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Expression of nuclear factor-kappa B and target genes in gastric precancerous lesions and adenocarcinoma:Association with Helicobactor pylori cagA (+) infection

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World Journal of Gastroenterology 2004年第4期10卷 491-496页

作者： Gui-FangYang Chang-ShengDeng Yong-YanXiong Ling-LingGong Bi-ChengWang JunLuo DepartmentofPathology ZhongnanHospitalWuhanUniversityWuhan430071HubeiProvinceChina DepartmentofGastroenterology ZhongnanHospitalWuhanUniversityWuhan430071HubeiProvinceChina

AIM:To examine the expression of nuclear factor kappaB (NF-κB) and its target genes in intestinal metaplasia (IM),dysplasia (DYS) and gastric carcinoma (GC) infected with Helicobacter pylori (H pylori) and to investigate the mechanism underlying Hpyloricytotoxin associated gene A(cag A) infection leading to gastric ***: Expressions of NF-κB/p65 and its target genes:c-myc, cyclinD1 and bcl-xl were immunohistochemically examined in 289 cases of gastric biopsy and resection specimens from patients with IM, DYS and GC infected with H pylori. H pylori in the above mentioned tissues was detected by Warthin-Starry stain and rapid urease *** antibody to cagA in sera of the patients was measured by ***:The positive rates of NF-κB/p65 were significantly higher in groups with cagA of IMI-Ⅱ(28/33), IM III(48/52),DYSI(27/31), DY5 Ⅱ-Ⅲ(28/32), GC(35/40) than in groups without cagA of IMI-Ⅱ(4/17), IMⅢ(3/20), DYSI(3/20),DYSⅡ-Ⅲ(6/21), GC(10/23). The expressions of c-myc,cyclinD1, and bcl-xl were significantly higher in groups with cagA of IM Ⅲ(47/52, 49/52, 46/52), DYSⅡ-Ⅲ(29/32, 26/32,25/32) than in groups without cagA of IM Ⅲ(8/20, 7/20,5/20), DYSⅡ-Ⅲ(10/21, 8/21, 3/21), which were in conformity with the expression of NF-κB in IM Ⅲ, and DYSⅡ-Ⅲ. Asignificantly higher expression level of NF-κB/p65, c-myc,cyclinD1 and bcl-xl was detected in intestinal type GC(27/28,18/28, 22/28, 24/28) than in diffuse type GC(8/12, 3/12,3/12, 6/12), ***: There may be two different molecular mechanisms in the occurrence of intestinal and diffuse type gastric carcinomas. Intestinal type gastric carcinoma is strongly associated with high expression of c-myc, cyclinD1 and bcl-xl through NF-κB/p65 activated by Hpylori *** the activity of NF-κB is an effective and promising way to prevent intestinal type gastric carcinoma.

关键词： NF-κB 胃癌癌前病变幽门螺杆菌目标基因细胞因子

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Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning

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World Journal of Gastroenterology 2004年第13期10卷 1934-1938页

作者： KaiSun Zhi-SuLiu QuanSun DepartmentofGeneralSurgery ZhongnanHospitalWuhanUniversityWuhan430071HubeiProvinceChina DepartmentofGeneralSurgery ZhongnanHospitalWuhanUniversityWuhan430071HubeiProvinceChina

AIM: To investigate the role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning (IPC).METHODS: A rat model of acute hepatic ischemia-reperfusion was established, 24 healthy male Wistar rats were randomly divided into sham-operated group, ischemia-reperfusion group (IR) and IPC group. IPC was achieved by several brief pre-reperfusions followed by a persistent *** of malondialdehyde (MDA) and activity of several antioxidant enzymes in hepatic tissue were measured respectively. Apoptotic cells were detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and expression of Bcl-2 protein was measured by immunohistochemical techniques. Moreover, mitochondrial ultrastructure and parameters of morphology of the above groups were observed by electron ***: Compared with IR group, the concentration of MDA and the hepatocellular apoptotic index in IPC group was significantly reduced (P<0.05), while the activity of antioxidant enzymes and OD value of Bcl-2 protein were markedly enhanced (P<0.05). Moreover, the injury of mitochondrial ultrastructure in IPC group was also obviously ***: IPC can depress the synthesis of oxygen free radicals to protect the mitochondrial ultrastructure and increase the expression of Bcl-2 protein that lies across the mitochondrial membrane. Consequently, IPC can reduce hepatocellular apoptosis after reperfusion and has a protective effect on hepatic ischemia-reperfusion injury.

关键词：线粒体细胞凋亡肝脏损害局部缺血多次灌注液保护作用缺血性后均衡 IR

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Hypermethylation of CpG island in O^6-methylguanine-DNA methyltransferase gene was associated with K-rasG to A mutation in colorectal tumor

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World Journal of Gastroenterology 2005年第13期11卷 2022-2025页

作者： JianQi You-QingZhu Mei-FangHuang DongYang DepartmentofGastrooenterology ZhongnanHospitalWuhanUniversityWuhan430071HubeiProvinceChina

AIM: To investigate the functions of promoter hypermethylation of O6-methylguanine-DNA methyltransferase (MGMT) gene in colorectal tumorigenesis and ***: The promoter hypermethylation of MGMT gene was detected in 27 sporadic colorectal adenomas,62 sporadic colorectal carcinomas and 20 normal colorectal mucosa tissues by methylation-specific PCR. At the same time, the expression of MGMT protein was carried out in the same samples using immunohistochemistry. Mutantallele-specific amplification was used to detect K-rasG to A point mutation in codon ***: None of the normal colorectal mucosa tissues showed methylated bands. Promoter hypermethylation was detected in 40.7% (11 of 27) of adenomas and 43.5% (27 of 62) of carcinomas. MGMT proteins were expressed in nucleus and cytoplasm of normal colorectal mucosa tissues. Loss of MGMT expression was found in 22.2% (6 of 27) of adenomas and 45.2% (28 of 62) of carcinomas. The difference between them was significant (P = 0.041). In the 6 adenomas and 28 carcinomas losing MGMT expression, 5 and 24 cases presented methylation,respectively (P = 0.027, P＜0.001). Thirteen of the 19 colorectal tumors with K-rasG to A point mutation in codon 12 had methylated MGMT(P = 0.011). The frequencies of K-rasG to A point mutation were 35.3% (12 of 34) and 12.7% (7 of 55) in tumors losing MGMT expression and with normal expression, ***: Promoter hypermethylation and loss of expression of MGMT gene were common events in colorectal tumorigenesis, and loss of expression of MGMT occurs more frequently in carcinomas than in adenomas in sporadic patients. Hypermethylation of the CpG island of MGMT gene was associated with loss of MGMT expression and K-ras G to A point mutation in colorectal tumor. The frequency of K-ras G to A point mutation was increased in tumors losing MGMT expression. It suggests that epigenetic inactivation of MGMT plays an important role in colorectal neoplasia.

关键词： O6-methylguanine-DNA methyltransferase CpG island DNA methylation Epigenetic change K-ras mutation

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Obesity and colorectal cancer risk: A meta-analysis of cohort studies

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World Journal of Gastroenterology 2007年第31期13卷 4199-4206页

作者： Zhe Dai Yan-Cheng Xu Li Niu DepartmentofEndocrinology ZhongnanHospitalWuhanUniversityWuhan430071HubeiProvinceChina

TO evaluate the association between obesity and colorectal cancer risk. METHODS： We searched PubMed, EMBASE, and the Cochrane Library up to January 1, 2007. Cohort studies permitting the assessment of causal association between obesity and colorectal cancer, with clear definition of obesity and well-defined outcome of colorectal cancer were eligible. Study design, sample size at baseline, mean follow-up time, co-activators and study results were extracted. Pooled standardized effect sizes were calculated.

关键词： Obesity Colorectal cancer Waist-to-hipratio Waist circumference Weight Cohort study Metaanalysis

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NOD2 3020insC frameshift mutation is not associated with inflammatory bowel disease in Chinese patients of Hart nationality

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World Journal of Gastroenterology 2004年第7期10卷 1069-1071页

作者： Qiu-ShaGuo BingXia YiJiang YanQü JingLi DepartmentofInternalMedicine ZhongnanHospitalWuhanUniversityWuhan430071HubeiProvinceChina

AIM: An insertion mutation at nucleotide 3020 (3020insC) in the Caspase recruitment domain gene (CARD15), originally reported as NOD2, is strongly associated with Crohn's disease. The C-insertion mutation at nucleotide 3020 (3020inC) in the leucine-rich repeat (LRR) region results in a frameshift in the 10^th LRR followed by a premature stop codon. This truncation mutation is responsible for the inability to activate nuclear factor (NF)-κB in response to bacterial lipopolysaccharide (LPS). The present study aimed to genotype NOD2/CARD15 gene 3020insC frameshift mutation in Chinese patients with inflammatory bowel disease. METHODS: We genotyped an insertion polymorphism affecting the leucine-rich region of the protein product by the allele specific PCR in 74 unrelated patients with ulcerative colitis of Han nationality in Hubei Province of China, 15 patients with Crohn's disease and 172 healthy individuals. RESULTS: No significant differences were found in the genotype and allele frequendes of the C-insertion mutation of NOD2 gene among patients with Crohn's disease and ulcerative colitis and healthy controls. CONCLUSION: NOD2 gene 3020insC frameshift mutation is not a major contributor to the susceptibility to both Crohn's disease and ulcerative colitis in Chinese Han patients.

关键词： NOD2基因基因突变炎性肠病中国汉族人群脂多糖细胞因子

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Effects of thalidomide on angiogenesis and tumor growth and metastasis of human hepatocellular carcinoma in nude mice

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World Journal of Gastroenterology 2005年第2期11卷 216-220页

作者： Zhong-LinZhang Zhi-SuLiu QuanSun DepartmentofGeneralSurgery ZhongnanHospitalWuhanUniversityWuhan430071HubeiProvinceChina

AIM: To investigate the effects of thalidomide on angiogenesis, tumor growth and metastasis of hepatocellular carcinoma in nude ***: Twenty-four nude mice were randomly divided into therapy group and control group, 12 mice in each group. Thalidomide dissolved in 0.5% sodium carboxyl methyl cellulose (CMC) suspension was administered intraperitoneally once a day at the dose of 200 mg/kg in therapy group, and an equivalent volume of 0.5% CMC in control group. Mice were sacrificed on the 30th d, tumor size and weight and metastases in liver and lungs were measured. CD34 and VEGF mRNA in tumor tissue were detected by immunohistochemistry and semi-quantitative RT-PCR respectively and microvessel density (MVD) was counted. Serum concentrations of TNF-α and ALT and AFP were also ***: MVD and VEGF mRNA in therapy group were less than those in control group (31.08±16.23 vessels/HP vs 80.00±26.27 vessels/HP, 0.0538±0.0165 vs 0.7373±0.1297,respectively, P＜0.05). No statistical difference was observed in tumor size and weight and metastases in liver and ***-α was significantly lower in therapy group than in control group (28.64±4.64 ng/L vs42.69±6.99 ng/L, P＜0.05). No statistical difference in ALT and AFP was observed between ***: Thalidomide can significantly inhibitangiogenesis and metastasis of hepatocellular *** has inhibitory effects on circulating TNF-α.

关键词： Hepatocellular carcinoma Thalidomide Angiogenesis Neoplasm metastasis

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Effects of low molecular weight heparin on platelet surface P-selectin expression and serum interleukin-8 production in rats with trinitrobenzene sulphonic acid-induced colitis

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World Journal of Gastroenterology 2004年第5期10卷 729-732页

作者： BingXia HongHan Ke-JianZhang JinLi Guang-SongGuo Ling-LingGong Xian-ChangZeng Jun-YanLiu DepartmentofInternalMedicine ZhongnanHospitalWuhanUniversityWuhan430071HubeiProvinceChina DepartmentofPathology ZhongnanHospitalWuhanUniversityWuhan430071HubeiProvinceChina DepartmentofImmunology MedicalSchoolWuhanUniversityWuhan430071HubeiProvinceChina

AIM:To observe the effects of low molecular weight heparin(LMWH) on platelet surface P-selectin expression and serum interleukin-8 production in rats with trinitrobenzene sulphonic acid (TNBS) induced ***:Colitis was induced in female Sprauge-Dawley rats by colonic administration of 2, 4, 6-TNBS. LMWH, a dalteparin (150U/kg, 300U/kg) was subcutaneously administrated one hour before induction of colitis and went on once a day for 6 days. Then a half dose was given for the next 7 days. Control animals received the same volume of normal saline once a day for 14 days after treated by *** were sacrificed at 24h, days 7 and 14 after induction of colitis. The colon was excised for the evaluation of macroscopic and histological findings and TNF-α immunohistochemical assay. Platelet surface P-selectin expression was determined by radioimmunoassay and serum IL-8 production was assayed by ELISA ***:LMWH treatment in a dose of 300U/kg for 14 days significantly improved colonic inflammation by histological examination. Serum IL-8 production in the 300U/kg treatment group was more significantly decreased at day 14 than that at 24h (P<0.05). However, platelet surface P-selectin expression and TNF-α staining in colonic tissue were not significantly different among the three ***:LMWH has an anti-infiammatory effect on TNBS induced colitis in rats. The effect is possibly related to inhibition of proinflammatory cytokine IL-8, but not involved platelet surface P-selectin expression.

关键词： P-选择素血清学检查白细胞介素-8 低分子量肝磷脂三硝基苯硫酸大肠炎动物模型

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Effect of complex amino acid imbalance on growth of tumor in tumor-bearing rats

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World Journal of Gastroenterology 2003年第12期9卷 2772-2775页

作者： Yin-ChengHe Yuan-HongWang JunCao Ji-WeiChen Ding-YuPan Ya-KuiZhou DepartmentofGeneralSurgery ZhongnanHospitalWuhanUniversityWuhan430071HubeiProvinceChina WuhanCentreforDiseasePreventionandControl Wuhan430022HubeiProvinceChina

AIM: To investigate the effect of complex amino acid imbalance on the growth of tumor in tumor-bearing (TB) ***: Sprague-Dawlley (SD) rats underwent jejunostomy for nutritional support. A suspension of Walker256 carcinosarcoma cells was subcutaneously *** rats were randomly divided into groups A, B, C and D according to the formula of amino acids in enteral nutritional solutions, respectively. TB rats received jejunal feedings supplemented with balanced amino acids (group A),methionine-depleted amino acids (group B), valine-depleted amino acids (group C) and methionine- and valine-depleted complex amino acid imbalance (group D) for 10 days. Tumor volume, inhibitory rates of tumor, cell cycle and life span of TB rats were ***: The G0/G1 ratio of tumor cells in group D (80.5±9.0) % was higher than that in groups A, B and C which was 67.0±5.1 %, 78.9±8.5 %, 69.2±6.2 %, respectively (P＜0.05). The ratio of S/G2M and PI in group D were lower than those in groups A, B and C. The inhibitory rate of tumor in groups B, C and D was 37.2 %, 33.3 % and 43.9 %,respectively (P＜0.05). The life span of TB rats in group D was significantly longer than that in groups B, C, and ***: Methionine/valine-depleted amino acid imbalance can inhibit tumor growth. Complex amino acids of methionine and valine depleted imbalance have stronger inhibitory effects on tumor growth.

关键词：肿瘤负荷小鼠肿瘤生成氨基酸发病机制新生血管生成

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Prevention and therapy of fungal infection in severe acute pancreatitis:A prospective clinical study

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World Journal of Gastroenterology 2003年第11期9卷 2619-2621页

作者： Yue-MingHe Xin-ShengLv Zhong-LiAi Zhi-SuLiu QunQian Ji-WeiChen Dao-XiongLei Cong-QingJiang Yu-FongYuan DepartmentofGeneralSurgery XiangyaHospitalCentralSouthUniversityChangsha410008HunanProvinceChina DepartmentofGeneralSurgery ZhongnanHospitalWuhanUniversityWuhan430071HubeiProvinceChina

AIM: To investigate the prevention and therapy of fungal infection in patients with severe acute pancreatitis (SAP).METHODS: Seventy patients with SAP admitted from Jan.1998 to Dec. 2002 were randomly divided into garlicin prevention group, fluconazole (low dosage) prevention group and control group. The incidence of fungal infection, the fungal clearance and mortality after treatment were ***: The incidence of fungal infection in garlicin group and fluconazole group was lower than that in control group (16 % vs30 %, P＜0.05 and 9 % vs30 %, P＜0.01,respectively). Amphotericin B or therapy-dose fluconazole had effects on patients with fungal infection in garlicin group and control group, but had no effects on patients with fungal infection in fluconzole ***: Prophylactic dosage of antifungal agents (garlicin or low dosage fluconazole) can reduce the incidence of fungal infection in patients with *** once fungal infection occurs, amphotericin B should be used as early as possible if fluconazole is not effective.

关键词：急性胰腺炎真菌感染临床研究药物疗法氟康唑大蒜素

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Risk Factors of Cervical Carcinoma and Countermeasures against Them in Mountainous Area of Wufeng County, China

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Wuhan University Journal of Natural Sciences 2005年第4期10卷 759-766页

作者： TAONing WUXu-feng QIUXiao-ping ZHAOMin TANYun WUXin-xing InstituteofVirology MedicalSchoolWuhanUniversityWuhan430071HubeiChina DepartmentofOncology ZhongnanHospitalWuhanUniversityWuhan430071HubeiChina

Cases (n=44) with squamous cell cervical cancer (SCCA) and age-matched healthy controls (n=176) were analyzed. Significant difference due to human papillomavirus (HPV) infection, ages at the first marriage, ages at the first sexual intercourse, ages at the first birth given to baby, number of gravidities, number of deliveries, Body Mass Index (BMI), education level of women and their husbands (p<0.05) was observed. According to multivariate logistic regression analysis, four factors have entered the model (p<0.05), including HPV infection [OR (odds ratio)=26.13, 95%CI (confidence interval)=9.40?72.60], education level of women (OR=0.41, 95%CI=0.21?0.79), education level of spouses (OR=0.45, 95%CI=0.22?0.94), BMI (OR=0.73, 95%CI=0.57?0.93). Moreover, HPV infection is relative to education level of women (r=?0.14), and their spouses (r=?0.21), age at the first marriage (r=?0.20), age at the first birth given to baby (r=?0.20) and BMI (r=?0.15).

关键词： Key words cervical carcinoma human papillomavirus (HPV) risk factor

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