奥曲肽联合罗非昔布增强对肝癌生长的抑制作用

目的 奥曲肽和罗非昔布均能抑制肝癌生长,但2种非细胞毒性药物的抗肿瘤机制不同。从多环节发挥抗癌作用的角度考虑,我们拟探讨奥曲肽联合罗非昔布能否协同抑制人肝癌细胞生长。方法 采用^3H-胸腺嘧啶核昔掺人法探讨奥曲肽和罗非昔布单独或联合应用对肝癌细胞株SMMC—7721增殖的影响,根据中效原理分析两者之间相互作用的关系。观察奥曲肽联合罗非昔布对人肝癌裸鼠原位移植瘤生长的影响。结果 奥曲肽联合罗非昔布在体外能显著抑制肝癌细胞生长,其合用浓度与^3H0-胸腺嘧啶核昔掺人量呈显著负相关(r＝—0．997,P＜0．01)。奥曲肽联合罗非昔布在大多数效应范围的合用指数小于1,具有明显的协同作用。联合用药组的抑瘤率(97．1％)较罗非昔布组(73．2％)明显提高(P＜0．05)。且联合组肿瘤内的纤维组织增生较对照组明显增多。在各组裸鼠的体内实验中末见明显不良反应。结论 奥曲肽联合罗非昔布可协同增加对人肝癌细胞在体外生长的抑制作用,也明显提高对肝癌裸鼠原位移植瘤的抑瘤率。     

奥曲肽联合wortmannin对人胃癌细胞BGC-823生长抑制作用的研究

目的 探讨奥曲肽与磷脂酰肌醇3激酶(PI3'K)通道抑制剂wortmannin联合用药对人胃癌细胞生长的影响及作用机制.方法 2007年6月至8月在武汉大学人民医院消化实验室培养人胃癌细胞BGC-823,以单用浓度为40nmol/L的wortmannin,奥曲肽4个稀释度10-5、10-4、10-3及10-2g/L及它们各稀释度与wortmannin(40nmol/L)的混合培养液作用24h后噻唑蓝(MTT)比色实验检测细胞存活率,单用奥曲肽稀释度为10-3g/L和wortmannin以及二者的混和液作用12、24、36、48 h检测细胞存活率,于24h检测细胞周期及各组p27基因信使核糖核苷酸(mRNA)和蛋白表达.结果 单用奥曲肽组随浓度增加,抑制作用增强,浓度为10-3g/L时,抑制作用明显较对照组增强;单用wortmannin,有较强的肿瘤细胞抑制生长作用,且两者联合用药抑制作用更加明显;单用奥曲肽浓度组随时间的延长其抑制效率逐渐下降,与wortmannin共同作用时,未见细胞明显耐药;通过细胞周期分析,奥曲肽和wortmannin均能抑制肿瘤细胞使其生长停留在G1期,两者联合用药抑制作用更强;在联合用药组中p27蛋白表达明显升高,且随奥曲肤浓度增加表达增加;p27基因mRNA表达在各组无明显差异.结论 奥曲肽和wortmannin对胃癌细胞BGC-823均有较强的抑制和杀伤作用,奥曲肽的抑制和毒性作用具有时间和浓度的依赖性,两者联合用药抑制和毒性效果更显著.P13'K抑制剂wortmannin和奥曲肽均能使肿瘤细胞停止生长在G1期.     

奥曲肽对人胃癌SGC-7901裸鼠种植瘤生长的影响

目的观察生长抑素类似物奥曲肽在体内对胃癌生长的影响。方法人胃癌细胞株SGC7901细胞接种于48只裸鼠背部皮下制成荷瘤动物模型。第8天将裸鼠随机分成4组:奥曲肽(Oct组,100μg/kg;s.c.qd);5Fu组(17mg/kg,ip,2次/周);奥曲肽和5Fu联合治疗组(联合治疗组);对照组,每组各12只裸鼠。连续用药6周。末次用药24小时后处死动物,检测肿瘤体积、重量、坏死体积,比较抑瘤率。结果奥曲肽组、5Fu组、联合治疗组、对照组的平均瘤体体积(cm3)分别为2.17±0.78、2.19±0.79、1.36±0.75、3.23±0.74(F=9.317,P=0.0001);平均瘤体重量(g)分别为6.88±2.06、7.22±2.47、4.47±2.28、10.30±2.80(F=5.452,P=0.0001);平均坏死体积(cm3)分别为0.55±0.38、0.52±0.53、1.14±0.83、0.32±0.27(F=13.987,P=0.0001);奥曲肽组、5Fu组、联合治疗组的抑瘤率分别为:33.20%、29.92%、56.60%(χ2=6.461,P=0.04)。结论奥曲肽可以抑制裸鼠胃癌移植瘤的生长。     

奥曲肽和奥美拉唑联合应用治疗食管静脉曲张破裂出血

目的观察奥曲肽和奥美拉唑联合应用对食管静脉曲张破裂出血的疗效．方法肝硬变食管静脉曲张破裂出血后患者47例，随机分为奥曲肽加奥美拉唑组（治疗组）32例，采用奥曲肽0．1mg加5％葡萄糖液静推后奥曲肽0．6mg加5％葡萄糖液静脉点滴25μg／h持续静点24h和奥美拉唑40mg，每12h静推1d后改口服奥美拉唑20mg，2次／d．奥曲肽对照组15例仅给予上述剂量奥曲肽治疗．结果两组患者经胃管内观察止血率分别为86．5％和80％（P＞0．05）．但大便潜血转阴率有显著差异，分别为87．5％和60％（P＜0．05）．结论奥曲肽与奥美拉唑联合治疗的效果优于单用奥曲肽组．     

奥曲肽抑制胃癌生长的实验研究

目的:研究生长抑素类似物奥曲肽在体内和体外对胃癌生长的影响及初步作用环节。方法:采用3H-胸腺嘧啶核苷(3H-TdR)掺入法及TdT介导的dUTP缺口末端标记(TUNEL)法检测奥曲肽对体外培养的SGC-7901胃癌细胞生长的影响及凋亡的诱导作用。建立裸鼠人胃癌原位移植瘤模型,给予奥曲肽治疗8周,观察其对裸鼠体内胃癌生长的影响。用免疫组化法检测奥曲肽对胃癌细胞及组织中增殖细胞核抗原(PCNA)表达的影响。用逆转录聚合酶链反应(RT-PCR)法检测胃癌细胞及组织中生长抑素受体(SSTR)-2和SSTR-3基因的表达。结果:奥曲肽可明显降低胃癌细胞的3H-TdR掺入,其效应与药物剂量呈明显正相关。奥曲肽可诱导SGC-7901胃癌细胞凋亡,其发生率为18.3%±2.7%。奥曲肽可抑制裸鼠人胃癌原位移植瘤的生长,其抑瘤率为62.3%。胃癌细胞及组织中PCNA的表达因奥曲肽的干预而明显下调。无论是胃癌细胞还是胃癌组织,均有SSTR-2和SSTR-3基因表达。结论:在体内及体外,奥曲肽通过SSTR-2和SSTR-3的介导可有效抑制胃癌生长。     

奥曲肽与奥美拉唑联合治疗儿童急性上消化道出血的疗效及安全性分析

目的探讨奥曲肽与奥美拉唑联合治疗儿童急性上消化道出血的疗效及安全性。方法回顾性分析2007年8月至2017年2月南京医科大学附属儿童医院收治的120例急性上消化道出血患儿的临床资料,按治疗方法的不同分为奥曲肽组、奥美拉唑组与联合组,每组各40例。所有患儿入院后均给予常规治疗,在此基础上,奥曲肽组给予单药奥曲肽治疗,奥美拉唑组给予单药奥美拉唑治疗,联合组给予奥曲肽联合奥美拉唑治疗。观察三组患儿治疗后的临床疗效、止血时间、住院时间及药物安全性。结果联合组临床总有效率(95. 00%)显著高于奥曲肽组(77. 50%)、奥美拉唑组(70. 00%),P均0. 05。联合组平均止血时间、平均住院时间显著短于奥曲肽组、奥美拉唑组(P均0. 05);奥曲肽组平均止血时间、平均住院时间显著短于奥美拉唑组(P均0. 05)。奥曲肽组、奥美拉唑组、联合组药物治疗期间不良反应总发生率分别为5. 00%、7. 50%、7. 50%,差异无统计学意义(P 0. 05)。结论应用奥曲肽与奥美拉唑联合治疗儿童急性上消化道出血较单药治疗更有利于提升临床疗效,显著缩短患儿止血时间及住院时间,且不明显增加药物不良反应,安全性较高,可作为临床治疗急性上消化道出血的常用方案。     

奥曲肽联合5-FU对人胃癌细胞株SGC-7901生长的影响

用不同浓度的奥曲肽联合5-FU作用SGC-7901细胞后，用MTT法测定细胞生长抑制率，流式细胞仪检测细胞中的Bel和Bax蛋白。结果奥曲肽作用于SGC-7901细胞24h后，可显著抑制胃癌细胞的生长，相同浓度奥曲肽加入80μg/ml 5-FU，细胞抑制率明显增强，与单用奥曲肽相比，P〈0.05；经奥曲肽及5-Fu处理的胃癌细胞，其Bcl蛋白表达显著减少，而Bax蛋白表达显著增加，二药联合与单药应用相比，P〈0.05。认为奥曲肽可显著抑制胃癌细胞的生长，奥曲肽联合5-FU对胃癌细胞的生长抑制作用增强；其作用机制是下调SGC-7901的Bel蛋白表达，而上调Bax蛋白表达。     

奥曲肽治疗肝硬化食管胃底静脉曲张破裂出血的疗效观察

目的观察国产奥曲肽治疗食管胃底静脉曲张破裂出血的临床效果。方法选择病人120例，随机分为奥曲肽组和垂体后叶素组两组。①奥曲肽组60例，给予国产奥曲肽200μg稀释缓慢注射后，再以50μg／h滴注，每天总量1200μg，有效者再连续用4d．②垂体后叶素组60例，给予垂体后叶素10IU稀释缓慢注射后，再以0．2IU／min滴注，每天总量288IU，有效者再连续用4d。结果两组治疗前的基本资料相似，有可比性。奥曲肽组的止血率在用药后12h、24h、48h、72h分别为71．6％、88．3％、91，6％、95．0％，均明显高于垂体后叶素组的51.7％、66．6％、70.0％、75.0％。国产奥曲肽组总有效率95．0％，亦明显高于垂体后叶素组的75．0％。国产奥曲肽再出血率为11．7％，明显低于垂体后叶素组再出血率23．3％。国产奥曲肽组未见明显不良反应。结论国产奥曲肽（50μg／h）治疗食管胃底静脉曲张破裂出血有显著的疗效，使用安全方便，缩短了止血时间，提高了止血成功率，再出血率低，未见明显的不良反应。     

塞来昔布联合奥曲肽抑制人胃癌生长的临床研究

目的 探讨环氧合酶-2（COX-2）抑制剂塞来昔布联合生长抑素类似物奥曲肽在人体内对胃癌生长的抑制作用。方法 51例胃癌患者随机分为对照组15例，术前不用药物；塞来昔布组18例，术前口服塞来昔布0．2g，每天1次，共7d；联合组18例，术前口服塞来昔布0．2g＋奥曲肽100μg皮下注射，每天1次，共7d。术中切除标本送组织学研究，分析胃癌组织坏死、炎性细胞浸润及纤维组织增生情况。免疫组化法检测胃癌组织微血管密度（MVD）及胃癌细胞COX-2表达情况，DNA末端原位标记染色法检测胃癌细胞凋亡。实时荧光定量逆转录聚合酶链反应法检测术前内镜活检的胃癌组织生长抑素受体（SSTR）的mRNA表达量。结果 与对照组比较，联合组胃癌组织坏死差异有统计学意义（P〈0．05），纤维组织增生明显（P〈0．05），胃癌细胞凋亡率（7．06％）高于对照组（6．23％），差异有统计学意义（P〈0．05）。联合组肿瘤组织中的MVD（20．44）较对照组（24．87）明显减少（P〈0．05），而各组COX-2表达差异无统计学意义（P〉0．05）。所有胃癌组织均有SSTR-1，SSTR-2，SSTR-3的mRNA表达。结论 塞来昔布联合奥曲肽对人体内胃癌生长具有明显抑制作用。     

奥曲肽和特利加压素单用或联用对肝硬化患者肝静脉压力梯度的影响

目的分别观察奥曲肽和特利加压素单用及二者联合对肝静脉压力梯度(HVPG)的影响。方法收集2011年1月-2014年4月山东大学附属省立医院消化科住院的肝硬化并静脉曲张患者49例,将患者分成奥曲肽组(A组)、特利加压素组(B组)、联合用药组(C组)。A组:奥曲肽0.1 mg静推(给药时间1 min),继以25μg/h泵入,分别测给药前及给药后1、5、10和15 min时的HVPG;B组:特利加压素1 mg静推(2 min内完成),分别测给药前及给药后10、20和30 min时的HVPG;C组:首先给予奥曲肽,分别测奥曲肽给药前及给药后1、5、10和15 min的HVPG,继以联合特利加压素静推,分别测定联合特利加压素后10、20和30 min时的HVPG。采用t检验、方差分析和卡方检验对数据进行统计学分析。结果 A组奥曲肽给药后1.5、10和15 min HVPG显著下降(t值分别为13.173、5.364、3.894、4.160,P值均<0.001),但5、10和15 min之间差异无统计学意义(P值均>0.05)。B组特利加压素给药20 min后HVPG显著下降(t=4.062,P=0.002),20和30 min HVPG之间差异有统计学意义(t=4.022,P=0.002)。C组加用特利加压素20 min后HVPG进一步下降(t=4.926,P<0.001),20和30 min HVPG之间差异无统计学意义(t=1.733,P=0.101)。三组疗效差异有统计学意义,C组疗效明显大于A、B组(F=10.423,P<0.05)。结论奥曲肽能很快降低肝硬化门静脉高压患者的HVPG,但短期内有所回升且趋于稳定。特利加压素单独应用亦能降低HVPG,起效时间比奥曲肽慢。奥曲肽加用特利加压素后可进一步降低HVPG,效果优于单独用药。     

阿司匹林对人胃癌细胞株的作用及机制探讨

目的 观察阿司匹林对人胃癌细胞株SGC7901生长及人胃癌裸鼠移植瘤生长的作用,并初步探讨其作用机制。方法 采用MTT法及流式细胞术检测不同浓度阿司匹林对胃癌细胞增殖及细胞周期的影响;Westem blot法检测阿司匹林对胃癌细胞COX-2、VEGF表达的影响;建立人胃癌裸鼠移植瘤模型,给予阿司匹林20天,观察肿瘤大小,免疫组化检测阿司匹林对肿瘤组织中COX-2、VEGF表达及MVD的影响。结果 阿司匹林对胃癌细胞的增殖具有抑制作用,且呈一定的时间、剂量依赖性;细胞周期分析表明阿司匹枳主要使细胞阻滞在G0/G1期;western blot检测表明阿司匹林能降低胃癌细胞COX-2、VEGF蛋白的表达;阿司匹林对裸鼠移植瘤的生长有抑制作用,免疫组化显示阿司匹林能降低移植瘤组织中(COX-2、VEGF的表达及MVD。结论 阿司匹林对胃癌细胞及裸鼠移植瘤均具有一定的抑制作用,其机制可能是通过对COX-2和VEGF等血管生成相关因子的抑制起作用。     

Effect of SU5416 on the inhibition of growth and metastasis of human gastric cancer implanted in nude mice

OBJECTIVE: To study the effects of the angio­genesis inhibitor SU5416 on the growth and liver metastasis of gastric cancer and to investigate its effects on the apoptosis of gastric cancer cells. METHODS: A model simulating the metastasis of human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into the gastric wall of nude mice, which were randomly divided into four groups: control group (saline solution), 5‐FU group (fluorouracil 30 mg/kg per day i.p), SU5416 group (SU5416 15 mg/kg per day i.p.), and combined treatment with 5‐Fu and SU5416. Eight weeks after implantation, the tumor weight, inhibition rate, intratumoral microvessel density (MVD), apoptotic index (AI), and the status of metastasis were evaluated after the mice were killed. RESULTS: Compared with the control group, the growth of the orthotopically‐implanted tumors was significantly inhibited, with reduced weight, and the tumor inhibition rate was 44.5%, 79.3%, and 84.4%, respectively, in the mice treated with 5‐FU, SU5416 and both. The incidence of liver metastasis was also significantly decreased in the 5‐Fu, SU5416, and combination groups compared with the control group (36.4%, 25.0%, and 0% vs 90.0%). The MVD of the 5‐FU group, the SU5416 group and the combined group was 13.1 ± 4.7, 3.9 ± 1.8 and 2.1 ± 1.5, respectively, which was decreased significantly compared with the control group (14.6 ± 5.8). The AI was increased significantly in the treated mice (6.81 ± 4.92%, 9.82 ± 3.76% and 17.65 ± 9.85% vs 3.76 ± 2.25%). The growth of and liver metastasis of the human gastric cancer implanted in the nude mice were both more significantly inhibited in the SU5416 group and the combined group than in the control and 5‐FU groups (P < 0.05). CONCLUSIONS: SU5416 can induce apoptosis in gastric cancer by inhibiting tumor angiogenesis and has a strong inhibitory effect on both the growth and liver metastasis of gastric cancer implanted in nude mice. The combination of SU5416 with other cytotoxic agents is more effective.     

维甲酸对胃癌生长和肝转移抑制作用的实验研究

[目的]研究维甲酸（RA）对裸鼠原位荷人胃癌细胞BGC-803移植瘤和肝转移的抑制作用。[方法]建立人胃癌裸鼠原位种植肝转移模型,分为2组,对照组和RA组,种植后第5天开始,分别自腹腔注射0．85％氯化钠、RA（1mg／kg）,每日1次,第8周处死动物,检测抑瘤率、胃癌细胞凋亡指数（AD,观察肿瘤细胞肝转移以及金属基质蛋白酶2（MMP-2）、增殖细胞核抗原（PCNA）的表达情况。[结果]RA组的抑瘤率为37．8％。与对照组相比,RA组胃癌生长、肝转移受到明显抑制（P〈0．05）,AI明显增高（P〈0．05）,MMP-2、PCNA的表达降低。[结论]RA对胃癌生长和肝转移的抑制可能通过诱导胃癌细胞凋亡、抑制细胞增殖以及肿瘤细胞外基质降解实现的。     

Inhibition of growth and metastasis of human gastric cancer implanted in nude mice by d-limonene

AIM:To investigate the effects and mechanism of d-limonene on the growth and metastasis of gastric cancer in vivo.METHODS: Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice. One percent d-limonene was orally administered at dose of 15 ml/kg every other day for seven weeks. Eight weeks after implantation, tumor weight,inhibition rate, apoptotic index (AI), microvessel density (MVD), vascular endothelial growth factor (VEGF), variation of ultrastructure, and the presence of metastasis were evaluated, respectively, after the mice were sacrificed.RESULTS: The tumor weight was significantly reduced in 5-FU group (2.55&#177;0.28 g), d-limonene group (1.49&#177;0.09 g)and combined treatment group (1.48&#177;0.21 g) compared with the control group(2.73&#177;0.23 g, P＜0.05). In 5-FU group, d-limonene group, combined treatment group, the inhibition rates were 2.60%,47.58% and 46.84% and 0,respectively;AI was (3.31&#177;0.33)%,(8.26&#177;1.21)%,(20.99&#177;1.84)% and (19.34&#177;2.19)%, respectively; MVD was (8.64&#177;2.81), (16.77&#177;1.39), (5.32&#177;4.26) and (5.86&#177;2.27), respectively; VEGF expression was (45.77&#177;4.79), (41.34&#177;5.41),(29.71&#177;8.92) and (28.24&#177;8.55), respectively. The incidences of peritoneal metastasis also decreased significantly in 5-FU group(77.8%), d-limonene group(20.0%) and combined group (22.2%) compared with control group (100%) versus 62.5%,30% and 22.2%)(P＜0.05). Liver metastasis was also inhibited and the incidences decreased significantly in 5-FU group, d-limonene group and combined group than that in control group (87.5% vs 55.5%, 20.0% and 22.2% respectively)(P＜0.05). The incidence of ascites in control group, 5-FU group, d-limonene group and combined group was 25.0%,22.2%, 0, 0, respectively and 12.5%, 11.1% 0, 0, with respect to the metastasis rate to other organs.CONCLUSION: d-limonene has antiangiogenic and proapoptotic effects on gastric cancer, thereby inhibits tumor growth and metastasis. Combination of d-limonene with cytotoxic agents may be more effective.     

重组反义c-myc 腺病毒对人胃癌细胞的体内及体外分子治疗

目的研究重组反义ｃｍｙｃ腺病毒对胃癌细胞的体内外生物学作用．方法采用ＬａｃＺ基因Ｘｇａｌ染色、ＭＴＴ,ＤＮＡ梯度降解试验、原位末端标记、流式细胞仪、ＰＣＲ分析、裸鼠致瘤性、裸鼠皮下移植瘤模型实验等方法,对反义ｃｍｙｃ重组腺病毒在人胃癌ＳＧＣ７９０１细胞系中的作用进行体内外研究．结果ＡｄＡＳｃｍｙｃ对ＳＧＣ７９０１细胞能产生明显的生长抑制作用,ＭＴＴ显示生长抑制率为４４１％．ＤＮＡ梯度降解试验、原位末端标记、流式细胞仪显示ＡｄＡＳｃｍｙｃ诱导了ＳＧＣ７９０１细胞凋亡．经ＡｄＡＳｃｍｙｃ处理的ＳＧＣ７９０１细胞裸鼠致瘤性消失．ＡｄＡＳｃｍｙｃ对裸鼠皮下移植瘤模型瘤内注射能有效降低肿瘤的生长速度,生长抑制率为６８９％．结论ＡｄＡＳｃｍｙｃ对胃癌细胞具有显著的体内外生长抑制及凋亡诱导作用     

Effects of mifepristone on invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 in vitro and in vivo

AIM： To investigate the effects of mifepristone on the invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 and its mechanisms. METHODS: After incubation with various concentrations of mifepristone (5, 10, 20 umol/L), the adhesion to artificial basement membrane, Matrigel, and the migration of MKN-45 cells were assayed using MTT assay and Transwell cell culture chambers, respectively. Enzyme- linked immunoabsorbent assay (ELISA) and flow cytometry were used to determine the expression of vascular endothelial growth factor (VEGF) and integrin 133 in the cells. After subcutaneous transplantation of MKN-45 cells in nude mice, mifepristone (50 mg/kg.d) was administrated subcutaneously for 8 wk to assess its effects on tumor metastasis. Immunohistochemical analysis was used to detect the expression of VEGF and microvascular density (MVD) in xenografted tumors. RESULTS: Mifepristone dose-dependently inhibited the heterotypic adhesion to Matrigel of MKN-45 cells. The inhibition was accompanied by a significant down-regulation of integrin 133 expression in the cells. After incubation with 5, 10, 20 umol/L mifepristone, the number of migrated MKN-45 cells was 72+8, 50+6, 41+5 in experiment group, and 94+16 in control group (P&lt;0.01). Meanwhile, secreted VEGF protein of MKN-45 cells in mifepristone-treated group (14.2+2.9, 8.9+3.1, 5.4+2.1 ng/g per liter) was significantly lower than that in control group (22.7+4.3 ng/g per liter, P&lt;0.01). In vivo, mifepristone decreased the number of metastatic foci in lungs of nude mice and down-regulated the expression of VEGF and MVD in the xenograted tumors. CONCLUSION: Mifepristone can effectively inhibit the invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 in vitro and in vivo through inhibition of heterotypic adhesion to basement membrane, cell migration and angiogenesis.     

Over-expressed and truncated midkines promote proliferation of BGC823 cells in vitro and tumor growth in vivo

AIM： To determine whether midkine （M/O and its truncated form （tMK） contribute to gastric tumorigenesis using in vitro and in vivo models. METHODS： Human MK and tMt（ plasmids were constructed and expressed in BGC823 （a gastric adenocarcinoma cell line） to investigate the effect of over-expressed MK or tMK on cell growth and turmorigenesis in nude mice. RESULTS： The growth of MK-transfected or tMK- transfected cells was significantly increased compared with that of the control cells, and tMK-transfected cells grew more rapidly than MK-transfected cells. The number of colony formation of the cells transfected with MK or tMK gene was larger than the control cells. In nude mice injected with MK-transfected or tMK-transfected cells, visible tumor was observed earlier and the tumor tissues were larger in size and weight than in control animals that were injected with cells without the transfection of either genes. CONCLUSION： Over-expressed MK or tMtC can promote human gastric cancer cell growth in vitro and in vivo, and bMK has greater effect than MK. tMK may be a more promising gene therapeutic target compared with MK for treatment of malignant tumors.     

rmhTNF对人胃癌细胞株裸鼠移植瘤模型的治疗作用

背景:重组改构人肿瘤坏死因子(rmhTNF)是原型TNF-α的改构体,前期实验显示其对体外培养的人胃癌细胞株具有抑制增殖和诱导凋亡作用。目的:初步研究rmhTNF对人胃癌细胞株裸鼠移植瘤模型的治疗作用。方法:雄性BALB/c裸鼠皮下接种人胃癌细胞株BGC-823构建移植瘤模型,随机予rmhTNF、TNF-α,5-氟尿嘧啶(阳性对照)和0.9%NaCl溶液(阴性对照)进行干预,观察各组裸鼠一般情况、移植瘤生长情况及其组织病理学改变。结果:建模裸鼠成瘤率为100%。各药物干预组移植瘤生长均明显减慢,其中rmhTNF组生长抑制最为明显,生长曲线较阴性对照组明显下移,抑瘤率显著高于TNF-α组和阳性对照组(83.1%对59.8%和50.1%,P0.01),一般情况与接种前相比无明显改变,移植瘤组织中可见较多凋亡和坏死细胞。结论:BGC-823细胞在BALB/c裸鼠皮下有良好的成瘤性。rmhTNF在体内能直接诱导胃癌细胞凋亡和坏死,对人胃癌细胞株裸鼠移植瘤模型具有治疗作用。     

Tumorigenicity,invasion, and metastasis of human gastric cancer in nude mice

Summary Tumors derived from 105 patients with gastric cancer were subcutaneously heterotransplanted into nude mice in order to study their tumorigenicity and malignant behavior. Of the 105 gastric cancers, 45 were successfully transplanted (a 42.9% tumorigenesis rate). The tumorigenesis rate of Borrmann type 1 and 2 cancers (77.8%) was significantly higher than that of type 3 and 4 cancers (34.6%). Also, the tumorigenesis rate of differentiated carcinoma (57.1 %) was significantly higher than that of undifferentiated carcinoma (30.9%). Spontaneous metastases from the subcutaneous tumors were observed in 5 of the 37 established tumor lines (13.5%), and macroscopic pulmonary metastases were common with one tumor line (SCK-29). Although most of the subcutaneous gastric cancers showed local expansion without distant metastasis, the same tumor cells implanted into the peritoneal cavity exhibited invasive growth and/or metastasis. Thus, the expression of a metastatic pheno-type by human gastric cancer was influenced by the host microenvironment. The SCK-29 tumor line with its high metastatic potential may be useful for studies on the mechanism of blood-borne metastasis.Abbreviations pap papillary adenocarcinoma - tub₁ well-differentiated adenocarcinoma - tub₂ moderately differentiated adenocarcinoma - por poorly differentiated adenocarcinoma - sig signet-ring cell adenocarcinoma - muc mucinus adenocarcinoma - giant giant cell adenocarcinoma - ud undifferentiated adenocarcinoma - ade ascitic adenocarcinoma This study was supported in part by a grant-in aid for cancer research (B.no. 63480309) from the Ministry of Education, Science and Culture, Japan