胃癌及癌前病变p53蛋白及Ki-67抗原检测的临床意义

应用免疫组织化学法检测胃癌和癌前病变p53蛋白、Ki-67抗原的表达.结果 正常胃黏膜无p53蛋白和Ki-67抗原表达.从萎缩性胃炎、肠上皮化生、胃黏膜异型增生至胃癌,p53蛋白和Ki-67抗原阳性表达率逐渐升高.胃癌及胃黏膜异型增生p53蛋白和Ki-67抗原阳性表达率显著高于萎缩性胃炎和肠上皮化生,差异有统计学意义（P＜0.05）;胃癌与胃黏膜异型增生、萎缩性胃炎与肠上皮化生比较p53蛋白和Ki-67抗原表达差异无统计学意义（P＞0.05）.认为p53蛋白和Ki-67抗原的检测有助于胃黏膜癌变的早期诊断.     

hMLH1基因甲基化在胃癌早期诊断中的应用价值

目的探讨hMLH1基因表达和甲基化与胃癌的关系,旨在为胃癌早期诊断治疗提供新思路。方法选取本院2013年5月至2015年7月收治的肠上皮化生34例、异型增生37例、胃癌41例,胃镜活组织检查收集病理组织,另选取同期医院门诊收集的30例正常胃黏膜组织作为对照组。通过甲基化特异聚合酶链反应和免疫组织化学方法检测hMLH1基因表达和甲基化水平,并进行组间对比分析。结果 hMLH1基因甲基化率依次为肠上皮化生组20.6%,异型增生组43.2%,胃癌组51.2%,对照组3.3%;与对照组相比较,肠上皮化生组hMLH1基因甲基化水平有所升高但差异无统计学意义(P0.05),异型增生组和胃癌组均显著升高,差异具有统计学意义(P均0.01),且异型增生组及胃癌组甲基化水平均显著高于肠上皮化生组(P均0.05)。组织样本中hMLH1基因蛋白表达阳性率分别为肠上皮化生组73.5%,异型增生组54.1%,胃癌组31.7%,对照组100%;与对照组相比较,肠上皮化生组、异型增生组及胃癌组hMLH1基因蛋白表达阳性率均显著降低,且差异有统计学意义(P均0.01)。hMLH1基因蛋白表达水平与基因甲基化水平呈负相关(r=-0.4675,P0.01)。结论 hMLH1基因启动子区高甲基化可通过调节hMLH1蛋白表达在胃癌发生发展中起作用。     

鸟苷酸环化酶C和尾型同源盒转录因子2在胃癌及癌前病变组织中的表达及意义

目的 研究鸟苷酸环化酶C(GC-C)和尾型同源盒转录因子2(CDX2)基因与蛋白在胃癌及癌前病变组织中的表达并探讨其临床意义.方法 收集30例手术切除的胃癌及相应癌旁5 cm胃黏膜组织,另32例非胃癌患者胃镜下取活检标本,其中23例肠上皮化生、9例异型增生.应用逆转录(RT)-PCR检测GC-C和CDX2 mRNA在胃癌及癌旁组织中的表达,Western印迹和间接免疫荧光组化技术检测GC-C和CDX2蛋白的表达,同时检测两者在肠上皮化生和异型增生中的表达.结果 RT-PCR显示GC-C和CDX2 mRNA在胃癌中的表达率分别为20/30和19/30,显著高于癌旁组织(0/30和0/30,P值均=0.000).Western印迹检测GC-C和CDX2蛋白在胃癌组织中表达率分别为19/30和17/30,显著高于癌旁组织(0/30和0/30,P值均=0.000).免疫荧光检测GC-C和CDX2在癌旁组织中不表达,在肠上皮化生组织中表达率为39.1 %和39.1%、异型增生组织为55.6%和55.6%、胃癌组织为56.7%和60.0%,与癌旁组织间差异有统计学意义(P值均=0.000).但在肠上皮化生、异型增生和胃癌间阳性率比较差异无统计学意义(P值均＞0.05).两者在肠型胃癌中的表达高于弥漫型(P值分别=0.009和0.024),但与年龄、性别、病灶大小、临床病理分期、分化程度和淋巴结转移等因素无关(P值均＞0.05).在肠上皮化生和胃癌中GC-C与CDX2的表达呈正相关(r分别=0.4524和0.3845,P分别=0.0371和0.0408).结论 GC-C和CDX2的异常表达与胃黏膜癌变的发生有关,可能参与人胃腺癌致癌过程的调节,检测GC-C与CDX2有助于早期胃癌和胃癌前病变诊断.     

PTEN蛋白在早期胃癌和癌前病变中的表达及与临床病理特征的相关性

目的:观察正常胃黏膜、肠上皮化生、异型增生和早期胃癌中抑癌基因PTEN的蛋白表达,探讨PTEN表达在胃癌早期发生过程中的作用.方法:共收集57例病变,按病理级别分为慢性胃炎伴肠上皮化生14例,异型增生27例,早期胃癌16例,另取20例正常胃黏膜作为对照.采用En Vision免疫组化方法检测各组黏膜中PTEN蛋白表达情况,并分析其与临床病理特征的关系.结果:PTEN在正常胃黏膜和肠上皮化生中全部表达,在异型增生和早期胃癌中的阳性率分别为92.6%(25/27),75.0%(12/16).PTEN在正常胃黏膜、肠上皮化生和异型增生三组间的表达无显著差异,在早期胃癌中的表达较前三组明显降低(P＜0.05).PTEN表达强度与病理级别呈明显的负相关(r=-0.488,P＜0.01).PTEN蛋白表达与患者年龄、性别、病变部位及H pylori感染无关(P＞0.05),但与血清CEA水平显著相关(P=0.001).结论:作为一种具有磷酸酶活性的抑癌基因,PTEN蛋白低表达在胃癌早期发生过程中发挥着重要的作用.     

COX-2在胃溃疡与胃癌的表达及其与幽门螺杆菌的关系

[目的]探讨COX-2在幽门螺杆菌(Hp)感染和非感染胃溃疡与胃癌的表达。[方法]选择胃病患者共285例,分为胃溃疡患者(胃溃疡组)200例(病理分型:肠上皮化生96例和异型增生104例),胃癌患者(胃癌组)85例;以正常胃黏膜者50例为对照组。根据胃镜检查和组织病理学检查受试者胃黏膜中COX-2蛋白的表达,并比较各病理分型及Hp感染与非感染者COX-2蛋白表达的差异。[结果]COX-2蛋白在胃溃疡组的肠上皮化生、异型增生中及胃癌组癌细胞中均有表达,在正常胃黏膜组织中不表达。胃溃疡组和胃癌组的COX-2阳性表达均强于对照组,差异有统计学意义(P0.05);胃癌组的COX-2阳性表达强于胃溃疡组,差异有统计学意义(P0.05);胃溃疡组异型增生者COX-2阳性表达强于肠上皮化生者,差异有统计学意义(P0.05);胃癌组Hp阳性COX-2阳性表达强于胃溃疡组Hp阳性者,差异有统计学意义(P0.05);胃癌组Hp阴性者COX-2阳性表达强于胃溃疡组Hp阴性者,差异有统计学意义(P0.05);胃溃疡组和胃癌组中Hp阳性者COX-2阳性表达均强于Hp阴性者,差异有统计学意义(P0.05)。[结论]Hp感染会促进胃溃疡COX-2的表达,Hp感染和COX-2过度表达会使胃溃疡患者癌变的概率大大增加。     

胃癌组织中hTERT基因表达及意义

目的探讨hTERT基因在胃癌发生、发展中的作用及机制。方法采用免疫组化SP法及核酸原位杂交法检测胃黏膜肠化生、异型增生及胃癌组织中hTERT蛋白及hTERT mRNA表达情况。结果胃黏膜肠化生、异型增生及胃癌组织中hTERT蛋白及hTERTmRNA阳性表达率均显著高于正常胃黏膜（P〈0.05）。hTERT蛋白表达阳性者hTERTmRNA表达阳性率显著高于hTERT蛋白表达阴性者（P〈0.01）。结论 hTERT基因与癌前病变及胃癌的发生有关,可能是胃癌的生物学标志之一。     

袁红霞教授用经方辨治慢性萎缩性胃炎癌前病变经验撷菁

正胃癌前病变是一个病理性概念,是指较易转变为胃癌组织的病理学变化,包括肠上皮化生(IM)和异型增生(Dys),是正常胃黏膜向胃癌转化过程中的一个重要阶段~[1]。慢性浅表性胃炎→慢性萎缩性胃炎→肠上皮化生→异型增生→胃癌的Correa级     

组织芯片检测胃癌及癌前病变中错配修复基因MSH2的表达及意义

目的探讨MSH2在胃癌及癌前病变组织中的表达及意义。方法构建包含正常胃黏膜组织、肠化生、异型增生、胃癌组织的组织芯片,免疫组化技术研究MSH2从正常胃黏膜到胃癌组织的表达变化趋势。结果在正常胃黏膜、肠化、异型增生、胃癌中MSH2表达呈递增趋势。结论组织芯片具有高效、快速、低耗、自身内对照和可比性强的特点。MSH2在胃癌及癌前病变组织的表达与正常胃黏膜比较均有较大差异,与胃癌的演变密切相关,     

pS2/TFF1蛋白在胃癌及其癌前病变组织中表达的研究

背景:pS2/TFF1蛋白属于三叶因子家族,是一类具有胃肠道黏膜保护和修复作用的生长因子类小分子多肽物质,研究pS2/TFF1蛋白可能为胃癌的防治开辟新的思路。目的:观察pS2/TFF1蛋白在胃癌及其癌前病变组织中的表达,探讨其与胃癌发生的关系。方法:采用免疫组化法检测30例慢性非萎缩性胃炎、35例慢性萎缩性胃炎、50例慢性萎缩性胃炎伴肠化生、37例异型增生、46例胃癌和30名健康志愿者胃黏膜组织中pS2/TFF1蛋白的表达。结果:正常胃黏膜组织-慢性非萎缩性胃炎-慢性萎缩性胃炎-慢性萎缩性胃炎伴肠化生-异型增生-胃癌组织中,pS2/TFF1蛋白阳性表达呈逐渐下降的趋势(分别为100%、93.3%、82.9%、78.0%、62.2%、56.5%),差异有统计学意义(P0.05)。与正常对照组、慢性非萎缩性胃炎组和慢性萎缩性胃炎组相比,慢性萎缩性胃炎伴肠化生组、异型增生组和胃癌组pS2/TFF1蛋白阳性表达均显著降低(P0.05),而后三组之间的差异无统计学意义(P0.05)。结论:pS2/TFF1蛋白表达降低是胃癌发生过程中的早期事件,有望成为诊断胃癌的标记物。     

胃黏膜癌变过程中SOX9、CDX2基因的表达及相关性研究

目的通过观察SOX9及CDX2基因在正常胃黏膜、慢性萎缩性胃炎、胃黏膜肠上皮化生(以下简称肠化)伴异型增生、胃癌组织中的表达水平,探讨其在胃黏膜癌变过程中的相关作用及意义,以期及早对胃癌前病变进行检测与干预。方法采用免疫组织化学染色SP法检测SOX9、CDX2在不同胃黏膜组织中的表达水平并进行统计学分析。结果各组中SOX9的表达差异显著,呈递增趋势;CDX2在胃黏膜肠化伴异型增生组中的表达显著高于其余各组,与胃癌组的差异显著,SOX9和CDX2在胃癌组中的表达呈显著负相关。结论 SOX9在胃癌进展过程中可能扮演着促癌基因的角色,CDX2在胃黏膜肠化伴异型增生进展为胃癌的过程中可能是一种抑癌基因,两者之间的相互作用可能参与胃黏膜的损伤及癌变,其有望成为胃癌早期诊断的新靶点。     

From gastric inflammation to gastric cancer

The majority of gastric adenocarcinomas are related to chronic inflammation induced by Helicobacter pylori infection. For intestinal-type gastric cancer, a multistep process of mucosal alterations leading from gastritis via glandular atrophy, intestinal metaplasia and dysplasia to invasive carcinoma is well recognized. Ongoing clinical studies focus on a 'point of no return'. It is defined as a situation when certain alterations are no longer reversible by H. pylori eradication and progression to gastric cancer may continue. H. pylori affects the mucosal as well as the systemic immune response by secretion of cytokines and the recruitment of distinct inflammatory cells. The immune response is characterized by a balance between a Th1-dominated response and the recruitment of antigen-specific regulatory T cells that allow the bacteria to persist in human gastric mucosa. Besides immune-mediated effects, H. pylori induces cellular alterations as well as genetic alterations in genes that are essential for the epigenetic integrity and mucosal homeostasis. These genetic alterations during gastric cancer development are in focus of intensive research and should ultimately allow the identification of risk factors involved in gastric carcinogenesis. The detection of individuals at high risk for gastric cancer would help to design appropriate strategies for prevention and surveillance.     

Control of gastric emptying by gastric tone

During ingestion of food, the stomach relaxes to accommodate the meal and, subsequently, a progressive gastric contraction parallels gastric emptying. Intestinal nutrients trigger feedback relaxatory mechanisms that regulate gastric tone and, hence, the nutrient load delivered into the small intestine. This regulation of gastric tone is mediated, at least in part, via the vagus. Defective gastric tone is associated with impaired gastric emptying, as seen in patients with postsurgical gastroparesis. However, increased intragastric pressure, corresponding with defective gastric accommodation, induces abdominal symptoms, but does not alter the gastric emptying pattern. These data indicate that gastric emptying is controlled by complementary mechanisms: gastric tone exerts an emptying force, but gastric outlet resistance is also an important regulator.     

胃起搏对胃动力紊乱犬胃排空及胃肌电活动的影响

目的　研究胃起搏对胃动力紊乱犬胃排空及胃电参数的影响。方法　采用双侧迷走神经干切断术联合应用胰高血糖素建立胃动力紊乱犬模型 ;采用 4导联胃肠电系统微机分析仪记录胃肠浆膜肌电活动 ;99mTc 植酸钠标记的半固体试餐 ,单光子计算机断层显像技术 (SPECT)检测胃半排空时间(GEt1/ 2 ) ;采用适宜起搏参数从胃体、胃窦在腹部投影部位输入起搏信号驱动胃电节律。结果　迷走神经干切断术后犬的GEt1/ 2 为 (79.4 2± 1.91)min ,较术前 (5 6 .35± 2 .99)min明显延迟 (P <0 .0 0 1) ,但行胃起搏治疗后GEt1/ 2 为 (6 4 .94± 1.75 )min ,较治疗前明显加快 (P <0 .0 0 1) ;胃起搏治疗前迷走神经干切断犬餐后的胃电频率为 (0 .0 81± 0 .0 0 7)Hz、胃电幅度为 (2 .32± 0 .35 )mV、慢波的传播速度为 (4 .0 6± 0 .4 0 )cm/s ,均较正常对照犬显著降低 [(0 .0 90± 0 .0 0 6 )Hz ,(4 .2 5± 0 .12 )mV ,(6 .92± 0 .2 4 )cm/s,(P <0 .0 5 ) ],治疗后其餐后胃电频率 (0 .0 92± 0 .0 0 5 )Hz、胃电幅度 (3.97± 0 .19)mV和慢波的传播速度 (5 .5 7± 0 .4 8)cm/s均明显高于治疗前 (P <0 .0 5 )。结论　采用适宜起搏参数输入起搏信号可完全触发胃电慢波 ,改善胃电参数 ,纠正药物导致的异常胃电节律 ,加速胃排空 ,恢     

Observations on benign gastric ulcer simulating gastric carcinoma

We have re-evaluated over-diagnosed cases which were first diagnosed, pre-operatively, as gastric cancer yet later confirmed as benign lesion (excavated lesion, in particular) in the post-operative histological examination of resected stomachs. We have experienced a total number of 1,358 cases which, being detected through mass survey, were diagnosed as cancer and, consequently, operated upon. On the other hand, 61 benign cases were misdiagnosed as cancer, 28 cases being protruded lesions and 33 cases excavated lesions. Among the misdiagnosed cases of excavated lesions, 27 cases were gastric ulcers or their scars, the remaining 6 cases being gastritis or gastric erosion. In 22 out of 33 cases of misdiagnosis, the wrong diagnosis was made by relying solely upon X-ray and endoscopy. Even after the addition of cytology, there were still 9 cases of misdiagnosis. Since, however, biopsy was introduced, there have been only 2 cases of wrong diagnosis. We may safely say that through these findings the absolute necessity of biopsy for the attainment of an accurate diagnosis of early gastric cancer has been sufficiently attested.     

The relationship between gastric microbiota and gastric disease

Traditionally, the stomach was believed to be a sterile organ unsuitable for microbiota growth. However, the discovery of H. pylori subverted this conception. With the development of molecular techniques, an abundance of microbiota of great diversity was found in the stomach. In addition, various lines of evidence suggest that the gastric microbiota plays a critical role in the development and progression of the gastric disease.The gastrointestinal microbiome plays an important role in various physiologic and pathologic processes.     

胃微生态与胃癌的研究进展

胃微生态平衡是人体健康的重要前提,幽门螺杆菌(Helicobacter pylori,Hp)是目前已发现的与胃癌相关的关键病原体之一,普遍存在于人胃黏膜上皮。Hp感染可引起胃内其他菌群的改变,还可引起长期慢性的胃黏膜损伤,导致一系列胃黏膜上皮恶性进展和胃癌的发生。本文就胃微生态与Hp感染的关系、Hp感染在胃癌发生中的作用、胃内其他菌群在胃癌发生中的作用及微生态制剂在胃癌治疗的作用进行综述。进一步揭示Hp感染对胃微生态平衡的影响,胃微生态平衡和Hp感染在胃癌发生发展中的作用及微生态制剂在胃癌治疗中的意义。