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1Detection of micrometastasis of gastric carcinoma in peripheral blood circulation显示文摘AIM:To detect the micrometastasis of gastric carcinoma in peripheral blood circulation using immunomagnetic beads sorting technique and RT-PCR technique,and to discuss its significance and the difference between the two methods.METHODS:Density gradient centrifugation was used to isolate mononuclear cells from peripheral blood,immunomagnetic beads sorting technique and RT-PCR technique were used to detect the disseminated carcinoma cells.HE,immunocytochemical and immunofluorescence staining were also used to identify the characteristics of the cells separated with immunomagnetic beads sorting technique.RESULTS:Cells expressing cytokeratin were separated and enriched from the peripheral blood specimens of patients suffering from gastric carcinoma or chronic gastritis. After HE staining, two kinds of ceils with little cytoplasm were found.Majority of these cells had small and round nuclei, even chromatins and the thickness of nuclear membrane was normal. Immunohistochemical staining indicated that there were CD34 and CD45 expression on the cell membrane ofthis kind of cells and these cells also showed expressed human telomerase reverse transcriptase by immunofluorescence staining, but the expression of carcinoembryonic antigen was absent.So,these cells might hematopoiesis precursors.Another kind of cells had larger and abnormal nuclei with thicker nuclear membranes. Massed chromatins and polynudeoli were found in the nudei. These cells expressed human telomerase reverse transcriptase and carcinoembryonic antigen,but CD34 and CD45 were not found on the cell membrane.So,these cells were considered as gastric carcinoma cells escaping from the original focuses and existing in the peripheral blood circulation.Cardnoma cells were found in 25 of 60(41.7%) specimens of peripheral blood from patients with gastric carcinoma, while there were no such cells separated from the blood specimens of chronic gastritis patients.The difference of positive rates of disseminated carcinoma cells between two groups was markedly significant (P<0.005).The expressions of CK20 mRNA in peripheral blood specimens were examinated withRT-PCR. CK20 mRNA was detected from 32 of 60(53.3%) peripheral blood specimens in the group of gastric carcinoma patients,while none of the specimens from patients suffering from chronic gastritis had CK20 mRNA. Significant difference was also found between two groups (P<0.005).Statistic analyses also showed that there was a significant difference between the positive rates of two methods in detecting the disseminated carcinoma cells from the peripheral blood circulation of gastric carcinoma patients (P<0.05).CONCLUSION:The results demonstrated that there were disseminated carcinoma cells in the peripheral blood circulation of some patients with gastric carcinoma.Disseminated carcinoma cells can be detected from the peripheral blood samples with immunomagnetic beads sorting technique and RT-PCR technique.The positive rate of RT-PCR technique is higher than that of immunomagnetic beads sorting technique in detecting micrometastasis.Xi-MeiChen Guo-YuChen Zhi-RongWang Feng-ShangZhu Xiao-LeiWang XiaZhang 2004World Journal of Gastroenterology2004,10,6:32
2Maspin expression and its clinicopathological significance in tumorigenesis and progression of gastric cancer显示文摘AIM:To investigate maspin expression in tumorigenesis and progression of gastric cancer and to explore its relevant molecular mechanisms.METHODS:Formalin-fixed and paraffin-embedded tissues from normal mucosa (n=182), dysplasia (n=69), cancer (n=l13) of the stomach were studied for maspin expression by immunohistochemistry. Microvessel density (MVD) in gastric cancer was labeled using anti-CD34 antibody. Maspin expression was compared with clinical parameters and MVD of tumors. Caspase-3 expression was also detected in gastric carcinoma by immunohistochemistry. The relationship between Caspase-3 and maspin expression was concerned as well.RESULTS:The positive rates of maspin expression were 79.8% (145/182), 75.4%(52/69) and 50.4%(57/113) in normal mucosa, dysplasia and cancer of the stomach,respectively.Cancer less frequently expressed maspin than normal mucosa and dysplasia (P<0.05).Maspin expression showed a significantly negative association with invasive depth, metastasis, Lauren's and Nakamura's classification (P<0.05),but not with tumor size, Borrmann's classification,growth pattern or TNIVl staging (P>0.05). The positive rate of Caspase-3 was significantly lower in gastric cancer than in normal gastric mucosa (P<0.05,32.7% vs 50.4%). It was noteworthy that maspin expression was negatively correlated with MVD, but positively correlated with expression of Caspase-3 in gastric cancer (P<0.05).CONCLUSION:Down-regulated maspin expression is a late molecular event in gastric carcinogenesis. Reduced expression of maspin contributes to progression of gastric cancer probably by inhibiting cell adhesion, enhandng cell mobility,decreasing cell apoptosis and facilitating angiogenesis.Additionally altered expression of maspin underlies the molecular mechanism of differentiation of gastric cancer and supports the different histogenetic pathways of intestinal and diffuse gastric cancers. Maspin expression can be considered as an effective and objective marker to reveal biological behaviors of gastric cancer.Meng-ChunWang Yan-MinYang Xiao-HanLi FangDong YanLi 2004World Journal of Gastroenterology2004,10,5:33
3Selection of optimal antisense accessible sites of survivin and its application in treatment of gastric cancer显示文摘AIM: To select the optimal antisense accessible sites of survivin, a highly expressed gene in tumor tissues, in order to explore a novel approach to improve biological therapy of gastric cancer.METHODS: The 20 mer random oligonucleotide library was synthesized, hybridized with in vitro transcribed total survivin cRNA, then digested by RNase H. After primer extension and autoradiography, the antisense accessible sites (AAS) of survivin were selected. Then RNADraw software was used to analyze and choose the AAS with obvious stem-loop structures, according to which the complementary antisense oligonucleotides (AS-ODNs) were synthesized and transferred into survivin highly- expressing gastric cancer cell line MKN-45. Survivin expression was detected by RT-PCR and Western Blotting. Cellular growth activities were assayed by tetrazolium bromide (MTT)colorimetry. Cellular ultrastructure was observed by electronic microscopy, while apoptosis was detected by annexin V-FITC and propidium iodide staining flow cytometry.RESULTS: Thirteen AAS of survivin were selected in vitro.Four AAS with stem-loop structures were chosen, locating at 207-226 bp, 187-206 bp, 126-145 bp and 44-63 bp of survivin cDNA respectively. When compared with nontranfection controls, their corresponding AS-ODNs (AS-ODN1,AS-ODN2, AS-ODN3 and AS-ODN4) could reduce Survivin mRNA levels in MKN-45 cells by 54.3±1.1% (t= 6.12, P<0.01),86.1±1.0% (t= 5.27, P<0.01), 32.2±1.3% (t= 7.34, P<0.01)and 56.2±0.9% (t= 6.45, P<0.01) respectively, while survivin protein levels were decreased by 42.2±2.5% (t = 6.26,P<0.01), 75.4±3.1% (t= 7.11, P<0.01), 28.3±2.0% (t= 6.04,P<0.01) and 45.8±1.2% (t = 6.38, P<0.01) respectively.After transfection with 600 nmol/L AS-ODN1~AS-ODN4 for24 h, cell growth was inhibited by 28.12±1.54% (t= 7.62,P<0.01), 38.42±3.12% (t = 7.75, P<0.01), 21.46±2.63%(t= 5.94, P<0.01) and 32.12±1.77% (t= 6.17, P<0.01)respectively. Partial cancer cells presented the characteristic morphological changes of apoptosis, with apoptotic rates being 19.31±1.16% (t=7.16, P<0.01), 29.24±1.94%(t = 8.15, P<0.01), 11.87±0.68% (t= 6.68, P<0.01) and21.68±2.14% (t = 7.53, P<0.01) respectively.CONCLUSION: The AAS of survivin could be effectively selected in vitro by random oligonucleotide library/RNase H cleavage method combined with computer software analysis, this has important reference values for further studying survivin-targeted therapy strategies for gastric cancer.Qiang-SongTong Li-DuanZheng Fang-MinChen Fu-QingZeng LiangWang Ji-HuaDong Gong-ChengLu 2005World Journal of Gastroenterology2005,11,5:27
4Expression and significance of VEGF-C and FLT-4 in gastric cancer显示文摘AIM:To investigate the expression of pathological factors of VEGF-C and its receptor FLT-4 in primary gastric cancer and adjacent normal tissues.METHODS: The expression of VEGF-C and FLT-4 was studied in 80 primary gastric cancers and adjacent normal tissues from the same patients by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immu mohistochemistry.RESULTS:Both primary gastric cancer and adjacent normal tissue could express VEGF-C and FLT-4, and FLT-4 expression was also detected in endothelial cells of stromal blood vessels and lymphatic vessels. There was a significant difference in expression of VEGF-C between primary tumor and adjacent normal tissue samples (P=0.01),and a statistical correlation between VEGF-C and FLT-4 expression in tumors (P=-0.00886). With regard to VEGF-C expression,there was a significant difference between moderate-poor differential type and high differential type (P=0.032), and a significant difference between positive and negative lymph node metastases (P=0.024).However,there was no significant difference between positive and negative serosal invasions (P=0.219).CONCLUSION: VEGF-C and its receptor FLT-4 play a role in the development of gastric cancer, and the tumors with expression of VEGF-C and FLT-4 are more likely to have lymph node metastasis.Xing-ELiu Xiao-DongSun Jin-MinWu 2004World Journal of Gastroenterology2004,10,3:27
5肿瘤治疗基本模式的转变——即从破坏性治疗策略向建设性治疗策略的转变显示文摘在人类征服癌症的历史上,传统外科手术、化疗、放疗无疑发挥了重要而积极的治疗和探索作用。但坦率地讲,传统的“根治性治疗”是以机体生理和免疫功能的巨大破坏甚至丧失为代价。尽管它反映了抗癌医师们一种善良的愿望和治疗肿瘤的决心、信心,然而在某种意义上有悖于人性化、理性化的治疗理念,在某种程度上制约着肿瘤治疗的进步。吴沛宏 高飞 黎升 王薏淇 2013中华医学杂志2013,93,19:12
6Correlation of tumor-positive ratio and number of perigastric lymph nodes with prognosis of patients with surgically-removed gastric carcinoma显示文摘AIM:To evaluate the tumor-positive ratio and number of perigastric lymph nodes as prognostic factors of gastric carcinoma in surgically-treated patients.METHODS:The postoperative survival of 169 patients with gastric cancer who were performed D2 curative gastrectomy was analyzed with regard to its lymph node metastasis ratio and number.Meanwhile correlation of tumor-positive ratio and number of perigastric lymph nodes with pathological parameters of these patients was studied.RESULTS:The overall 5-year survival rate of all the patients studied was 29.6%.The 5-year cumulative survival rate in patients with 1%-20% and more than 20% of tumor-positive lymph nodes was 70.6% and 12.0% respectively,and 46.6% and 17.4% in those with 1-5 and more than 5 of tumorpositive lymph nodes respectively, which were significantly decreased with the increment of involved lymph nodes assessed by either numbers or ratio (P<0.05).Multiple stepwise regression analysis showed that both the positive ratio and number of tumor-involved lymph nodes were sensitive prognostic factors in these surgically-treated patients, which were also significantly correlated with tumor size and depth of submucosal invasion (P<0.05).CONCLUSION:Tumor-positive ratio and number of perigastric lymph nodes are associated with cancer progression and five-year survival rate, and may serve as valuable prognostic factors of gastric cancer in surgically-treated patients.Yong-BinDing Guo-YuChen Jian-GuoXia Xi-WeiZang Hong-YuYang LiYang Xue-XianLiu 2004World Journal of Gastroenterology2004,10,2:11
7基质金属蛋白酶-7表达与胃癌临床病理生物学行为的关系显示文摘目的:研究基质金属蛋白酶-7(MMP-7)表达在胃癌发生和演进中的作用。方法:采用S-P免疫组化方法利用抗MMP-7、抗CD34抗体研究 113例胃癌原发灶中 MMP-7表达和微血管密度(MVD),比较 MMP-7 表达和 MVD与胃癌临床病理特征的关系,分析胃癌组织中MMP—7表达与MVD的关系。结果:MMP-7在胃癌旁黏膜中阳性表达率为29.2%(33/113),低于胃癌组织的阳性率 69.0%(78/113);MMP-7表达与胃癌肿块大小、浸润深度、转移和TNM 分期密切相关(P<0.05),而与胃癌的生长方式和分化程度无显著相关性(P>0.05);胃癌组织中MVD与肿块大小、浸润深度、转移和TNM分期关系密切(P<0.05),但与胃癌的组织分化和生长方式无显著相关性(P>0.05);特别是MVD的大小依赖于胃癌组织中 MMP—7表达(P<0.05)。结论:MMP-7在胃癌中表达上调,可作为揭示胃癌生物学行为的客观指标,其可能通过参与胃癌的生长、浸润、转移和血管形成而在胃癌的发生和演进中起到重要作用。孙晋民 郑华川 杨雪飞 辛彦 张荫昌 2003世界华人消化杂志2003,11,9:6
8槲皮素联合顺铂对胃癌SGC-7901细胞增生和凋亡的影响显示文摘目的:探讨槲皮素(quercetin,QU)联合顺铂(DDP)对胃癌SGC-7901细胞增生、凋亡及凋亡相关基因Bcl-XL mRNA表达的影响. 方法:用槲皮素和顺铂处理胃癌SGC-7901细胞后,应用光镜、电镜、MTT法、流式细胞仪和RT-PCR 技术研究胃癌细胞的形态学变化、生长抑制、诱导凋亡和对凋亡相关基因Bcl-XL mRNA表达的影响. 结果:药物作用于细胞24 h后,可看到较为典型的细胞凋亡形态学变化.DDP和QU均可以抑制胃癌SGC-7901 细胞增生或诱导其凋亡,且有时间和剂量依赖效应,联合应用具有协同效应.联合组的诱导凋亡率及增生抑制效应显著高于单用DDP组(P<0.01),干预48 h后,Bcl- XLmRNA的表达下调,QU可以加强下调作用. 结论:人胃癌SGC-7901细胞体外实验中,QU和顺铂可以抑制其增生并诱导凋亡,二者联合应用有一定的协同效应,且呈剂量依赖关系.王海忠 王沁 2005世界华人消化杂志2005,13,3:6
9肠型胃癌基因表达的cDNA微阵列分析显示文摘目的:研究肠型胃癌发生发展的基因表达变化. 方法:利用肠型胃癌和相应非癌组织的mRNA通过逆转录方法,将Cy3和Cy5两种荧光分别标记到两种cDNA上制成探针,然后与表达谱芯片(含4 096条基因)进行杂交后扫描,通过计算机辅助判别基因的差异表达. 结果:肠型胃癌和相应非癌组织组织中差异表达的基因有666条,上调表达333条,下调表达333条.参与细胞增生、凋亡、分化和转移调控的多种基因的表达水平发生了明显改变. 结论:高通量、高灵敏度的cDNA微阵列芯片技术提供了全面了解肠型胃癌基因表达谱的新思路,一些与肿瘤发生相关的差异表达基因有可能发展成为生物标记物或肿瘤早期诊断和治疗的靶点.李新华 张万岱 王波涛 肖冰 张振书 2004世界华人消化杂志2004,12,1:6
10Screening and identification of mimotope of gastric cancer associated antigen MGb1-Ag显示文摘AIM: Using a monoclonal antibody against gastric cancer antigen named MGbl to screen a phage-displayed random peptide library fused with coat protein plII in order to get some information on mimotopes.lV^37BODS: Through affinity enrichment and EUSA screening,positive clones of phages were amplified. 10 phage clones were selected after three rounds of biopanning and the ability of specific binding of the positive phage clones to MGb1-Ab were detected by ELISA assay (DNA sequencing was performed and the amino acid sequences were deduced)By blocking test, specificity of the mimic phage epitopes was identified.RESULTS: There were approximately 200 times of enrichment about the titer of bound phages after three rounds of biopanning procedures. DNA of 10 phage clones after the third biopanning was assayed and the result showed that the positive clones had a specific binding activity to MGbl-Ab and a weak ability of binding to control mAb or to mouse IgG. DNA sequencing of 10 phage clones was performed and the amino acid sequences were deduced.According to the homology of the amino acid sequences of the displayed peptides, most of the phage clones had motifs of H(x)Q or L(x)S. And these 10 phage clones could also partly inhibit the binding of MGbl-Ab to gastric cancer cell KATO-Ⅲ. The percentage of blocking was from (21.0±1.6) %to (39.0±2.7) %.CONCLUSION: Motifs of H(x)Q and L(x)S selected and identified show a high homology in the mimic epitopes of gastric cancer associated antigen. There may be one or more clones which can act as candidates of tumor vaccines.Zhe-YiHan Kai-ChunWu Feng-TianHe Quan-LiHan Yong-ZhanNie YingHan Xiao-NanLiu 3ian-YongZheng Mei-HongXu Dai-MingFan 2003World Journal of Gastroenterology2003,9,9:2
11抑癌基因RUNX3在胃癌中的表达及临床意义显示文摘目的探讨胃癌组织中RUNX3基因表达与胃癌临床病理的关系及其对预后的判断价值。方法应用免疫组织化学SP技术和图像分析技术,研究RUNX3在胃癌和正常胃黏膜组织中的表达情况及阳性表达面积、强阳性表达面积,分析与病理参数的关系,并采用Kaplan-Meier生存曲线分析不同表达水平对术后生存率的影响。结果发现胃癌组织RUNX3表达阳性率、阳性面积、强阳性面积均明显低于正常胃黏膜组织(P<0.01)。胃癌组织RUNX3表达与胃癌组织分化程度、浸润深度、淋巴转移、肿瘤分期明显正相关(r=0.86,P<0.05),术后3、5年生存率低表达者明显低于高表达者(P均<0.05)。结论 RUNX3基因表达低下或丢失与胃癌发生、浸润、转移有关,可作为预测胃癌患者术后生存率的指标。程智勇 韩猛 门晓彦 易喜贤 2011河北医科大学学报2011,32,10:1
12RUNX3在进展期胃癌中的表达及意义显示文摘目的探讨runt相关转录因子3(RUNX3)在进展期胃癌中的表达情况及其意义。方法用免疫组织化学技术(SP法)检测60例胃癌、癌旁和远癌黏膜中RUNX3的表达情况,并比较各临床病理特征分组间的差异。结果RUNX3表达主要位于细胞核膜和细胞浆上,在60例胃癌组织、癌旁组织和远癌胃黏膜组织中,RUNX3表达的阳性率分别为58.3%(35/60),85.0%(51/60),98.3%(59/60),3组间差异有显著性(P<0.05)。弥漫型胃癌的RUNX3表达明显低于肠型胃癌(40.0%vs67.5%,P<0.05)。伴有淋巴结转移的胃癌组织RUNX3表达明显低于不伴有淋巴结转移者(47.2%vs75.0%,P<0.05);但患者的年龄、性别及TNM分期分组间RUNX3的表达差异无显著性(P>0.05)。结论与非癌胃黏膜组织相比,RUNX3在胃癌组织中呈低表达;其表达与胃癌的Lauren分型和有无淋巴结转移有关。陈志康 葛杰 伍韶斌 袁伟杰 陈子华 2008中国普通外科杂志2008,17,3:1
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