AIM:To explore the expression of heparanase gene, CD44v6,MMP-7 and nm23 proteins in human gastric carcinoma as well as their relationship with the dinicopathological factors.METHODS: Reverse transcription polymerase c...AIM:To explore the expression of heparanase gene, CD44v6,MMP-7 and nm23 proteins in human gastric carcinoma as well as their relationship with the dinicopathological factors.METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expressions of heparanase mRNA in 43 human gastric carcinomas and 10 adjacent normal gastric tissues. Streptavidin-peroxidase (S-P) two step method was used to measure the immunohistochemical expression of CD44v6,MMP-7 and nm23protein in 43 human gastric carcinomas.RESULTS:The expression of heparanase gene was positivein 29 cases of gastric cancer with a positive rate of 67.4%,which was significantly higher than those in adjacent normal gastric tissues (P<0.05).The heparanase mRNA expression was significantly related to advanced stage of disease, serosal infitration,lymph node metastasis and size of tumors (P<0.05),but not related to tumor location, gross and histological types of the cancer, peritoneal dissemination and liver metastasis(P>0.05).The positive rate of CD44v6,nm23 and MMP-7 proteins was 76.7%,37.2% and 60.5%,respectively.The CD44v6 protein expression was significantly related to serosal infiltration,lymph node metastasis and TNM stage of disease(P<0.05).The nm23 protein expression was significantly related to the tumor gross appearance,lymph node and peritoneal metastasis (P<0.05).The MMP-7 protein expression was significantly related to serosal infiltration and TNM stage of disease (P<0.05).In an attempt to measure the association between these agents, we found that the expression of heparanase mRNA had significantly negative correlation with the expression of CD44v6 and MMP-7 protein (P<0.05), the expression of MMP-7 protein had significantly positive correlation with the expression of CD44v6 protein (r=0.568, P<0.05), the expression of MMP-7 protein had no correlation with the expression of nm23 protein (P>0.05),and the expression of nm23 protein had no correlation with the expression of CD44v6 protein (P>0.05).CONCLUSION: Despite their different mechanisms of action, heparanase, CD44v6 and nm23 may play important roles in the invasive infiltration and lymph node metastasis in gastric carcinomas. Instead of metastatic spreading, MMP-7 may be just related to the invasion of gastric carcinomas.However, co-detection of these factors may be important to predict metastatic spreading in such patients.展开更多
AIM: To explore the expression and correlation of CD44v6, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and matrix metalloproteinase (MMP)-9 in Krukenberg and primary epithelial ov...AIM: To explore the expression and correlation of CD44v6, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and matrix metalloproteinase (MMP)-9 in Krukenberg and primary epithelial ovarian carcinoma. METHODS: The expressions of CD44v6, VEGF, MMP-2 and MMP-9 were detected by immunohistochemical method in 20 cases of normal ovarian tissues, 38 cases of Krukenberg tumor and 45 cases of primary epithelial ovarian carcinoma. RESULTS: The expression of CD44v6 (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: χ^2= 4.516, P= 0.034; Krukenberg tumor tissue vsnormal ovarian tissue: χ^2 = 19.537, P = 0.001) and VEGF (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: P = 0.026; Krukenberg tumor tissue vs normal ovarian tissue: χ^2 = 22.895, P = 0.001) was significantly higher in primary epithelial ovarian carcinoma tissue and Krukenberg tumor tissue than in normal ovarian tissue. The positive expression rate of MMP-2 and MMP-9 was 0% in the normal ovarian tissue. The positive expression rate of CD44v6 ( χ^2= 10.398, P= 0.001), VEGF ( χ^2= 13.149, P = 0.001), MMP-2 ( χ^2 = 33.668, P = 0.001) and MMP-9 ( χ^2= 38.839, P = 0.001) was remarkably higher in Krukenberg tumor than in primary epithelial ovarian carcinoma. The correlation of CD44v6, VEGF, MMP-2, and MMP-9 was observed in primary epithelial ovarian carcinoma and Krukenberg tumor. CONCLUSION: CD44v6, VEGF, MMP-2, and MMP-9 are involved in ovarian carcinoma, gastric cancer and Krukenberg tumor. Detection of CD44v6, VEGF, MMP-2 and MMP-9 may contribute to the diagnosis of ovarian carcinoma, gastric cancer, and Krukenberg tumor.展开更多
This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The expression of matrix metalloproteinase 2, 9 (MMP 2, MMP 9), tissue inhibitor 1 of matrix metalloproteinase (TIMP 1), c...This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The expression of matrix metalloproteinase 2, 9 (MMP 2, MMP 9), tissue inhibitor 1 of matrix metalloproteinase (TIMP 1), cell adhesion molecule 44 variant 6 (CD44v6), HER2/neu and p53 was investigated in 154 patients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP 2, MMP 9, TIMP 1, CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68.18%, 98.05%, 55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there was close positive relationship ( P <0.05) between the expression of MMP 2 and MMP 9, TIMP 1 and CD44v6, HER2/neu and MMP 9, MMP 2 and p53. Up regulation of MMP 2 was accompanied by advanced T stage ( P <0.01) . There was also a trend of MMP 2 expression being related with tumor metastasis. Increased expression of HER2/neu was found in patients with tumor recurrence( P <0.05). The expression of TIMP 1 was higher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non keratinizing SCC than that in basaloid SCC( P <0.05). These findings suggested that MMP 2 and MMP 9, HER2/neu and MMP 9, MMP 2 and p53 had a coordinate function in aggression of tumor; that MMP 2 had a more important function than MMP 9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker for poor prognosis in HNSCC.展开更多
OBJECTIVE To investigate the effect of polyethylene imine glycol (PEI-PEG)/siRNA nanocomposites in the in vitro transfection of human gastric cancer SGC7901 cell lines and the down-regulation of gene expression of t...OBJECTIVE To investigate the effect of polyethylene imine glycol (PEI-PEG)/siRNA nanocomposites in the in vitro transfection of human gastric cancer SGC7901 cell lines and the down-regulation of gene expression of the adherence factor CD44v6. METHODS PEI-PEG/siRNA nanoparticles, in different N/P ratios, were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the control group. The transfection efficiencies were observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay (mononuclear cell direct cytotoxicity assay), and the down-regulation effect of siRNA on CD44v6 gene was evaluated by Western blot. Based on the different N/P ratios, PEI-PEG/siRNA composites were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the controls. The transfection efficiency was observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay and the down-regulation effect of siRNA on CD44v6 gene was evaluated by Western blot. RESULTS After transfection, the transfection efficiency of the PEI-PEG/siRNA nanocomposites increased incrementally in N/P ratio value. The transfection efficiency improved with an increase in N/P ratio. When the N/P value was 15, fluorescence became more intense in the PEI-PEG/siRNA group than in the Lipo2000/siRNA group. At the same time, cell viability was (80.4 ± 5.6)% in the MTT reduction assay, which was similar to that in the Lipo2000/siRNA group. The results of Western blot analysis showed that the expression level of CD44v6 protein decreased to (59.7 ± 3.0)% after siRNA-CD44v6 was inhibited. CONCLUSION PEI-PEG could effectively form the nanocomposite in combination with siRNA, be transfected into the SGC7901 gastric cancer cell lines and inhibit CD44v6 protein expression. Moreover, as a genetic carrier, PEI-PEG copolymer has greater advantages, including high transfection e. ciency, less cytotoxicity and an easily alterable vector structure.展开更多
文摘目的 探究蛋白磷酸酶2A癌性抑制因子(CIP2A)和CD44v6在尖锐湿疣(CA)患者皮损组织中的表达,分析二者与CA患者HPV基因型分布及其预后的相关性。方法 选取本院2020年4月至2023年4月收治的CA患者100例作为研究组,根据预后情况将患者分为预后良好组和不良组,收集术中保留的皮损组织;另选取本院同期行外阴整形或包皮环切术者100例作为对照组,收集切下的外阴组织或正常包皮组织。实时荧光定量PCR法检测组织标本中的CIP2A、CD44v6 mRNA表达水平。比较研究组与对照组、不同HPV分型组、预后良好组与预后不良组中CIP2A、CD44v6 mRNA的表达水平,分析CA组织中CIP2A、CD44v6的表达与临床特征的关系,采用多因素COX回归分析CA患者预后的影响因素;绘制ROC曲线分析CIP2A、CD44v6对CA患者预后不良的预测价值。结果 研究组CIP2A、CD44v6 mRNA的表达水平显著高于对照组(CIP2A:2.19±0.40 vs 1.01±0.24,t=25.24,P<0.05;CD44v6:1.75±0.33 vs 1.02±0.22,t=18.41,P<0.05)。低危组、高危组和混合组CIP2A、CD44v6 mRNA表达水平均依次升高(均P<0.05)。预后不良组CIP2A、CD44v6 mRNA表达水平显著高于预后良好组(CIP2A:3.58±0.62 vs 1.62±0.31,t=21.05,P<0.05;CD44v6:2.57±0.49 vs 1.42±0.26,t=15.26,P<0.05)。CIP2A、CD44v6的表达与疣体数目和直径有关(均P<0.05)。多因素COX回归分析结果显示,CIP2A、CD44v6的表达以及疣体数目、直径是影响CA患者预后的危险因素(P<0.05)。ROC曲线显示,CIP2A预测CA患者预后不良的AUC为0.866,CD44v6的AUC为0.860,二者联合的AUC为0.928,二者联合优于各自单独预测(Z_(联合vs CIP2A)=2.72、Z_(联合vs CD44v6)=2.73,P均<0.05)。结论 CA患者组织中CIP2A、CD44v6的表达水平显著升高,二者均与HPV基因型分布及其预后有关。CIP2A和CD44v6联合可提高对CA患者预后预测的准确性。
基金Supported by the National Natural Science Foundation of China,No 30271276
文摘AIM:To explore the expression of heparanase gene, CD44v6,MMP-7 and nm23 proteins in human gastric carcinoma as well as their relationship with the dinicopathological factors.METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expressions of heparanase mRNA in 43 human gastric carcinomas and 10 adjacent normal gastric tissues. Streptavidin-peroxidase (S-P) two step method was used to measure the immunohistochemical expression of CD44v6,MMP-7 and nm23protein in 43 human gastric carcinomas.RESULTS:The expression of heparanase gene was positivein 29 cases of gastric cancer with a positive rate of 67.4%,which was significantly higher than those in adjacent normal gastric tissues (P<0.05).The heparanase mRNA expression was significantly related to advanced stage of disease, serosal infitration,lymph node metastasis and size of tumors (P<0.05),but not related to tumor location, gross and histological types of the cancer, peritoneal dissemination and liver metastasis(P>0.05).The positive rate of CD44v6,nm23 and MMP-7 proteins was 76.7%,37.2% and 60.5%,respectively.The CD44v6 protein expression was significantly related to serosal infiltration,lymph node metastasis and TNM stage of disease(P<0.05).The nm23 protein expression was significantly related to the tumor gross appearance,lymph node and peritoneal metastasis (P<0.05).The MMP-7 protein expression was significantly related to serosal infiltration and TNM stage of disease (P<0.05).In an attempt to measure the association between these agents, we found that the expression of heparanase mRNA had significantly negative correlation with the expression of CD44v6 and MMP-7 protein (P<0.05), the expression of MMP-7 protein had significantly positive correlation with the expression of CD44v6 protein (r=0.568, P<0.05), the expression of MMP-7 protein had no correlation with the expression of nm23 protein (P>0.05),and the expression of nm23 protein had no correlation with the expression of CD44v6 protein (P>0.05).CONCLUSION: Despite their different mechanisms of action, heparanase, CD44v6 and nm23 may play important roles in the invasive infiltration and lymph node metastasis in gastric carcinomas. Instead of metastatic spreading, MMP-7 may be just related to the invasion of gastric carcinomas.However, co-detection of these factors may be important to predict metastatic spreading in such patients.
基金Supported by Foundation for Scholars Abroad of Ministry of Education of China, No. [2003]406Foundation of Heilongjiang Office of Education, No. 9551138
文摘AIM: To explore the expression and correlation of CD44v6, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and matrix metalloproteinase (MMP)-9 in Krukenberg and primary epithelial ovarian carcinoma. METHODS: The expressions of CD44v6, VEGF, MMP-2 and MMP-9 were detected by immunohistochemical method in 20 cases of normal ovarian tissues, 38 cases of Krukenberg tumor and 45 cases of primary epithelial ovarian carcinoma. RESULTS: The expression of CD44v6 (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: χ^2= 4.516, P= 0.034; Krukenberg tumor tissue vsnormal ovarian tissue: χ^2 = 19.537, P = 0.001) and VEGF (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: P = 0.026; Krukenberg tumor tissue vs normal ovarian tissue: χ^2 = 22.895, P = 0.001) was significantly higher in primary epithelial ovarian carcinoma tissue and Krukenberg tumor tissue than in normal ovarian tissue. The positive expression rate of MMP-2 and MMP-9 was 0% in the normal ovarian tissue. The positive expression rate of CD44v6 ( χ^2= 10.398, P= 0.001), VEGF ( χ^2= 13.149, P = 0.001), MMP-2 ( χ^2 = 33.668, P = 0.001) and MMP-9 ( χ^2= 38.839, P = 0.001) was remarkably higher in Krukenberg tumor than in primary epithelial ovarian carcinoma. The correlation of CD44v6, VEGF, MMP-2, and MMP-9 was observed in primary epithelial ovarian carcinoma and Krukenberg tumor. CONCLUSION: CD44v6, VEGF, MMP-2, and MMP-9 are involved in ovarian carcinoma, gastric cancer and Krukenberg tumor. Detection of CD44v6, VEGF, MMP-2 and MMP-9 may contribute to the diagnosis of ovarian carcinoma, gastric cancer, and Krukenberg tumor.
文摘This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The expression of matrix metalloproteinase 2, 9 (MMP 2, MMP 9), tissue inhibitor 1 of matrix metalloproteinase (TIMP 1), cell adhesion molecule 44 variant 6 (CD44v6), HER2/neu and p53 was investigated in 154 patients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP 2, MMP 9, TIMP 1, CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68.18%, 98.05%, 55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there was close positive relationship ( P <0.05) between the expression of MMP 2 and MMP 9, TIMP 1 and CD44v6, HER2/neu and MMP 9, MMP 2 and p53. Up regulation of MMP 2 was accompanied by advanced T stage ( P <0.01) . There was also a trend of MMP 2 expression being related with tumor metastasis. Increased expression of HER2/neu was found in patients with tumor recurrence( P <0.05). The expression of TIMP 1 was higher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non keratinizing SCC than that in basaloid SCC( P <0.05). These findings suggested that MMP 2 and MMP 9, HER2/neu and MMP 9, MMP 2 and p53 had a coordinate function in aggression of tumor; that MMP 2 had a more important function than MMP 9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker for poor prognosis in HNSCC.
基金This work was supported by the following funds: National Natural Science Foundation of China (No.30670951) Guangdong Provincial+5 种基金 Natural Science Foundation (No.06021322) Fund of Guangzhou Municipal Scientific Problem-Solving Program (No. 2003 Z 3-E0381) Fund of Guangdong Provincial Scientific Problem-Solving Program (No.2005 B31211002) Guangdong Provincial Government and Ministry of Education Project com- bining project initiation, study and research (No.2009B090300277).
文摘OBJECTIVE To investigate the effect of polyethylene imine glycol (PEI-PEG)/siRNA nanocomposites in the in vitro transfection of human gastric cancer SGC7901 cell lines and the down-regulation of gene expression of the adherence factor CD44v6. METHODS PEI-PEG/siRNA nanoparticles, in different N/P ratios, were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the control group. The transfection efficiencies were observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay (mononuclear cell direct cytotoxicity assay), and the down-regulation effect of siRNA on CD44v6 gene was evaluated by Western blot. Based on the different N/P ratios, PEI-PEG/siRNA composites were synthesized and transfected into gastric cancer cells. Lipo2000/siRNA was used in the controls. The transfection efficiency was observed under fluorescence microscope. The cytotoxicity of the nanoparticles was measured using the MTT assay and the down-regulation effect of siRNA on CD44v6 gene was evaluated by Western blot. RESULTS After transfection, the transfection efficiency of the PEI-PEG/siRNA nanocomposites increased incrementally in N/P ratio value. The transfection efficiency improved with an increase in N/P ratio. When the N/P value was 15, fluorescence became more intense in the PEI-PEG/siRNA group than in the Lipo2000/siRNA group. At the same time, cell viability was (80.4 ± 5.6)% in the MTT reduction assay, which was similar to that in the Lipo2000/siRNA group. The results of Western blot analysis showed that the expression level of CD44v6 protein decreased to (59.7 ± 3.0)% after siRNA-CD44v6 was inhibited. CONCLUSION PEI-PEG could effectively form the nanocomposite in combination with siRNA, be transfected into the SGC7901 gastric cancer cell lines and inhibit CD44v6 protein expression. Moreover, as a genetic carrier, PEI-PEG copolymer has greater advantages, including high transfection e. ciency, less cytotoxicity and an easily alterable vector structure.