裸鼠皮下人肝癌移植瘤模型的建立

目的建立裸鼠皮下肝癌移植瘤模型。方法BLBA/c裸鼠颈背部皮下注射人肝癌SMMC-7721细胞悬液5×106个.0.2m l-1.只-1,观察肿瘤生长情况,45d处死。瘤组织作病理及电镜检查;取裸鼠周围血作甲胎蛋白(AFP)的检测;用免疫组化法检测肿瘤微血管密度(MVD)。结果该模型具有类似人原发性肝癌的形态学特征。结论成功建立了人肝癌裸鼠皮下移植瘤模型。     

人前列腺癌裸鼠皮下移植瘤模型的建立

目的 建立人前列腺癌裸鼠皮下移植瘤模型.方法 采用人前列腺癌细胞株PC-3细胞接种于裸鼠的颈背部皮下,计算成瘤潜伏期、成瘤百分率,观察移植瘤大体生长情况,绘制生长曲线,并对移植瘤进行病理鉴定.结果 采用人前列腺癌细胞株PC-3细胞皮下接种方式建立移植瘤的平均成瘤潜伏期为24天,成瘤百分率为100％,瘤体积倍增时间为10天左右,移植瘤的形态和功能特性与原发肿瘤基本相似.结论 本动物模型的建立可为前列腺癌的放射免疫显像以及放射免疫治疗提供一个有价值的实验平台.     

人肺腺癌裸鼠皮下移植瘤淋巴转移模型的构建与筛选

目的构建人肺腺癌的裸鼠皮下移植瘤模型,探讨不同注射部位对肿瘤生长和淋巴转移的影响。方法 20只BALB/c裸鼠随机分为4组,每组5只。分别于左侧背部近腋窝、右侧背部近腋窝、左侧后肢和左后爪垫皮下注射A549细胞株,建立人肺腺癌移植瘤模型,考察各组裸鼠肿瘤生长和淋巴结转移情况。结果各组裸鼠成瘤明显,模型构建成功。背部近腋窝种植2组裸鼠肿瘤比后肢和爪垫种植的肿瘤出现时间早,生长速度快(P<0.05)。左侧背部近腋窝、右侧背部近腋窝、左侧后肢和左后爪垫皮下移植瘤的淋巴结转移率分别为41.7%、42.9%、23.1%和21.4%。其中左侧背部近腋窝注射最为方便。结论裸鼠左侧背部近腋窝皮下注射A549细胞操作方便,肿瘤易生长,淋巴转移率高,是构建人肺腺癌皮下移植瘤淋巴转移模型的优选方案。     

长必安协同顺铂抑制裸鼠移植瘤生长和转移的研究

中药长必安冲剂是一个新研制的抗肿瘤转移中药 ,为证实其在高转移人卵巢癌裸鼠移植瘤模型中具有抗肿瘤和抗转移疗效 ,我们进行裸鼠体内实验性治疗 ,为临床肿瘤病人应用中药长必安提供实验依据。一、材料和方法1 中药长必安冲剂 :浙江省中医药研究院研制。方剂由黄芪、龟板、白术、鳖甲、川芎、益母草、山楂组成。2 裸鼠与肿瘤接种 :42只 5～ 6周龄雄性ＢＡＬＢ/Ｃ ,ｎｕ/ｎｕ裸小鼠 ,体重 2 0～ 2 7ｇ(购自中国医学科学院上海药物研究所 ) ,在每只鼠右肋部皮下用 1ｍｌ针管接种高转移人卵巢癌裸鼠皮下移植癌模型[1] 第 2 1代移植瘤组织匀浆…     

人直肠粘液腺癌裸鼠移植瘤模型的建立及其生物学特性

A model of transplantable human mucoid adenocarcinoma of rectum in BALB/C nu/nu nude mice (TNB 92), was established and 18 sub-transplantations were performed. The success rate of transplantation was 98% and the average tumor bearing life time of mice was 112 days. Histology and ultrastructures showed that the transplantable tumor retained the original structures of the human tumor. Chromosomal analysis of the tumor cells exhibited the same features of the human carcinoma and it also retained the function of secreting CEA. Frozen tissue of the tumor in liquid nitrogen after rehabilitation could be successfully retransplanted into nude mice again. It seems to be a useful model for further study of human rectal adenocarcinoma.     

人胃癌转移鼠模型的构建及移植瘤的阶段性研究

目的：建立人胃癌的“转移鼠”模型,为研究胃癌转移打下基础。方法：将人胃低分化粘液腺癌ＭＧＣ－８０３细胞悬液先在裸小鼠皮下接种成瘤,再取瘤组织块分别接种到裸鼠的皮下、胃壁上（转移鼠模型）,分早（〈２０天）、中（２０～４０天）、晚（〉４０天）,４个阶段观察移植瘤的生长侵袭转移情况。结果：皮下组移植成瘤率为８２．１％（２３／２８）,早、中阶段未见转移,晚期肺转移率５７．１％（４／７）。胃壁组移植成瘤率为     

裸鼠皮下种植性肝癌模型的建立

背景：目前采用Huh7肝癌细胞在BALB/c裸小鼠皮下种植性成瘤的报道较多,但对其成瘤后稳定性的研究较少。 目的：建立稳定的皮下种植性裸鼠肝癌模型。 方法：取1.5×10⁶个对数期细胞Huh7肝癌细胞,种植于裸鼠皮下。成瘤后从体质量、大体形态,肿瘤生长情况,反转录-聚合酶链式反应,苏木精-伊红染色及免疫组织化学多方面进行稳定性及病理学特征鉴定。 结果与结论：肿瘤形成的潜伏期约12 d,肿瘤成功率为92.8%。种植肿瘤组小鼠体质量较正常对照小鼠明显减轻,肿瘤生长迅速,甲胎蛋白基因及蛋白强阳性表达,细胞分裂明显。表明成功建立了稳定的裸鼠皮下种植性肝癌模型。     

高转移人卵巢癌细胞系HO-8910PM的建立及其生物学特性

我们在建立高转移人卵巢癌裸鼠皮下移植瘤模型的基础上［１］，又建立高转移人卵巢癌体外细胞系ＨＯ８９１０ＰＭ。现将建系过程及其生物学特性介绍如下。一、材料和方法１材料来源：取高转移人卵巢癌皮下移植瘤模型第７代３７０号裸鼠皮下肿块，在无菌条件下剪碎至１...     

人外周血γδT 细胞免疫治疗裸鼠皮下人肝癌细胞移植瘤的体内实验研究

目的:研究不同剂量的人外周血γδT 细胞对裸鼠人肝癌细胞(SMMC-7721)移植瘤模型的免疫治疗作用。方法: 用人肝癌细胞株SMMC-7721 接种BALB/ c 裸鼠皮下,建立肝癌裸鼠模型。于从健康人外周血中提取单核细胞,体外特异性扩增γδT 细胞。将已建立的肝癌裸鼠模型随机分为5 组,阳性对照组为5-氟尿嘧啶(5-Fu),阴性对照组为生理盐水,治疗组用不同剂量的γδT 细胞 分别注入裸鼠尾静脉,阳性对照组用5-Fu 裸鼠腹腔注射,阴性对照组用生理盐水裸鼠尾静脉注射。观察不同剂量的γδT 细胞对肿瘤的抑制效果,包括治疗前后的体重、食物摄取量及生长状况等,并与阳性对照组和阴性对照组比较肿瘤体积(TV)、相对肿瘤体积(RTV)和相对肿瘤增殖率[T/ C(%)]变化。结果:不同剂量的γδT 细胞对裸鼠移植瘤的生长有不同程度的抑制,RTV 与生理盐水阴性对照组比较差异有统计学意义(P<0.05);与5-Fu 阳性对照组比较,TV 增长明显低于5-Fu 阳性对照组,RTV 各剂量组抑制程度相似,均略高于5-Fu 阳性对照组,T/ C(%)各剂量组比5-Fu 对照组的相对肿瘤增殖率稍低,但无显著性差异。结论:人外周血γδT 细胞对肝癌裸鼠移植瘤具有显著的抑瘤作用,为建立肝癌免疫治疗新方法提供实验依据。     

人外周血γδT细胞免疫治疗裸鼠皮下人肝癌细胞移植瘤的体内实验研究北大核心CSCD

目的:研究不同剂量的人外周血γδT细胞对裸鼠人肝癌细胞(SMMC-7721)移植瘤模型的免疫治疗作用。方法:(1)用人肝癌细胞株SMMC-7721接种BALB/c裸鼠皮下,建立肝癌裸鼠模型。(2)从健康人外周血中提取单核细胞,体外特异性扩增γδT细胞。(3)将已建立的肝癌裸鼠模型随机分为5组,阳性对照组为5-氟尿嘧啶(5-Fu),阴性对照组为生理盐水,治疗组用不同剂量的γδT细胞(1×105、5×10~5及25×10~5)分别注入裸鼠尾静脉,阳性对照组用5-Fu裸鼠腹腔注射,阴性对照组用生理盐水裸鼠尾静脉注射。观察不同剂量的γδT细胞对肿瘤的抑制效果,包括治疗前后的体重、食物摄取量及生长状况等,并与阳性对照组和阴性对照组比较肿瘤体积(TV)、相对肿瘤体积(RTV)和相对肿瘤增殖率[T/C(%)]变化。结果:不同剂量的γδT细胞对裸鼠移植瘤的生长有不同程度的抑制,RTV与生理盐水阴性对照组比较差异有统计学意义(P<0.05);与5-Fu阳性对照组比较,TV增长明显低于5-Fu阳性对照组,RTV各剂量组抑制程度相似,均略高于5-Fu阳性对照组,T/C(%)各剂量组比5-Fu对照组的相对肿瘤增殖率稍低,但无显著性差异。结论:人外周血γδT细胞对肝癌裸鼠移植瘤具有显著的抑瘤作用,为建立肝癌免疫治疗新方法提供实验依据。     

人弥漫性大B细胞淋巴瘤移植瘤模型的建立及生长特性观察

目的 建立人弥漫性大B细胞淋巴瘤(DLBCL)细胞株LY8裸鼠皮下移植瘤模型并观察其生长特性,为探讨淋巴瘤发病机制及治疗策略提供手段.方法 将人DLBCL细胞株LY8种植于裸鼠右前肢肩胛背侧皮下,成瘤后无菌套管针抽吸法抽取约1.5 mm×1.5 mm×1.5 mm大小组织块进行皮下种植,观察成瘤率和组织形态特点;用免疫组织化学EnVision法观察白细胞共同抗原(LCA)、CD20、CD79α、Ki-67、CD3、CD45RO、bcl-6、MUM-1、CD10、bcl-2等指标的表达;用聚合酶链反应(PCR)扩增检测移植瘤和LY8细胞株的IgH基因克隆性重排和针对3个微卫星位点(D14S68、D18S69、D20S199)的基因组DNA微卫星序列.结果 运用LY8细胞株成功进行了人DLBCL的种植,且生长稳定,已传至第9代,共移植裸鼠124只,其中114只成瘤,成瘤率达91.9%.每代移植瘤的生长特点均相似,于移植后约2周长出,约在3周左右长至最大径1.3 cm,随后即进入快速生长期,4周左右达2.0 cm大小.移植瘤形态符合DLBCL,肿瘤细胞免疫组织化学显色呈LCA、CD20、CD79α、bcl-6、MUM-1、CD10、bcl-2阳性;裸鼠移植瘤与LY8有相同的IgH基因克隆性重排,经3个位点的微卫星引物扩增后获得相同片段的产物.表明移植瘤与人DLBCL细胞相似,并证实了其生长的稳定性和可重复性.结论 建立了可稳定传代的DLBCL的裸鼠模型,为研究人DLBCL的生物学特性及试验治疗提供了较理想的动物模型.

Abstract：

Objective To establish a diffuse large B-cell lymphoma (DLBCL)-mice model using human DLBCL cell line LY8, to investigate its characteristics of growth and to provide a model for in vivo study of DLBCL pathogenesis and treatment. Methods LY8 cells were injected subcutaneously into the right flank of nude mice. Harvested tumor tissues were cut into small pieces of 1.5 mm × 1.5 mm × 1.5 mm and implanted subcutaneously into nude mice. Tumor growth was visualized and the histologic characteristics were documented. Expression of LCA, CD20, CD79α, Ki-67, CD3, CD45RO, bcl-6, MUM-1, CD1O and bcl-2 were examined by using immunohistochemistry. IgH clonal rearrangement and status of three microsatellite loci (D14S68, D18S69, D20S199) in the xenografted tumor samples and the parental cell line LY8 were detected using PCR amplification followed by PAGE. Results The subcutaneous xenograft DLBCL model was successfully established by using cell line LY8, and a stable growth was achieved up to the 9th generation. The tumor in each generation showed similar growth characteristics and the rate of subcutaneous tumor formation was 91.9% (114/124). The tumor growth was observed from the 2nd week after implantation, reaching 1.3 cm in major diameter at the 3rd week and 2. 0 cm at the 4th week. The tumor had identical morphological characteristics with those of human DLBCL, and expressed LCA, CE0,CD79α, bcl-6, MUM-1, CD1O and bcl-2. The tumor of xenograft mice and cell line LY8 showed identical IgH rearrangement and microsatellite length. Conclusions A human DLBCL bearing mouse model was successfully established. The mice model is similar to human counterpart with high stability and repeatability. Therefore, it provides an ideal animal model for in vivo studies of the biological characteristics and treatment of DLBCL.     

Relaxin promotes differentiation of human breast cancer cells MCF-7 transplanted into nude mice

Previous studies showed that the hormone relaxin acts on human breast cancer MCF-7 cells in vitro by modulating cell proliferation and promoting cell differentiation toward a duct epithelial phenotype. The present study was designed to investigate whether relaxin retains these properties when acting in vivo on MCF-7 cell tumors developed in athymic nude mice. Mice bearing MCF-7 cell tumors transplanted under the mammary fat pad and estrogenized to sustain tumor growth were treated systemically with relaxin (10 μg/day) for 19 days. Vehicle-treated mice were used as controls. Thirty days later, the mice were sacrificed and tumor fragments were analyzed by light and electron microscopy and immunocytochemistry. Measurements of tumor volume were recorded weekly for the overall experimental period. The results obtained indicate that relaxin treatment promotes differentiation of tumor cells towards both myoepithelial-like and epithelial-like cells, as judged by the ultrastructural features of the cells and by the increased expression of smooth muscle actin and cadherins. Measurements of tumor size and of the number of cycling cells show that relaxin, at the doses and times of exposure used in this study, does not significantly influence tumor growth and cell proliferation. Received: 3 March 1999 / Accepted: 28 May 1999     

细胞角蛋白7和20在卵巢转移癌中的表达

目的 观察卵巢转移癌的临床资料、病理形态和免疫组织化学改变,为鉴别卵巢转移癌与原发癌提供依据。方法 对27例卵巢转移癌（其中胃癌12例,结肠癌11例,其他4例）进行了临床和病理形态观察,同时采用免疫组织化学（SP法）对其分别进行细胞角蛋白[CK（AE1/AE3）]、细胞角蛋白7（CK7）、细胞角蛋白20（CK20）、癌胚抗原、波形蛋白、nm23抗原检测。结果 卵巢转移性胃癌12例中11例为双侧实性,卵巢转移性结肠癌11例中7例为单侧囊实性,组织学检查胃癌卵巢转移12例全部以印戒细胞癌或低分化腺癌散在分布为特征,而结肠癌卵巢转移则11例中8例与子宫内膜样癌相似,CK20阳性染色使卵巢转移性胃癌7例及结肠癌8例得到明确诊断,在转移性结肠癌中CK20有稳定的表达,卵巢转移性胃肠道癌中CK7多数阴性,癌胚抗原、波形蛋白、nm23的联合使用使转移性胃癌11例,结肠癌10例得到明确诊断,结论 CK7和CK20在鉴别来自胃肠道的卵巢转移癌中具有重要意义。当几种抗体联合使用时意义更大。     

Mendelian analysis of a metastasis-prone substrain of BALB/c nude mice using a subcutaneously inoculated human tumour

Most nude mice do not allow the formation of metastases after heterotransplantation of human malignant tumours. Here we describe a substrain of BALB/c nude mice (BALB/c/AnNCr) that reproducibly allows some human cancers to metastasize. By Mendelian analysis of hybrids between this substrain and C57BL/6J +/+ mice we found that the ability to allow a human tumour (MDA-MB-435 BAG) to express its metastatic phenotype is determined by a recessively inheritable trait in the mouse host. We are presently working to identify the genetics responsible for development of metastases. The study also includes immunohistochemical and electron microscopic analysis of the test tumour, originally assumed to be a human mammary carcinoma, but shown to possess characteristics of a malignant melanoma (1). The ultimate aim of our ongoing study is to establish a substrain of nude mice that will allow metastasis in all recipients.     

CK7单克隆抗体在鉴别卵巢原发性与胃肠道源性转移癌中的意义

目的研究ＣＫ７单克隆抗体在鉴别卵巢原发性癌和来源于胃肠道的卵巢转移性癌中的意义。方法采用免疫组织化学ＡＢＣ方法对４６例卵巢原发性癌、３４例原发灶在胃的卵巢转移性癌和３０例原发灶在肠的卵巢转移性癌进行了ＣＫ７单克隆抗体表达的检测。结果４６例卵巢原发性癌ＣＫ７均呈阳性表达,而３０例来源于肠的卵巢转移性癌ＣＫ７均为阴性,３４例来源于胃的卵巢转移性癌５０％呈ＣＫ７阳性表达。两组卵巢转移性癌的ＣＫ７阳性率与原发癌相比均有显著性差异（Ｐ＜０００１）。结论ＣＫ７单克隆抗体作为一个原发性卵巢癌的特异性标记,对鉴别卵巢原发性癌和来源于胃肠道的卵巢转移癌有重要意义     

具有不同转移潜能的肺癌细胞亚系的分离鉴定

自人肺巨细胞癌系分离了多个单细胞克隆，经体外侵袭实验和裸鼠体内接种相结合进行了初步鉴定后，挑选其中３个克隆化细胞亚系（ＰＧＢＥ＿１、ＰＧＣＬ＿３和ＰＧＬＨ＿７）进行形态、染色体众数、体外生长和侵袭，以及棵鼠体内成瘤率和自发性转移率检测。结果显示ＰＧＢＥ＿１、ＰＧＣＬ＿３和ＰＧＬＨ＿７在裸鼠体内的成瘤率均为１００％，淋巴结转移率分别为９４％、９４％和５０％，肺转移率则分别为８８％、６７％和４４％。表明人肺巨细胞癌母系为一异质性的细胞群体。     

Local and metastatic growth and in vivo differentiation of human myeloid leukemia cells transplanted in nude mice

Summary Cells from the established human myeloid cell lines KG-1, KG-1a, and HL-60, transplanted subcutaneously (sc) into nude mice, developed discrete tumors (myelosarcomas). These myelosarcomas had a host's age-associated pattern of growth identical to that of experimental tumors produced by sc transplantation of cells derived from malignant solid neoplasias. Thus, leukemia cells yielded either localized myelosarcomas at the site of inoculation or a disseminated neoplastic growth after inoculation inadult (more than 4 weeks old) ornewborn (1–3 days old) nude mice, respectively. Human myeloid leukemia cells proliferating in the nude mice preserved the human karyotype and a surface antigenic determinant and did not influence the hematopoietic tissues of the host.The KG-1 and HL-60 cell lines consistently attained varying degrees of differentiation along the myeloid series in vitro, and these features were maintained during proliferation in the mice. Furthermore, cells of the variant subline KG-1a, which had a blastic morphology, developed signs of differentiation that were not seen in culture. The presence of readily identifiable markers, such as cytoplasmic granules containing myeloperoxidase, in the cell lines tested makes these models particularly useful for studying the influence of a biological environment on cell differentiation and its influence on tumor growth. These experimental systems are also suitable for investigating the mechanism(s) of metastases and for in vivo experimental therapeutic trials.This investigation was supported by a grant from the Physicians Medical Education and Research Foundation, University of Tennessee Memorial Research Center and Hospital, Knoxville, TN, and by an NIH Institutional Biomedical Research Support Grant FR-5541     

Tumor cell line characterization of a malignant histiocytosis transplanted into nude mice

Summary The successful transplantation of a human malignant histiocytosis into nude mice allowed the examination of its atypical histiocytic cell proliferation. Histiocytic type cells were identified by positive reactions with acid phosphatase and non-specific esterase and with anti human DR or OKI1 antisera. Presence of OKT9 antigen and negative results obtained with most OKT antisera, rosettes, erythrophagocytosis and lysozyme corroborate the histiocytic immature state of the cells and preclude another type of tumor. All positive tests to prove a mature mononuclear phagocytic origin were attributable to the murine host cell reaction.     

卡托普利对AGS胃癌裸鼠移植瘤模型的调控作用*

 目的： 观察血管紧张素转换酶抑制剂卡托普利对胃癌发生与发展的调控作用,探索其应用于胃癌临床治疗的可行性。方法: 制备AGS裸鼠移植瘤模型,随机分为3组：阳性对照（5-氟尿嘧啶,5-Fu）组、对照（生理盐水）组和实验（卡托普利）组。各组分别腹腔注射或灌胃后,观察肿瘤生长情况,组织取样,采用实时荧光定量PCR和免疫组化法检测Ki-67、STAT3、Bax和Bcl-2表达情况,TUNEL+DAPI染色法检测细胞凋亡。Western blotting 检测STAT3及p-STAT3表达。结果: 造模成功后,各组小鼠均出现差异不明显的肿瘤结块。14 d后,各组差异明显加大。对照组裸鼠肿瘤块生长最快,卡托普利组次之,阳性对照组最慢。实时荧光定量PCR与免疫组化检测结果显示,卡托普利组Bax较对照组表达升高,而STAT3、Ki-67以及Bcl-2的表达则降低（P<0.05）,卡托普利组上述因子表达趋势与5-Fu组表达趋势相一致,但2组间差异显著（P<0.05）;凋亡结果显示,相较于对照组,其它2组细胞凋亡率明显升高（P<0.05）; Western blotting结果也显示,5-Fu组及卡托普利组的p-STAT3与STAT3蛋白表达水平较对照组明显降低（P<0.05）。结论: 血管紧张素转换酶抑制剂卡托普利对AGS裸鼠胃癌有较为明显的治疗效果,推测其可能具有较为可行的应用性。其分子机制可能是通过对STAT3转录活化因子以及Bax、Bcl-2、Ki-67等的调控,促使肿瘤细胞凋亡或抑制其生长。