目的 研究缺氧诱导因子-1α(HIF-1α)与基质金属蛋白酶-2(MMP-2)在低分化胃癌中的表达,并探讨两者在低分化胃癌浸润、转移过程中的相互关系及作用。方法 采用SP免疫组化方法,检测54例低分化胃癌及20例正常胃组织石蜡标本中HIF-1α和MMP-2蛋白表达水平。结果 低分化胃癌组织中HIF-1α和MMP-2蛋白表达阳性率明显高于正常胃组织(Plt;0.05)。两者的表达与肿瘤的浸润深度、淋巴转移和TNM分期均有关(Plt;0.05),HIF-1α与MMP-2的表达呈正相关(r=0.580, Plt;0.05)。结论 HIF-1α和MMP-2在低分化胃癌的侵袭、转移过程中存在一定的协同作用,两者可能成为判断胃癌预后的指标。
Objective To study the expressions and clinical significance of matrix metalloproteinases-2 (MMP-2) and vascular endothelial growth factor-C (VEGF-C) in patients with papillary thyroid carcinoma (PTC). Methods SP immunohistochemical technique was used to detect the expressions of MMP-2 and VEGF-C in 78 cases of PTC and 18 cases of thyroid benign tumors.Results The positive expression rates of MMP-2 and VEGF-C in PTC (80.77%, 75.64%) were significantly higher than those of the thyroid benign tumor (11.11%, 22.22%), P<0.05. The expressions of MMP-2 and VEGF-C were correlated to the degree of infiltration and lymph node metastasis in PTC: In those which infiltrated to or over the thyroid capsular, or had clinical neck lymph node metastasis, the positive expression rates were significantly higher than those in the other cases which had confined invasion of thyroid capsular or non-clinical metastasis of neck lymph node (P<0.05). And during the follow-up of 41 patients who didn’t have clinical neck lymph node metastasis before operation, the positive expression rates of those who had clinical neck lymph node metastasis were significantly higher than those in the other patients who didn’t have neck lymph node metastasis (P<0.05). There was significantly positive correlation between the expressions of MMP-2 and VEGF-C in PTC (Gamma=0.846, P<0.05). Conclusions MMP-2 and VEGF-C may be used to distinguish malignant and benign thyroid tumor; The expressions of MMP-2 and VEGF-C are correlated with the degree of infiltration and neck lymph node metastasis in PTC; Combined detection of MMP-2 and VEGF-C will be more accurate to predict condition of lymph node metastasis.
Objective To study the expressions of phosphatese and tensin homolog deletedin chromosom ten (PTEN), Fas/FasL system and matrix metalloproteinnases-2 (MMP-2) in human gastric cancer. Methods Seventy-five cases of gastric carcinoma were selected from paraffin wax embodied specimens with full clinicopathological data, and another 15 cases of normal gastric mucosa specimens were selected as the control group. SP immunohistochemistry was used to measure the expressions of PTEN, Fas/FasL and MMP-2 in them. The data was statistically analyzed by χ2 test and relative analysis. Results The expressions of PTEN, Fas/FasL and MMP-2 were correlated with the lymphatic metastasis, degree of infiltration, clinical TMN stage and pathological histological differentiated degree of gastric cancer (Plt;0.05). PTEN was positive correlated with Fas/FasL (r=0.401, Plt;0.001). MMP-2 was negative correlated with Fas/FasL (r=-0.720, Plt;0.001). MMP-2 was negative correlated with PTEN (r=-0.336, Plt;0.001). Conclusion There is guidance meaning in testing the expressions of PTEN, Fas/FasL and MMP-2 in gastric cancer to estimate the prevention, diagnoses, therapy and prognosis of gastric cancer.
ObjectiveTo investigate expressions and biological function of membrane type matrix metallopro-teinase-1 (MT1-MMP) and matrix metalloproteinase-2 (MMP-2) in papillary thyroid carcinoma. MethodsThe expre-ssions of MT1-MMP and MMP-2 in 164 cases of papillary thyroid carcinoma and paracancerous tissues were detected by immunohistochemistry.The association between the expressions of MT1-MMP and MMP-2 and clinicopathological characteristics of papillary thyroid carcinoma was analyzed. ResultsIn paracancerous tissues, the positive expression rate of MT1-MMP was 11.0% (18/164), and the positive expression rate of MMP-2 was 14.0% (23/164).In papillary thyroid carcinoma tissues, the positive expression rates of MT1-MMP and MMP-2 was 61.6% (101/164) and 67.7% (111/164), respectively.The expressions of MT1-MMP and MMP-2 in carcinoma tissues and para carcinoma tissues were statistically significant differences (P < 0.05).The expressions of MT1-MMP and MMP-2 in papillary thyroid carcinoma tissues correlated with the lymph node metastasis (P < 0.05).In addition, the expression of MMP-2 in papillary thyroid carcinoma tissues correlated with capsule invasion (P < 0.05).The positive correlation was found between the expressions of MT1-MMP and MMP-2 in papillary thyroid carcinoma tissues (r=0.256, P < 0.05). ConclusionsMT1-MMP and MMP-2 may be involved the thyroid capsule invasion and lymph node metastasis of papillary thyroid carcinoma.MT1-MMP and MMP-2 may be involved in the progression of papillary thyroid carcinoma.
Objective To explore the expression of matrix metalloproteinase (MMP)-2 in patients with papillary thyroid cancer (PTC) recurrence or residuum and its value of clinical application. Methods The serums from 68 patients with thyroid disease underwent operation and 15 health examinations under stomachs empty from March 2009 to December2009 in this hospital were gathered. Sixty-eight patients with thyroid disease were divided into PTC with lymph node metastasis (LNM) group (n=19),PTC recurrence or residuum with LNM group (n=17),PTC without LNM group (n=10),and benign thyroid disease group (n=22) according to the postoperative pathological findings,15 health examinations as control group. The expression of MMP-2 of serum sample was detected by ELISA method. The difference of the expression of MMP-2 in each group was analyzed. Results The expressions of MMP-2 in the PTC recurrence or residuum with LNM group,PTC with LNM group,PTC without LNM group, benign thyroid disease group,and the control group were (1 724.00±762.24) ng/ml,(1 329.16±776.59) ng/ml,(1 489.61±546.53) ng/ml,(1 264.87±817.27) ng/ml,and (608.43±88.63) ng/ml,respectively. The expressions of MMP-2 in the PTC with LNM group and PTC recurrence or residuum with LNM group were significantly higher than those in the benign thyroid disease group (P<0.05) and the control group (P<0.05),respectively,which in the PTC without LNM group was significantly higher than that in the control group (P<0.05). There was no significant difference of MMP-2 expression of serum between the benign thyroid disease group and the control group (P>0.05),which were no significant difference among the other threemalignant disease groups (P>0.05). The MMP-2 positive expression rates were 79%,76%,80%,41%,and 20% in the PTC with LNM,PTC recurrence or residue with LNM group,PTC without LNM group,benign thyroid disease group,and control group,respectively. The MMP-2 positive expressions rates of serums were not significantly different among three malignant disease groups (P>0.05),but which were significantly higher than those of the benign thyroid disease group (P<0.01) and control group (P<0.01),respectively. Conclusions The MMP-2 level of serum can be used as an index to judge preoperative thyroid nodules,which can not be use to determine whether PTC metastasis or not.
Objective To explore the influence on the expressions of vascular endothelial growth factor (VEGF) gene and matrix metalloproteinase-2 (MMP-2) gene in hepatocellular carcinoma of SMMC-7721 cells with RNA interference (RNAi) silencing the expression of hypoxia inducible factor-1α (HIF-1α) gene. Methods Firstly, constructed short hairpin RNA (shRNA) targeting for HIF-1α gene, and then transfected it to SMMC-7721 cells after combining with plasmid. The SMMC-7721 cells were divided into three groups, silencing group, negative control group, and blank control group, which were transfected with HIF-1α-shRNA-pGenesil-1 recombinant vector, shRNA-HK-pGenesil-1 recombinant vector, and pGenesil-1 vector respectively. Transfection cells were screened by the concentration of 500 μg/mL G418, and then positive and negative cell clones with transfection recombination carrier were obtained. Detected the expressions of HIF-1α mRNA, VEGF mRNA, and MMP-2 mRNA in the 3 groups with real time PCR (RT-PCR) technology, under the condition of hypoxic training 6 h, 12 h, and 24 h, as well as conventional oxygen training. Results There was no expression of HIF-1α mRNA at conventional oxygen condition in the 3 groups, and there was no significant difference in expressions of VEGF mRNA and MMP-2 mRNA among the 3 groups (P>0.05) at the condition of conventional oxygen training. The expressions of HIF-1α mRNA, VEGF mRNA, and MMP-2 mRNA in the silencing group, compared with the the negative control group and the blank control group, were obviously decreased (P<0.05) under the condition of hypoxic training (6, 12, and 24 h), while there was no significant difference between the negative control group and the blank control group at each time point (P>0.05), but the expressions of HIF-1α mRNA, VEGF mRNA, and MMP-2 mRNA in the 3 groups under every condition of hypoxic training were all higher than those of conventional oxygen condition (P<0.05). Under the condition of hypoxic training, the expressions of HIF-1α mRNA, VEGF mRNA, and MMP-2 mRNA in the 3 groups decreased over time, and there was significant difference between any 2 time points in each group (P<0.05). Conclusion RNAi technique can effectively silence the expression of HIF-1α mRNA of SMMC-7721 cells, and then silence the expressions of VEGF and MMP-2 mRNA, to inhibit the invasion and metastasis of hepatocellular carcinoma.
ObjectiveTo observe the dynamic changes of the concentrations of serum matrix metalloproteinase (MMP)-2 and MMP-9, and to discuss its clinical significance. MethodsFrom January to May 2014, 50 cases of clinically diagnosed cerebral infarction patients were included in the study as the cerebral infarction group, and we randomly selected 30 healthy volunteers at the same time in the same age group as the control group. The serum MMP-2 and MMP-9 of patients with acute cerebral infarction were detected in the onset of 24 hours, 7th day and 14th day respectively, which were compared with the control group accordingly. The patients with cerebral infarction were divided into small infarction group (1.5-3.0 cm), middle infarction group (3.1-5.0 cm) and large infarction group (>5.0 cm) according to the infraction volume. According to neurological functional deficit score they were divided into mild (0-15 points), moderate (16-30 points) and severe group (31-45 points). Changes of the level of MMP-9 and MMP-2 were compared in patients with different cerebral infarction volume and different impairment degree. ResultsFor the cerebral infarction group, the serum MMP-2 and MMP-9 levels were significantly higher in the onset of 24 hours, 7th day and 14th day[MMP-2:(2.36±0.76), (2.86±0.87), and (2.20±0.79) ng/mL; MMP-9:(238.8±99.6), (360.4±141.8), and (152.2±80.4) ng/mL] than the control group[MMP-2:(1.20±0.27) ng/mL; MMP-9:(124.8±28.2) ng/mL] (P<0.05). The larger the infarction volume was in the patients with acute ischemic stroke, the higher the levels of serum MMP-9 and MMP-2. The severer the neurologic impairment degree was in the patients with acute ischemic stroke, the higher the levels of serum MMP-9 and MMP-2 were. ConclusionFor patients with acute cerebral infarction, the levels of serum MMP-2 and MMP-9 are closely related to time of onset, infarct volume and neurological deficits, which can be used as an important basis to estimate the condition and assess the prognosis.
Objective To explore the expressions of E-cadherin, matrix metalloproteinases-2 (MMP-2) protein,and matrix metalloproteinases-9 (MMP-9) protein in gastric cancer tissues, and to analyze the possible statistical relati-onship between the expressions of E-cadherin, MMP-2 protein, and MMP-9 protein, and clinicopathological features ofgastric cancer. Methods The ABC immunohistochemical staining was adopted to examine the expressions of E-cadherin,MMP-2 protein, and MMP-9 protein in 40 paraffin slices of gastric cancer (gastric cancer group), with the adjacent tissue as the control group (adjacent tissue group). The positive rates of 3 kinds of protein were compared between the2 groups, in addition, the statistical relationship between the expressions of the 3 kinds of protein and clinicopathological features of gastric cancer was examined respectively by SPSS 19.0 software. Results The expressions of E-cadherin, MMP-2 protein, and MMP-9 protein were all found in gastric cancer tissues and adjacent tissues. In gastric cancer tissue group, the expression of E-cadherin downregulated while the expressions of MMP-2 protein and MMP-9 protein upregulated in comparison to adjacent tissue group (P<0.05). The significant association was found between the expre-ssion of E-cadherin and the gastric cancer tissues of T3+T4 stage, N1-N3 stage, and Ⅲ+Ⅳ stage, which had lower positive expression rate (P<0.05). The expression of MMP-2 protein in gastric cancer tissues of M1 stage and Ⅲ+Ⅳstage upregulated (P<0.05), and the expression of MMP-9 protein upregulated in gastric cancer tissues of T3+T4 stage,Ⅲ+Ⅳ stage, or lowlydifferentiated+undifferentiated (P<0.05). No significant relationship was found in other clinical-pathological features and 3 kinds of protein except aforementioned significant relationship (P>0.05). Conclusions In the development progress of gastric cancer, the E-cadherin may get involved in the mechanism of tumor invasion and lymph node metastasis, MMP-2 protein may get involved in the mechanism of distant metastasis, and MMP-9 protein may get involved in the mechanism of differentiation and tumor invasion. The examination of those 3 kinds of markers may play an role in the judgment of tumor stage and estimation of prognosis in gastric cancer clinically.