含人N-ras反意基因的假型逆转录病毒对裸小鼠体内人肝癌移植瘤生长和N-ras表达的作用

含人反意基因的假型逆转录病毒已在许多实验室构建,并用于抑制病毒的或细胞的基因表达。抑制基因活性是一个新的遗传分析方法,其机制是通过一条互补于正常RNA的反意链与有意义链的结合而影响其功能,它的优点是能根据目的基因的转录产物设制有效的反意RNA,研究该基因在细胞中的生物学作用。RNA逆转录病毒因其独特性结构和繁衍形式,已成为理想的基因转移载体。含人     

酪丝缬肽对裸小鼠人肝癌BEL-7402移植瘤的抑制作用

目的观察酪丝缬肽对裸小鼠人肝癌BEL-7402移植瘤的抑瘤作用,并初步探讨其可能的作用机制。方法通过动物模型观察酪丝缬肽对裸小鼠人肝癌BEL-7402移植瘤肿瘤重量及体积的影响;以电镜观察肿瘤细胞超微结构的改变;以免疫组化法观察瘤组织中增殖细胞核抗原(PCNA)的表达;以利用TUNEL法检测瘤组织细胞的凋亡情况。结果给药剂量为80μg·kg~(-1)·d~(-1)和160μg·kg~(-1)·d~(-1)时,酪丝缬肽可以显著抑制裸小鼠BEL-7402移植瘤的生长,抑瘤率分别为64．02%和66．27%,与生理盐水及相应氨基酸混合物组比较,差异均有统计学意义(P＜0．05)。酪丝缬肽可引起肿瘤细胞超微结构改变,导致肿瘤细胞广泛坏死和凋亡。酪丝缬肽给药组与生理盐水组比较,肿瘤组织细胞的PCNA表达明显降低,凋亡细胞明显增多。结论酪丝缬肽可显著抑制人肝癌BEL-7402细胞在裸小鼠体内的生长,抑制肿瘤细胞增殖,促进瘤细胞凋亡。     

新城疫病毒D817对裸小鼠人结肠癌移植瘤的抑制作用

Objective To study the anti-tumor effects of Newcastle disease virus (NDV) strain D817 on human colon carcinoma model in nude mice. Methods The nude mouse model of human colon carcinoma was established by subcutaneous inoculation of human colon cancer LOVO cells. The tumor-bearing mice were given PBS, 5-Fu, high-dose NDV D817, moderate-dese NDV D817 or low-dose NDV D817 via caudal vein injection. The tumor size and weight of mice were measured. The liver damages were examined by histopathology. Apoptosis and necrosis of tumor ceils were detected by flow cytometry. The endotumoral content of TNF-α was detected using a mouse TNF-a ELISA kit. The live vires was detected by bemagglutination (HA) test. Results The moderate-dose NDV D817 inhibited the tumor growth more apparently than 5-Fu. The tumor growth inhibition rate reached to 48.1%. The liver damage and the weight change caused by NDV were less severe. NDV D817 made an increased apoptosis index and induced production of TNF-α. Live virus was not detected in important organs except in the tumor of nude mice by HA test. Conclusion In the anti-tumor process in nude mice bearing xenografts of human colon carcinoma, a suitable dose of NDV D817 is more safe and effective.     

新城疫病毒D817对裸小鼠人结肠癌移植瘤的抑制作用

Objective To study the anti-tumor effects of Newcastle disease virus (NDV) strain D817 on human colon carcinoma model in nude mice. Methods The nude mouse model of human colon carcinoma was established by subcutaneous inoculation of human colon cancer LOVO cells. The tumor-bearing mice were given PBS, 5-Fu, high-dose NDV D817, moderate-dese NDV D817 or low-dose NDV D817 via caudal vein injection. The tumor size and weight of mice were measured. The liver damages were examined by histopathology. Apoptosis and necrosis of tumor ceils were detected by flow cytometry. The endotumoral content of TNF-α was detected using a mouse TNF-a ELISA kit. The live vires was detected by bemagglutination (HA) test. Results The moderate-dose NDV D817 inhibited the tumor growth more apparently than 5-Fu. The tumor growth inhibition rate reached to 48.1%. The liver damage and the weight change caused by NDV were less severe. NDV D817 made an increased apoptosis index and induced production of TNF-α. Live virus was not detected in important organs except in the tumor of nude mice by HA test. Conclusion In the anti-tumor process in nude mice bearing xenografts of human colon carcinoma, a suitable dose of NDV D817 is more safe and effective.     

新城疫病毒D817对裸小鼠人结肠癌移植瘤的抑制作用

Objective To study the anti-tumor effects of Newcastle disease virus (NDV) strain D817 on human colon carcinoma model in nude mice. Methods The nude mouse model of human colon carcinoma was established by subcutaneous inoculation of human colon cancer LOVO cells. The tumor-bearing mice were given PBS, 5-Fu, high-dose NDV D817, moderate-dese NDV D817 or low-dose NDV D817 via caudal vein injection. The tumor size and weight of mice were measured. The liver damages were examined by histopathology. Apoptosis and necrosis of tumor ceils were detected by flow cytometry. The endotumoral content of TNF-α was detected using a mouse TNF-a ELISA kit. The live vires was detected by bemagglutination (HA) test. Results The moderate-dose NDV D817 inhibited the tumor growth more apparently than 5-Fu. The tumor growth inhibition rate reached to 48.1%. The liver damage and the weight change caused by NDV were less severe. NDV D817 made an increased apoptosis index and induced production of TNF-α. Live virus was not detected in important organs except in the tumor of nude mice by HA test. Conclusion In the anti-tumor process in nude mice bearing xenografts of human colon carcinoma, a suitable dose of NDV D817 is more safe and effective.     

新城疫病毒D817对裸小鼠人结肠癌移植瘤的抑制作用

Objective To study the anti-tumor effects of Newcastle disease virus (NDV) strain D817 on human colon carcinoma model in nude mice. Methods The nude mouse model of human colon carcinoma was established by subcutaneous inoculation of human colon cancer LOVO cells. The tumor-bearing mice were given PBS, 5-Fu, high-dose NDV D817, moderate-dese NDV D817 or low-dose NDV D817 via caudal vein injection. The tumor size and weight of mice were measured. The liver damages were examined by histopathology. Apoptosis and necrosis of tumor ceils were detected by flow cytometry. The endotumoral content of TNF-α was detected using a mouse TNF-a ELISA kit. The live vires was detected by bemagglutination (HA) test. Results The moderate-dose NDV D817 inhibited the tumor growth more apparently than 5-Fu. The tumor growth inhibition rate reached to 48.1%. The liver damage and the weight change caused by NDV were less severe. NDV D817 made an increased apoptosis index and induced production of TNF-α. Live virus was not detected in important organs except in the tumor of nude mice by HA test. Conclusion In the anti-tumor process in nude mice bearing xenografts of human colon carcinoma, a suitable dose of NDV D817 is more safe and effective.     

新城疫病毒D817对裸小鼠人结肠癌移植瘤的抑制作用

Objective To study the anti-tumor effects of Newcastle disease virus (NDV) strain D817 on human colon carcinoma model in nude mice. Methods The nude mouse model of human colon carcinoma was established by subcutaneous inoculation of human colon cancer LOVO cells. The tumor-bearing mice were given PBS, 5-Fu, high-dose NDV D817, moderate-dese NDV D817 or low-dose NDV D817 via caudal vein injection. The tumor size and weight of mice were measured. The liver damages were examined by histopathology. Apoptosis and necrosis of tumor ceils were detected by flow cytometry. The endotumoral content of TNF-α was detected using a mouse TNF-a ELISA kit. The live vires was detected by bemagglutination (HA) test. Results The moderate-dose NDV D817 inhibited the tumor growth more apparently than 5-Fu. The tumor growth inhibition rate reached to 48.1%. The liver damage and the weight change caused by NDV were less severe. NDV D817 made an increased apoptosis index and induced production of TNF-α. Live virus was not detected in important organs except in the tumor of nude mice by HA test. Conclusion In the anti-tumor process in nude mice bearing xenografts of human colon carcinoma, a suitable dose of NDV D817 is more safe and effective.     

新城疫病毒D817对裸小鼠人结肠癌移植瘤的抑制作用

Objective To study the anti-tumor effects of Newcastle disease virus (NDV) strain D817 on human colon carcinoma model in nude mice. Methods The nude mouse model of human colon carcinoma was established by subcutaneous inoculation of human colon cancer LOVO cells. The tumor-bearing mice were given PBS, 5-Fu, high-dose NDV D817, moderate-dese NDV D817 or low-dose NDV D817 via caudal vein injection. The tumor size and weight of mice were measured. The liver damages were examined by histopathology. Apoptosis and necrosis of tumor ceils were detected by flow cytometry. The endotumoral content of TNF-α was detected using a mouse TNF-a ELISA kit. The live vires was detected by bemagglutination (HA) test. Results The moderate-dose NDV D817 inhibited the tumor growth more apparently than 5-Fu. The tumor growth inhibition rate reached to 48.1%. The liver damage and the weight change caused by NDV were less severe. NDV D817 made an increased apoptosis index and induced production of TNF-α. Live virus was not detected in important organs except in the tumor of nude mice by HA test. Conclusion In the anti-tumor process in nude mice bearing xenografts of human colon carcinoma, a suitable dose of NDV D817 is more safe and effective.     

新城疫病毒D817对裸小鼠人结肠癌移植瘤的抑制作用

Objective To study the anti-tumor effects of Newcastle disease virus (NDV) strain D817 on human colon carcinoma model in nude mice. Methods The nude mouse model of human colon carcinoma was established by subcutaneous inoculation of human colon cancer LOVO cells. The tumor-bearing mice were given PBS, 5-Fu, high-dose NDV D817, moderate-dese NDV D817 or low-dose NDV D817 via caudal vein injection. The tumor size and weight of mice were measured. The liver damages were examined by histopathology. Apoptosis and necrosis of tumor ceils were detected by flow cytometry. The endotumoral content of TNF-α was detected using a mouse TNF-a ELISA kit. The live vires was detected by bemagglutination (HA) test. Results The moderate-dose NDV D817 inhibited the tumor growth more apparently than 5-Fu. The tumor growth inhibition rate reached to 48.1%. The liver damage and the weight change caused by NDV were less severe. NDV D817 made an increased apoptosis index and induced production of TNF-α. Live virus was not detected in important organs except in the tumor of nude mice by HA test. Conclusion In the anti-tumor process in nude mice bearing xenografts of human colon carcinoma, a suitable dose of NDV D817 is more safe and effective.     

新城疫病毒D817对裸小鼠人结肠癌移植瘤的抑制作用

Objective To study the anti-tumor effects of Newcastle disease virus (NDV) strain D817 on human colon carcinoma model in nude mice. Methods The nude mouse model of human colon carcinoma was established by subcutaneous inoculation of human colon cancer LOVO cells. The tumor-bearing mice were given PBS, 5-Fu, high-dose NDV D817, moderate-dese NDV D817 or low-dose NDV D817 via caudal vein injection. The tumor size and weight of mice were measured. The liver damages were examined by histopathology. Apoptosis and necrosis of tumor ceils were detected by flow cytometry. The endotumoral content of TNF-α was detected using a mouse TNF-a ELISA kit. The live vires was detected by bemagglutination (HA) test. Results The moderate-dose NDV D817 inhibited the tumor growth more apparently than 5-Fu. The tumor growth inhibition rate reached to 48.1%. The liver damage and the weight change caused by NDV were less severe. NDV D817 made an increased apoptosis index and induced production of TNF-α. Live virus was not detected in important organs except in the tumor of nude mice by HA test. Conclusion In the anti-tumor process in nude mice bearing xenografts of human colon carcinoma, a suitable dose of NDV D817 is more safe and effective.     

新城疫病毒D817对裸小鼠人结肠癌移植瘤的抑制作用

Objective To study the anti-tumor effects of Newcastle disease virus (NDV) strain D817 on human colon carcinoma model in nude mice. Methods The nude mouse model of human colon carcinoma was established by subcutaneous inoculation of human colon cancer LOVO cells. The tumor-bearing mice were given PBS, 5-Fu, high-dose NDV D817, moderate-dese NDV D817 or low-dose NDV D817 via caudal vein injection. The tumor size and weight of mice were measured. The liver damages were examined by histopathology. Apoptosis and necrosis of tumor ceils were detected by flow cytometry. The endotumoral content of TNF-α was detected using a mouse TNF-a ELISA kit. The live vires was detected by bemagglutination (HA) test. Results The moderate-dose NDV D817 inhibited the tumor growth more apparently than 5-Fu. The tumor growth inhibition rate reached to 48.1%. The liver damage and the weight change caused by NDV were less severe. NDV D817 made an increased apoptosis index and induced production of TNF-α. Live virus was not detected in important organs except in the tumor of nude mice by HA test. Conclusion In the anti-tumor process in nude mice bearing xenografts of human colon carcinoma, a suitable dose of NDV D817 is more safe and effective.     

新城疫病毒D817对裸小鼠人结肠癌移植瘤的抑制作用

Objective To study the anti-tumor effects of Newcastle disease virus (NDV) strain D817 on human colon carcinoma model in nude mice. Methods The nude mouse model of human colon carcinoma was established by subcutaneous inoculation of human colon cancer LOVO cells. The tumor-bearing mice were given PBS, 5-Fu, high-dose NDV D817, moderate-dese NDV D817 or low-dose NDV D817 via caudal vein injection. The tumor size and weight of mice were measured. The liver damages were examined by histopathology. Apoptosis and necrosis of tumor ceils were detected by flow cytometry. The endotumoral content of TNF-α was detected using a mouse TNF-a ELISA kit. The live vires was detected by bemagglutination (HA) test. Results The moderate-dose NDV D817 inhibited the tumor growth more apparently than 5-Fu. The tumor growth inhibition rate reached to 48.1%. The liver damage and the weight change caused by NDV were less severe. NDV D817 made an increased apoptosis index and induced production of TNF-α. Live virus was not detected in important organs except in the tumor of nude mice by HA test. Conclusion In the anti-tumor process in nude mice bearing xenografts of human colon carcinoma, a suitable dose of NDV D817 is more safe and effective.     

新城疫病毒D817对裸小鼠人结肠癌移植瘤的抑制作用

目的 观察新城疫病毒DK/HK/817/1980(NDV D817)对裸小鼠人结肠癌移植瘤的抑制作用.方法 采用LoVo细胞株建立裸小鼠人结肠癌移植瘤模型,分别给予裸小鼠尾静脉注射PBS、氟尿嘧啶(5-Fu)以及NDV D817高、中、低3个剂量,观察不同剂量NDV D817对移植瘤的抑制作用,病理学观察NDV D817对移植瘤和肝细胞的损伤程度,流式细胞术检测肿瘤细胞的凋亡和坏死情况,酶联免疫吸附试验(ELISA)试剂盒检测荷瘤小鼠体内肿瘤坏死因子-α(TNF-α)的含量,血凝实验检测荷瘤小鼠体内活病毒量.结果 中剂量NDV D817可明显抑制移植瘤的生长,肿瘤抑制率达48.1%.NDV D817对荷瘤小鼠体重和肝脏的损伤较小,且具有诱导肿瘤细胞凋亡和诱导机体产生TNF-α的能力.荷瘤小鼠处死后只在瘤内检测到活病毒,而在血清和其他脏器中并没有检出活病毒.结论 在对裸小鼠人结肠癌移植瘤的抑制过程中,NDV D817有明显的抑瘤效果,适当剂量的NDVD817更安全有效.     

自然杀伤细胞对小鼠HepS肝癌移植瘤的抑制作用研究

目的 研究自然杀伤(NK)细胞对原发性肝癌Heps移植瘤小鼠的治疗作用和机理。方法 建立小鼠移植性肝癌(Heps)实体瘤模型,随机分为生理盐水(NS)组、治疗1组(输注的NK细胞数为1×10⁴/只)、治疗2组(输注的NK细胞数为1×10⁵/只)和治疗3组(输注的NK细胞数为1×10⁶/只),每组15只。接种肝癌细胞当天,分别于尾静脉注射不同数量的NK细胞,对照组注射NS。观测小鼠移植瘤体积及各组小鼠平均生存时间。各组于输注NK细胞后第15天分别处死2只小鼠,对移植瘤组织切片进行HE染色,用流式细胞术(FCM)检测脾细胞NK的含量;乳酸脱氢酶(LDH)释放法检测脾细胞杀伤活性。结果 接种移植瘤后第8天,治疗3组移植瘤的生长速度较其他组小鼠显著减慢(P＜0.05)。第20天时治疗1组移植瘤体积明显小于对照组(P＜0.05),治疗2组和3组移植瘤体积非常显著小于对照组(P＜0.01)。治疗1组小鼠平均生存期明显长于对照组和治疗2、3组(P＜0.01)。治疗1-3组脾细胞杀伤活性以及NK细胞的含量高于对照组(P＜0.01)。结论 适量输注NK细胞可以有效抑制HepS肝癌移植瘤的生长,延长小鼠的生存期,为临床应用NK细胞治疗时数量的选择提供了实验依据。     

重组人生长激素对人肝癌细胞Bel-7402裸小鼠移植瘤生长的影响

背景与目的:在原发性肝癌患者围手术期应用重组人生长激素(recombinanthumangrowthhormone,rhGH),于改善患者状况同时是否会促进原有肿瘤生长、转移与复发,鲜见相关的研究报道。大多数原发性肝癌能表达生长激素受体(growthhormonereceptor,GHR),本研究拟探讨rhGH对表达GHR的人肝癌细胞Bel-7402裸小鼠移植瘤生长的影响。方法:放射配体分析法证实肝癌细胞Bel-7402表达GHR后行裸鼠肝内移植,将32只肝内移植人肝癌细胞Bel-7402的裸小鼠随机分为4组:1组为对照组,实验组则根据rhGH剂量不同分为3组[即0.5u·(kg·d)-1、1.0u·(kg·d)-1、2.0u·(kg·d)-1]。在肝脏肿瘤移植术后2周开始动物皮下注射rhGH2周,实验结束处死动物,检查肿瘤情况;用抗增殖细胞核抗原(proliferationcellnuclearantigen,PCNA)单克隆抗体免疫组化染色检测瘤组织PCNA表达情况。结果:移植瘤组织的重量与体积在rhGH1.0u·(kg·d)-1、2.0u·(kg·d)-1组与对照组之间比较有显著性差异(P<0.05),但0.5u·(kg·d)-1组与对照组无显著性差异(P>0.05)。各实验组肿瘤PCNA标记指数(labelingindex,LI)均高于对照组(P<0.05),各实验组之间相互比较差异亦有统计学意义(P<0.05)。rhGH用药剂量与LI显著相关(r=0.779,P<0.001)。结论:rhGH能促进裸小鼠肝脏人肝癌细胞Bel-7402移植瘤的生长,其作用有随用药量增加而增强的趋势,两者之间存在一定相关性。     

自然杀伤T细胞对小鼠肝癌移植瘤的抑制作用

Objective:The aim of this study was to investigate the inhibition effect of natural killer T(NKT) cells on transplantation hepatocellular carcinoma in mice.Methods:α-galactosylceramide(α-GalCer)-pulsed DC and Hep S were prepared as stimulus.Hepatoma xenograft model was established and mice were randomly divided into 4 groups(n=13 each group):(1) control group,intravenous injection of the same volume of saline.(2) mature DC group,intravenous injection of mature DC cells(4×106 cells).(3) α-GalCer-pulsed HepS ...     

绿茶儿茶素对BEL-7402人肝癌细胞裸小鼠异种移植瘤生长的影响

目的:探讨绿茶儿茶素(GTC)对BEL-7402人肝癌细胞在BALB/C裸小鼠体内生长的影响。方法:将受100μg/mlGTC作用4天的BEL-7402细胞接种于BALB/C裸小鼠,记录裸小鼠的发瘤时间。接种50天后处死裸小鼠,取瘤组织,测量其体积和重量。通过电镜、TUNEL和免疫组化等方法检测移植瘤细胞的凋亡情况。结果:GTC作用后的BEL-7402细胞在裸小鼠体内平均成瘤时间推迟,实验组:19.29±12.92(9～47)天,对照组:12.14±7.86(4～24)天;肿瘤平均体积缩小,实验组:0.35±0.22(0.05～0.73)cm3,对照组:1.45±1.20(0.17～3.28)cm3;平均重量减轻,实验组:0.18±0.14(0.03～0.42)g,对照组:0.65±0.48(0.14～1.31)g;瘤细胞凋亡增加,TUNEL阳性细胞计数均值,实验组和对照组分别为7.87±3.75/油镜视野和2.49±0.96/油镜视野。结论:GTC作用后的BEL-7402细胞在裸小鼠体内的生长受到抑制,其生长抑制作用可能与肿瘤细胞凋亡增加有关。     

裸小鼠原位移植建立人肝癌高转移模型

采用组织学完整的病人标本，以裸小鼠肝被膜下植入方法，从３０例人肝癌标本中筛选出一株人肝癌高转移瘤株，在裸小鼠体内成功地建立了人肝癌高转移模型ＬＣＩ－Ｄ２０。目前该瘤株在裸鼠体内生长１年，传代１６次，其移植生长率与自发转移率达１００％，表现为区域侵犯、肝内、淋巴结和肺转移、腹腔种植与血性腹水，并保持分泌甲胎蛋白的特性。组织病理学和电镜观察，流式细胞仪ＤＮＡ相对含量分析及染色体核型分析结果表明，移植瘤细胞与来源人肝癌细胞相似。本模型为原位移植模型，移植瘤的生长与转移，完全模拟了人肝癌的自然过程，为研究人肝癌转移机制和抗转移治疗提供了一个理想模型。     

裸小鼠移植瘤的转移研究

Rygaad和Povlsen 1969年首次将人结肠癌在裸小鼠移植成功,迄今大多数人恶性肿瘤均可在裸小鼠移植。大量研究表明裸小鼠人癌移植瘤是目前人体外最接近人类肿瘤的整体实验模型。但人癌裸小鼠移植后,能否保持其原浸润转移的恶性生物学行为,研究结果意见不一。利用人癌裸小鼠移植瘤模型研究人类肿瘤