p53基因内含子与肺癌

内含子是确保基因mRNA正常转录的必需结构,并且影响基因的表达。部分基因的内含子具有核酶作用,能降解特定的mRNA。内含子碱基在数量上占据基因DNA结构的绝大多数,许多酶切位点位于内含子上,通过核酶内切酶的作用使DNA降解是细胞凋亡的重要机制,而肿瘤是一种与细胞凋亡密切相关的疾病。通过这些机制,p53基因内含子的结构变化与肺癌的发生、发展有关。     

非小细胞肺癌p53基因内含子7多态性分析

p53基因有10个内含子，其中存在多处多态性变化，有报道p53基因内含子多态性与肺癌等恶性肿瘤有关。近年发现p53基因内含子7上有2个多态性位点，其中第1个多态性位点有GGGCCC→GGGTCC变化；构成ApaI限制性核酸内切酶识别序列的多态性变化；正常人这两个多态性位点呈连锁性变化。本研究旨在分析p53基因内含子7多态性是否与非小细胞肺癌(NSCLC)有关。     

热盐水所致大鼠萎缩性胃炎胃黏膜组织细胞p53和ras表达的实验研究

慢性萎缩性胃炎属于癌前状态 ,它是胃癌发生的重要环节。我们以人类饮食中不可缺少的两大因素———食物的热度与咸度 ,创建了快速建立慢性萎缩性胃炎动物模型的方法 ,并从分子水平探索从正常胃黏膜到萎缩性胃炎到胃癌的演变过程。一、材料与方法1.实验动物和主要试剂 :10 0只 7周龄的雄性SD大鼠 ,体重 2 0 0～ 2 5 0g ,由第四军医大学实验动物中心提供。SABC即用型试剂盒 ,p5 3和ras一抗 ,生物素化的二抗均购自武汉博士德公司。余化学试剂均购自第四军医大学。2 .大鼠萎缩性胃炎模型的制作 :采用 5 5℃、15 %的盐水连续灌胃 12周 ,制成…     

Hp感染与胃癌及萎缩性胃炎c-myc,p53基因表达的关系

目的研究Hp感染与胃癌及萎缩性胃炎中c-myc,p53基因改变的相互关系,以探讨Hp可能的致癌机制.方法应用PCR扩增及电泳带激光扫描测定c-myc基因扩增情况、PCR/SSCP方法观察p53第8外显子突变情况,快速尿素酶法和HE染色检测胃癌及萎缩性胃炎组织中Hp感染情况.结果萎缩性胃炎组Hp感染23例(23/30,76.67%),胃癌组Hp感染21例(21/30,70%),两者无显著差异(P>0.05).萎缩性胃炎组织中c-myc基因无扩增.p53基因第8外显子突变1例(1/30,3.33%),为Hp阳性者.胃癌组织c-myc基因扩增10例(10/30,33.33%),其中Hp阳性8例(8/10,80%),c-myc基因扩增多发生在低分化腺癌中.胃癌组织p53第8外显子突变17例(17/30,56.67%),其中Hp阳性14例(14/21,66.67%).p53第8外显子突变例数在Hp阳性组与Hp阴性组之间差异显著.结论Hp感染者具有更多肿瘤生物学行为,可以引起c-myc基因扩增、p53基因第8外显子突变,Hp可能为促癌剂在胃癌的发生发展中起一定作用     

慢性萎缩性胃炎与胃癌

萎缩性胃炎是指胃的固有腺体数目减少甚至消失,常伴有广泛的肠上皮化生和异型增生,肠上皮化生及异型增生为胃癌的癌前病变。正常胃黏膜．浅表性胃炎一萎缩性胃炎一肠上皮化生一异型增生一胃癌是Correa提出的慢性胃炎向胃癌演变的规律模式,已得到相关学者的广泛认同。越来越多证据表明,慢性萎缩性胃炎作为一种癌前疾病与胃癌的发生及发展密切相关。     

p53基因多态性与鼻咽癌遗传易感性的关系

目的研究广西南宁鼻咽癌患者p53基因遗传多态性与鼻咽癌发生的关系。方法采用病例-对照研究方法,以200例鼻咽癌患者、200例对照人群为研究对象。选取p53基因SNP rs117562731位点作为遗传标记,用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)和测序方法检测rs117562731位点基因型频率和等位基因频率,比较两组不同基因型与鼻咽癌易感性的关系。结果通过对rs117562731位点多态基因型检测分型发现,在鼻咽癌组和对照组CC、CT、TT基因型频率分别为80.0%、17.0%、3.0%和93.0%、5.5%、1.5%。rs117562731位点等位基因及基因型频率在鼻咽癌组与对照组间分布有显著性差异(P0.05)。结论 p53基因SNP rs117562731位点多态性与鼻咽癌之间存在显著的相关性。     

萎缩性胃炎及异型增生ras p21的表达

萎缩性胃炎及异型增生ｒａｓｐ２１的表达倪桂宝我们应用ＡＢＣ免疫组化法进行了ｒａｓ癌基因产物ｐ２１单克隆抗体检测，旨在探讨ｒａｓ癌基因在胃癌前状态中的表达及其与胃癌发生的关系。一、材料和方法材料选自本院１９８８～１９９３年间胃镜活检标本，其中慢性萎缩性...     

肿瘤坏死因子基因多态性与慢性萎缩慢胃炎和胃腺癌的相关性

研究发现 ,肿瘤坏死因子 (ＴＮＦ)基因多态性与ＴＮＦ的分泌有关[1] ,甚至可调节其转录水平[2 ] 。ＴＮＦ基因多态性是否与人类某些肿瘤、自身免疫性疾病、感染性疾病相关 ,国外学者的研究尚无定论。迄今为止 ,国内外有关ＴＮＦ基因多态性与慢性萎缩性胃炎和胃癌关系的报道极少。因此 ,我们对湖北地区汉族人群ＴＮＦ α和ＴＮＦ β基因多态性分布与慢性萎缩性胃炎和胃腺癌的相关性进行了分析 ,以阐明ＴＮＦ基因多态性在慢性萎缩性胃炎和胃腺癌中的作用。一、对象随机选取健康体检者 16 4例 ,其中男 113例 ,女 5 1例 ,平均年龄 (5 2 3± 11 …     

萎缩性胃炎中P53和PCNA的表达

目的了解Ｐ５３，ＰＣＮＡ在胃粘膜癌前病变中的表达意义．方法慢性萎缩性胃炎（ＣＡＧ）８９例，慢性浅表性胃炎（ＣＳＧ）２０例和胃腺癌２０例，作ＳＰ法观察Ｐ５３和ＰＣＮＡ的表达．结果Ｐ５３在ＣＳＧ和ＣＡＧ的单纯型、增生型和肠化型中不表达，异型性型中阳性表达率为１９０％（４／２１）．ＰＣＮＡ在ＣＳＧ和ＣＡＧ的单纯型、增生型、肠化型中无显著性差异（Ｐ＞００５）；而ＣＡＧ的异型性阳性细胞明显增多（Ｐ＞００１）．结论Ｐ５３表达与胃粘膜向癌的演变有关．ＰＣＮＡ随细胞增生活跃程度递增．二者结合对胃癌前病变的诊断、分级、治疗、预后有辅助价值．     

慢性萎缩性胃炎黏膜上皮中P53和C-erbB-2表达的临床意义

目的:探讨慢性萎缩性胃炎(CAG)黏膜上皮中P53及C-erbB-2的表达及意义．方法:用免疫组化技术(SP法)检测正常胃黏膜56例、慢性萎缩性胃炎429例(腺体囊性扩张61例,大肠型化生73例,轻、中、重度不典型增生各120、91和84例)和早期胃癌57例中P53和C-erbB-2的表达,分析P53和C-erbB-2表达及其与CAG胃黏膜病变类型的关系．结果:正常胃黏膜,囊性扩张腺体,轻、中度不典型增生,大肠型化生,重度不典型增生,早期胃癌P53和C-erbB-2表达的阳性率呈上升趋势．前三组间表达率差异无统计学意义(P>0．05);正常胃黏膜与中度不典型增生、大肠型化生、重度不典型增生及胃癌组P53和C-erbB-2的表达差异有统计学意义(P<0．01)．Spearman等级相关分析显示P53和C-efbB-2表达呈正相关(r=0．867,P<0．05)．年龄<40岁和≥40岁组间、性别组间P53表达阳性率差异有统计学意义(x2=12．393,P<0．01;x2=8．799, P<0．01)．C-erbB-2的表达在上述年龄组间差异有统计学意义(x2=7．706,P<0．01),而在性别组间无统计学意义(P>0．05)．结论:检测慢性萎缩性胃炎中P53和C-erbB-2的表达,有助于监测CAG癌前病变的进展及胃癌的早期发现．     

萎胃康治疗大鼠慢性萎缩性胃炎的Akt-Mdm2-P53机制

目的研究中药萎胃康治疗慢性萎缩性胃炎(CAG)的疗效及其对蛋白激酶B(Akt)-鼠双微基因(Mdm)2-P53信号通路的影响。方法健康雄性SD大鼠60只,按随机数字表分为正常组,模型组,萎胃康高、中、低剂量组,西药组各10只。造模成功后,正常组和模型组灌胃生理盐水,治疗组分别给予不同浓度的萎胃康水溶液及维酶素。治疗30 d后,苏木素-伊红(HE)法染色观察各组胃黏膜组织形态学变化,免疫组化法检测各组胃黏膜Akt、Mdm2、P53蛋白的表达情况。结果与正常组相比,模型组Akt和Mdm2的表达明显增加(P<0.05),P53表达明显降低(P<0.05)。与模型组相比,各治疗组Akt和Mdm2表达明显减少(P<0.05);P53表达明显上调(P<0.05),其中以萎胃康高剂量组变化最为明显。药物治疗后,各治疗组与高剂量组相比差异显著(P<0.05)。结论中药萎胃康对CAG具有治疗作用,其作用机制可能与调控Akt-Mdm2-P53信号通路,抑制Akt和Mdm2蛋白的表达,提高P53蛋白的表达有关。     

慢性萎缩性胃炎中医治法分布及方剂运用规律

目的:探讨慢性萎缩性胃炎中医治法分布及方剂运用规律,为制定CAG规范化治疗方案提供依据.方法:通过网络数据库检索近10年中医药治疗CAG文献,从2300余篇文献中撷取了含有具体病例统计数据的文献206篇,对确诊CAG病例8056例进行归纳、整理和总结其相关中医治法分布及方剂运用信息,然后进行统计学处理、分析.结果:中医治法排在首位的是:健脾益气(构成比35.45%),其余依次是疏肝和胃(构成比22.24%)、益气养阴和清热化湿(构成比分别为16.68%,15.14%,均P<0.01),上述4种治法构成比总和达85%以上.4种证型的治法使用方剂频次居首的分别是:香砂六君子汤、柴胡疏肝散、益胃汤和半夏泻心汤(使用频率依次为:25.23%,60.87%,34.67%,26.76%;均P<0.01).结论:健脾益气为CAG基本治法,疏肝和胃、益气养阴和清热化湿为临床常见治法,分别以香砂六君子汤、柴胡疏肝散、益胃汤,沙参麦冬汤和半夏泻心汤为各证型首选方剂.其结果对制定CAG规范化治疗方案具有参考价值.     

Severity of atrophic gastritis related to antiparietal cell antibody and gastric carcinogenesis, including p53 mutations

BACKGROUND AND AIMS: Infection with Helicobacter pylori (Hp) has been linked to atrophic gastritis, an inflammatory precursor of non-cardia gastric carcinoma. Mutations in the p53 gene are one of the most frequent genetic alterations in gastric carcinoma. In a subgroup of atrophic gastritis, antiparietal cell antibody (APCA) has been detected. This study was aimed to clarify the role of APCA in the progression of atrophic gastritis and gastric carcinogenesis, and to determine the relationship of the severity of atrophic gastritis to gastric carcinoma and to p53 mutations. METHODS: In 494 control subjects and 284 gastric carcinoma patients, serum APCA was evaluated and all subjects and patients were classified into four groups using serologic markers (anti-Hp IgG antibody and pepsinogen (PG) test: positive; PG I < 70 microg/L and PG I/II ratio < 3.0) as follows: A, HP- PG-; B, HP+ PG-; C, HP+ PG+ and D, HP- PG+. p53 mutations were analyzed in 174 of 284 patients. RESULTS: Antiparietal cell antibody seropositivity increased from group B to D, however, no difference in its positivity was found between controls and patients. The incidence of gastric carcinoma increased from A to D, especially the intestinal subtype. The frequency of p53 gene mutations was higher in PG+ than in PG- gastric carcinoma. CONCLUSIONS: Antiparietal cell antibody seropositivity is involved in the progression of a subgroup of atrophic gastritis, but not associated with gastric carcinogenesis. Severe atrophic gastritis is associated with susceptibility to gastric carcinoma, especially the intestinal subtype, and p53 mutations.     

血清胃蛋白酶原检测在慢性萎缩性胃炎筛查中的价值

目的探讨血清胃蛋白酶原Ⅰ(PGⅠ)、胃蛋白酶原Ⅰ/胃蛋白酶原Ⅱ(PGⅠ/PGⅡ)比值(PGR)与慢性萎缩性胃炎的关系,确定其在萎缩性胃炎中的变化规律。方法选择在我院消化科行胃镜检查符合入选研究标准的200例患者,根据组织病理学诊断结果分为慢性非萎缩性胃炎组(135例)和慢性萎缩性胃炎组(65例)。采用化学发光方法定量测定空腹血清PGⅠ、PGⅡ,并计算PGⅠ/PGⅡ比值(PGR)。结果慢性萎缩性胃炎组与非萎缩性胃炎组血清PGⅠ分别为(78.55±15.42)μg/L和(130.51±55.23)μg/L,有显著差异(P<0.05)。PGR分别为4.09±2.15和8.95±5.18,显著差异(P<0.05);以PGⅠ≤70μg/L且PGR≤3.0为界值来计算诊断慢性萎缩性胃炎的敏感性和特异性分别为72.3%和93.3%。结论检测血清PG及PGR可用于慢性萎缩性胃炎的筛查,如有异常,应进一步行胃镜检查以确诊并指导治疗。     

慢性萎缩性胃炎免疫状态与幽门螺杆菌感染的关系

本文对１１０例老年人慢性萎缩性胃炎检测幽门螺杆菌及免疫球蛋白ＩｇＡ、ＩｇＧ，Ｔ细胞标民，和超氧化物歧化酶等局部粘膜免疫状态。结果显示老年ＣＡＧ的ＨＰ感染率比非老年ＣＡＧ的ＨＰ感染率为低。局部粘膜ＩｇＡ、ＩｇＧ阳性增强，且体液免疫ＩｇＡ、ＩｇＧ强于细胞免疫ＴｕｃＨＬ，有ＳＯＤ减弱现象。示感染ＨＰ的老年ＣＡＧ患者存在粘膜免疫功能亢进，以及清除自由基能力下降。     

Effects of He-Ne laser irradiation on chronic atrophic gastritis in rats

AIM: To study the effects of He-Ne laser irradiation on experimental chronic atrophic gastritis (CAG) in rats. METHODS: Sixty-three male adult Wistar rats were randomly divided into five groups including normal control group, model control group and three different dosages He-Ne laser groups. The chronic atrophic gastritis (CAG) model in rats was made by pouring medicine which was a kind of mixed liquor including 2% sodium salicylate and 30% alcohol down the throat for 8 wk to stimulate rat gastric mucosa, combining with irregular fasting and compulsive sporting as pathogenic factors; 3.36, 4.80, and 6.24 J/cm2 doses of He-Ne laser were used, respectively for three different treatment groups, once a day for 20 d. The pH value of diluted gastric acid was determined by acidimeter, the histopathological changes such as the inflammatory degrees in gastric mucosa, the morphology and structure of parietal cells were observed, and the thickness of mucosa was measured by micrometer under optical microscope. RESULTS: In model control group, the secretion of gastric acid was little, pathologic morphological changes in gastric mucosa such as thinner mucous, atrophic glands, notable inflammatory infiltration were found. After 3.36 J/cm2 dose of He-Ne laser treatment for 20 d, the secretion of gastric acid was increased (P<0.05), the thickness of gastric mucosa was significantly thicker than that in model control group (P<0.01), the gastric mucosal inflammation cells were decreased (P<0.05). Morphology, structure and volume of the parietal cells all recuperated or were closed to normal. CONCLUSION: 3.36 J/cm2 dose of He-Ne laser has a significant effect on CAG in rats.     

慢性萎缩性胃炎和胃腺癌肿瘤坏死因子微卫星遗传易感性研究

目的 探讨中国湖北地区汉族人群中肿瘤坏死因子（TNF）a,TNFb和TNFc微卫星多态性分布，分析其与慢性萎缩性胃炎和胃腺癌的相关性。方法 应用PCR结合变性聚丙烯酰胺凝胶高压电泳和AgNO3染色，对164例健康者，53例慢性萎缩性胃炎和56例胃腺癌患者的TNFa,TNFb和TNFc微卫星进行分型，并将PCR产物克隆及测序鉴定。结果 慢性萎缩性胃炎中的TNFa10基因频率为19．81％，显著高于正常人中的11．84％（P．04）。进一步分析显示TNFa10等位基因与患者的年龄，性别,黏膜萎缩程度，肠上皮化生等无关。TNFa6b5c1单倍体纯合子在胃腺癌中的频率为1．79％，显著低于正常人中的15．85％（P＝0．006）。克隆测序发现，相同TNFa等位基因包含的（AC／GT）重复序列拷贝数与国外文献报道中不一致。结论 TNFa等位基因的定义内涵尚需进一步确定。TNFa10等位基因与慢性萎缩性胃炎的易感性相关，TNFa6b5c1单倍体纯合子在慢性萎缩性胃炎至胃腺癌移行过程中发挥其抵抗作用。     

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis

AIM To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis(CAG). METHODS A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination fromSeptember 2013 to September 2016 were selected for this study. The age of these patients ranged within 18-to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori(H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration.Furthermore,CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve(R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12 deficiency may be considered in patients with CAG. Furthermore, the timely supplementation of vitamin B12 during the clinical treatment of CAG can reduce or prevent peripheral nervous system lesions.