河南林州地区贲门癌和癌旁组织中p16基因启动子甲基化及蛋白表达

目的探讨贲门癌变过程中p16基因启动子区甲基化和p16蛋白表达变化特征和规律及其相互关系。方法采用甲基化特异PCR（MSP）及免疫组化方法,检测林州地区32例贲门癌患者癌组织、癌旁不典型增生组织和正常组织p16基因启动子区甲基化状态及蛋白表达情况。结果p16基因在癌组织中表达缺失18例（56%）,不典型增生组织中表达缺失8例（73%）;26例（81%）癌组织、7例（64%）不典型增生组织和18例（67%）正常组织发生了p16基因启动子区的甲基化。贲门癌组织中p16基因甲基化与表达缺失一致率为56%。差异无统计学意义,P〉0.05。结论p16蛋白表达缺失可能是贲门癌变过程中的重要分子事件,p16基因启动子区甲基化可能是导致其蛋白表达缺失的机制之一。     

胸腹联合切口切除贲门癌598例体会

目的：探讨胸腹联合切口在贲门癌手术中的应用。方法：回顾性分析1996年6月～2006年2月采用胸腹联合切口治疗贲门癌598例临床资料。结果：根治性切除576例（切除率96.3%）,姑息性切除15例,单纯探查7例。并发症发生率为4.7%（28/598）,其中吻合口瘘4例,吻合口狭窄3例,呼吸衰竭3例,肺部感染11例,脓胸2例,乳糜胸1例,心衰4例（死亡1例）。结论：经胸腹联合切口治疗贲门癌有利于肿瘤切除及周围淋巴结清扫,能够提高手术切除率,并发症少,在一定程度上优于左侧单纯开胸或剖腹手术。     

食管胃椭圆形吻合法的动物实验及临床应用研究

 目的　为避免或减少食管胃吻合术后吻合口狭窄、返流性食管炎及 吻合口瘘;设计了食管胃椭圆形吻合法。方法　实验与临床均随机分为椭圆 形 吻合法组与传统吻合法组进行对比研究。结果　椭圆形吻合法组无论是吻合 口径、组织愈合过程、抗返流、食管粘膜充血、水肿及食管粘液pH值测定等方面均优于传统 吻合法(P<0.05)。结论　椭圆形吻合法是食管胃消化道重建中更为理 想的手术方法。     

贲门癌间质微血管密度和细胞增殖指数

目的研究贲门癌不同生长特性和类型中间质微血管密度和细胞增殖活性。方法40例贲门癌切除标本,肿瘤区和非肿瘤区分别取材。HE染色和V因子相关抗原及增殖细胞核抗原(PCNA)行免疫组化染色。镜下计量肿瘤区和非肿瘤区Ⅱ、不同大体类型、分化程度、浸润深度和有无淋巴结转移的微血管密度和细胞增殖指数。结果肿瘤区微血管密度(58±27)／mm     

Methylation‐mediated repression of GADD45A and GADD45G expression in gastric cardia adenocarcinoma

The growth arrest DNA damage‐inducible gene (GADD45) family, which is composed of GADD45A, GADD45B, and GADD45G, may play similar but not identical roles in tumorigenesis. Genetic changes associated with or responsible for their dysregulation are in general uncommon. This study was to detect the role of GADD45 gene family in gastric cardia adenocarcinoma (GCA) and the relationship of GADD45A and GADD45G methylation to a series of pathological parameters in a large GCA sample, in order to elucidate more information on the role of GADD45 gene family with regard to the pathogenesis of GCA. Decreased mRNA and protein expression of GADD45A and GADD45G but not GADD45B were found in 138 GCA tumor tissues. The methylation frequency of 5′ 4 CpG region located in distal promoter of GADD45A and proximal promoter of GADD45G in GCA tumor tissues was significantly higher than that in corresponding normal tissues. The expression levels of GADD45A and GADD45G were inversely correlated with methylation levels. GADD45B expression was not correlated with GCA patients survival, while GADD45A and GADD45G methylation status and protein expression were independently associated with GCA patients' survival. These results suggest that GADD45A and GADD45G gene may act as functional tumor suppressor but being frequently inactivated epigenetically in patients with GCA. Silencing of GADD45A and GADD45G, negative regulator of cell growth, is most likely responsible for conferring a selective growth advantage during GCA evolution and outgrowth.     

贲门溃疡104例内镜检查分析

目的:通过贲门溃疡胃镜下表现的分析,探讨贲门良性溃疡与恶性溃疡的区别及并发症的差异.方法:纤维胃镜检查的同时采取相应部位的病理标本并行病理学检查,记数资料采用卡方检验比较差异性.结果:病例共104例,其中良性溃疡66例,恶性溃疡30例,癌前病变8例,恶性溃疡73%合并有慢性萎缩性胃炎,良性溃疡25%合并有十二指肠球部溃疡.结论:贲门良性溃疡(16/66)与十二指肠疾患密切相关,恶性溃疡(22/30)于慢性萎缩性胃炎密切相关,临床工作中遇有慢性萎缩性胃炎患者,应高度警惕,定期随访,及时发现恶变.     

胃癌病人术后早期营养支持对营养等状况恢复的比较

目的:探讨胃底贲门癌病人术后早期应用全肠外营养(TPN)和肠内营养(EN)对营养等状况恢复的比较分析.方法:将73例胃底贲门癌病人随机分为EN组(37例)和PN组(36例).于术后48 h内开始给予等氮、等热量营养支持,观察两组病人手术前、后的营养和免疫指标、术后肠鸣音恢复、肛门排气时间和并发症发生的情况.结果:两组病人术后营养支持的营养及免疫指标明显改善(P＜0.05),EN组前清蛋白和免疫指标较PN组明显提高(P＜0.05);EN组较PN组术后胃肠道功能恢复的更早,同时并发症的发生率亦明显减低.结论:胃底贲门癌病人术后早期肠内营养支持,既能促进胃肠道功能尽早恢复,又可改善病人术后营养状况和免疫功能.     

Atrogin-1基因在贲门腺癌组织中的表达及其异常甲基化

目的：探讨atrogin-1基因在贲门腺癌（gastric cardia adenocarcinoma,GCA）中的异常甲基化及表达,并分析其临床意义。方法: 选用河北医科大学第四医院2004—2008年间的贲门腺癌患者手术标本共139例,分别应用亚硫酸氢盐转换-甲基化特异性PCR（bisulfite conversion-methylation specific polymerase chain reaction,BS-MSP）、RT-PCR和免疫组织化学法检测贲门腺癌组织及相应癌旁（距癌灶边缘3～5 cm）组织中atrogin-1基因的甲基化、mRNA和蛋白表达情况,应用免疫组织化学法检测相应组织中Smad4蛋白的表达。结果: 贲门腺癌组织中atrogin-1基因启动子区的甲基化率\[44.6%（62/139）\] 显著高于癌旁组织\[3.6%(5/139)\]（χ2=63.891,P=0.001）,且atrogin-1基因的甲基化与TNM分期及肿瘤的组织学分化程度密切相关（χ2=6.144, P<0.05）。贲门腺癌组织中atrogin-1基因的mRNA和蛋白表达水平显著低于癌旁组织\[(0.482 5±0.175 4) vs (0.896 9±0.290 1),t=10.62, P=0.01;34.5% vs 82.0%, χ2=4.441,P=0.001\],且与其启动子区的甲基化状态之间有明显的相关性(r=-0.256,P=0.001)。贲门腺癌组织中Smad4蛋白表达的阳性率显著低于癌旁组织（46.0% vs 95.7%; χ2=2.945,P=0.001）,且与atrogin-1蛋白表达之间呈明显的正相关(r=0.604,P=0.001）。结论: Atrogin-1基因启动子区高甲基化导致的基因沉默可能是贲门癌组织中此基因表达降低的机制之一。     

NDRG2基因在贲门腺癌中的甲基化状态及表达

目的： 探讨贲门腺癌(GCA)中NDRG2(N-myc downstream-regulated gene 2)基因启动子区的甲基化状态,并分析其甲基化与表达之间的相关性。方法：应用甲基化特异性PCR(MSP)方法检测97例贲门腺癌组织及相应癌旁组织中NDRG2基因的甲基化状态,应用RT-PCR和免疫组织化学方法检测97例贲门腺癌组织及相应癌旁组织中NDRG2的mRNA和蛋白表达情况。结果：NDRG2基因启动子区在贲门腺癌组织中的甲基化率(49.5%)显著高于癌旁正常组织(5.1%)(P<0.05),且Ⅲ期和Ⅳ期贲门腺癌患者中NDRG2基因甲基化的比率显著高于Ⅰ期和Ⅱ期患者,低分化组中NDRG2基因发生甲基化的比率显著高于高中分化组。贲门腺癌组织中NDRG2 mRNA表达水平显著低于癌旁正常组织(P<0.05)。贲门腺癌组织中NDRG2蛋白表达阳性率为44.3%(43/97),显著低于相应癌旁正常组织的蛋白表达94.8%(92/97)(P<0.01),且贲门腺癌组织中NDRG2蛋白表达缺失与其启动子区的甲基化有明显的相关性(r=-0.510,P<0.01)。结论：NDRG2基因启动子区的高甲基化导致的基因沉默可能是贲门腺癌中此基因表达降低的机制之一。     

Association of MTHFR C677T and SHMT<Subscript>1</Subscript> C1420T with susceptibility to ESCC and GCA in a high incident region of Northern China

Objective To assess the association between the C to T transition in the methylenetetrahydro folate reductase gene (MTHFR C677T) and the C to T transition in the serine hydroxymethyltransferase ₁ gene (SHMT ₁ C1420T) and the increased risk of carcinogenesis of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in a population of high incident region of Northern China. Methods The polymorphisms were genotyped by polymerase chain reaction–restriction fragment length polymorphism and PCR-confronting two-pair primers analysis respectively among 1051 cancer patients (584 ESCC and 467 GCA) and 540 healthy controls. Results The MTHFR 677T/T genotype significantly increased susceptibility to both ESCC and GCA compared with the C/C genotype, the adjusted OR was 2.13 (95% CI = 1.50–3.02) and 1.28 (95% CI = 1.07–1.53, respectively. For the SHMT ₁ C1420T polymorphism, the C/C genotype was significantly associated with the increased risk of ESCC and GCA, compared with the C/T genotype (the adjusted OR = 1.43 and 1.35, 95% CI = 1.02–2.00 and 1.11–1.63, respectively). The interactive influence of the MTHFR and SHMT ₁ polymorphisms in the risk of ESCC and GCA was also observed. Conclusion The association between the MTHFR C677T and SHMT ₁ C1420T polymorphisms and the risk of ESCC and GCA was demonstrated. Yimin Wang, Wei Guo and Yutong He contributed equally to this work. Supported by Grants from the National Natural Science Foundation (No. 30371591), National High Technique Research and Development Project (No. 2002BA711A08), and Natural Science Foundation of Hebei Province (No. C0400062).