Expression of semaphorin 6D in gastric carcinoma and its significance

INTRODUCTION The semaphorin family is characterized by a phylogene- tically conserved sema domain in the extracellular region[1]. This family has been subdivided into eight groups, which play a crucial role in formation of nervous system,embryogenesis, an…     

VEGF-C及CD105在胃癌侵袭和转移中的作用研究

VEGF-C、CD105与胃癌的发生、发展、转移、预后密切相关。VEGF-C通过促进胃癌淋巴管生长、改变胃癌微循环,从而促进胃癌的生长、转移;CD105作为血管标志物,与血管内皮细胞的关系密切,在胃癌血管生长过程中发挥了重要的作用。现就近年来国内外关于VEGF-C及CD105在胃癌侵袭、转移中的作用作一概述。     

癌基因C-erbB-2在结直肠癌中的表达及其与浸润转移的相关性

目的:探讨癌基因C-erbB-2在结直肠癌中的表达及其与局部浸润和淋巴结转移的相关性.方法:采用免疫组化SP法检测69例原发性结直肠癌患者根治性手术切除的癌组织及周围组织中C-erbB-2的表达.结果:C-erbB-2基因主要为细胞膜及胞质内表达.结直肠癌组织中C-erbB-2阳性表达率为65.2%(45/69),而在结直肠良性肿瘤中仅有2例表达(2/20),两者存在显著差异(P<0.01);其阳性表达率在结直肠癌组织(65.2%)及周围组织(系膜组织47.8%、癌旁组织30.4%、远端切缘组织13.0%)中有显著差异(P<0.05);其表达与肿瘤大体类型、肿瘤细胞分化程度、临床分期(Dukes分期)及淋巴结转移关系密切(P<0.05),而与结直肠癌患者年龄、性别、肿瘤部位及大小和远处转移无明显关系(P>0.05);C-erbB-2在系膜组织及癌旁组织中的表达证实免疫组织化学方法同常规病理检测比较有显著差异(P<0.05).结论:C-erbB-2在结直肠癌中阳性表达与肿瘤浸润转移密切相关,可作为预测预后的指标.     

Semaphorin6D在胃癌中的表达及其意义

目的:探讨Semaphorin6D在胃癌中的表达及其意义.方法:应用RT-PCR和Westenblot检测30例胃癌患者的癌组织及胃切缘正常胃黏膜Semaphorin6D的mRNA和蛋白表达.结果:胃癌组织中的Semaphorin6D蛋白及mRNA的表达明显高于胃正常黏膜(0.26±0.09vs0.20±0.10,P=0.0194;0.24±0.06vs0.19±0.07,P=0.013).结论:Semaphorin6D在胃癌发生、发展中发挥重要作用.     

Mitogen-activated protein kinase signaling pathway and invasion and metastasis of gastric cancer

The mortality rate of gastric cancer worldwide is as high as 70%, despite the development of novel therapeutic strategies. One reason for the high mortality is the rapid and uninhibited spread of the disease, such that the majority of patients are diagnosed at a stage when efficient therapeutic treatment is not available. Therefore, in-depth research is needed to investigate the mechanism of gastric cancer metastasis and invasion to improve outcomes and provide biomarkers for early diagnosis. The mitogen-activated protein kinase(MAPK) signaling pathway is widely expressed in multicellular organisms, with critical roles in multiple biological processes, such as cell proliferation, death, differentiation, migration, and invasion. The MAPK pathway typically responds to extracellular stimulation. However, the MAPK pathway is often involved in the occurrence and progression of cancer when abnormally regulated. Many studies have researched the relationship between the MAPK signaling pathway and cancer metastasis and invasion, but little is known about the important roles that the MAPK signaling pathway plays in gastric cancer. Based on an analysis of published data, this review aims to summarize the important role that the MAP kinases play in the invasion and metastasis of gastric cancer and attempts to provide potential directions for further research and clinical treatment.     

Tumorigenicity,invasion, and metastasis of human gastric cancer in nude mice

Summary Tumors derived from 105 patients with gastric cancer were subcutaneously heterotransplanted into nude mice in order to study their tumorigenicity and malignant behavior. Of the 105 gastric cancers, 45 were successfully transplanted (a 42.9% tumorigenesis rate). The tumorigenesis rate of Borrmann type 1 and 2 cancers (77.8%) was significantly higher than that of type 3 and 4 cancers (34.6%). Also, the tumorigenesis rate of differentiated carcinoma (57.1 %) was significantly higher than that of undifferentiated carcinoma (30.9%). Spontaneous metastases from the subcutaneous tumors were observed in 5 of the 37 established tumor lines (13.5%), and macroscopic pulmonary metastases were common with one tumor line (SCK-29). Although most of the subcutaneous gastric cancers showed local expansion without distant metastasis, the same tumor cells implanted into the peritoneal cavity exhibited invasive growth and/or metastasis. Thus, the expression of a metastatic pheno-type by human gastric cancer was influenced by the host microenvironment. The SCK-29 tumor line with its high metastatic potential may be useful for studies on the mechanism of blood-borne metastasis.Abbreviations pap papillary adenocarcinoma - tub₁ well-differentiated adenocarcinoma - tub₂ moderately differentiated adenocarcinoma - por poorly differentiated adenocarcinoma - sig signet-ring cell adenocarcinoma - muc mucinus adenocarcinoma - giant giant cell adenocarcinoma - ud undifferentiated adenocarcinoma - ade ascitic adenocarcinoma This study was supported in part by a grant-in aid for cancer research (B.no. 63480309) from the Ministry of Education, Science and Culture, Japan     

Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells

AIM： To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved. METHODS： Human gastric carcinoma MKN28 cells were stably transfected with Twist sense plasmid, and MKN45 cells were stably transfected with Twist antisense plasmid using the lipofectamine transfection technique. RT-PCR, Western blotting, EMSA, gelatin zymography assay, and in vitro invasion and migration assays were performed. Nude mice metastasis models were established by the abdominal cavity transfer method. RESULTS： Cell models （TwistS-MKN28） that steadily expressed high Twist protein were obtained. Compared with MKN28 and pcDNA3-MKN28 cells, adherence, migration and invasion ability of TwistS -MKN28 cells were clearly raised. The number of cancer nodules was increased significantly in the abdominal cavity and liver of nude mice inoculated with TwistS-MKN28 cells. Overexpression of Twist in MKN28 cells increased Tcf-4/ Lef DNA binding activity, and promoted expression of Tcf-4’s downstream target genes cyclin D1 and MMP-2. However, suppression of Twist （TwistAS-MKN45） inhibited MKN45 cell invasion and the expression of cyclin D1 was reduced. The activity of MMP-2 was also decreased. CONCLUSION： These results indicate that Twist promotes gastric cancer cell migration, invasion and metastasis, and Twist may play an important role in Wnt/ Tcf-4 signaling.     

MTA1基因表达与人胃癌的浸润和转移

目的:探讨MTA1基因在胃癌及癌周组织中的表达及其表达水平与胃癌浸润和转移潜能的相关性.方法:采用荧光定量PCR及Western印迹技术,分别在mRNA和蛋白水平检测42例手术切除的人胃癌组织及癌旁组织中MTA1的表达,结合胃癌的临床生物学特征分析MTA1表达与胃癌病理类型、淋巴结转移的关系.结果:胃癌组织中MTA1mRNA相对量的表达显著高于癌旁胃黏膜组织(0.6711vs0.3940,P<0.01),蛋白水平表达与mRNA一致.低分化胃腺癌组织中的MTA1mRNA的相对量表达显著高于中高分化胃腺癌组织(0.7475vs0.3460,P<0.01),而伴有淋巴结转移的胃癌组织中MTA1mRNA的相对量表达明显高于不伴有淋巴结转移的胃癌组织(0.8128vs0.4933,P<0.01).结论:MTA1的表达与促进胃癌的转移相关,检测MTA1表达可作为预测胃癌生物学行为、判断胃癌患者预后的一个参考指标.     

Role of cancer-associated fibroblasts in invasion and metastasis of gastric cancer

Cancer-associated fibroblasts(CAFs) are important components of various types of tumors,including gastric cancer(GC).During tumorigenesis and progression,CAFs play critical roles in tumor invasion and metastasis via a series of functions including extracellular matrix deposition,angiogenesis,metabolism reprogramming and chemoresistance.However,the mechanism of the interaction between gastric cancer cells and CAFs remains largely unknown.Micro RNAs(mi RNAs) are a class of non-coding small RNA molecules,and their expression in CAFs not only regulates the expression of a number of target genes but also plays an essential role in the communication between tumor cells and CAFs.In this review,we provide an overview of recent studies on CAF mi RNAs in GC and the relevant signaling pathways in gastrointestinal tumors.Focusing the attention on these signaling pathways may help us better understand their role in tumor invasion and metastasis and identify new molecular targets for therapeutic strategies.     

胃癌组织中EGFR和COX-2表达的意义及其相关性

目的:探讨表皮生长因子受体(EGFR)和环氧化酶-2(COX-2)的表达与胃癌侵袭、转移因素的关系以及EGFR与COX-2在胃癌组织中表达的相关性.方法:用免疫组化的方法检测61例胃癌组织和相应的20例癌旁组织石蜡切片中EGFR、COX-2表达情况:用Western blot方法检测10例胃癌组织和相应的癌旁组织中EGFR、COX-2蛋白的表达.结果:免疫组化检测胃癌组织中EGFR及COX-2的阳性表达率分别为36.07%、59.02%均明显高于癌旁组织的0%、25%(χ~2=9.903,P<0.01;χ~2=6.972,P<0.01);COX-2表达与浸润深度、淋巴结转移、TNM分期和病理分化程度有关(χ~2=6.333,P<0.05;χ~2=5.588,P<0.05;χ~2=8.826,P<0.01;χ~2=5.653,P<0.05).EGFR表达与淋巴结转移和TNM分期有关(χ~2 =10.648,P<0.01;χ~2=4.150,P<0.05).EGFR与COX-2表达呈明显相关(r=0.316,P<0.05).Western blot方法检测胃癌组织中EGFR及COX-2的蛋白表达高于癌旁组织(35.89±12.50 vs 15.14±2.15,P<0.01;51.29±23.42 vs 27.65±7.42,P<0.05).结论:EGFR、COX-2在胃癌组织中高表达,EGFR、COX-2的表达与胃癌的侵袭、转移密切有关,COX-2表达与EGFR显著相关.     

Tumor metastasis and the reciprocal regulation of heparanase gene expression by nuclear factor kappa B in human gastric carcinoma tissue

AIM: To investigate whether NF-kB is activated in human gastric carcinoma tissues and, if so, to study whether there is any correlation between NF-kB activity and heparanase expression in gastric carcinoma. METHODS: NF-kB activation was assayed by immunohistochemical staining in formalin-fixed, paraffin-embedded specimens from 45 gastric carcinoma patients. Electrophoretic mobility shift assay (EMSA) method was used for nuclear protein from these fresh tissue specimens. Heparanase gene expression was quantified using quantitative RT-PCR. RESULTS: The nuclear translocation of RelA (marker of NF-kB activation) was significantly higher in tumor cells compared to adjacent and normal epithelial cells [(41.3±3.52)% vs (0.38±0.22) %, t=10.993, P= 0.000<0.05; (41.3±3.52)% vs(0±0.31)%, t=11.484, P= 0.000<0.05]. NF-kB activation was correlated with tumor invasion-related clinicopathological features such as lymphatic invasion, pathological stage, and depth of invasion (Z= 2.148, P= 0.032<0.05; t = 8.758, P= 0.033<0.05; t = 18.531, P = 0.006<0.05). NF-KB activation was significantly correlated with expression of heparanase gene (r= 0.194, P=0.046<0.05). CONCLUSION: NF-KB RelA (p65) activation was related with increased heparanase gene expression and correlated with poor clinicopathological characteristics in gastric cancers. This suggests NF-kB as a major controller of the metastatic phenotype through its reciprocal regulation of some metastasis-related genes.     

整合素在胃癌侵袭转移及靶向药物治疗中的研究进展

整合素作为黏附分子中的一大类家族,广泛的参与机体的各种病理生理活动,包括细胞生存、生长、分化、迁移、炎症反应、血小板聚集、组织修复以及肿瘤侵袭转移等多个过程.自整合素发现20多年来,已有许多整合素介导的靶向药物相继应用于临床,而且每年有更多新的药物进行临床试验,其中有些药物显示出广阔的临床应用前景.此外,基于整合素在肿...     

Relationship between co-stimulatory molecule B7-H3 expression and gastric carcinoma histology and prognosis

AIM:To investigate the expression of co-stimulatorymolecule B7-H3 in gastric carcinoma and adenomatissue as well as normal gastric tissue and to explore therelationship between B7-H3 expression and pathologicalfeatures and prognosis of gastric carcinoma.METHODS:B7-H3 expression was detected in 102samples of human gastric carcinoma and 10 samples ofgastric adenoma and 10 samples of normal gastric tissueby immunohistochemical assay.Correlation betweenthe expression of B7-H3 and the patients'age,sex,gastric carcinoma locus,tumor size,tissue type,tumorinfiltration depth,differentiation degree,lymph nodemetastasis,and survival time was analyzed.RESULTS:B7-H3 was expressed in all gastric adenomasamples and in 58.8% samples of gastric carcinoma.B7-H3 expression in gastric carcinoma samples wasnot related with the patients'age,sex,lymph nodemetastasis,and tumor size(P>0.05),but with thesurvival time,infiltration depth of tumor and tissue type.CONCLUSION:Detection of B7-H3 expression in gastriccarcinoma tissue is beneficial to the judgment of theprognosis of gastric carcinoma patients and the choice oftreatment.     

Up-regulation of PIK3CA promotes metastasis in gastric carcinoma

AIM:To explore expressions of PIK3CA in the progression of gastric cancer from primary to metastasis and its effects on activation of phosphatidylinositol 3-kinase(PI3K)/Akt pathway.METHODS:mRNA and protein levels of PIK3CA were assessed,respectively,by real-time quantitative polymerase chain reaction and immunohistochemistry in specimens of normal gastric mucosa,primary foci and lymph node and distant metastasis of gastric cancer.Akt and phosphorylated Akt protein were also examined by Western blotting in these tissues,in order to analyze the effect of PIK3CA expression level changes on the activation of PI3K/Akt signaling pathway.RESULTS:PIK3CA mRNA in lymph node metastasis were approximately 5 and 2 folds higher,respectively,than that in the corresponding normal gastric mucosa and primary gastric cancer tissues(P<0.05),while no statistical significance was found compared with distant metastasis.Immunohistochemically,PIK3CA protein expression was discovered in 7(35%)specimens of 20 primary foci vs 10(67%)of 15 of lymph node metastasis or 11(61%)of 18 of distant metastasis(35%vs 67%,P=0.015;35%vs 61%,P=0.044).With the increased level of PIK3CA expression,the total Akt protein expression remained almost unchanged,but p-Akt protein was upregulated markedly.CONCLUSION:Increased expression of PIK3CA is expected to be a promising indicator of metastasis in gastric cancer.Up-regulation of PIK3CA may promote the metastasis of gastric cancer through aberrant activation of PI3K/Akt signaling.     

Notch信号通路与肿瘤侵袭、转移的研究进展

Notch信号通路是一条在生物进化过程中高度保守的通路,广泛存在于无脊椎动物和脊椎动物中,主要通过调控细胞的增殖、凋亡及分化影响组织和器官的正常发育。近年来,有关Notch信号通路与肿瘤的研究取得了较大的进展,对其与肿瘤的发生、发展有了更深的认识,并有研究表明,Notch信号参与肿瘤的侵袭、转移。本文就Notch信号通路在肿瘤侵袭、转移中的作用和可能的分子机制作一综述。     

5-Aza-dC及TSA对人胃癌细胞株SGC-7901 Runx3基因甲基化及表达水平的影响

目的:探讨5-Aza-dC及TSA对人胃癌细胞系SGC-7901中抑癌基因Runx3启动子区甲基化、mRNA及蛋白表达水平的影响.方法:单独或联合应用5-Aza-dC及TSA处理体外培养的SGC-7901细胞,提取各组细胞的DNA、RNA及蛋白质,应用甲基化特异性定量PCR法(QMSP)检测Runx3基因启动子区甲基化状态,逆转录PCR法(RT-PCR)检测Runx3mRNA的表达,免疫印迹法(Western blotting)法检测Runx3蛋白表达水平.结果:5-Aza-dC和TSA均能降低Runx3基因启动子区的甲基化水平(5-Aza-dC组及TSA组分别为对照组的0.70倍、0.63倍),提高mRNA表达水平(0.29±0.01、0.28±0.03vs0.14±0.03,P<0.05)及蛋白表达水平(0.35±0.02、0.37±0.02vs0.09±0.01,P<0.05);与单独使用5-Aza-dC和TSA相比,两药联合组Runx3基因启动子区甲基化水平(对照组的0.37倍)及mRNA表达水平(0.45±0.02)和蛋白表达水平(0.50±0.01)均较单药组效果更明显(P<0.05).结论:5-...     

肝细胞癌组织中信号素3F 蛋白表达变化及其与患者预后的关系

目的：探讨肝细胞癌（HCC）组织中信号素3F（SEMA3F）蛋白表达与患者预后的关系。方法采用Western blot法检测32例HCC患者手术切除的HCC组织（ HCC组）和相应癌旁肝组织（对照组）标本中的SEMA3F蛋白表达,分析SEMA3F蛋白表达水平与HCC临床病理特征、复发转移及预后的关系。结果 HCC组及对照组SEMA3F蛋白表达阳性率分别为84％、97％,HCC组SEMA3F蛋白表达量低于对照组（P＜0．05）。肿瘤有包膜者SEMA3F蛋白表达量高于无包膜者,肿瘤为单个结节者表达量高于多个结节者（P均＜0．05）。 HCC组有、无肝硬化者的SEMA3F蛋白表达量差异无统计学意义。15例SEMA3F蛋白低表达者复发率显著高于17例高表达者,生存时间短于高表达者（P均＜0．05）。结论 SEMA3F可能在抑制HCC的侵袭转移中起重要作用。癌组织中SE-MA3F表达水平有助于判断HCC患者的预后。