RegIα蛋白表达与原发性胃癌发展过程的病理特性和相关性研究

目的探讨RegIα蛋白表达与原发性胃癌发展过程的病理特性和相关性。方法收集本院胃癌标本138例，设胃癌组和癌旁正常黏膜组，采用免疫组化观察RegIα蛋白在原发胃癌的表达，并对2年原发性胃癌患者生存率进行分析。结果与对照组比，胃癌RegIα阳性率为64．1％；早期胃癌和进展期胃癌RegIα表达无差异，但Borrmann IV RegIα阳性表达强于其他分期；阳性主要集中在胃窦；印戒细胞癌阳性表达较高；淋巴细胞转移与血行转移RegIα阳性表达较高；临床分期、分化程度与RegIα表达有关，与年龄、性别、肿瘤位置、肿瘤大小无关。胃癌患者RegIα蛋白表达阴性的2年生存率为84．9％。结论Reg1α可作为评价胃癌预后的参考指标。     

狭叶红景天的毒理学研究

经小鼠灌胃给药和腹腔注射给药两种途径进行小鼠急性毒性试验，结果小鼠灌胃给药的最大耐受量为３８ｇ／ｋｇ，最小致死量为５０ｇ／ｋｇ，小鼠腹腔注射给药的ＬＤ５０为８．６ｇ／ｋｇ。Ｗｉｓｔａｒ大鼠６周口服给药长毒试验结果显示，该药除使大鼠体重增长有较明显的减缓外，其余指标未见明显毒性反应。     

胃癌组织及区域淋巴结MUC1、CD44v6、nm23表达与胃癌侵袭转移及预后的关系

背景与目的:研究证实胃癌浸润深度和淋巴结转移是多基因及其蛋白表达产物协调作用的结果,寻找与胃癌转移相关的分子生物学标志物有助于胃癌的研究。本实验旨在探讨胃癌组织及区域淋巴结中MUC1、CD44v6、nm23表达与胃癌侵袭转移及预后的关系。方法:采用SP免疫组织化学方法对110例胃癌组织及613枚区域淋巴结中的MUC1、CD44v6、nm23基因蛋白的表达进行检测。结果:①胃癌组织中的MUC1蛋白阳性表达在低分化癌组、浸润型组、T3+T4组、淋巴结转移组、Ⅲ～Ⅳ期组、生存期<5年组分别为84.6%、88.1%、87.3%、91.7%、94.4%、95.5%,CD44v6分别为79.5%、74.6%、79.4%、81.7%、87.0%、87.9%,nm23分别为38.5%、32.2%、30.2%、25.0%、25.9%、18.2%。MUC1和CD44v6表达低分化癌组显著高于高、中分化癌组(78.9%vs57.7%),浸润型组高于局限型组(72.6%vs54.9%),T3+T4组高于T2组(72.3%vs46.8%),淋巴结转移组高于无淋巴结转移组(68.0%vs46.0%),TNMⅢ～Ⅳ期组高于Ⅰ～Ⅱ期组(67.9%vs44.6%),生存期<5年组高于≥5年组(59.1%vs31.8%),各组间差异均具有显著性(P<0.01或P<0.05)。而nm23除分化程度、Borrmann分型不同的两组之间差异无显著性外,T3+T4组低于T2组(51.1%),有淋巴结转移组低于无淋巴结转移组(56.0%),TNMⅢ～Ⅳ期组低于Ⅰ～Ⅱ     

Expression and localization of Reg IV in human neoplastic and non-neoplastic tissues: Reg IV expression is associated with intestinal and neuroendocrine differentiation in gastric adenocarcinoma

Regenerating islet-derived family, member 4 (Reg IV) is a candidate marker for cancer and inflammatory bowel disease. In the present study, immunohistochemical analysis of Reg IV was performed in various human neoplastic (n = 289) and non-neoplastic tissues. In the stomach, foveolar epithelium was negative for Reg IV, whereas goblet cells of intestinal metaplasia and neuroendocrine cells at the base of intestinal metaplasia expressed Reg IV. Neuroendocrine cells of the small intestine and colon showed strong expression of Reg IV, whereas goblet cells of the small intestine and colon showed weak or no expression of Reg IV. Insulin-producing beta cells of the endocrine pancreas were positive for Reg IV. Among 143 gastric adenocarcinomas, Reg IV expression was detected in 42 (29.4%) and was associated with both the intestinal mucin phenotype and neuroendocrine differentiation. No association was found between Reg IV expression and clinical characteristics such as tumour stage and patient prognosis. Of 36 colorectal adenocarcinomas, 13 (36.1%) were positive for Reg IV, which was associated with tumour stage (p = 0.0379, Fisher's exact test). Expression of Reg IV was detected in 14 (93.3%) of 15 colorectal carcinoid tumours. Reg IV expression was also detected in 5 (21.7%) of 23 ductal adenocarcinomas of the pancreas. In contrast, lung cancers (n = 30) and breast cancers (n = 30) did not express Reg IV. This is the first immunohistochemical analysis of the expression and distribution of Reg IV protein in human tumours. These data suggest that Reg IV is expressed by gastrointestinal and pancreatic tumours, including adenocarcinomas and carcinoid tumours, and that Reg IV is associated with intestinal and neuroendocrine differentiation of the stomach and gastric carcinoma.     

Synergistic inhibitory effects of gastrin and histamine receptor antagonists on Helicobacter-induced gastric cancer

BACKGROUND & AIMS: Apart from its importance as an acid secretogogue, the role of histamine as a downstream target of gastrin has not been fully explored. Previous studies have shown that the combination of hypergastrinemia and Helicobacter infection resulted in accelerated gastric cancer in mice. We used this model to examine the role of cholecystokinin 2 (CCK2)/gastrin receptor and histamine H2-receptor signaling in the development of gastric atrophy and cancer. METHODS: Male hypergastrinemic mice (INS-GAS mice) were infected with Helicobacter felis and given the CCK2/gastrin receptor antagonist YF476 and/or the histamine H2-receptor antagonist loxtidine for 3 or 6 months. In addition, mice were treated with omeprazole alone or in combination with either YF476 or loxtidine for 3 months. RESULTS: Mice treated with YF476 or loxtidine alone showed partial suppression of both gastric acid secretion and progression to neoplasia. The combination of YF476 plus loxtidine treatment resulted in nearly complete inhibition of both parameters. YF476 and/or loxtidine treatment did not alter the overall level of H. felis colonization but did result in significant down-regulation of the growth factors regenerating gene I and amphiregulin. Loxtidine treatment, with or without YF476, induced a mild shift in T-helper cell polarization. In contrast, omeprazole treatment resulted in mild progression of gastric hyperplasia/dysplasia, which was ameliorated by the addition of YF476 or loxtidine. CONCLUSIONS: The combination of CCK2/gastrin- and histamine H2-receptor antagonists has synergistic inhibitory effects on development of gastric atrophy and cancer in H. felis/INS-GAS mice, while the proton pump inhibitor showed no such effects. These results support an important role for the gastrin-histamine axis in Helicobacter-induced gastric carcinogenesis.     

RegⅣ、MMP-9和CD34在胃癌组织中的表达及其相关性研究

目的通过对不同分化和高低转移的胃癌组织中RegⅣ、MMP-9和CD34的表达情况的检测,探讨RegⅣ、MMP-9和CD34与胃癌恶化程度及转移之间的关系。方法应用（S—P）免疫组织化学染色法检测手术切除101例胃癌组织中RegⅣ、MMP-9和CD34的表达,用CD34标记血管内皮细胞并计算微血管密度值（MVD）,结合临床病理特征分析。结果101例胃癌组织中RegⅣ和MMP-9蛋白表达均明显高于正常胃组织;胃癌组织中平均MVD为（53．65±1．32）／mm^2,明显高于正常胃组织。RegⅣ、MMP-9和CD34的表达呈正相关。RegⅣ、MMP-9和CD34的表达分别与肿瘤分化呈负相关（P〈0．05）,与癌组织浸润深度、淋巴转移和TNM分期呈正相关（P〈0．05）。结论RegⅣ、MMP-9和CD34在胃癌组织中呈高表达,并与胃癌的分化、转移密切相关。三者联合检测可作为判断胃癌生物学行为的重要指标。     

胃泌素与 Reg 基因在胃癌组织中的表达及临床意义的研究进展

随着研究的深入,胃泌素（ Gastrin）及其受体与Reg基因家族,尤其是RegⅠ和RegⅣ与消化系统肿瘤的生物学行为、发生发展和预后有密切的关系,其中后者可能起到类似癌基因的作用。所以胃泌素联合Reg基因的检测可能有助于早期胃癌的诊断,并为胃癌的防治提供新的靶点。本文就胃泌素及其受体与Reg基因在胃癌组织中的表达及临床意义的相关研究进展做一综述。     

RegⅣ在结肠癌中的表达及其与结肠癌发生发展的关系

目的研究正常组织和结肠癌组织中RegⅣ蛋白的表达,探讨其与结肠癌的发生发展关系。方法采用SABC免疫组织化学法分析102例结肠癌组织及50例正常结肠黏膜中RegⅣ表达,结合临床病理资料采用检验进行统计学分析,并做RegⅣ表达与结肠癌临床分期的回归分析,探讨RegⅣ与结肠癌的表达及发生发展的关系。结果正常结肠粘膜中RegⅣ无表达,结肠癌组织中RegⅣ阳性表达率为34.31%。其中,G1、G2和G3期结肠癌阳性率分别为0.00%、22.22%和68.66%,病理分级间比较差异具有统计学意义(P<0.05);临床分期的阳性率分别为T0(0.00%)、T1(33.33%)、T2(44.44%)、T3(52.38%)、T4(71.42%),各期间比较差异有统计学意义(P<0.05),两者回归方程为Y=5.955+15.83x,相关系数r=0.973。结论 RegⅣ在结肠癌的高表达与其病理分级及临床分期有密切的关系,可作为判断结肠癌分化程度的一个指标。