胃泌素受体在胃癌组织中表达的特征及其预后价值

目的探讨胃泌素受体（ｇａｓｔｒｉｎｒｅｃｅｐｔｏｒ,ＧＲ）在胃癌自分泌生长中的作用及其与胃癌预后的关系。方法应用胃泌素受体的放射配基结合分析法,测定３４例胃癌组织胃泌素受体的含量及其亲和力。结果３４例胃癌中,胃癌组织胃泌素受体阳性１６例,其中低亲和力胃泌素受体２例;高亲和力胃泌素受体１４例,高含量胃泌素受体９例,低含量胃泌素受体５例。２４例Ⅲ、Ⅳ期胃癌中,胃癌组织胃泌素受体阳性１５例;１０例Ⅰ、Ⅱ期胃癌中,胃癌组织胃泌素受体阳性仅１例。胃癌组织胃泌素受体的表达与胃癌临床病理分型无关。胃泌素受体阳性的胃癌细胞Ｓ期细胞比例及超５倍体细胞比例均高于胃泌素受体阴性者。对３１例胃癌患者随访３１～６９个月,胃泌素受体阴性或低亲和力胃泌素受体的胃癌患者,其预后较高亲和力胃泌素受体者好。结论胃泌素受体易于在晚期胃癌中表达,其对评估胃癌患者的预后有一定参考价值。     

胃泌素受体拮抗剂抑制胃癌细胞生长的可行性研究

目的　探讨应用胃泌素受体拮抗剂治疗胃癌的可行性。方法　在体外条件下观察胃泌素及其受体拮抗剂丙谷胺对胃癌细胞株ＭＫＮ４５ 的细胞活力、细胞内ｃＡＭＰ浓度及细胞凋亡的影响;在体内条件下观察胃泌素受体拮抗剂丙谷胺对胃癌细胞株ＭＫＮ４５ 移植瘤的面积、重量及胃癌细胞ＤＮＡ 的影响。结果　在体外条件下,胃泌素能促进胃癌细胞株ＭＫＮ４５ 的增殖,细胞内ｃＡＭＰ浓度增高,细胞凋亡百分率降低,而丙谷胺能完全阻断胃泌素的作用。在体内条件下,丙谷胺能抑制胃癌细胞株ＭＫＮ４５ 移植瘤的生长,肿瘤面积、重量及胃癌细胞ＤＩ、ＤＮＡ 含量、ＳＰＦ均低于对照组。结论　胃泌素受体拮抗剂能够抑制胃泌素受体阳性的胃癌细胞生长,有望为胃癌的治疗提供一种新手段。     

胃泌素受体拮抗剂抑制胃癌细胞生长的可行性研究

目的 探讨应用胃泌素受体拮抗剂治疗胃癌的可行性。方法 在体外条件下观察胃泌素及其受体拮抗剂丙谷胺对胃癌细胞株MKN45的细胞活力、细胞内cAMP浓度及细胞凋亡的影响；在体内条件下观察胃泌素受体拮抗剂丙谷胺对胃癌细胞株MKN45移植瘤的面积、重量及胃癌细胞DNA的影响。结果 在体外条件下，胃泌素能促进胃癌细胞株MKN45的增殖．细胞内cAMP浓度增高，细胞凋亡百分率降低，而丙谷胺能完全阻断胃泌素的作用。在体内条件下．丙谷胺能抑制胃癌细胞株MKN45移植瘤的生长，肿瘤面积、重量及胃癌细胞DNA、DNA含量、SPF均低于对照组。结论 胃泌素受体拮抗剂能够抑制胃泌素受体阳性的胃癌细胞生长．有望为胃癌的治疗提供一种新手段。     

胃泌素、胃泌素受体与结肠癌(文献综述)

结肠癌细胞能合成并自分泌胃泌素,作为自身生长因子刺激其生长,血清中胃泌素含量不能反映肿瘤组织中胃泌素的变化.结肠癌细胞表面的胃泌素受体含量决定了细胞对胃泌素的反应性及预后.胃泌素受体拮抗剂呈剂量依赖性抑制结肠癌细胞的生长,有广阔的应用前景.     

丙谷胺阻断胃泌素促胃癌细胞增殖作用的机制研究

目的 探讨丙谷胺治疗胃癌的可行性。方法 应用ＭＫＮ４５胃癌细胞株进行体外培养,经胃泌素及其受体拮抗剂丙谷胺作用后,观察细胞增殖率、周期分布以及细胞内ＣＡＭＰ浓度变化。结果 胃泌素可明显促进ＭＫＮ４５细胞的增殖、促进细胞由Ｇ０／Ｇ１期向Ｓ、Ｇ２／Ｍ期转化,经胃泌素作用０．５小时后细胞内ＣＡＭＰ浓度增加,与对照组相比Ｐ〈０．０１,而丙谷胺能完全阻断上述作用。结论胃泌素通过其受体介导了细胞内信号传导,促     

胃泌素及其受体拮抗剂对 BGC-823细胞骨架微丝结构的作用

目的 探讨胃泌素及其受体拮抗剂对人胃癌BGC-823细胞系细胞骨架微丝结构的作用。方法 在体外用胃泌素和受体拮抗剂处理胃癌BGC-823细胞系,制备光镜和电镜标本并观察细胞骨架,结果 胃泌素组细胞核增大,胞浆内微丝量明显减少,微丝部位不定,不呈束结构紊乱;而胃泌素和受体拮抗剂组胞浆内边缘微丝、中间微丝、核周微丝均明显增多,排列规则并呈束,其结构和数量均大体相似于对照组,结论 胃泌素能增强BGC-823细胞系的运动,有促进肿瘤细胞转移的作用,而受体拮抗剂可抑制胃泌素的这种作用。     

胃泌素及其受体拮抗剂对胃癌细胞PCNA、p53基因表达的影响

为探讨胃泌素促肿瘤细胞增殖作用的机制,我们观察了胃泌素及其受体拮抗剂对MKN45胃癌细胞PCNA、p5 3基因表达的影响。一、材料与方法1.主要试剂:MKN45胃癌细胞株(上海市消化疾病研究所提供) ,5肽胃泌素(上海丽珠东风生物技术公司产品) ,丙谷胺(江苏金坛制药厂赠) ,PCNA、p5 3单抗及ABC免疫组织化学试剂盒购自华美生物工程公司(Sigma产品)。2 .细胞培养:MKN45胃癌细胞株培养于含10 %小牛血清的RPMI 164 0培养液中,置3 7℃二氧化碳培养箱,隔天换液,3d传代。3 .试剂配制及实验分组:用体积分数为0 .0 5小牛血清的164 0培养液将胃泌素…     

胃泌素依赖性胃癌的研究

胃泌素依赖性胃癌的研究李哲夫，王德昭，胡义利，孙旭东，乐竹琴，余枫癌细胞能分泌某种激素，其细胞膜上有该激素受体，释放的激素刺激自身增殖。胃癌中是否存在胃泌素依赖性癌，我们就此进行研究。材料和方法一、材料及方法取已培养的ＭＫＮ＿４５株（中科院上海细胞所...     

胃泌素,胃泌素受体与结肠癌

结肠癌细胞能合成并自分泌胃泌素，作为自身生长因子刺激其生长，血清中胃泌素含量不能反映肿瘤组织中胃泌素的变化。结肠癌细胞表面的胃泌素受体含量决定了细胞对胃泌素的反应性及预后。胃泌素受体拮抗剂呈剂量依赖性抑制结肠癌细胞的生长，有广阔的应用前景。     

胃泌素与结肠癌(文献综述)

多数研究认为,某些结肠癌组织或细胞株有胃泌素基因表达,胃泌素通过受体介导的细胞内信号传导途径促进结肠癌的生长;结肠癌患者血浆胃泌素水平升高对肝转移等预后判断可能有一定临床参考价值。胃泌素及其受体拮抗剂将为结肠癌内分泌治疗开辟新的途径。     

Expression of gastrin in developing gastric adenocarcinoma

BACKGROUND: A stepwise progression through premalignant stages has been identified for the intestinal type of gastric carcinoma. As gastrin has been identified as a growth factor for the intestinal type of gastric adenocarcinoma, the aim of this study was to investigate whether gastrin is expressed in premalignant gastric conditions. METHODS: Ninety archival samples of atrophic gastritis, intestinal metaplasia, mild gastric epithelial dysplasia, moderate gastric epithelial dysplasia, severe gastric epithelial dysplasia and intestinal-type gastric adenocarcinoma were obtained. Immunocytochemistry was performed using antibodies directed against gastrin and its post-translational precursors, and the gastrin/cholecystokinin B receptor. Positive staining was identified using the avidin--biotin immunoperoxidase method and quantified using an image analysis system. RESULTS: Gastrin and its receptor were shown to be expressed in specimens of atrophic gastritis, intestinal metaplasia, epithelial dysplasia and the intestinal type of gastric carcinoma. CONCLUSION: Gastrin seems to be an important growth factor in gastric carcinogenesis.     

胆囊收缩素及胃泌素对体内生长胆管癌细胞增殖的影响

目的 探讨胆囊收缩素（ＣＣＫ）、胃泌素（ｇａｓｔｒｉｎ）对体内生长胆管癌细胞增殖的影响。方法 将胆管癌细胞ＱＢＣ９３９（ＱＢ）接种在裸鼠背部皮下，１４ｄ后皮下注射ＣＣＫ、胃泌素或／和胆囊收缩素－Ａ受体拮抗剂Ｌ３６４，７１８（Ｌ１８）、胆囊收缩素－Ｂ／胃泌素受体拮抗剂Ｌ３６５，２６０（Ｌ６０），治疗３周后活杀，计算移植瘤体积及重量并用流式细胞仪测定增殖指数和蛋白质总量。结果 ＣＣＫ－８硫酸盐（ＣＣＫ     

Effect of proton pump inhibitors on glycemic control in patients with diabetes

Gastrin is a linear peptide hormone which is secreted mostly in the stomach pyloric antrum G cells. Although the main role of this hormone is the promotion of the secretion of gastric acid from the stomach parietal cells, gastrin can also behave as a growth factor and stimulate gastric cell proliferation. It is also reported that gastrin promotes β cell neogenesis in the pancreatic ductal complex, modest pancreatic β cell replication, and improvement of glucose tolerance in animal models, in which the remodeling of pancreatic tissues is promoted. These findings suggest the possibility that gastrin has the potential to promote an increase of β cell mass in pancreas, and therefore that gastrin may improve glucose tolerance. Proton pump inhibitors(PPIs) are wildly used clinically for the therapy of gastro-esophageal reflex disease, gastritis due to excess stomach acid, and gastric ulcers. PPIs indirectly elevate serum gastrin levels via a negative feedback effect. Recent evidence has revealed the beneficial effect of PPIs on glycemic control especially in patients with type 2 diabetes mellitus(T2DM), probably via the elevation of the levels of serum gastrin, although the detailed mechanism remains unclear. In addition, the beneficial effects of a combination therapy of gastrin or a PPI with a glucagon-like peptide-1 receptor agonist on glycemic control in animal models have been demonstrated. Although PPIs may be possible candidates for a new approach in the therapy of diabetes, a prospective, longterm, randomized, double-blind, placebo-controlled study is needed to establish the effect of PPIs on glycemic control in a large number of patients with T2 DM.     

Pathophysiology of the fundic enterochromaffin-like (ECL) cell and gastric carcinoid tumours.

The genesis of human gastric carcinoma is ill understood but is invariably related to achlorhydria. Gastrin secretion is negatively regulated by luminal acid and hypergastrinaemia is thus associated with low acid states which may be natural (atrophic gastritis) or owing to acid inhibitory therapy. Apart from its acid secretory activity, gastrin is trophic to the mucosa, via stimulation of the fundic enterochromaffin-like (ECL) cells to secrete histamine. In conditions of elevated gastrin levels, ECL cell hyperplasia and even neoplasia have been noted. The relationship between low acid, hypergastrinaemia, ECL cell hyperplasia, and neoplasia may be of relevance since ECL cells secrete histamine and TGF alpha which are both recognised mitogens. We studied the rodent mastomys, which spontaneously develop gastric carcinoid tumours, which can be generated in 4 months under conditions of drug-induced acid inhibition and inhibited by octreotide administration. A pure (90-95%) cell preparation was used to evaluate ECL cell physiology and trophic regulation. A gastrin/CCKB receptor responsible for histamine secretion and DNA synthesis was identified, cloned and sequenced. Octreotide lowers plasma gastrin levels, decreases ECL cell neoplasia and, in vitro, inhibits ECL cell DNA synthesis. H1 receptor antagonists inhibited DNA synthesis in vitro and ECL neoplasia in vivo without altering gastrin levels. Hypergastrinaemia increased TGF alpha/EGF receptor and TGF alpha production and TGF alpha massively stimulated ECL cell DNA synthesis. Since ECL cells produce both histamine and TGF alpha and regulate parietal cells which produce TGF alpha, it is possible that achlorhydria-generated ECL cell dysfunction may play an initiative role in the pathobiology of gastric adenocarcinoma. The long-term clinical consequences of drug-induced sustained acid inhibition are worthy of further consideration.     

胃泌素对大鼠胃黏膜的影响

目的探讨胃泌索对大鼠胃黏膜的影响。方法使用胃泌素刺激Wistar大鼠，空白对照组（22只）：自由饮用纯净水；胃泌素组（38只）：连续每天每只皮下注射胃泌素300斗g／kg，共30天。第12周开始取材，每隔4周取材一次，共观察56周，空白对照组每次处死2只，胃泌素组每次3只，比较2组胃组织的变化，并测量胃泌酸区黏膜层的厚度，同时采用免疫组化方法检测胃泌素抗体和作为肠嗜铬样细胞标记的组胺酸脱羧酶（HDC）抗体在2组中的表达。结果胃泌素组动物与空白对照组相比，胃黏膜层厚度增加，且胃泌素抗体和HDC抗体在胃泌素组中的表达升高。结论胃泌素通过与其特异性受体结合，引起胃黏膜的增生，尤其引起肠嗜铬样细胞过度增殖，提示肠嗜铬样细胞的异常增殖是胃泌素促进胃黏膜增厚的可能机制之一。     

大肠癌病人肿瘤、癌旁粘膜中胃泌素、生长抑素及其分泌细胞的变化

通过观察大肠癌病人肿瘤和癌旁粘膜中胃泌素、生长抑素(SS)及其分泌细胞的变化,探讨病人体内胃泌素、SS变化的原因和意义。方法:采用放射免疫法(RIA)测定26例大肠癌病人肿瘤和癌旁粘膜中胃泌素、SS水平,并对其分泌细胞行免疫细胞化学观察。结果:肿瘤和癌旁粘膜中胃泌素含量极低且无胃泌素细胞存在。癌远旁粘膜(CDM,距肿瘤约5cm)SS水平低于癌近旁粘膜(CAM,距肿瘤0～2cm),高于肿瘤,两两相比相差均非常显著(P<0.01)。肿瘤中未见SS细胞;癌旁粘膜中SS细胞的形态、位置近于正常。CAM中SS水平与SS细胞数间呈非常显著之正相关(P<0.01)。结论:大肠癌与胃泌素、SS间存在着肯定的联系;CAM中SS上升的主要原因是粘膜中SS细胞数量增多并分泌大量的SS。这可能有助于延缓肿瘤的发生、发展,是机体对病灶的一种局部防御反应。     

胃癌及邻近黏膜表达胃泌素受体的差异及其意义

目的 揭示胃泌素受体（gastrin receptor,GR)在胃癌自分泌生长中的作用。方法 应用受的放射配基结合分析法，测定34例胃癌及其邻近黏膜的GR含量和新和力（Kd)，比较胃癌及基邻近黏膜表达GR的差异。结果 34例胃癌组织中，GR阳性16例。胃体癌表达高亲和力GR的阳性率为77．8％（7／9），胃底贲门癌为50．0％（3／6），而胃窦癌为21．1％（4／19）。晚期胃癌（Ⅲ、Ⅳ期）表达高样和力GR的阳性率为52．2％（13／24），早、中期癌（Ⅰ、Ⅱ）为10．0％（1／10）。34例黏膜组织中，GR阳性16例。有30例胃癌及其邻的黏膜组织表达GR基本一致。胃癌表达含量GR的平均含量较邻近黏膜高。结论 胃癌较周围黏膜易于表达高含量GR，其表达与肿瘤的部位和分期相关。