尼美舒利对乙基硝基亚硝基胍诱导大鼠胃癌的化学预防作用

目的　探讨选择性环氧合酶 2 (COX 2 )抑制剂尼美舒利对乙基硝基亚硝基胍 (ENNG)诱发大鼠胃癌的化学预防作用。方法　 96只雄性Wistar大鼠分成 6组分别饮用不同药物 :阴性对照组 (P组 ,纯净水 )、胃癌模型组 (M组 )、尼美舒利小剂量干预组 (MNL 组 )和大剂量干预组 (MNH 组 )、尼美舒利小剂量对照组 (NL 组 )和大剂量对照组 (NH 组 )。喂养 (2 8± 2 )周后观察各组大鼠的胃黏膜病变。结果　 89只 (92 .7% )大鼠完成实验。M组大鼠胃癌发生率为 5 6 .3% (9/ 16 ) ,显著高于MNL 组的 7.4 %(1/ 14 )和MNH 组的 6 .3% (1/ 16 ,P <0 .0 1) ,但MNL 组和MNH 组之间胃癌发生率差异无显著性 (P >0 .0 5 ) ;P组、NL 组和NH 组均无胃癌发生。M组大鼠胃黏膜萎缩、肠化和异型增生发生率也显著高于MNL 组和MNH 组 (P <0 .0 5 )。M组、MNL 组和MNH 组胃黏膜COX 2蛋白表达的阳性率分别为6 8.7% (11/ 16 )、2 1.4 % (3/ 14 )和 12 .5 % (2 / 16 ,P <0 .0 1)。结论　选择性COX 2抑制剂尼美舒利能有效抑制ENNG诱导的大鼠胃癌及癌前状态的发生 ,这为COX 2抑制剂对人类胃癌有潜在化学预防作用提供了证据。     

尼美舒利增强丝裂霉素抑制体外培养人胃癌细胞的细胞增殖及诱导凋亡的实验研究

丝裂霉素是胃癌化疗常用药物之一，不良反应主要有骨髓毒性、肾毒性及胃肠道反应等，寻求新的胃癌化疗药物及方案，以增强疗效及减少毒副作用一直是研究的热点。近年来，众多的流行病学及实验室资料表明非甾体类消炎药(NSAIDs)对消化道肿瘤具有防治作用，能减少消化道肿瘤的发生及增强传统抗癌化疗药物的抗癌作用，其作用在于抑制环氧合酶-2(COX-2)。目前，国外这方面的研究主要针对     

N-甲基-N′-硝基-N-亚硝基胍胃癌前病变大鼠造模联合因素的探讨

N-甲基-N′-硝基-N-亚硝基胍（MNNG）是目前使用最广泛的胃癌癌前病变（PLGC）大鼠模型的造模用药,但造模时间过长。多种因素联合造模可缩短造模时间,促进造模效果。国内外文献中,除MNNG外,还有其他多种理化造模因素可供选用,是否适合与MNNG联合造模,笔者探讨如下。     

尼美舒利抑制结肠癌LOVO细胞增殖及转移的机制

目的 研究选择性COX2抑制剂尼美舒利(Nimesulide)对结肠癌细胞株LOVO生长的影响以及其参与抑制肿瘤血管转移的可能机制.方法 采用四甲基偶氮唑蓝(MTT)比色法观察尼美舒利对结肠癌细胞增殖的抑制,电镜下观察尼美舒利作用后细胞的超微结构变化,ELISA法检测尼美舒利对上清液中血管内皮生长因子(VEGF)的影响.结果 MTT显示尼美舒利能抑制LOVO的增殖,呈剂量和浓度依赖性.0.2 mmol/L尼美舒利作用72 h后电镜观察可见典型的凋亡小体.尼美舒利作用后上清液中VEGF的含量呈剂量依赖性下调.结论 尼美舒利可抑制结肠癌细胞株LOVO的生长,促进其凋亡,还可下调细胞上清中的VEGF含量,推测其通过抑制VEGF释放,从而抑制肿瘤的生长及浸润转移.     

尼美舒利抑制人结肠癌细胞增殖及诱导凋亡

目的　研究尼美舒利对结肠癌细胞株 (HT 2 9)增殖的影响 ,探讨其可能的使用机制。方法　以人结肠癌细胞株作为研究对象 ,采用噻唑蓝 (MTT)法、流式细胞仪 (FCM)、电镜和细胞免疫组化等技术 ,研究尼美舒利对结肠癌细胞增殖的抑制和促进凋亡的可能机制。结果　MTT显示尼美舒利对Eca 10 9有细胞毒作用 ,且与药物浓度和作用时间有相关性 (r=0 .9760 ,P <0 .0 5。FCM显示DNA直方图上出现典型的亚二倍体“凋亡峰” ,凋亡率在 6.2 8%～ 3 9.3 % ,使S期、G2 /M期细胞比例升高 ,G1期比例下降 ,呈一定剂量效应关系。电镜下见典型的细胞凋亡形态学特征 :细胞核染色质致密浓缩 ,凋亡小体形成等。并能在体外抑制结肠癌细胞的COX 2和Bcl 2表达。结论　体外尼美舒利能抑制人结肠癌细胞的增殖 ,可能与诱导细胞凋亡和阻止细胞周期的进展 ,抑制COX 2和Bcl 2的表达有关     

甲基硝基亚硝基胍对日本血吸虫成虫培养细胞骨架作用的研究

目的 通过观察N－甲基－N－硝基－N－亚硝基胍（MNNG）诱导日本血吸虫培养细胞后骨架的改变,研究MNNG对培养细胞转化、增殖的作用。方法 将日本血吸虫成虫培养细胞接种于小盖玻片上,培养1周时用浓度为3mg/L的MNNG处理48h,然后用RPMI－1640含20％小牛血清附加常量抗菌素的培养基培养2周,再换用RPMI－1640含5％小牛血清的培养基继续培养,用考马斯亮兰染色法和鬼笔环肽荧光染色法显示培养细胞骨架。结果 MNNG诱导后,在培养第4、5周时部分培养细胞骨架排列紊乱,微丝集聚于细胞边缘。结论 MNNG有一定诱导日本血吸虫成虫培养细胞转化、促进其分裂的作用。     

环氧合酶-2、核因子-κB在胃癌、癌前病变中的表达及尼美舒利逆转其表达的实验研究

目的探讨环氧合酶（COX）-2、核因子（NF）-κB在胃癌及异型增生中的表达，并研究尼美舒利对人胃癌SGC-7901细胞增殖及COX-2、NF-κB表达的影响。方法采用免疫组化Powervi-sionTM两步法对84例胃癌和54例胃异型增生组织中COX-2、NF-κB的表达进行检测；在体外实验中对人胃癌SGC-7901细胞采用细胞培养，MTT法检测不同浓度尼美舒利对人胃癌SGC-7901细胞增殖的抑制作用，免疫组化、Western blot方法检测药物对COX-2、NF-κB表达的影响。结果COX-2、NF-κB在胃癌中的阳性表达率分别为66．67％、59．52％，均高于异型增生（P〈0．05），COX-2表达与肿瘤的大小、淋巴转移呈正相关（P〈0．05），并与NF-κB的表达相关（P〈0．05），COX-2与肿瘤浸润深度正相关（P〈0．05）。体外实验中结果显示尼美舒利可以抑制人胃癌SGC-7901细胞生长并具有浓度、时间依赖性；与阴性对照组相比，药物作用48h后尼美舒利100、200 μmol／L组COX-2、NF-κB蛋白表达明显减弱并具有剂量依赖性（P〈0．05），COX-2、NF-κB之间正相关（P〈0．05）。结论COX-2、NF-κB与胃癌的发生转移相关，并且NF-κB蛋白作为上游调控因子调节COX-2的表达。尼美舒利可以抑制人胃癌SGC-7901细胞增殖，抑制COX-2、NF-κB的表达在其抑制肿瘤机制中可能具有一定作用。     

甲基硝基亚硝基胍对日本血吸虫成虫培养细胞磷酸酶影响的研究

目的 研究甲基硝基亚硝基胍（MNNG）对日本血吸虫成虫培养细胞碱性磷酸酶（AKP）和酸性磷酸酶（ACP）活性的影响。方法 将虫龄26d的日本血吸虫成虫细胞接种于小盖玻片上，在RPMI－1640含20％小牛血清附加常量抗生素的常规培养基中培养第7天时，随机分为实验组和对照组，实验组用含浓度为3μg/mlMNNG的常规培养基处理48h，对照组用不含MNNG的常规培养基处理同样时间，随后换用常规培养基培养3周，当再换用含5％小牛血清的培养基培养1周时，分别用Gomori钙钴法和Gomori硫化铅法对两组培养细胞进行AKP和ACP细胞化学染色，用实验组培养细胞的AKP、ACP活性明显高于对照组培养细胞的活性（P＜0．01）。结论 MNNG能增强日本血吸虫成虫培养细胞AKP、APC的活力，对培养细胞有促生长或／或诱导其转化的作用。     

选择性COX-2抑制剂尼美舒利对肺癌放射治疗增敏作用及其机制研究

目的 观察选择性环氧化酶抑制剂与放射治疗联合应用对人肺腺癌A549裸鼠移植瘤生长的影响并进一步探讨其放疗增敏机制.方法 首先构建人肺腺癌A549裸鼠移植瘤模型,待裸鼠移植瘤长至最长径6.0 mm时随机分为4组:对照组、尼美舒利组、放疗组、尼美舒利联合放疗组.尼美舒利溶于0.5％羟甲基纤维素钠中,采用灌胃方式给药,剂量为60 mg·kg1·d-1,共28 d.移植瘤最大径长至6.0 mm时予以局部单次大剂量放疗10 Gy.观察各组移植瘤最长径由6 mm长至12 mm所需时间,以移植瘤体积绘制生长曲线,计算抑瘤率,用免疫组化方法检测增殖细胞核抗原(PCNA)、前凋亡蛋白Bax、凋亡抑制蛋白Bcl-2在组织中表达情况,应用流式细胞技术测定细胞周期分布及凋亡率.结果 尼美舒利联合放疗对肺腺癌裸鼠移植瘤生长有明显抑制作用.对照组移植瘤最长径由6 mm增长至12 mm所需时间为(7.12±0.72)d,放疗组为(8.34±0.71)d,尼美舒利组为(11.29±0.78)d,尼美舒利联合放疗组为(14.62±0.19)d.放疗组抑瘤率为21.2％,尼美舒利组为18.3％,尼美舒利联合放疗组为41.7％.应用免疫组化方法检测移植瘤中PCNA和Bcl-2表达的阳性面积百分比及灰度值:尼美舒利联合放疗组、放疗组、尼美舒利组均低于对照组(P值均＜0.05),且尼美舒利联合放疗组低于放疗组及尼美舒利组(P值均＜0.05);Bax表达阳性面积百分比及灰度值:尼美舒利联合放疗组、放疗组、尼美舒利组均高于对照组(P值均＜0.05),且尼美舒利联合放疗组高于放疗组及尼美舒利组(P值均＜0.05).流式细胞仪检测细胞凋亡率及细胞周期分布:尼美舒利联合放疗组、放疗组、尼美舒利组凋亡率均高于对照组(P值均＜0.05),且尼美舒利联合放疗组高于放疗组及尼美舒利组(P值均＜0.05);G0/G1期各组差异无统计学意义(F＝2.731,P＞0.05);S期尼美舒利联合放疗组、放疗组、尼美舒利组均低于对照组(P值均＜0.05),且尼美舒利联合放疗组低于放疗组及尼美舒利组(P值均＜0.05);G2/M期尼美舒利联合放疗组同其他各组相比增多(P值均＜0.05),对照组、放疗组、尼美舒利组差异无统计学意义(P＞0.05).结论 尼美舒利可抑制人肺腺癌A549裸鼠移植瘤的生长,尼美舒利增强人肺腺癌A549裸鼠移植瘤对放射治疗的敏感性.其机制可能同抑制PCNA表达,从而抑制肿瘤细胞的生长,并通过抑制Bcl-2表达、增强Bax表达,而诱导A549细胞凋亡有关;还可能与细胞周期分布中对放疗不敏感的S期细胞数减少而对放疗敏感的G2/M期细胞数增加有关.     

新的肿瘤标志物GP87在老年胃癌及胃癌前病变组织中表达的研究

目的探讨新的肿瘤标志物ＧＰ８７在老年胃癌及胃癌前病变中表达的情况,从而确定其在上述病变中的应用价值。方法采用ｓＡＢＣ免疫组化染色法对２８３例标本进行染色分析。结果正常胃体、胃窦均为阴性,浅表性胃炎组阳性率为７．１％,明显低于癌症组及癌前病变组（Ｐ＜０．０１）。胃癌组阳性率为６２．０％,明显低于癌前病变各组阳性率（Ｐ＜０．０５）,癌旁粘膜组阳性率亦较高,在８０．０％左右。结论新的肿瘤标志物ＧＰ８７在胃癌及胃癌前病变中均有较高表达,特别是在胃癌前病变中的表达更高,故认为ＧＰ８７是检测胃癌前病变较好的肿瘤标志物,可用于胃癌高危人群的普查,筛选出具有明确癌前病变的病人,定期随访、长期追踪,无疑有助于发现早期胃癌。     

善胃系列方分阶段辨治胃癌前病变的临床疗效观察

背景 胃镜及靶向活检技术对胃癌前病变(precancerous lesion of gastric cancer,PLGC)早期精确诊断有优势;中医药治疗虽疗效确切,但多基于主观症状,缺少客观依据.本文结合胃镜精检技术与中医分期辨治,探讨PLGC不同分期中医证候与胃镜病理的相关性.目的 探究善胃系列方分阶段治疗PLGC...     

Treatment of gastric precancerous lesions with Weiansan

INTRODUCTIONGastric precancerous lesion (GPL) is one of the diseases of the digestive system, easily occurring in gastric mucosa with changes such as gastric epithelial dysplasia (GED) and intestinal metaplasia (IM) resulting in chronic atrophic gastritis…     

亚甲蓝染色对胃癌前病变的诊断价值

目的研究胃镜下亚甲蓝染色对胃癌前病变的诊断价值。方法胃镜下有胃黏膜异常表现的46例患者,用0.5%的亚甲蓝均匀喷洒于胃黏膜,然后在染色的部位取活检送病理组织学检查。将同期胃镜下有胃黏膜异常表现但未染色的50例作为对照组。结果染色组有29例存在胃黏膜肠上皮化生(gastric intestinal metaplas,GIM)和不典型增生(atypical hyperplasia,ATP),检出率63.04%,对照组检出率为24%。结论胃镜下亚甲蓝染色可明显提高胃癌前病变的检出率。     

Long-term course of precancerous lesions arising in patients with gastric MALT lymphoma

Background and aimsTo evaluate the prevalence and the long-term course of gastric precancerous lesions in patients with GML.Patients and methodsIn this retrospective single-centre study, we included 179 patients with GML, 70 with gastric diffuse large B-cell lymphoma (GDLBCL) and 152 with Helicobacter pylori-associated gastritis (HpG), from January 1995 to January 2014. The presence of atrophic gastritis, intestinal metaplasia and neoplastic lesion has been assessed at baseline and during follow-up.ResultsAtrophic gastritis was more frequent in the GML group whereas there was also a trend for intestinal metaplasia and gastric dysplasia. In patients with GML, atrophic gastritis, intestinal metaplasia and gastric dysplasia were more frequent in the GML area than in other part of the stomach. During follow-up, the prevalence of atrophic gastritis remained stable overtime whereas intestinal metaplasia and dysplasia tend to increase overtime. In multivariate analysis, the occurrence of dysplasia or carcinoma was associated with the presence of intestinal metaplasia at baseline and male gender.ConclusionGML is associated with gastric precancerous lesion to a higher extent than GDLBCL and HpG. Those precancerous lesions do not regress despite achievement of complete remission of GML and tend to increase overtime.     

Interventional effect of Ginkgo biloba extract on the progression of gastric precancerous lesions in rats

OBJECTIVE: To investigate the effect of Ginkgo biloba extract on gastric precancerous lesions in rats. METHODS: 80 4‐week‐old Wistar rats were randomly divided into four groups: a control group, a model group, a low and a high dose Ginkgo biloba extract intervention group; 20 in each group. Gastric precancerous lesions were induced by giving them 100 mg/L N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) solution to drink ad libitum for 20 weeks. In addition to the MNNG, the intervention groups were lavaged with Ginkgo biloba extract (0.5 mg/kg/d in the low dose group, 1.5 mg/kg/d in the high dose group) for 20 weeks. Starting from week 21 all the rats were fed with normal rat chow and tap water. At the end of week 30 the rats were killed. The histopathological changes of their gastric mucosa, ISA, NGI, the serum and gastric mucosal SOD/MDA and the expressions of oncogenes were studied. RESULTS: The incidence of mild to severe intestinal metaplasia and dysplasia were significantly lower in the intervention groups than those in the model group (P < 0.01). The ISA and NGI in the intervention groups were significantly lower than those in the model group (P < 0.01). In the intervention groups the activity of SOD was increased and the concentration of MDA was decreased (P < 0.01). Expressions of Bcl‐2, c‐myc and FasL decreased in the intevention groups, whereas the expression of Fas increased. When compared with the model group, the differences were statistically significant (P < 0.01, P < 0.05, respectively). CONCLUSION: Ginkgo biloba extract can increase anti‐oxidative activity and inhibit the progression of gastric precancerous lesions via the regulation of cell proliferation and apoptosis.     

Expression of ornithine decarboxylase in precancerous and cancerous gastric lesions

AIM: To investigate the expression of ornithine decarboxylase (ODC) in precancerous and cancerous gastric lesions. METHODS: We studied the expression of ODC in gastric mucosa from patients with chronic superficial gastritis (CSG,n = 32),chronic atrophic gastritis CAG,n = 43; 15 with and 28 without intestinal metaplasia (IM),gastric dysplasia (DYS,n = 11) and gastric cancer (GC,n = 48) tissues using immunohistochemical staining. All 134 biopsy specimens of gastric mucosa were collected by gastroscopy. METHODS: The positive rate of ODC expression was 34.4%,42.9%,73.3%,81.8% and 91.7% in cases with CSG,CAG without IM,CAG with IM,DYS and GC,respectively (P < 0.01),The positive rate of ODC expression increased in the order of CSG < CAG (without IM) < CAG (with IM) < DYS and finally,GC. In addition,ODC positive immunostaining rate was lower in well-differentiated GC than in poorly-differentiated GC (P < 0.05). CONCLUSION: The expression of ODC is positively correlated with the degree of malignity of gastric mucosa and development of gastric lesions. This finding indicates that ODC may be used as a good biomarker in the screening and diagnosis of precancerous lesions.     

Effect of Helicobacter pylori infection on Bax protein expression in patients with gastric precancerous lesions

AIM: To investigate the effect of Helicobacter pylori (H pylori) infection on Bax protein expression, and explore the role of H pylori in gastric carcinogenesis. METHODS: H pylori was assessed by rapid urease test and Warthin-Starry method, and expression of Bax protein was examined immunohistochemically in 72 patients with pre-malignant lesions. RESULTS: Bax protein was differently expressed in intestinal metaplasia and gastric dysplasia, and showed 63.99% positivity. The positivity of Bax protein expression in Hpylori-positive gastric precancerous lesions (72.3%) was significantly higher than that in H pylori-negative gastric precancerous lesions (48.0%, X~2=4.191, P<0.05). H pylori infection was well correlated with the expression of Bax protein in gastric precancerous lesions (r=0.978, P<0.01). After eradication of H pylori, the positivity of Bax protein expression significantly decreased in H pylort-positive gastric precancerous lesions (X~2=5.506, P<0.05). In the persisting H pylori-infected patients, the positivity of Bax protein expression was not changed. CONCLUSION: H pylori infection may be involved in the upregulation of Bax gene, which might be one of the mechanisms of H pylori infection-induced gastric epithelial cell apoptosis. H pylori might act as a tumor promoter in the genesis of gastric carcinoma and eradication of H pylori could inhibit gastric carcinogenesis.     

幽门螺杆菌感染在胃癌及癌前病变中的研究

目的　研究胃癌及癌前病变与Hp感染的关系 ,以探讨Hp可能的致癌机制。 方法　经内镜和病理明确诊断的胃癌及癌前病变者共 5 48例 ,包括慢性浅表性胃炎 (CSG) 16 3例、慢性萎缩性胃炎 (CAG) 2 0 7例、肠上皮化生 (IM) 71例 ,异型增生(DYS) 4 5例及胃癌 (GC) 6 2例。每例均活检胃窦大小弯、胃角及胃体大小弯共 5块 ,以WS法检测Hp。结果　癌前病变及胃癌Hp感染均较高 ,CAG(4 2 .5 % ) ,IM(76 .1% ) ,DYS(88.9% )和GC(72 .5 % ) ,与CSG(2 3.9% )有显著性差异 (P <0 .0 5或P <0 .0 1)。随着年龄增大 ,CAG、IM、DYS和GC逐步增多 ,而且≥ 5 6岁年龄组IM、DYS和GC显著多于≤ 40岁组 (P <0 .0 5 ) ,但CSG则相反。肠型胃癌和Hp感染密切相关 (P <0 .0 5 ) ,从胃窦小弯和大弯、胃角及胃体小弯和大弯顺序 ,Hp感染随着CSG、CAG、IM、DYS和GC病变而增高 ,Hp感染部位也在上移 ,尤其在胃体小弯及大弯 ,IM、DYS和GC的Hp感染显著高于CSC部位 (P <0 0 5 )。结论　Hp感染是导致从胃炎→胃萎缩→肠化→异型增生→癌变序列发展的危险因子 ,肠型胃癌和Hp感染密切相关 ,胃镜检查应该多部位取活检作病理及Hp检测 ,尤其是高位