几种镍剂对小鼠致癌作用的实验研究

应用某镍冶炼厂作业环境中存在的几种镍剂,给三种小鼠右腋皮下注射,每鼠5mg,观察62周。仅见镍精砂(主要含Ni_3S_2)有局部诱癌作用。其病理组织学表现以纤维肉瘤为主,亦见2例横纹肌肉瘤,大多数肿瘤分化差,有浸润性,个别发生肝、肺转移。此结果提示该厂环境中存在的镍精砂可能对人类也具有致癌危险性,在考虑劳保措施和职业癌的防治中应引起足够重视。     

三种镍化合物诱发转化细胞恶性度的鉴别与分析

目的 :利用已建立的三种镍化合物体外转化细胞进行裸鼠体内成瘤实验研究 ,比较它们恶性度的差异。方法 :三种镍化合物转化细胞接种BALB/C裸鼠 ,进行肿瘤细胞和转化细胞的透射电镜及扫描电镜观察。结果 :硫化镍 ,氯化镍 ,硫酸镍分别诱发的转化细胞都能在BALB/C裸鼠皮下形成肿瘤 ,病理组织学检查确定为纤维肉瘤。经扫描电镜与透射电镜观察瘤细胞形态与转化细胞有一定差别。结论 :本文进一步说明了三种镍化合物所诱发的细胞转化为恶性转化 ,且都具有体内致瘤性。     

气功外气对人鼻咽癌细胞株裸鼠成瘤的双盲试验

本项研究应用细胞培养技术,以裸鼠为实验动物,按双盲法进行了两次实验:由气功师发放外气作用于人鼻咽低分化鳞癌细胞株(CNE-2),然后将受功组和非受功组(对照组)细胞分别接种于16只雌性裸鼠(NC-Z裸小鼠),结果显示受功组成瘤受到明显抑制,两次实验抑制率为100％(3/3)、100％(4/4),两次实验组织检查证实受功组裸鼠接种癌细胞部位的组织均未见癌,肝、肺组织也未见癌细胞,非受功组裸鼠瘤组织均为低分化鳞癌,除第1次实验的2号鼠见肺转移癌外,其余各裸鼠肝、肺均未见癌细胞。本项研究提示有进一步研究气功外气抑瘤及其机理的必要性和可能性。     

蜂胶对小鼠移植肿瘤的抑制作用

目的　探讨蜂胶对移植小鼠肿瘤的抑制作用 ,寻找最佳抑瘤搭配。方法　采用有重复的正交试验设计 ,根据正交表L16 ( 4 2 × 2 9)安排试验因素 ,并进行试验 ,取得试验指标数据 ,分析不同的蜂胶浓度在不同的饲喂时间对不同肿瘤的抑制作用。结果　蜂胶浓度 (A)、饲喂时间 (B)、对不同肿瘤细胞株 (D)的抑瘤作用差异有显著性 (P <0 .0 1或P <0 .0 5) ,性别间 (C)差异无显著性 (P >0 .0 5) ,各显著性试验因素各水平的最优搭配为A4 B3D2 。结论　一定浓度的蜂胶饲喂一段时间后对移植的小鼠肿瘤有显著的抑制作用     

Effect of Allicin in Antagonizing Mice's Bladder Cancerin vitro and in vivo

Objective: To explore anti-tumor effect and mechanism of Allicin in treating murine bladder tumor. Methods: To observe Allicin's effect on MBT-2 tumor cells in vitro, 100 μg/ml Allicin was added to the tumor cell culture, and the morphology of tumor cells was observed by phase contrast microscope 6 hrs later. The direct effects of Allicin on tumor cell growth in vitro in the MTT Assay was also evaluated. To determine anti-tumor effect of Allicin in vivo, C3H/He mice were randomly grouped prior to initiation of experiment. The mice received 1×105 MBT-2 cells administered subcutaneously into the right posterior flank on the Day 0 the experiment started. Allicin was injected at the site near tumor transplantation on the Day 1. The mice were examined for tumor development and the tumors were measured in two dimensions with calipers twice a week. On Day 21 the tumors were resected and examined pathologically to see the immune response. Results: The observation of morphology of MBT-2 cells in vitro and MTT a     

蜂胶对小鼠移植肿瘤的抑制作用

目的　探讨蜂胶对移植小鼠肿瘤的抑制作用 ,寻找最佳抑瘤搭配。方法　采用有重复的正交试验设计 ,根据正交表 L16( 4 2× 2 9)安排试验因素 ,并进行试验 ,取得试验指标数据 ,分析不同的蜂胶浓度在不同的饲喂时间对不同肿瘤的抑制作用。结果　蜂胶浓度 ( A)、饲喂时间 ( B)、对不同肿瘤细胞株 ( D)的抑瘤作用差异有显著性 ( P <0 .0 1或 P <0 .0 5 ) ,性别间 ( C)差异无显著性 ( P >0 .0 5 ) ,各显著性试验因素各水平的最优搭配为 A4 B3D2 。结论　一定浓度的蜂胶饲喂一段时间后对移植的小鼠肿瘤有显著的抑制作用。     

苦参总黄酮体内外抗肿瘤作用实验研究

目的：考察苦参总黄酮（kushenflavonoids，KS—Fs）的体内外抗肿瘤作用。方法：采用甲基噻唑基四唑（methylthiazolyltetrazolium，MTT）比色法检测KS—Fs对多种肿瘤细胞株的生长抑制作用；构建S180肉瘤、H22肝癌和Lewis肺癌小鼠肿瘤模型和人非小细胞肺癌H460、食管癌Eca-109裸小鼠移植肿瘤模型，研究KS—Fs体内抗肿瘤作用；急性毒性试验考察KS—Fs的毒副作用。结果：KS—Fs和苦参酮（kurarinone，Kur）在体外有比苦参总碱（kushenalkaloids。KS—As）更强的细胞毒作用（半数抑制率：KSFs4．9～29．4〉g／ml，Kur2．0～13．1〉g／ml，KSAs〉200／lg／m1）。体内研究表明KSFs和Kur不仅能有效抑制小鼠H22肝癌、S180肉瘤、Lewis肺癌（瘤质量抑瘤率60％～80％），而且能显著抑制人非小细胞肺癌H460和人食管癌Eca109裸小鼠移植肿瘤的生长（瘤质量抑瘤率在41％～47％）。小鼠口服和静脉注射KS—Fs的最大耐受剂量分别大于2．8g／kg和750mg／kg，远远超过苦参碱（口服半数致死量为1．18g／kg），且无明显毒副作用。结论：研究表明KSFs或Kur是新颖的高效低毒的抗肿瘤候选药物。     

No inhibitory effects of (-)-epigallocatechin gallate and lycopene on spontaneous hepatotumorigenesis in C3H/HeN mice

Although several studies have indicated that (-)-epigallocatechin gallate (EGCG) and lycopene, representative dietary antioxidants, inhibit chemically induced animal tumorigenesis, only a few studies have examined the inhibitory effects of these compounds on spontaneous liver tumorigenesis in rodents. In this study, we investigated the inhibitory effects of these compounds on the formation of spontaneous liver tumors in C3H/HeN mice. We used xeroderma pigmentosum group A (XPA) gene-deficient mice to simultaneously examine whether the knockout mice could be used as a sensitive animal model. Inaddition, we examined the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG)--a marker of reactive oxygen species-induced DNA injury--in liver tissue. Male XPA +/+, XPA +/-, and XPA -/- mice with a C3H/HeN genetic background were divided into 3 groups: control, EGCG, and lycopene. Autopsy at 18 months of age revealed that EGCG and lycopene did not exhibit obvious suppressive effects on the development of liver tumors in any XPA genotype; further, the XPA genotype did not influence any susceptibility to liver tumors. With regard to 8-OHdG levels in non-tumorous liver tissue at 8 months of age, EGCG showed no significant inhibitory effects and lycopene showed significant inhibitory effects only in XPA +/- mice. The present study demonstrates that contrary to previous reports of the inhibitory effects of EGCG and lycopene on the development of various carcinogen-induced animal tumors, these compounds exert no chemopreventive effects on spontaneous liver tumorigenesis in C3H/HeN mice. EGCG and lycopene may inhibit carcinogen-induced tumors through properties other than their antioxidant abilities.     

CONSTRUCTION OF HU-PBL／SCID CHIMERAS AND DEVELOPMENT OF EBV-RELATED LYMPHOMAS

Objective To construct hu-PBL/SCID chimeras and to investigate the development of lymphoma and oncogenicity of the Epstein-Barr virus (EBV). Methods Human peripheral blood lymphocytes (PBLs) were isolated from healthy adult donors and transplanted intraperitoneally into severe combined immunodeficient (SCID) mice. Mice with hu-PBL engraftment from healthy EBV seronegative donors were injected intraperitoneally with EBV-containing supematant from suspension culture of B95-8 cell line (active infection), whereas mice receiving lymphocytes from healthy EBV seropositive donors were not re-infected with B95-8 derived EBV (latent infection). Pathological examination and molecular analysis were performed on experimental animals and induced neoplasms. Results In the early stage of this experiment, 12 mice died of acute graft-versus-host disease, mortality was 34.3% (12/35 mice) with an average life span of 17.5 days. In 19 survival hu-PBL/SCID chimeric recipients from 12 healthy donors,tumor incidence was 84.2% (16/19 mice). The average survival time of tumor-bearing mice was 65.5 days. EBV-related neoplasms in SCID mice were nodular tumors with aggressive and fatal features. Histological morphology of tumors exhibited diffuse large cell lymphomas. Immunohistochemistry revealed that LCA (CD45) and L26 (CD20) were positive, but both PS1 (CD3) and UCHL-1 (CD45RO) were negative, and EBV products ZEBRA, LMP1, and EBNA2 were expressed in a small number of tumor cells. EB virus particles were seen in the nuclei of some tumor cells by electron microscopy, and EBV DNA could be amplified in the tumor tissues by PCR. In situ hybridization indicated that the nuclei of tumor cells contained human-specific Alu sequence. Conclusions EBV-induced tumors were human B-cell malignant lymphomas. We obtained direct causative evidence dealing with EBV-associated tumor deriving from normal human cells.     

血管内皮生长因子促进肺转移相关受体通路的研究

目的 探讨肺癌细胞分泌的血管内皮生长因子(VEGF)促进肺转移的受体相关机制。方法 应用噻唑蓝(MTT)与酶联免疫吸附(ELISA)方法测定9种肺癌细胞系的增殖状况和培养上清液中VEGF水平,筛选出差异表达VEGF且增殖无明显差异的两株细胞系。将两株细胞分别接种于SCID小鼠背部观察肿瘤生长,肺癌细胞经尾静脉注射建立肺转移模型,采用HE染色和免疫荧光实验检测肺转移瘤及血管密度。应用两种VEGFR中和抗体(MF-1和DC101)腹腔注射治疗肺转移小鼠,观察肺转移瘤数改变。结果 9种肺癌细胞系分泌VEGF水平不同,其中最高的是A549(182.7ng/mL),最低的是SPCA1(13.39ng/mL),A549细胞和SPCA1细胞的增殖差异无统计学意义(P>0.05)。A549细胞在小鼠背部形成的肿瘤体积明显大于SPCA1细胞,肿瘤组织内新生血管明显增多。A549细胞形成肺转移瘤数为SPCA1细胞的2.3倍。抗VEGFR-1治疗使肺转移瘤数明显减少,而抗VEGFR-2治疗后差异无统计学意义(P>0.05)。结论 肺癌细胞分泌的VEGF促进肿瘤生长、转移和肿瘤血管生成,VEGF通过VEGFR1通路促进肺转移。