人胃癌裸鼠原位移植模型的生物学行为研究

目的建立人胃癌裸鼠胃壁原位移植瘤模型，并与相应的皮下移植瘤作比较，以探讨宿主器官微环境对胃癌细胞浸润及转移等生物学行为的影响．方法将人胃癌细胞系ＭＧｃ８０３及其克隆株Ｃ１１癌细胞分别接种于裸鼠胃壁及背部皮下，比较原位和皮下移植瘤的成瘤率、生长率、生长方式及浸润、转移等生物学行为，以及体外回复培养后瘤细胞的增殖能力．结果胃壁原位及皮下移植瘤体内成瘤率、生长率及形态学上均无明显不同；其体外增殖能力也无显著性差异．但皮下移植瘤多呈局限性生长，无肝、脾、肾转移，其转移仅限于肺及个别局部淋巴结．胃壁原位移植瘤则浸润破坏胃壁各层组织结构，并直接蔓延到邻近各器官组织．其转移既有经血道至肝、肺、脾、肾等部位，也有经淋巴道至多数局部及远处淋巴结，其淋巴结的转移率较皮下移植瘤有显著增高（Ｐ＜００５）；且多伴有腹、盆腔内广泛种植性转移．结论裸鼠胃壁微环境较皮下组织更适合于人胃癌ＭＧｃ８０３及Ｃ１１移植瘤的浸润及转移的表达，该原位移植瘤模型的恶性生物学行为更接近临床胃癌患者的体内侵袭及转移的实际．     

Liver metastasis models of human colorectal carcinoma established in nude mice by orthotopic transplantation and their biologic characteristics

ＩＮＴＲＵＤＵＣＴＩＯＮＳｏｍｅｍｏｄｅｌｓｏｆｎｕｄｅｍｉｃｅｔｈａｔｆｒｅｓｈｈｕｍａｎｃｏｌｏｒｅｃｔａｌｃａｒｃｉｎｏｍａｔｉｓｕｅｏｒｃｅｌｓｗｅｒｅｓｕｃｃｅｓｆｕｌｙｔｒａｎｓｐｌａｎｔｅｄｓｕｂｃｕｔｅｎｅｏｕｓｌｙｈａｖｅｂｅｅｎｒ...     

Phase tissue intercellular adhesion molecule-1 expression in nude mice human liver cancer metastasis model

AIM To study the phase cancer tissue intercellular adhesion molecule-1 (ICAM-1) expression of human cancer metastasis model in nude mice, and to analyze the relationship between ICAM-1 expression and the metastasis and recurrence of hepatocellular cancinoma (HCC).METHODS HCC tissues from liver cancer metastasis model in nude mice (LCI-D20) was orthotopically implanted, and ICAM-1 expression in HCC tissues at different growing time were detected by immunodot blot. Tumor size, intrahepatic and extrahepatic metastasis foci were observed by naked eyes and under light microscope.RESULTS ICAM-1 was positively correlated to the tumor growing time (r=0.88, P＜0.01) and tumor size r=0.5, P＜0.05). It was higher in metastatic HCC than in nonmetastatic HCC (8.24±0.95 vs 3.03±0.51, P＜0.01). ICAM-1 content in cancer tissues increased suddenly after metastasis occurred and then maintained in a high level. ICAM-1 was also higher in multimetastasis group than in monometastasis group (10.05±1.17 vs 5.48±0.49, P＜0.05).CONCLUSION Tissue ICAM-1 could predict not only the metastasis of human liver cancer metastasis model in nude mice early and sensitively, but also the metastasis degree. So tissue ICAM-1 may be a potential index indicating the status of metastasis of HCC patients.     

Phase tissue intercellular adhesion molecule-1 expression in nude mice human liver cancer metastasis model

Ｐｈａｓｅｔｉｓｓｕｅｉｎｔｅｒｃｅｌｕｌａｒａｄｈｅｓｉｏｎｍｏｌｅｃｕｌｅ１ｅｘｐｒｅｓｓｉｏｎｉｎｎｕｄｅｍｉｃｅｈｕｍａｎｌｉｖｅｒｃａｎｃｅｒｍｅｔａｓｔａｓｉｓｍｏｄｅｌＳＵＮＪｉｎｇＪｉｎｇ,ＺＨＯＵＸｉｎＤａ,ＬＩＵＹｉｎＫ...     

Effects of Linomide on growth and metastasis of implanted human gastric cancer in nude mice

ＥｆｅｃｔｓｏｆＬｉｎｏｍｉｄｅｏｎｇｒｏｗｔｈａｎｄｍｅｔａｓｔａｓｉｓｏｆｉｍｐｌａｎｔｅｄｈｕｍａｎｇａｓｔｒｉｃｃａｎｃｅｒｉｎｎｕｄｅｍｉｃｅＴＡＯＨｏｕＱｕａｎ，ＬＩＮＹａｎＺｈｅｎ，ＹＩＮＨａｏＲａｎ，ＧＵＱｉｎＬｏｎｇ，ＺＨＵ...     

Studies on mechanism of Sialy Lewis-X antigen in liver metastases of human colorectal carcinoma

INTRODUCTION Sialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .     

高转移MHCC97H细胞裸鼠原位移植瘤姑息性肝癌切除模型的建立

目的 模拟临床肝癌切除病例构建姑息性肝切除裸鼠模型,用于研究手术对残癌的影响并探索干预策略. 方法 采用肝左叶单瘤源接种技术,构建高转移潜能MHCC97H细胞裸鼠原位移植瘤模型,成功建模后14 d行姑息性肝切除.姑息术后14d,分析肿瘤相关基因差异表达；观察35 d,检测肝内、肺脏及腹腔转移；剩余裸鼠用于观察生存期.计量资料比较用t检验,生存分析用Kaplan-Meier法(Log Rank检验),P＜0.05为差异有统计学意义. 结果 原位移植瘤模型成功率100％,成功构建裸鼠姑息性肝切除模型,无手术相关死亡裸鼠.姑息组裸鼠肝内转移结节多于假手术组[(11.7±4.7)个对比(6.3±2.8)个,t=-2.412,P＜0.05],腹腔转移结节多于假手术组[(9.8±3.4)个对比(5.2±2.6)个,t=-2.641,P＜0.05],肺转移结节也多于假手术组[(14.3±4.7)个对比(8.7±4.7)个,t=-2.348,P＜0.05].应用生物信息学技术进一步分析发现,肿瘤转移抑制蛋白1、肿瘤坏死因子β1、Smad2、白细胞介素1β及基质金属蛋白酶7基因在姑息组残癌基因功能网络中处于核心位置.姑息组裸鼠生存期为(60.8±2.7)d,假手术组裸鼠生存期为(51.3±1.4)d,差异有统计学意义(x2=12.850,P＜0.01).结论 单瘤源姑息性肝切除模型能有效模拟临床肝切除病例,为术后残癌生物学特性的研究及干预提供一个新的平台.     

5-氟脲嘧啶腹腔化疗预防裸鼠人结肠癌细胞肝转移研究

目的探索预防大肠癌根治术后肝转移局部区域性辅助化疗新途径.方法利用裸鼠人结肠癌细胞肝转移模型观察术后早期大剂量大容积5-氟脲嘧啶腹腔化疗预防裸鼠经睥接种的人结肠癌细胞肝转移的疗效.结果术后早期5-氟脲嘧啶40 mg/生理盐水40 ml/kg,1次/d,连续2 d 的腹腔化疗可使裸鼠肝转移发生率降低40%,平均每只裸鼠肝转移瘤数目减少50.89%,平均每只裸鼠生存时间延长48.21%.结论腹腔化疗是一个预防大肠癌根治术后肝转移有效的辅助化疗新途径.     

ATRA inhibits experimental liver metastasis of gastric cancer cells in nude mice

AIM To study the effects of ATRA on experimental liver metastasis of gastric cancer cells.METHODS MGc80-3 and SGC-7901 cells were injectied into spleen subcapsule of nude mice, who weresubsequently administrated with ATRA every other day. Food-intake and body weight of mice were measuredweekly. After six weeks, the nude mice were executed, tumors in spleen and liver were examinedpathologically, microtumor vessel density (MVD) was accounted by immunohistochemical method and serumCEA was measured by radioimmunoassay.RESULTS Nude mice administrated with ATRA, the growth of spleen tumor and its metastatic ability toliver were inhibited, the metastatic rate was decreased by 33.3% (MGc80-3) and 50.0% (SGC-7901). SpleenMVD and liver MVD were reduced by 28.6% and 22.9% (MGc80-3), 23.7% and 37.6% (SGC-7901),respectively. The serum CEA was lowered by 43.4% (MGc80-3).CONCLUSION ATRA can effectively inhibit the experimental liver metastasis of gastric cancer cells,which is relavant with the decrease of MVD and CEA.     

结直肠癌肝转移外科治疗的共识与争议

结直肠癌肝转移是导致结直肠癌患者死亡的主要原因。目前,循证医学证据表明手术切除是结直肠癌肝转移患者有效且可能获得长期生存的惟一治疗方式。随着外科技术尤其是微创外科技术的进步,越来越多的患者可从外科手术中获益。化学药物的发展以及贝伐单抗和西妥昔单抗等靶向药物的应用,使不可切除的结直肠癌肝转移转化为可切除,从而使更多患者获得治愈的机会。对于无法根治性切除的患者,外科手术联合射频治疗的方法可延长生存期。多学科合作团队诊治模式的广泛应用,使结直肠癌肝转移的治疗更加精准。     

人原发性直肠恶性淋巴瘤裸小鼠原位移植模型的建立及其生物学特性

目的:建立人原发性直肠恶性淋巴瘤裸小鼠原位移植模型,探讨其生物学特性.方法:采用人直肠原发性恶性淋巴瘤术中的新鲜瘤组织块植入裸鼠的直肠黏膜层内,观察原位移植的成瘤率,移植瘤的侵袭和转移率.进行形态学(光镜、电镜、免疫组织化学),染色体核型,流式细胞分析.结果:依据WHO新的分类标准,建成1株人直肠原发性(非霍奇金B细胞性)恶性淋巴瘤裸鼠原位移植模型HRBL-0305.移植瘤组织病理学为(非霍奇金B细胞性)高度恶性淋巴瘤;免疫组织化学示CD19,CD20,CD22,CD45阳性,CD3,CD7阴性.染色体众数56-69条,流式细胞DI值为1.57-1.61,均为异倍体.HRBL-0305已传至31代;共移植裸鼠187只.其肿瘤移植生长率和液氮冻存复苏成活率均为100.0%,肝转移率为45.4%,淋巴结和腹腔种植转移率均为38.0%,移植瘤在裸鼠的直肠内自主侵袭性生长,发生血液、淋巴转移和腹腔内种植性转移,移植瘤组织病理学,超微结构的观察,流式细胞DNA含量测定及染色体核型的分析,表明与人源直肠恶性淋巴瘤细胞相一致.结论:HRBL-0305是首次成功建立的人直肠原发性恶性淋巴瘤裸鼠原位移植模型,完整地重现了人直肠原发性恶性淋巴瘤的自然临床病理过程,且转移模式与临床患者相似,为研究直肠恶性淋巴瘤的生物学特性和治疗提供了理想动物模型平台.     

Proteomic analysis of differentially expressed proteins involving in liver metastasis of human colorectal carcinoma

BACKGROUND:Early diagnosis of liver metastasis of colorectal carcinoma is very important for the appropriate treatment of such patients.However,there has been no effective approach available for clinical application.The present study aimed to investigate the differential expression of proteins in patients with liver metastasis of colorectal carcinomas using proteomic analysis and evaluate its potentiality in clinical diagnosis. METHODS:Fluorescence two-dimensional differential in-gel electrophoresis(2-D DIG...     

Prevention of liver metastasis by intraperitoneal 5-FU chemotherapy in nude mice inoculated with human colon cancer cells

AIM: To prevent hepatic metastasis by regional adjuvant chemotherapy after radical surgery for colon cancer. METHODS: A nude mouse model of human colon cancer (HCC) was used to evaluate the prevention of metastasis of HCC cells following the application of early postoperative intraperitoneal (IP) high-dose 5-fluorouracil chemotherapy. RESULTS: The incidence of liver metastasis was decreased by 40%, and the mean number of metastatic liver nodules was reduced by 50.89%. Compared with controls, 5-FU 40 mg in NS 40 mL/kg IP for 2 consecutive days prolonged mean survival by 48.21%. CONCLUSION: IP is a promising and effective novel regional adjuvant chemotherapy for the prevention of liver metastasis of HCC cells after radical surgery for colon cancer.     

小鼠结肠癌完整组织块原位种植及肝转移模型的建立方法

[目的]研究快速建立模拟临床过程的小鼠结肠癌原位移植瘤及肝转移模型方法。[方法]采用小鼠结肠癌细胞CT26接种于裸鼠皮下,形成稳定传代的皮下种植瘤。再取该肿瘤组织块,用原位医用胶黏合法种植于BALB/c小鼠盲肠壁,建立模拟于临床的结肠癌肝转移模型,定时观察小鼠全身情况,分不同时期处死,观察其生长及转移特性。[结果]原位种植成瘤率100%,术后3周肝转移率100%,4周后动物消瘦,萎靡,行动迟缓,反应迟钝,部分可见腹水形成,濒临死亡。中位生存期29d。[结论]小鼠结肠癌完整组织块通过"生物胶黏贴法"原位种植BALB/c小鼠盲肠壁,速度快,方法简便,能较好的重现结肠癌临床转移的过程,为人类结肠癌生长、肝转移机制及干预肝转移治疗的研究提供一种较理想的动物模型。     

5-FC/CD 系统对荷大肠癌裸鼠肿瘤的杀伤效应

目的研究ｃｄ基因对大肠肿瘤的特异杀伤作用，探索自杀基因靶向治疗大肠癌的有效途径．方法逆转录病毒感染法将Ｇ１ｃｅａｃｄＮａ及ｐｃｄ２分别转导入高分泌ＣＥＡ的大肠癌细胞Ｌｏｖｏ中，再分别接种到裸鼠皮下．成瘤后腹腔给予５ＦＣ（５００ｍｇ／ｋｇ）治疗，观察肿瘤重量的变化及病理学特点．结果含Ｇ１ｃｅａｃｄＮａ及ｐｃｄ２逆转录病毒载体的病毒滴度分别为：１３×１０７及２１×１０８ＣＦＵ／Ｌ．所有转基因成功并接种动物均成瘤．腹腔给予５ＦＣ治疗后发现，转由ＣＥＡ基因顺式转录调控序列（ＴＲＳ）驱动ｃｄ基因的组织特异性重组逆转录病毒载体Ｇ１ｃｅａｃｄＮａ的肿瘤对５ＦＣ的敏感性明显高于转非ｃｅａ调控ｃｄ基因的肿瘤，治疗结束后肿瘤重量分别为３１ｍｇ±８ｍｇ及１１３ｍｇ±２３ｍｇ（Ｐ＜００１）．结论本实验提示ｃｅａ转录调控序列可控制ｃｄ基因在ＣＥＡ阳性的大肠癌组织中高效表达，进而在前药５ＦＣ的作用下发挥选择性杀伤肿瘤的作用     

伴有肝外远处器官转移的原发性肝癌患者血液AFPmRNA表达

目的探讨伴有肝外远处器官转移的原发性肝癌周围静脉血液AFPmRNA表达情况．方法应用巢式RT－PCR检测93例伴有与不伴有肝外远处器官转移的原发性肝癌血液AFPmRNA。结果21例伴有肝外远处器官转移的原发性肝癌血液AFPmRNA均表达阳性（100％），对例不伴有肝外远处器官转移的原发性肝癌中有29例血液AFPmRNA表达阳性（40．28％，P＜0．01）结论血液AFPmRNA可以作为肝癌远处器官转移的标志性指征     

Tumor radioimmunoimaging of chimeric antibody in nude mice with hepatoma xenograft

ＴｕｍｏｒｒａｄｉｏｉｍｍｕｎｏｉｍａｇｉｎｇｏｆｃｈｉｍｅｒｉｃａｎｔｉｂｏｄｙｉｎｎｕｄｅｍｉｃｅｗｉｔｈｈｅｐａｔｏｍａｘｅｎｏｇｒａｆｔＧＯＮＧＹｉ１,ＬＩＵＫａｎｇＤａ１,ＺＨＯＵＧｅ１,ＸＵＥＱｉｏｎｇ１,ＣＨＥＮＳｈａｏＬｉａｎｇ...     

裸鼠皮下泡型棘球蚴病移植瘤模型的建立

目的建立裸鼠皮下泡型棘球蚴病移植瘤模型,为进一步深入研究泡型棘球蚴病奠定基础。方法选取25只裸鼠进行20%泡型棘球蚴原头节混悬液0.1 ml颈背部皮下注射接种,观察记录病灶生长状况,术后6个月行台盼蓝染色观察原头节细胞活性。结果术后8 d左右可见皮下病灶结节;模型建立3个月后裸鼠存活率为92%(23/25),泡型棘球蚴感染率为100%(23/23);少量原头节死亡,台盼蓝染色蓝色,原头节细胞活力为98%。结论泡型棘球蚴能够成功移植于裸鼠皮下,可为进一步建立泡型棘球蚴病的动物模型提供参考。     

Detection of blood AFPmRNA in nude mice bearing human HCC using nested RT-PCR and its significance

ＤｅｔｅｃｔｉｏｎｏｆｂｌｏｏｄＡＦＰｍＲＮＡｉｎｎｕｄｅｍｉｃｅｂｅａｒｉｎｇｈｕｍａｎＨＣＣｕｓｉｎｇｎｅｓｔｅｄＲＴＰＣＲａｎｄｉｔｓｓｉｇｎｉｆｉｃａｎｃｅＬＩＵＹａｎｇ,ＺＨＡＮＧＢａｉＨｅ,ＱＩＡＮＧｕａｎｇＸｉａｎｇ,ＣＨＥＮＨａ...     

Molecular mechanism about lymphogenous metastasis of hepatocarcinoma cells in mice

AIM: To investigate the correlation between lymphogenous metastasis and matrix metalloproteinases (MMPs) activity and the expression of Fas ligand of tumor cells in lymph nodes. METHODS: Fifty-six inbred 615-mice were equally divided into 2 groups and inoculated with Hca-F and Hca-P cells. Their lymph node metastatic rates were examined. Growth fraction of lymphocytes in host lymph nodes was detected by flow cytometry. The Hca-F and Hca-P cells were cultured with extract of lymph node, liver or spleen. The quantity of MMPs in these supernatants was examined by zymographic analysis. The expression of Fas ligand, PCNA, Bcl-2 protein of Hca-F and Hca-P cells in the mice were examined by immunohistochemistry. The apoptosis signals of macro-phages in lymph nodes were observed with in situ DNA fragmentation. RESULTS: On the 28th day post-inoculation, the lymph node metastatic rate of HcaF was 80%(16/20), whereas that of Hca-P was 25%(5/20). The growth fraction of lymphocytes was as follows: in the Hca-F cells, the proliferating peak of lymphocytes appeared on the 14th day post inoculation and then decreased rapidly, while in HcaP cells, the peak appeared on the 7th day post inoculation and then kept at a high level. With the extract of lymph node, the quantity of the MMP-9 activity increased (P<0.01) and active MMP-9 and MMP-2 were produced by both Hca-F and Hca-P tumor cells, which did not produce MMPs without the extract of lymph node or with the extracts of the liver and spleen. The expression of Fas Ligand of Hca-F cells was stronger than that of Hca-P cells (P <0.01). The expressions of PCNA and Bcl-2 protein of Hca-F cells in the tumors of inoculated area were the same as that of Hca-P cells. In situ DNA fragmentation showed that the positive signals of macrophages were around Hca-F cells. CONCLUSION: Secretion of MMPs which was associated with metastatic ability of Hca-F and Hca-P tumor cells depends on the environment of lymph nodes. The increased expression of Fas ligand protein of Hca-F tumor cells with high lymphogenous metastatic potential in lymph nodes may help tumor cells escape from being killed by host lymphocytes.