胃癌组织中三叶肽因子1的表达与血管形成的关系

目的:研究三叶肽因子1(TFF-1)在人胃癌组织中的表达及其与胃癌血管形成的关系。方法:应用免疫组织化学S-P法检测TFF-1在40例原发性胃癌及10例正常胃黏膜组织中的表达,同时检测微血管密度(MVD,以抗CD 34标记)。结果:10例正常胃黏膜组织TFF-1全部阳性表达,40例胃癌组织TFF-1表达阳性率为40％(16/40)。其阳性表达与胃癌细胞的低分化程度有关(P<0.05),而与患者的性别、肿瘤的浸润程度、淋巴结转移与否无关。胃癌组织MVD明显高于正常胃黏膜组织。TFF-1阳性及阴性表达组MVD均值分别为34.06±6.08、27.96±9.72,两组间MVD均值差异有统计学意义(P<0.05)。结论:胃癌组织中TFF-1常有表达缺失,而其高表达与肿瘤微血管形成、胃癌细胞低分化程度有关。     

TFF2在胃癌、癌旁及正常胃黏膜组织中的表达及其与血管生成的关系

目的:探讨三叶因子2(TFF2)、血管内皮生长因子(VEGF)和微血管密度(MVD)在胃癌发生、发展、浸润和转移中的作用.方法:选取广西医科大学第一附属医院2008-01/2009-06接受胃大部切除术的胃癌标本50例,采用SP免疫组织化学方法检测30例正常胃黏膜组织、50例癌旁组织和50例胃癌组织中TFF2、VEGF...     

胃癌树突状细胞浸润的临床意义及与肿瘤血管生成的相关性

目的:探讨树突状细胞(dendritic cells,DCs)浸润对胃癌生物学行为的影响,并探讨DCs浸润程度与肿瘤血管生成的相关性.方法:采用免疫组织化学染色SP法检测胃原发癌35例及其中淋巴转移癌23例组织中S-100~ DCs的密度,同法检测35例胃原发癌血管内皮生长因子(VEGF)的表达及CD34标记的微血管密度(MVD).结果:随着胃癌浸润程度的增加,间质S-100~ DCs密度的下降,浆膜浸润的胃癌S-100~ DCs密度显著下降,S-100~ DCs与肿瘤浸润深度呈显著负相关(P=0.023);有淋巴转移胃癌S-100~ DCs密度明显低于无淋巴转移者,但无统计学意义;在胃癌转移的淋巴结.随着胃癌转移程度的增加,S-100~ DCs密度显著下降,两者呈显著负相关(r=-0.923,P<0.01);VEGF阳性表达的胃癌S-100~ DCs密度明显低于VEGF阴性表达的胃癌(P=0.157),两者呈负相关(r=-0.128,P=0.464),但均无统计学意义;S-100~ DCs低密度胃癌的MVD显著高于S-100~ DCs高密度胃癌(P=0.013);高MVD胃癌S-100~ DCs密度明显低于低MVD胃癌,胃癌MVD与S-100~ DCs密度呈显著负相关(r= -0.322,P=0.059).结论:胃癌组织的S-100~ DCs浸润程度与胃癌侵袭和淋巴转移密切相关;胃癌DCs浸润程度与肿瘤血管生成的活力密切相关,胃癌细胞释放的VEGF等促血管生成因子可能是肿瘤源性免疫逃逸的重要分子机制之一.     

三叶因子1与胃癌关系研究进展

三叶因子1(TFF1)属三叶因子家族,是近年来被人们注意到的具有胃肠道粘膜保护及修复作用的生长因子类小分子多肽物质。其基因现已被认为是一个重要的胃癌抑癌基因。现就三叶因子1的结构、功能、分布、表达及其与胃癌关系的研究进展作一综述。     

肝细胞癌中缺氧诱生因子1α的表达与血管生成的关系

目前有关肝细胞癌 (ＨＣＣ)中缺氧诱生因子 1α(ＨＩＦ 1α)与血管内皮生长因子 (ＶＥＧＦ)及血管生成之间关系的临床研究尚少有报道 ,我们对此进行研究。一、材料与方法1.临床资料 :取中南大学湘雅医院 2 0 0 0年 3月至 2 0 0 1年 10月手术切除的ＨＣＣ标本 ,共计 36例。所有病例术前均未接受其他治疗。其中男 32例 ,女 4例 ,年龄 19～ 77岁 ,平均年龄 45 .9岁。全部病例乙肝表面抗原均阳性。癌旁肝组织为光镜下ＨＣＣ组织周围的非癌肝组织。正常肝组织 6例 ,取自 2 0 0 0年 1月至 2 0 0 1年 7月切除之肝血管瘤或肝囊肿周围正常肝组织。2 .…     

TFF3在胃癌、癌前病变及胃腺瘤中的表达及其与血管生成的关系

目的:分析三叶因子3(TFF3)在不同胃黏膜病变中的表达及其与间质微血管密度(MVD)值的关系,探讨其在胃癌、癌前病变及胃腺瘤发生、发展中的作用.方法:应用免疫组织化学PV6000法检测20例正常胃黏膜、20例胃腺瘤、20例萎缩性胃炎伴肠化生、20例不典型增生、40例胃癌组织中TFF3的表达,同时检测MVD值,以抗CD34标记.结果:TFF3在胃腺瘤、萎缩性胃炎伴肠化生、不典型增生和胃癌各组表达均高于正常组(50.0%,65.0%,70.0%,57.5% vs 5.0%,均P<0.01).胃癌MVD值高于正常胃黏膜、胃腺瘤、萎缩性胃炎伴肠化生和不典型增生(30.65±6.04 vs 14.87±3.06,22.33±3.78,23.16±3.20,25.22±4.66,均P<0.01),各组MVD值均高于正常胃黏膜组(均P<0.01).TFF3表达和MVD值与胃癌淋巴结转移和分期有关(均P<0.05),MVD值还与胃癌浸润深度有关(P<0.05).TFF3阳性表达组的MVD值明显高于TFF3阴性组(34.53±4.45 vs 25.39±3.25,P<0.01).结论:TFF3可能是胃黏膜癌变过程中的早期分子事件,在胃黏膜癌变和癌变后的恶性演进过程中起作用,对胃癌早期诊断和预测胃癌发生转移可能具有重要的提示作用.     

胃癌血管内皮生长因子与微血管密度的关系

血管生成与肿瘤的生长密切相关。最近的一些研究报道指出，血管内皮生长因子（ＶＥＧＦ）是一种重要的促肿瘤血管生长因子［１］，ＦⅧ因子是血管内皮的特异标记物。我们用ＶＥＧＦ和ＦⅧ因子染色的免疫组化技术，观察了胃癌组织不同区域ＶＥＧＦ阳性表达和微血管密度（Ｍ...     

三叶因子1表达与胃黏膜损伤及胃癌的关系

目的　测定三叶因子 1(TFF1)在正常及病理条件下胃黏膜中的表达情况 ,探讨TFF1在胃黏膜损伤修复及胃癌抑制中的作用及意义。方法　应用免疫组化方法测定正常及不同病理条件下胃黏膜中TFF1的表达情况 ,通过图像分析软件分析阳性信号平均吸光度值以了解其表达情况。结果　胃炎、胃溃疡及十二指肠球部溃疡患者TFF1表达明显高于正常胃黏膜 (0 .5 1± 0 .0 5 ,0 .5 1± 0 .0 6 ,0 .5 0± 0 .0 6比 0 .4 4± 0 .0 6 ;P值均 <0 .0 1)。胃腺癌患者癌旁组织表达 (0 .5 1± 0 .0 7)明显高于正常胃黏膜 ,而腺癌组织的表达强度则与癌组织的分化程度呈正比 ,分化程度愈低 ,表达愈弱 ,低分化腺癌无阳性表达 ,中、高分化腺癌表达 (0 .4 1± 0 .0 7)略低于正常黏膜 ,但差异无显著性 (P >0 .0 5 )。结论　TFF1表达随黏膜损伤程度的加重而表达增强 ,提示其在胃黏膜保护及促进上皮重建机制中具有一定的作用。TFF1在癌旁组织中表达增强提示其可能与肿瘤抑制及分化机制有关 ,而在癌组织中表达减弱可能与其分泌减少有关。     

LKB1和血管内皮生长因子在胃癌组织中的表达及其临床意义

目的探讨LKB1和血管内皮生长因子(VEGF)在胃癌中的表达及临床意义。方法采用免疫组织化学(SP)法检测115例胃癌组织和20例胃正常组织中LKB1和VEGF的表达,并探讨其与胃癌分期、淋巴结转移、Lauren's分型及预后的关系。结果 LKB1在胃癌组织中的阳性率为20.9%,低于正常胃组织中的95.0%(P0.01);VEGF在胃癌组织中的阳性率为64.3%,高于正常胃组织中的5.0%(P0.01)。LKB1在胃癌组织中的低表达与胃癌的TNM分期、淋巴结转移、Lauren's分型及预后有关(P0.05);VEGF在胃癌中的表达与淋巴结转移、远处转移、TNM分期及预后相关(P0.05)。结论 LKB1的低表达与胃癌的发生、发展有关,对胃癌恶性生物学行为的评估及预后判断具有重要的指导意义。     

胃癌及癌前病变中的TFF-1、EGFR表达与血管再生的相关性研究

目的 探讨胃癌及癌前病变中三叶因子-1(trefoil factorl,TFF-1)、表皮生长因子受体(epidermal growthfactor receptor,EGFR)与血管形成的关系.方法 将121例患者存档标本分为萎缩性胃炎伴肠化生、不典型增生、高分化胃癌和低分化胃癌4组,另取29例体检正常人标本作为正常组.采用免疫组化SP方法测定TFF-1、EGFR值;同时所有对象用抗CD 34血管标记物表达测微血管密度(microvessel density,MDV)值,并进行相关性分析.结果 在正常对照组及萎缩性胃炎伴肠化生、不典型增生、高分化胃癌和低分化胃癌各组中,TFF-1阳性表达率分别为100.0%、85.18%、81.82%、64.00%、38.39%,呈逐渐减弱趋势.后4组与正常组比较有显著差异,高分化胃癌组表达高于低分化胃癌组(P<0.05);而EGFR在正常组、萎缩性胃炎伴肠化生、不典型增生、高分化胃癌和低分化胃癌组中的表达分别为24.13%、40.74%、42.42%、56.00%、72.22%,呈逐渐增加趋势.后4组与正常组比较有显著差异,高分化胃癌组表达低于低分胃癌组(P<0.05).结论 实验结果显示TFF-1与EGFR呈负相关(r=-0.913,P<0.01).EGFR值与MDV呈正相关(r=0.936,P<0.01).TFF-1与EGFR在胃癌的早期诊断中起重要作用,可以作为判断肿瘤转移与否及手术前肿瘤是否复发的评判标准.     

三叶因子Ⅰ和Ⅱ在胃癌和癌前状态中的表达

目的　探讨三叶因子Ⅰ (trefoilfactor1,TFF1)和Ⅱ (TFF2 )与癌前状态及胃癌发生及发展的关系。方法　对 14 0例经病理证实的不同胃黏膜病变 ,采用免疫组化方法进行TFF1、TFF2蛋白的定位和半定量检测。结果　在慢性浅表性胃炎、胃溃疡、慢性萎缩性胃炎和胃癌 4种病变中 ,TFF1表达呈逐渐减弱趋势 (P <0 0 5)。TFF2在上述 4种病变中的表达差异亦有显著性 (P <0 0 5) ,其中在胃溃疡、慢性萎缩性胃炎和胃癌组织中 ,TFF2表达逐渐降低 (P <0 0 5)。结论　TFF1和TFF2蛋白在癌前状态和胃癌的表达降低 ,TFF1和TFF2的作用机制以及临床应用前景有待于进一步研究     

Relationship between trefoil factor 1 expression and gastric mucosa injuries and gastric cancer

AIM: To determine whether trefoil factor 1 (TFF1) is associated with mucosa healing and carcinoma suppression, we assess the expression of trefoil factor 1 in normal and pathologic gastric mucosa. METHODS: TFF1 in normal and pathologic gastric mucosa was assessed by immunohistochemical method, and the average positive A was estimated by Motic Images Advanced 3.0 software. RESULTS: Increased TFF1 was detected in gastritis, gastric ulcer and duodenal ulcer compared with normal mucosa. The same result could be seen in multiple and compound ulcer compared with simple ulcer. There was no significant difference between gastric ulcer and duodenal ulcer, gastritis and simple ulcer respectively. Increased TFF1 was detected in the peripheral mucosa of the gastric adenocarcinoma compared with normal mucosa. The expression of TFF1 in gastric adenocarcinoma was related to the differentiation of adenocarcinoma. The lower the differentiation of adenocarcinoma, the weaker the expression of TFF1. There was no TFF1 expressed in low-differentiated adenocarcinoma. The expression of TFF1 in middle and highly differentiated adenocarcinoma was a little lower than that in normal mucosa. But there was no significant difference. No TFF1 was assessed in esophageal squamous carcinoma and peripheral tissue. There was no significant difference between male and female. CONCLUSION: The expression of TFF1 was higher in gastritis and peptic ulcer than that in normal mucosa, and was also higher in multiple and compound ulcer than in simple ulcer. It seems that TFF1 plays a role in gastric mucosa protection and epithelial restitution. Increased expression of TFF1 in peripheral tissue suggests that TFF1 is associated with mechanism of carcinoma suppression and differentiation. Decreased expression of TFF1 in carcinoma and its relativity to the differentiation suggests that TFF1 is related to gland and cell destruction of carcinoma.     

Relationship between trefoil factor 1 expression and gastric rnucosa injuries and gastric cancer

AIM: To determine whether trefoil factor 1 (TFF1) is associated with mucosa healing and carcinoma suppression, we assess the expression of trefoil factor 1 in normal and pathologic gastric mucosa.METHODS: TFF1 in normal and pathologic gastric mucosa was assessed by immunohistochemical method, and the average positive A was estimated by Motic Images Advanced 3.0 software.RESULTS: Increased TFF1 was detected in gastritis, gastric ulcer and duodenal ulcer compared with normal mucosa. The same result could be seen in multiple and compound ulcer compared with simple ulcer. There was no significant difference between gastric ulcer and duodenal ulcer, gastritis and simple ulcer respectively. Increased TFF1 was detected in the peripheral mucosa of the gastric adenocarcinoma compared with normalmucosa. The expression of TFF1 in gastric adenocarcinoma was related to the differentiation of adenocarcinoma. The lower the differentiation of adenocarcinoma, the weaker the expression of TFF1. There was no TFF1 expressed in low-differentiated adenocarcinoma. The expression of TFF1 in middle and highly differentiated adenocarcinoma was a little lower than that in normal mucosa. But there was no significant difference. No TFF1 was assessed in esophageal squamous carcinoma and peripheral tissue. There was no significant difference between male and female.CONCLUSION: The expression of TFF1 was higher in gastritis and peptic ulcer than that in normal mucosa, and was also higher in multiple and compound ulcer than in simple ulcer. It seems that TFF1 plays a role in gastric mucosa protection and epithelial restitution. Increased expression of TFF1 in peripheral tissue suggests that TFFLis associated with mechanism of carcinoma suppression and differentiation. Decreased expression of TFF1 in carcinoma and its relativity to the differentiation suggests that TFF1 is related to gland and cell destruction of carcinoma.     

Expression of TRAP1 in gastric cancer tissue and its correlation with malignant biology

Objective:To study the expression of tumor necrosis factor receptor-associated protein 1(TRAP1)in gastric cancer tissue and its correlation with malignant biology.Methods:Gastric cancer tissue and adjacent normal tissue were collected,and mRNA content and protein content of TRAP1 were detected;gastric cancer cell lines SGC7901,BGC823,AGS and MGC803 were cultured,and mRNA contents and protein contents of TRAP1,CyclinB1,CyclinD1,CyclinE,MMP-2 and VEGF were detected.Results:mRNA and protein expression levels of TRAP1 in gastric cancer tissue were significantly higher than those in adjacent normal tissue,and mRNA and protein expression levels of TRAP1 in gastric cancer tissue with muscularis and serosa infiltration,lymph node metastasis,distant organ metastasis and TNM Ⅲ/Ⅳ stage were significantly higher than those in gastric cancer tissue with mucosa and submucosa infiltration,non-lymph node metastasis,non-distant organ metastasis and TNM Ⅰ/Ⅱ stage.mRNA and protein expression levels of TRAP1,CyclinB1,CyclinD1,CyclinE,MMP-2 and VEGF in MGC803 were the highest,and mRNA and protein expression levels of TRAP1,CyclinB1,CyclinD1,CyclinE,MMP-2 and VEGF in SGC7901 were the lowest.mRNA and protein expression levels of TRAP1 in gastric cancer cell lines were positively correlated with mRNA and protein expression of CyclinB1,CyclinD1.CyclinE,MMP-2 and VEGF.Conclusions:The expression of TRAP1 significantly increases in gastric cancer tissue;TRAP1 may regulate the malignant biology of cells by increasing the expression of CyclinB1,CyclinD1,CyclinE,MMP-2 and VEGF,thereby resulting in the occurrence and development of gastric cancer.     

Expression of trefoil factors 1 and 2 in precancerous condition and gastric cancer

AIM: To study the expression of trefoil factor 1 (TFF1) and TFF2 in precancerous condition and gastric cancer and to explore the relationship between TFFs and tumorigenesis, precancerous condition and gastric cancer. METHODS: The expression of TFF1 and TFF2 was immunohistochemically analyzed in paraffin-embedded samples from 140 patients including 35 cases of chronic superficial gastritis (CSG), 35 cases of gastric ulcer (GU), 35 cases of chronic atrophic gastritis (CAG) and 35 cases of gastric cancer (GC). RESULTS: TFF1 and TFF2 were located in cytoplasm of gastric mucous cells. In CSG, GU, CAG and GC, the level of TFF1 expression had a decreased tendency (P<0.05). The expression of TFF2 was higher in GU than in CSG, but the difference was not significant. The expression of TFF2 also had a decreased tendency in GU, CAG, and GC (P<0.05). CONCLUSION: The reduced expression of TFF1 and TFF2 in precancerous conditions and gastric cancer may be associated with the proliferation and malignant transformation of gastric mucosa. More investigations are needed to explore the mechanism of TFFs and the relationship between TFFs and gastric cancer.     

Somatic mutations of the trefoil factor family 1 gene in gastric cancer

BACKGROUND & AIMS: There is increasing evidence that trefoil factor family 1 (TFF1) is a stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents. TFF1 knockout mice developed multiple gastric adenomas and carcinomas, suggesting that TFF1 is a gastric-specific tumor-suppressor gene. METHODS: We analyzed the somatic mutations and loss of heterozygosity (LOH) of the TFF1 gene using an intragenic polymorphic marker in 61 gastric tumors. The expression pattern of TFF1 was also examined by immunohistochemistry. RESULTS: We detected a total of 8 somatic mutations-1 (5.5%) of 18 adenomas and 7 (16.3%) of 43 carcinomas-that were all missense mutations confined to the loop I and loop II structure of TFF1. We detected LOH in 5 (1 in adenoma and 4 in cancer) of 30 (16.7%) informative gastric tumors with an intragenic polymorphic marker -2 base pairs (bp) upstream of the coding region of the TFF1 gene. Although 2 cases were noninformative, the 7 gastric cancers with mutation seemed to show the loss of the remaining allele except in 1 case, suggesting that TFF1 is a tumor-suppressor gene. We found loss of TFF1 expression in 44.2% of the gastric carcinomas, but there is no correlation between immunoreactivity and genetic alterations of the TFF1 gene. CONCLUSIONS: These results indicate that genetic alterations of TFF1 may lead to gastric mucosal barrier defects and contribute to the pathogenesis of gastric cancer.     

胃癌组织中5-脂氧合酶的表达及其与磷酸化Akt相的关性

目的: 检测5-脂氧合酶(5-lipoxygenase,5-LOX)在胃癌组织中的表达,并探讨5-LOX对磷酸化Akt(phosphorylatedAkt,p-Akt)表达的影响.方法: 采用逆转录-聚合酶链反应(RT-PCR)检测30例新鲜胃癌及癌旁正常组织标本中5-LOX mRNA表达水平;免疫印迹法(Westernblot)检测5-LOX和p-Akt蛋白的表达水平.结果: 5-LOX在胃癌组织中的表达显著高于癌旁正常组织(76.7% vs 40%,P＜0.05,mRNA水平;56.7%vs30%,P＜0.05,蛋白水平).p-Akt蛋白在胃癌组织中的表达也显著高于癌旁正常组织(56.7%vs26.7%,P＜0.05).相关性分析表明,胃癌组织中5-LOX蛋白表达和p-Akt水平间无明显相关性(r=0.186,P＞0.05).结论: 5-LOX蛋白对胃癌的发生、发展有一定促进作用,但与PI3-K/Akt信号通路无关.     

胃癌组织中5-脂氧合酶的表达及其与磷酸化Akt相的关性

目的:检测5-脂氧合酶(5-lipoxygenase,5-LOX)在胃癌组织中的表达,并探讨5-LOX对磷酸化Akt(phosphorylatedAkt,p-Akt)表达的影响.方法:采用逆转录-聚合酶链反应(RT-PCR)检测30例新鲜胃癌及癌旁正常组织标本中5-LOXmRNA表达水平;免疫印迹法(Westernblot)检测5-LOX和p-Akt蛋白的表达水平.结果:5-LOX在胃癌组织中的表达显著高于癌旁正常组织(76.7%vs40%,P<0.05,mRNA水平;56.7%vs30%,P<0.05,蛋白水平).p-Akt蛋白在胃癌组织中的表达也显著高于癌旁正常组织(56.7%vs26.7%,P<0.05).相关性分析表明,胃癌组织中5-LOX蛋白表达和p-Akt水平间无明显相关性(r=0.186,P>0.05).结论:5-LOX蛋白对胃癌的发生、发展有一定促进作用,但与PI3-K/Akt信号通路无关.     

Molecular forms of trefoil factor 1 in normal gastric mucosa and its expression in normal and abnormal gastric tissues

INTRODUCTION Trefoil factor 1 (TFF1) is a member of the trefoil factor family, which is a group of small molecule polypeptides mainly secreted by gastrointestinal mucous cells. TFF1 is mainly expressed in epithelial cytoplasm of the mucosa in gastric body…