重组人生长激素联合5-Fu对人直肠癌小鼠移植瘤生长的影响

[目的]研究重组人生长激素（RHGH）及其联合氟尿嘧啶（5-Fu）对人直肠癌移植瘤生长的影响。[方法]雄性BALB/c小鼠45只建立CTX免疫抑制模型,行人直肠癌小鼠肾被膜下移植术（SRCA）,随机分成5组：对照组、RHGH1组、RHGH2组、联合组（RHGH1＋5-Fu组）及化疗组（5-Fu组）,连续用药7d。各组小鼠随机留3只待其自然死亡,观察其生存期,余6只小鼠术后10d处死,观察小鼠移植瘤末初体积差（△TS）、抑瘤率（IR）、组织学变化（HE染色）及PCNA、cyclinD1和p16蛋白表达的变化。[结果]对照组与RHGH两亚组、联合组与化疗组间移植瘤△TS和IR比较差异均无统计学意义（P〉0.05）,联合组、化疗组与其他各组比较均有显著性差异（P〈0.01）。对照组和RHGH两亚组的组织病理形态相似,差异不大;联合组和化疗组表现为实质细胞减少,间质增多。对照组与RHGH两亚组、联合租与化疗组间PCNA、cy-clinD1及p16蛋白表达无显著性差异（P〉0.05）。联合组及化疗组表达率与其他各组比较均有显著性差异（P〈0.05）。[结论]RHGH对人直肠癌小鼠肾包膜下移植瘤生长无明显促进作用,且RHGH和5-Fu联用对5-Fu的抑瘤作用无明显影响。     

羟基喜树碱对三种人体异种移植肿瘤的抑制作用

本文利用小鼠肾被膜下接种法(SRC)研究羟基喜树碱对3种人体异种移植肿瘤的抑制作用。结果表明,羟基喜树碱(2.5mg/kg/d,ip×5)对人体肺鳞癌和肝癌有明显的抑制作用,分别为37.3％和44.3％,P<0.01。但对人肺腺癌的作用不明显(28.6％,P>0.05)。病理组织学研究显示羟基喜树碱对肿瘤组织有明显的破坏作用。     

肿瘤化疗药物敏感性测定与肾包膜下移植法

肿瘤化疗药敏检测越来越受到人们的重视。体外法药敏测定种类繁多 ,但目前尚无能真正显示其临床实用性的方法。体内法肾包膜下移植肿瘤药敏试验 ,可模拟体内用药环境 ,已显示出其独特的优势和特点     

化疗药物在测敏实验中促进肿瘤生长的作用

对已做SRC实验中所见某些抗癌药物具有促进肿瘤生长作用的材料进行了观察分析。共做SRC药敏测定实验50例,其中3例因标本质量差为不可评价,47例属可评价范围,共有明显抗药性的药物16药次,其中一次MMC给药组肿瘤末体积明显大于对照组,P值<0.05,具有促进该肿瘤生长的作用。有此作用的MMC在全部该药测定中占5％。抗癌药物同时也具有引起肿瘤作用的情况早有报告。国外一些学者对广谱抗肿瘤药阿霉素进行研究,发现它能引起实验大鼠发生癌瘤。我们也曾用阿霉素做了类似实验,结果表明阿霉素在中国的实验大鼠身上也能引起肿瘤发生。以上都是实验动物所得结果,而药物对人类肿瘤是否具有类似作用虽有怀疑,但一直缺少深入研究。近来有人在用SRC(肾包膜下移植)法对人体肿瘤进行化疗药物敏感性预测工作中发现,某些化疗药物具有促进人类肿瘤生长的作用。     

肾包膜下接种法预测人体肿瘤化疗敏感性的可行性探讨

本文从病理组织学和临床治疗两万面探讨SRCA作为抗癌药物敏感试验可行性.96例病理组织学研究表明,4至5天SRCA移值物重量的增加与宿主细胞浸润无明显相关性,但移植物中瘤细胞保存仍不太理想,未观察到明显分裂增殖现象,约45%的病例可观察到药物作用反应.42例中晚期病人临床观察,治疗反应(CR PR)有效率为78%.作者认为,移值后在药物作用基础上产生的不同程度水肿可能是导致移植物大小改变的重要因素之一.4天SRCA作为一种选择抗癌药物的预测方法,具有一定的客观实用性.     

Evaluation of Mizoribine as an Immunosuppressant in Subrenal Capsule Assay Using Immunocompetent Mice

We studied the application of mizoribine (MZR) to normal immunocompetent mice in subrenal capsule assay (SRCA) by means of tumor growth curve determination, histological analysis and autoradiography. At 400 mg/kg, MZR prolonged the actual tumor growth and moderately reduced the host reaction. Doses below 200 mg/kg did not effectively suppress the host reaction. The maximal weight loss of mice in the 400 mg/kg group reached 29%, but did not exceed 10% within 8 days. Hence, we applied 400 mg/kg of MZR to SRCA for up to eight days for cancer chemotherapy testing. This dose of MZR did not affect the labeling index of tumor cells compared with the control.     

肿瘤体内药物敏感性测定与肾包膜下移植法

肿瘤对各种化疗药物的敏感性存在明显的个体差异。抗肿瘤药药敏检测越来越受到人们的重视，体内肾包膜下移植肿瘤药敏实验虽存在一些问题，但它可以模拟体内用药环境，与临床相关性好，是目前较敏感的体内药敏检测法。     

肾包膜下移植瘤模型应用于肿瘤新生血管生成的研究

[目的]观察胃癌肾包膜下移植瘤模型是否适用于血管生成方面的研究.[方法]建立昆明种小鼠癌细胞接种的肾包膜下移植瘤模型后饲养6天,处死.PAS染色证实肿瘤细胞存活,通过HE染色及免疫组化法观察种植肿瘤区域有无血管生成.[结果]实验动物全部存活,PAS染色表明模型建立成功,肿瘤种植区域无血管生成.[结论]使用癌细胞接种的肾包膜下移植瘤模型较适用于研究癌细胞的分化与凋亡,不适于新生血管生成的研究.     

Migration Pathways of Human Glioblastoma Cells Xenografted into the Immunosuppressed Rat Brain

Diffuse invasion of the brain by tumor cells is a hallmark of human glioblastomas and a major cause for the poor prognosis of these tumors. This phenomenon is only partially reproduced by rodent models of gliomas that display a very high rate of proliferation and limited cell migration. We have analyzed the development of human glioblastoma cells (GL15) xenografted into the brain of immunosuppressed rats, in order to define the characteristics of tumor cell invasion. As identified by the specific immunolabeling of the tumor cells for the human HLA-ABC antigen, GL15 tumors reproduced the three types of intraparenchymal invasion observed in patients. First, a majority of multipolar tumor cells intermingled rapidly and profusely with host neural cells in the margin of the injection site. This progressively enlarging area was principally responsible for the tumor growth over time. Second, in the gray matter, columns of thin bipolar tumor cells aligned along capillary walls. Third, in the white matter, elongated bipolar isolated tumor cells were observed scattered between axonal fibers. The maximum migration distances along white matter fibers remained significantly higher than the maximum migration distances along blood vessels, up to two months after injection. Development of the tumor was associated with a significant increase of vascularization in the area of tumor spread. Xenografting of human GL15 glioblastoma cells into the immunosuppressed rat brain allowed to differentiate between the three classical types of invasion identified in the clinic, to quantify precisely the distances of migration, and to evaluate cell morphology for each of these routes. The present results support the existence of host/tumor cells interactions with specific characteristics for each type of invasion.     

More Reasonable Animal Model for Study the Effect of Pneumoperitoneum on Abdominal Tumor Cells

Background: Many animal experimental studies showed that abdominal tumor cells will be widely spread during laparoscopic treatment and grow into metastases. These results are different from clinical observations. There is a hypothesis that too much tumor cells was injected in the animals lead to the results of theses bias. We aim to learn the difference of abdominal cavity volume between human body and the nude mice and to determine reasonable amount of tumor cells in the animal experiments. Methods: The insufflated CO2 volume which represents the capacity of the abdominal cavity was recorded during laparoscopic process in 212 patients and 20 nude mice respectively, the relative volume of nude mice and human body was calculated.Based on data from the literature and this study , the amount of tumor cells in the animal experiments was determined.According to these data, we set up a new animal model and a traditional one respectively,and compared the rate of successful modeling and tumor formation between two animal models. Results: The intraperitoneal volumes of humans and nude mice were 3.01±0.36 L and 0.011±0.001 L respectively.The number of tumor cells that be uesd in animal should be approximately 0.26×105 in terms of known data in human beings.Compared with the traditional animal model which formed a large number of intraperitoneal tumor metastasis, the new animal model was shows more moderately,and the rate of successful modeling was similar. Conclusion:In animal experiments, to simulate the clinical situation, about 0.26×105 tumor cells should be inject in peritoneal cavity of the nude mice.     

抗肿瘤药物敏感试验的实验研究：组织细胞学因素分析

本文从组织细胞学角度,就影响SRCA移植实验的可变因素进行了分析讨论。结果表明:以SRCA作为抗肿瘤药物敏感试验,对于肿瘤类型、取材部位的选择性不强,具有适应范围较广的特点。但对于肿瘤组织细胞本身的质量要求较高,是实验中的重要质量控制因素之一。此外,肿瘤细胞分化的高低与移植成功率也有密切关系,在分析无可评价性实验结果的影响因素时应将其考虑在内。而移植前快速、准确的印片细胞学诊断对控制上述因素的影响有所裨益。     

人ACHN肾癌裸鼠荷瘤模型建立及相关特性研究

[目的]探讨建立肾癌ACHN细胞系裸鼠皮下移植瘤及转移瘤模型的适宜条件。[方法]MTT法观察细胞生长情况。将裸鼠分组，分别用2、0×10^6／100μl（A组）、3．0×10^6／100μl（B组）和4．0×10^6／100μl（C组）的细胞接种浓度．注入裸鼠后项中间皮下：用4．0×10^6／100μl的细胞接种浓度，分别接种于裸鼠后项中间（C组）、背部（D组）和前肢腋窝皮下（E组）；分别用第20代（F组），第30代（G组）和第10代（C组）的肿瘤细胞4．0×10^6／100μl，注入裸鼠后项中间，观察各组成瘤情况。尾静脉注射瘤细胞1.0×10^6／ml建立转移模型。[结果]第4天细胞进入对数生长期。A组成瘤率为33.3％、B组和C组的成瘤率均为100％，但C组的成瘤速度明显高于B组：C组、D组和E组的成瘤率均为100％，注射肿瘤细胞后第10天，C组、D组和E组的肿瘤生长平均相对体积，各组间尚无明显差异；注射后第30天，C组的肿瘤生长平均相对体积显著高于D组和E组（P〈0．05）；G组的成瘤率为83.3％，F组的成瘤率为100％，与C组相比，无显著性差异（P〉0．05）。尾静脉注射组全部出现转移灶。[结论]使用ACHN细胞株，控制好浓度、接种部位以及传代次数后能获得较理想的裸鼠肾癌皮下移植瘤模型：使用传统尾静脉注射法可以建立裸鼠转移模型。