，Mg^2 -ATPase活性；对肿瘤细胞膜上活性异常升高的Na^ ，K^ -ATPase及Ca^2 ，Mg^2 -ATPase有显著的抑制作用。结论甘草黄酮调节红细胞膜和肿瘤细胞膜Na^ ，K^ -ATPase及Ca^2 ，Mg^2 -ATPase活性功能可能是其抗肿瘤作用机理之一。     

珍珠梅提取物对小鼠S180肉瘤的抑制作用

目的：探讨珍珠梅乙酸乙酯提取物的抗肿瘤作用。方法：按照标准方法给36只小鼠接种S180肉瘤后，随机分成3组：Ⅰ实验1组：每天灌胃珍珠梅提取物16．7g／Kg；Ⅱ实验2“组：每天灌胃珍珠梅提取物8．4g／Kg。Ⅲ对照组：每天灌胃生理盐水10ml／Kg，连续10d，观察瘤重及体重。结果:16．7g／Kg、8．4g／Kg珍珠梅乙酸乙酯提取物对S180肉瘤抑制率分别为46％、57％，实验组与对照组体重变化无显著差异。结论：珍珠梅乙酸乙酵提取物对小鼠S180肉瘤有抑制作用。     

丝裂霉素与无水乙醇瘤灶内注射治疗肿瘤效果比较

比较丝裂霉素与无水乙醇瘤灶内注射的抗肿瘤效果。方法：２４只荷Ｗ２５６肿瘤大鼠随机分为三组，分别肿瘤内注射丝裂霉素，无水乙醇和等渗盐水，观察大鼠体重，肿瘤体积、行为状态、生存主肿瘤组织学变化。结果：丝裂霉素组肿瘤控制优于其它两组，但毒性亦较明显；无水乙醇组肿瘤控制优于     

Antitumor effects in mice of the intravenous injection of attenuated Salmonella typhimurium

Salmonella typhimurium genetically modified at the purI and msbB genes to increase dependence on adenine and decrease stimulation of tumor necrosis factor-alpha production were injected intravenously into C57BL/6 mice bearing subcutaneous tumor or lung metastases. Decreased tumor growth and prolonged survival were seen in some, but not all of nine transplantable tumors. Salmonella increased in number in the tumor and reached levels 10,000 times higher than in the normal liver reservoir of these bacteria. Histologic studies revealed Salmonella growth in areas of the tumor although, in all cases, a viable rim of tumor survived and ultimately resulted in progressive tumor growth in all mice. These studies demonstrate that Salmonella can localize to transplantable murine tumors and partially inhibit tumor growth; however, additional modifications of the bacteria may be necessary if this approach is to develop into an effective treatment for patients with cancer.     

Antitumor effect of a splenic injection of 5-fluorouracil on metastatic liver cancer in mice

The regional administration of 5-fluorouracil (5-FU) has been the fundamental therapy against liver metastases for the improvement of patient prognosis; however, there have been few reports about the immunological effects of this agent. It is also unknown whether it affects the spleen, one of the major lymphoid organs. The objective of the present study was to determine the immunological effect of an intrasplenic injection of 5-FU against liver metastases. We investigated the effect of an intrasplenic injection of 5-FU on the formation of experimental liver metastasis resulting from an intraportal vein injection of colon 26 carcinoma cells in BALB/c mice and elucidated some of the underlying mechanisms involving the effects of this on cellular immunity. Liver metastases were significantly diminished by the splenic injection of 5-FU, particularly in comparison with the portal injection or systemic administration. This was followed by augmentation of the interleukin-12 (IL-12) level in the spleen and activation of hepatic mononuclear cells. In those cells, NK1.1+ (NKT) cells played a central role against metastases. A splenic injection of 5-FU is more effective on the involution of liver metastases than portal or systemic injection. This effect may be attributed to the augmentation of the IL-12 level in the spleen and of NKT cells in the liver rather than to the original effect of 5-FU, which is the so-called inhibition of DNA synthesis.     

Systemic dissemination of viral vectors during intratumoral injection

Intratumoral injection is a routine method for local viral gene delivery that may improve interstitial transport of viral vectors in tumor tissues and reduce systemic toxicity. However, the concentration of transgene products in normal organs, such as in the liver, may still exceed normal tissue tolerance if the products are highly toxic. The elevated concentration in normal tissues is likely to be caused by the dissemination of viral vectors from the tumor. Therefore, we investigated transgene expression in the liver, the serum, and a mouse mammary carcinoma (4T1) in mice after intratumoral injection of adenoviral vectors for mouse interleukin-12, luciferase, enhanced green fluorescence protein, or beta-galactosidase. We also performed numerical simulations of virus transport in tumors after intratumoral injection, based on the Krogh cylinder model. Our experimental data and numerical simulations demonstrated that virus dissemination was significant in mice and it occurred mainly during the intratumoral injection. To reduce virus dissemination, we mixed these vectors with a viscous alginate solution and injected the mixture into the tumors. Our data showed that the alginate solution could significantly reduce virus dissemination while having minimal effects on transgene expression in tumors and on interleukin-12-induced tumor growth delay. These data suggest that virus dissemination is a potential problem in local viral gene therapy of cancer and that the dissemination could be significantly reduced by the alginate solution without compromising the efficacy of gene therapy.     

复方中药99-克星超声介入治疗肝癌裸鼠移植瘤免疫研究

目的探讨超声引导瘤内注射复方中药99-克星治疗肝癌SMMC-7721裸鼠移植瘤的免疫作用.方法取人肝癌SMMC-7721裸鼠皮下移植模型28只,随机分为99-克星中药治疗组14只,无水乙醇治疗组7只,生理盐水组7只.全部裸鼠在接种10 d后每隔5 d向肿瘤内注入治疗药物,共4次,治疗20d后处死.应用流式细胞仪(FCM)进行T细胞亚群分析以及电镜观察肿瘤组织的超微结构变化.结果电镜发现克星组以肿瘤肿胀变性坏死为主,并且伴有淋巴细胞明显攻击癌细胞现象(8/14);流式细胞仪(FCM)进行T细胞亚群分析结果显示克星组的CD 3/CD 122双阳性细胞在肿瘤组织、脾脏组织、外周血内含量均明显高于乙醇组和盐水组.结论复方中药99-克星能够促进机体局部组织炎症反应和淋巴细胞活跃,显著刺激裸鼠体内CD 3/CD 122双阳性细胞T细胞胸腺外分化,研究结果表明复方中药99-克星具有强大的破坏与抑制肿瘤细胞生长的作用,复方中药99-克星抗肿瘤的作用机制明显不同于无水乙醇,尤其以激发或诱导机体细胞免疫的作用机制在抗肿瘤中具有重要的意义.本研究为传统中药治疗肝癌提供了一个新的给药途径与理论依据,其在肿瘤治疗研究中具有重要的意义和良好的发展前景.     

Antitumor activity of recombinant interleukin 6 in mice

IL-6 possesses multiple biologic activities that affect a broad range of cells including those directly involved in immune responses as well as cells important in the systemic response to infection or trauma. We now show that purified human rIL-6, when administered alone at relatively high doses that are comparable to therapeutic levels of IL-2, mediated substantial reductions in the number of pulmonary and hepatic micrometastases from four distinct syngeneic tumors. Unlike IL-2, IL-6 injections resulted in neither observable toxicity nor death of the treated mice at the dose regimens used. Host immunosuppression by sublethal total-body irradiation before the initiation of therapy prevented the IL-6 antitumor effect, thus suggesting that IL-6 acted through a radiosensitive host component rather than directly on the tumor itself. Moreover, the systemic administration of relatively low doses of IL-6 in combination with subtherapeutic doses of TNF to mice bearing an established weakly immunogenic, syngeneic tumor at a subcutaneous site resulted in marked tumor regression and cure rates. These studies represent the first demonstration of tumor regression mediated by recombinant IL-6 in vivo.     

蓖麻毒素温敏型凝胶经皮瘤内注射治疗移植肝癌的实验研究

目的 探讨蓖麻毒素温敏型凝胶经皮瘤内注射治疗实验性肝癌的有效性和可行性.方法 建立裸鼠皮下移植肝癌模型32只,随机分成4组,分别经皮瘤内注射生理盐水、空白凝胶、游离蓖麻毒素和蓖麻毒素温敏型凝胶,每周超声测量肿瘤体积,第7、14 d每组处死裸鼠1只行肿瘤组织病理检查,余裸鼠记录生存时间.结果 游离蓖麻毒素组治疗后7、14、21 d肿瘤体积均小于生理盐水对照组(P<0.01),生命延长率为36.8%;蓖麻毒素温敏型凝胶组治疗后第5 d肝癌组织明显坏死,第3周肿瘤消退,病理检查见肿瘤组织大片坏死,伴大量炎性细胞浸润,裸鼠在生存时间的最终观察点均未见死亡.结论 蓖麻毒素温敏型凝胶瘤内注射可彻底消融灭活肝癌,安全高效且操作简便.     

经皮经肝穿刺肝癌瘤内注射治疗研究进展

原发性肝癌主要是指肝细胞性肝癌(HCC), 我国每年约有13万人死于肝癌,占我国癌症死亡病因排位的第2位.据估计我国的原发性肝癌的发病人数约占全世界肝癌总数的55%, 且有上升趋势.     

Antitumor efficacy of a urokinase activation-dependent anthrax toxin

Previously, we have generated a potent prodrug consisting of modified anthrax toxins that is activated by urokinase plasminogen activator (uPA). The cytotoxicity of the drug, PrAg-U2 + FP59, is dependent on the presence of receptor-associated uPA activity. Local intradermal administration of PrAg-U2 + FP59 adjacent to the tumor nodules in mice with transplanted solid tumors had a potent antitumor effect. In succession of these experiments, we have now investigated the systemic antitumor efficacy of PrAg-U2 + FP59. C57Bl/6J mice bearing syngenic tumors derived from B16 melanoma, T241 fibrosarcoma, or Lewis lung carcinoma cells were treated with different mass ratios and doses of PrAg-U2 + FP59. Tumor volumes were recorded daily by caliper measurements. In some experiments, dexamethasone was coadministered. Our data show a significant antitumor effect of systemic administration of PrAg-U2 + FP59 in three syngenic tumor models. Optimal antitumor effect and low toxicity was obtained with a 25:1 mass ratio between the two components (PrAg-U2 and FP59). The experiments show that PrAg-U2 + FP59 displays a clear dose-response relationship with regard to both antitumor efficacy and systemic toxicity. Dose-limiting toxicity seemed to be due to activation of the prodrug by uPA and its receptor in the intestinal mucosa. Concurrent treatment with dexamethasone was found to prevent dose-limiting toxicity. Taken together, these data indicate that uPA-activated toxins may be promising candidates for targeted therapy of human cancers that overexpress uPA and its receptor.     

超声介入瘤内注射治疗肝癌的研究进展

超声介入瘤内注射治疗以其经济、操作简便、可重复、只需普通超声设备等优点在临床肝癌治疗中得到广泛应用,已成为提高患者生存质量、延长其生存期的重要手段,本文综述几种常用瘤内注射方法的治疗机制、疗效、局限性及发展前景。