Expression of TGF-β1, Snail, E-cadherin and N-cadherin in Gastric Cancer and Its Significance

OBJECTIVE To investigate the expression of TGF-β1,Snail,E-cad-herin and N-cadherin in gastric cancer(GC),and to examine its relationship to malignant features of the tumors. METHODS The expression of TGF-β1,Snail,E-cadherin and N-cadherin proteins was detected in GC and adjacent tissues by immunohistochemical staining,and compared with the clinico-pathological data. RESULTS Positive rates of expression for TGF-β1,Snail,E-cadherin and N-cadherin were 63.5%,83.3%,37.5%and 44.8%in GC,and 28.8%, 41.3%,100%,11.3%in adjacent tissues,respectively.The expression of all four proteins showed a significant difference between the GCs and adjacent tissues(P<0.05).The positive rate of TGF-β1,Snail and N-cadherin,or the negative rate of E-cadherin expression was significantly related to the differentiated degree,histological type,invasion and metastasis of GC.In addition,the expression of N-cadherin was positively related to that of TGF-β1, but negatively related to that of E-cadherin.There was negative correlation between expression of E-cadherin and TGF-β1 and Snail in GC(P<0.05). CONCLUSION The over-expression of TGF-β1 and Snail and decreased expression of E-cadherin and the abnormal expression of N-cad-herin were involved in the process of invasion and metastasis of GC.The data showed that E-cadherin might switch to N-cadherin.TGF-β1 and Snail might play a fundamental role in the process.     

Role of TGF-β1 and its Receptors in Breast Carcinogenesis： Evaluation of Gene Expression Pattems and Clinical Implications

OBJECTIVE Transforming growth factor β1 （TGF-β1） is a multifunc- tional cytokine that may play an important role in tumor development and progression. METHODS We evaluated gene expression patterns of TGF-β1 and its receptors [transforming growth factor β type Ⅰ receptor （TβR- Ⅰ ） and transforming growth factor β type Ⅱ receptor （TβR- Ⅱ ）] in tumor tissue from patients with breast cancer or with benign breast diseases （BBD） and adjacent normal tissue from the patients with breast cancer. Included in the study were 527 breast cancer patients and 213 BBD patients who participated in the Shanghai Breast Cancer Study. RESULTS The expression levels of the TGF-β1, TβR- Ⅰ and TβR-Ⅱ genes in breast tissue were quantified using real-time PCR. TIER- Ⅱ expression in cancer tissue was decreased by over 50% as compared to either adjacent normal tissue from the same patients or benign tumor tissue from BBD patients （p〈0.001）. TGF-β1 expression was lower by approximately 20% in cancer tissue compared to adjacent normal tissue （p=0.14） or to benign tumor tissue （p=0.002）. Although TβR-Ⅰ expression was also reduced in cancer tissue compared to adjacent normal tissue, or benign tumor tissue, the magnitude of the reduction was less apparent than that for TβR- Ⅱ. Compared to patients with the lowest tertile value for TβR- Ⅱ, patients with median tertile value for TβR- Ⅱ had more favorable overall survival （HR 0.47, 95% CI 0.27-0.85） and disease-free survival （HR 0.65, 95% CI 0.39-1.06）. No apparent associations, however, were observed between TGF-β1 or TβR- Ⅰ expression and overall or disease-free survival. CONCLUSION The results from this study support the hypothesis that a decreased level of TβR-Ⅱ gene expression, and thus reduced TGF-β1 sensitivity, is related to breast tumor progression.     

Role of TGF-β1 and its Receptors in Breast Carcinogenesis:Evaluation of Gene Expression Patterns and Clinical Implications

OBJECTIVE Transforming growth factor β1 (TGF-β1) is a multifunc-tional cytokine that may play an important role in tumor development and progression. METHODS We evaluated gene expression patterns of TGF-β1 and its receptors [transforming growth factor β type I receptor (TβR-Ⅰ) and transforming growth factor β type II receptor (TβR-Ⅱ)] in tumor tissue from patients with breast cancer or with benign breast diseases (BBD) and adja-cent normal tissue from the patients with breast cancer. Included in the study were 527 breast cancer patients and 213 BBD patients who participated in the Shanghai Breast Cancer Study. RESULTS The expression levels of the TGF-β1, TβR-Ⅰand TβR-Ⅱ genes in breast tissue were quantified using real-time PCR. TβR-Ⅱ expres-sion in cancer tissue was decreased by over 50% as compared to either adjacent normal tissue from the same patients or benign tumor tissue from BBD patients (p<0.001). TGF-β1 expression was lower by approximately 20% in cancer tissue compared to adjacent normal tissue (p=0.14) or to be-nign tumor tissue (p=0.002). Although TβR-Ⅰ expression was also reduced in cancer tissue compared to adjacent normal tissue, or benign tumor tissue, the magnitude of the reduction was less apparent than that for TβR-Ⅱ. Compared to patients with the lowest tertile value for TβR-Ⅱ, patients with median tertile value for TβR-Ⅱ had more favorable overall survival (HR 0.47, 95% CI 0.27-0.85) and disease-free survival (HR 0.65, 95% CI 0.39-1.06). No apparent associations, however, were observed between TGF-β1 or TβR-Ⅰ expression and overall or disease-free survival. CONCLUSION The results from this study support the hypothesis that a decreased level of TβR-Ⅱ gene expression, and thus reduced TGF-β1 sensitivity, is related to breast tumor progression.     

环氧合酶-2和基质金属蛋白酶-9在宫颈癌中的表达及其临床意义

Objective： To investigate the expressions of cyclooxygenase （COX）-2 and matrix metalloproteinase （MMP）-9 in cervical carcinoma and their clinical significance. Methods： Immunohistochemistry SP method was used to detect the expressions of COX-2 and MMP-9 in 72 cases of invasive carcinoma of cervix （ICC） and 16 cases of normal cervical epithelium remote from tumor （NCE）. The relationships between the expressions of COX-2, MMP-9 in ICC and some characteristics relating to clinical pathology of cervical carcinoma such as histological grading, lymph node metastasis, stromal invasion and FIGO stage were analyzed statistically. Results： The rates of the positive expressions of COX-2 and MMP-9 in ICC were significantly higher than those in NCE. COX-2： 88.9% （64/72）in group ICC and 12.5% （2/16）in group NCE, P = 0.000; MMP-9： 94.4% （68/72） in group ICC and 43.8% （7/16） in group NCE, P = 0.000. The expression of COX-2 was positively correlated with lymph node metastasis （r= 0.296, P = 0.012） and stromal invasion （r = 0.257, P = 0.029）. The expression of MMP-9 was positively correlated with FIGO stage （r = 0.329, P = 0.005） and histological grading （r = 0.351, P = 0.003）. The expression of COX-2 was positively correlated with the expression of MMP-9 in ICC （r=0.297, P = 0.011）. Conclusion： The overexpressions of COX-2 and MMP-9 were closely related to the invasion and growth of cervical carcinoma. The tissue with the overexpression of COX-2 had strong invasion ability. COX-2 and MMP-9 had synergistic effect on proliferation, invasion and metastasis of cancer cells. Detecting the coexpression of COX-2 and MMP-9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.     

The expression of TGF-β1, ADAM12 and HB-EGF in primary hepatic carcinoma

Objective: To detect the expression and location of TGF-β1, ADAM12 and HB-EGF in primary hepatic carcinoma and study their effect on the growth and metastasis of hepatoma carcinoma cell. Methods: TGF-β1, ADAM12 and HB-EGF were detected by RT-PCR and immunohistochemistry in 30 cases of hepatic carcinoma tissues, 30 cases of adjacent carci-noma tissues and 5 cases of normal hepatic tissues. Results: RT-PCR analyses showed that the mRNA expression of TGF-β1, ADAM12 and HB-EGF were markedly increased in each hepatic carcinoma tissue compared with its adjacent tissue (P < 0.01), but no signal was detected in normal hepatic tissue, tmmunohistochemistry showed the same outcome on the expression of above three factors in hepatic tissues as RT-PCR. Proteins location analyses showed the proteins of TGF-β1, ADAM12 and HB-EGF all distributed in the stroma of hepatic carcinoma tissues. The positive correlation was found between TGF-β1 and ADAM12 (r=0.6137, P < 0.05), as well as ADAM12 and HB-EGF (r=0.5763, P < 0.05). The protein expression of TGF-β1, ADAM12 and HB-EGF were correlated with the size of tumors, degree of differentiation of hepatoma carcinoma cells, portal vein thrombus and the metastasis of absorbent glands, especially with hepatic cirrhosis caused by hepatitis B virus. Conclu-sion: TGF-β1, ADAM12 and HB-EGF possibly play an important role in the process of growth, invasion and metastasis of hepatoma carcinoma cell, meanwhile, the above three factors may collectively participate in the transition from hepatic cirrhosis caused by hepatitis B virus to hepatocellular carcinoma.     

α-、β-catenin和cyclin D1在乳腺癌中的表达及意义

Objective:To study the relationship between expressions of α-,β-catenins and cyclin D1 and the occurrence,infiltration and metastasis of breast cancer.Methods:High sensitive S-P immunohistochemical method was used to detect the protein expressions of α-,β-catenins and cyclin D1 in the 60 cases of breast cancer tissues.Results:Abnormal immunoreactivities of α- and β-catenins were observed in 37(61.7%)and 42(70%)cases of breast Cancer tissues,respectively.There were 28 cases(46.7%)who showed cyclin D1 overexpression.The abnormal expression rates of α -and β-catenins in infiltrating lobular carcinoma(ILC)were significantly higher than those in infiltrating ductal Carcinoma(IDC)(P＜0.05),but they had no relations to the extenl of differentiation and lymphatic metastasis of breasl Cancer(P＞0.05).The overexpression rate of cyclin D1 was correlated with tumor stage and lymphatic metastasis of breast cancer(P＜0.05),but not with histological type and lhe extent of differentiation(P＞0.05).Cyclin D1 overexpression was observed in 57.1%(24/42)of these cases that showed abnormal staining of β-catenin,but only observed in 22.2%(4/18)of these cases with normal membranous staining of β-catenin.There was a significantly positive correlation between the abnormal expression of β-catenin and overexpression of cyclin D1(rs=0.321.P＜0.05).Conclusion:The abnormal expression of β-Catenin may play an important role in the genesis of breast cancer by triggering cyclin D1 overexpression in breast cancer.The abnormal expressions of α- and β-catenins are not a key factor in malignant cell metastasis in breast cancer,but may also involve in the progress.     

Clinical significance of XRCC1 gene expression in human breast cancer and its cell and molecular mechanisms北大核心CSCD

Objective: To investigate the expression of X-ray repair cross complementing 1 (XRCC1) in human breast cancer and its relationship with the clinical characteristics, and to analyze the effects of XRCC1 over-expression on the proliferation and migration of breast cancer MB-231 cells and the molecular mechanism. Methods: The expression level of XRCC1 mRNA in breast cancer cell lines and human breast cancer tissues was detected by real-time fluorescent quantitative PCR. The expression of XRCC1 protein in human breast cancer tissues was detected by immunohistochemistry. The relationship between the expression of XRCC1 protein and the clinicopathological characteristics of breast cancer patients was analyzed. The pcDNA3.1(+)-Flag-XRCC1 plasmids were transfected into breast cancer MB-231 cells for the overexpression of XRCC 1 gene. Then the proliferation activity was detected by CCK-8 and soft agar plate clone formation assay. The cell cycle and apoptosis were detected by FCM method. The cell migration and invasion were detected by Transwell chamber assay. The expressions of cell cycle-, apoptosis- and migration-related proteins were detected by Western blotting. Results: The expression level of XRCC1 mRNA was significantly decreased in most breast cancer cell lines (all P < 0.001). As compared with the normal mammary epithelium and the paired adjacent breast tissues, the expression levels of XRCC1 mRNA and protein were downregulated in human breast cancer tissues (all P < 0.001). The expression level of XRCC1 mRNA was positively correlated with the prognosis of breast cancer patients (γ 2 =0.052, P =0.046), and XRCC1 protein expression was correlated with tumor diameter, lymph node metastasis, histological grade and TNM stage (all P < 0.05). After the overexpression of XRCC 1 gene, the proliferation, colony formation, invasion and migration of breast cancer MB-231 cells were significantly inhibited (all P < 0.01), the cell cycle was significantly blocked in G1 phase (P < 0.001), and the apoptosis rate was significantly increased (P < 0.001). Furthermore, the expressions of p21, p27, Bax, cleaved caspase-3 and E-cadherin were significantly upregulated (all P < 0.001), while the expressions of cyclin-dependent kinase 4/6 (CDK4/6), cyclin D1, Bcl-2, N-cadherin and vimentin were down-regulated (all P < 0.001) in MB-231 cells with XRCC1 overexpression. Conclusion: XRCC1 expression is down-regulated in breast cancer cell lines and tissues, and its expression level is positively correlated with the prognosis of breast cancer patients. Restoring XRCC 1 gene expression can inhibit cell growth, migration and invasion, and can induce apoptosis. So XRCC1 may be a potential tumor suppressor regulating the occurrence and development of human breast cancer. © 2019 by TUMOR.     

Correlation between Expression of P38 MAPK-Signaling and uPA in Breast Cancer

OBJECTIVE To study the expression of phosphorylated p38 mitogen-activated protein kinase(p-p38)and uPA and the correlation of their expression with breast cancer clinicopathological characteristics,and to investigate the role of the p38MAPK-signaling pathway in regulating uPA expression in breast cancer cells. METHODS Immunohistochemistry(S-P) was used to test the expression of p-p38 and uPA in 60 specimens of breast cancer tissues.Western blots were adopted to detect expression of the p-p38 and uPA proteins in MDA-MB-231 and MCF-7 breast cancer cells,and uPA expression a er treatment with SB203580,a specific inhibitor of p38 MAPK. RESULTS The positive rate of the p-p38 protein and uPA protein expression in the breast cancer tissues was 56.7% and 60.0%,respectively.The expression of p-p38 was positively related to the expression of uPA(r=0.316,P<0.05).The expression of p-p38 and uPA was related to lymph node metastas is and the TNM stage(P<0.05),but it was not related to the patient’s age or tumor size(P>0.05).The expression of p-p38 and uPA in MDA-MB-231 cells was higher than that in MCF-7 cells.SB203580 inhibited the p38 MAPK pathway and reduced uPA protein expression. CONCLUSION The p38 MAPK-signaling pathway promotes breast cancer malignant progression by up-regulating uPA expression,and it may be an important process in breast cancer invasion and metastasis.     

EXPRESSION OF E-CADHERIN/CATENIN COMPLEX IN BREAST CANCER

Objective： To detect the expressions of E-cadherin, α-catenin and β-catenin and analyze the relationship between Ecadherin-catenin adhesion complex and clinicopathological features in breast cancer. Methods： The expressions of E-cadherin, α-cadherin and β-catenin in specimens of 54 breast cancer, 21 normal breast tissues around tumor, 15 breast hyperplasia of usual type and 15 breast atypical hyperplasia were detected by immunohistochemical method. Results： In 21 normal breast tissues, E-cadherin and α-catenin were expressed on cell membrane of ductal and acinic cells, showing cellular contour and border among cells. The staining character of the three proteins in breast hyperplasia of usual type was the same as that in normal breast tissue. In breast atypical hyperplasia, the abnormal expression rates of E-cadherin, α-catenin and β-catenin were 6.7%, 13.3% and 26.7%, respectively. The total abnormal expression rate of E-cadherin-catenin complex was 33.3%. In breast cancer, the abnormal expression rates of E-cadherin, α＋catenin and β-catenin were 51.9%, 63.0% and 61.1%, respectively. The total abnormal expression rate of E-cadherin-catenin complex was 88.9%. Abnormal expression of E-cadherin and α-catenin were significantly correlated with histological grade. Abnormal expressions of α-catenin and β-catenin were significantly correlated with TNM staging, axillary lymph nodes metastasis and postoperative distant metastasis. Abnormal expression of E-cadherin-catenin complex was correlated with TNM staging, histological grade and axillary lymph nodes. Abnormal expression of β-catenin was negatively correlated with expression of HER-2. COX multiple factor analysis showed that E-cadherin or α-catenin or β-catenin was not independent prognostic indicator. Conclusion： Abnormal expressions of E-cadherin, α-catenin and β-catenin frequently occur in breast cancer. Abnormal expression of E-cadherin-catenin complex is correlated with differentiation disturbance and metastasis. Combined measurement of E-caherin, α-catenin and β-catenin may improve accuracy and sensitivity of predicting metastasis and prognosis of breast cancer.     

Expression of MMP-13 and its correlation with prognosis in non-small cell-lung cancer

Objective： To investigate the expression of MMP-13 in non-small cell lung cancer （NSCLC）, so as to analyze its correlation with prognosis of NSCLC. Methods： MMP-13 expression was detected in 99 NSCLC tissues and 32 normal lung tissues by immunohistochemical method. Results： （1） Expression of MMP-13 （51.5%, 51/99） in cancer tissues was significantly higher than that in normal tissues 0% （P 〈 0.05）. Expression level of MMP-13 was significantly related to lymph node metastasis and clinical stage （P 〈 0.01）. （2） Kaplan-Meier analysis showed that expression level of MMP-13 was closely cor- relate with the prognosis of NSCLC. Multivariate Cox model analysis suggested that the survival time was significantly related to clinical stage and the expression of MMP-13. Conclusion： MMP-13 is an independent factor that affect prognosis.     

RhoB-mRNA在喉癌中的表达及其临床意义

Objective To study the expression of RhoB-mRNA,and periphery regions in human laryngeal carcinoma.Methods The expression of RhoB-mRNA were examined by RT-PCR method.Results It was noted that the expression of RhoB-mRNA was positively correlated well with the clinical stages.The expression of RhoB-mRNA in carcinoma with node metastasis group was significantly higher than that without node metastasis.The difference between the two groups was statistically significant(P＜0.05).The expression of RhoB-mRNA in different types and stages of laryngeal carcinoma was significantly different(P＜0.05).The expression of RhoB in laryngeal carcinoma negtive correlation with the stages of laryngeal carcinoma(r=0.557).Conclusion The expression of RhoB plays an inhibitive role in the growth,invasion and local node metastasis of human laryngeal carcinoma.RhoB promote the formation,invasion and lymph node metastasis as oncogenes.It may be valuable as predictors for lymph node metastasis and prognosis.     

Analysis of the Relationship between Expressions of TF and MMP-9 and Prognosis of Breast Cancer Patients

OBJECTIVE To investigate expression of the tissue factor (TF)and matrix metalloproteinase-9(MMP-9)in breast cancers, and to assess their expression in relation to possible prognostic significance. METHODS The expression of TF and MMP-9 in 71 breast cancer specimens were determined by EnVision immunohistochemistry, and the positive expressions related to the patient clinical outcome. RESULTS Positive rates of TF and MMP-9 staining were respectively 43.7%and 42.3%.K-M monofactorial analysis showed that the 5-year survival rate of the patients with a positive expression of TF and MMP-9 was lower than those with negative expression(P<0.05).However,the COX multifactorial analysis indicated that TNM staging and lymph node metastasis were the prognostic factors for breast cancer patients,and that TF and MMP-9 could not be used as the independent prognostic factors(P >0.05). CONCLUSION The positive rates of TF and MMP-9 were considerably high in breast cancers,which could provide useful information for patient prognosis.     

HIF-1α和VEGF-C在乳腺癌淋巴管生成中的作用机制

Objective To investigate the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor-C (VEGF-C) and the correlations with clinic parameters, and to make sure the effect of DOI:10.3760/cma.j.issn.1673-422X.2013.10. 基金项目：安徽省卫生厅自然科学基金（09C230）作者单位：241000 安徽省芜湖市第二人民医院乳腺外科（赵迎春、朱永云、罗传瑜）,病理科（李勇）通信作者：赵迎春,E-mail: lcy0508@hotmail.com 联系人: 赵迎春 lcy0508@hotmail.com 电话：05533909558 手机：18155317401 the two genes in the lymphangiogenesis and lymph node metastasis of breast cancer. Methods The expressions of HIF-1α and VEGF-C were investigated by means of immunohistochemistry in samples from 78 cases of breast cancer and 20 cases of breast benign lesions. The density of the lymphatic microvessels immunohistochemically stained by D2-40 antibody was calculated. The relationships between HIF-1α, VEGF-C, LVD and clinicopathological parameters were analyzed statistically. Results HIF-1α expression occurred in 52 out of the 78 tumor samples (66.67%), while VEGF-C expression was observed in 41 out of the 78 tumor samples (52.56%). HIF-1α and VEGF-C expressions in breast cancer were significantly higher than those in beingn disease (15% and 10%; χ²=17.26, P=0.000; χ²=11.71, P=0.001). The expressions of HIF-1α and VEGF-C were significantly correlated with regional lymph nodal involvement (χ²=5.80, P=0.016; χ²=7.26, P=0.007) as well as late TNM classification (χ²=8.51, P=0.004; χ²=6.02, P=0.014), disregarding the patient’s age, tumor diameter, histological grade and pathologic type (P＞0.05). In addition, HIF-1α expression was positively correlated with VEGF-C expression (r=0.254, P=0.025). Higher LVD was found in both high HIF-1α and high VEGF-C expression cases (t=2.19, P=0.017; t=3.25, P=0.001). Conclusion HIF-1α may play a crucial role in the lymphangiogenesis and lymph node metastasis by regulating the expression of VEGF-C in breast cancer. Therefore, HIF-1α may become a particularly promising target for controlling lymph node metastasis in breast cancer.     

吲哚胺2,3双加氧酶在乳腺癌中的表达及其与预后的关系

目的 探讨吲哚胺2,3双加氧酶(IDO)在乳腺癌中的表达及其与乳腺癌临床病理特征、预后的关系.方法 收集40例乳腺癌蜡块,应用免疫组化SP法检测乳腺癌组织中IDO的表达,并对全部标本用CD31和CD105对肿瘤血管内皮细胞进行染色,计数肿瘤微血管密度(MVD),结合患者的临床病理特征及预后进行分析.结果 乳腺癌组织中IDO蛋白高表达率为67.5%(27/40),其表达与临床分期和淋巴结转移相关(均P＜0.05).IDO高表达组与低表达组的3年、 5年无瘤生存率差异均无统计学意义(P=0.211,P=0.523).乳腺癌组织中IDO表达与CD105标记的MVD值呈正相关(r=0.659,P＜0.05),与CD31标记的MVD值无关.结论 IDO可能通过促进新生血管形成加速乳腺癌的进展和转移,IDO表达与乳腺癌患者预后的关系需要进一步扩大样本量加以明确.

Abstract：

Objective To investigate the expression of indoleamine 2,3-dioxygenase (IDO) in breast cancer and its correlation with clinicopathologic factors and prognosis. Methods The expression of IDO, CD31, CD105 proteins in 40 specimens of breast cancer were assessed by immunohistochemistry. Results The overexpression rate of IDO in breast cancer was 67.5% (27/40), and expression of IDO was closely associated with clinical stage and lymph nodes metastasis. The disease-free survival rate in patients with IDO overexpression was not significantly lower than that in patients with negative or low expression of IDO(P>0.05). Moreover, the expression of IDO was positively correlated with CD105-labeled microvessel density (r=0.659,P<0.05). Conclusions Expression of IDO is associated with clinical stage and lymph nodes metastasis, and microvessel densitty. IDO expression may promote the growth and metastasis of breast cancer, probably via the increased agiogenesis. A larger sample study is needed to verify whether the prognosis of beast cancer is significantly correlated with IDO expression.     

High Expression of the RECK Gene in Breast Cancer Cells is Related to Low Invasive Capacity

OBJECTIVE To investigate the expression of the RECK gene in human breast (cancer) cell lines, and to determine the relationship between RECK gene expression and the invasive capacity of the breast cancer cell lines. METHODS The invasive capacity of breast (cancer) cell lines including HBL-100, MCF-7 and MDA-MB-435S were determined by the Tran-swell method. The protein expression levels of RECK, MMP-2 and MMP-9 genes in these three cell lines were measured by immunocytochemical methods. The expressions of the RECK gene and protein level were measured by RT-PCR and Western blots in the cell lines respectively. RESULTS The order of the invasive capacity of the breast (cancer) cell lines was MDA-MB-435S, being the highest, and HBL-100, being the lowest. The invasive capacity difference between any two groups among the three groups was significant (P<0.01). The protein expression level of the RECK gene in the HBL-100 cell line was highest, and no expression was detected in MDA-MB-435S cells. Moreover, the expression of the RECK gene was negatively correlated with the expression of the MMP-2 and MMP-9 genes. The mRNA level of the RECK gene in HBL-100 cells was the highest, but no expression was found in the MDA-MB-435S cells (P<0.001). CONCLUSION There was a significant negative correlation between the expression level of the RECK gene and invasive capacity in vitro, and the RECK gene expression showed an inverse proportion to that of the MMP-2, MMP-9 genes.     

赖氨酰氧化酶和基质金属蛋白酶2在胃癌组织中的表达及其与胃癌转移的关系

目的 探讨赖氨酰氧化酶(LOX)和基质金属蛋白酶2(MMP-2)在胃癌组织中的表达及其与胃癌转移的关系.方法 收集手术切除新鲜胃癌及相应的癌旁胃组织,用逆转录聚合酶链反应(RT-PCR)方法检测LOX mRNA和MMP-2 mRNA表达,Western blot方法检测LOX蛋白和MMP-2蛋白表达.结果 LOX mRNA在胃癌组织和癌旁胃组织中的相对表达量分别为0.5328±0.1367和0.2436±0.1372(P<0.01),MMP-2 mRNA在胃癌组织和癌旁胃组织中的相对表达量分别为0.7980±0.1571和0.3231±0.1672(P<0.05);LOX mRNA在有淋巴结转移和无淋巴结转移的胃癌组织中的相对表达量分别为0.6336±0.1547和0.4914±0.1408,MMP-2 mRNA在有淋巴结转移和无淋巴结转移的胃癌组织中的相对表达量分别为0.8762±0.1381和0.6362±0.1936,差异均有统计学意义(均P<0.05).LOX蛋白在胃癌组织和癌旁胃组织中的相对表达量分别为0.5237±0.1426和0.2972±0.1480(P<0.05),在有淋巴结转移和无淋巴结转移的胃癌组织中相对表达量分别为0.6880±0.1263和0.4944±0.1217(P<0.05);MMP-2蛋白在胃癌组织和癌旁胃组织中的相对表达量分别为0.7365±0.1607和0.3321±0.1480(P<0.05),在有淋巴结转移和无淋巴结转移的胃癌组织中相对表达量分别为0.8097±0.1632和0.5132土0.1366(P<0.05).胃癌组织中,LOX mRNA与MMP-2 mRNA、LOX蛋白与MMP-2蛋白相对表达量呈正相关(r=0.873,P<0.001;r=0.881,P<0.001);在伴有淋巴结转移的胃癌组织中,LOX mRNA与MMP-2 mRNA、LOX蛋白与MMP-2蛋白相对表达量也呈正相关(r=0.923,P<0.001;r=0.972,P<0.001).结论 LOX和MMP-2在胃癌组织中的表达明显高于相应的癌旁胃组织;在伴有淋巴结转移的胃癌组织中,LOX和MMP-2表达高于无淋巴结转移的胃癌组织,且LOX和MMP-2表达呈正相关,提示LOX和MMP-2对胃癌的发生和转移有促进作用,且两者可能有协同作用.

Abstract：

Objective To compare the expressions of lysyl oxidase (LOX) and matrix metalloproteinases-2 (MMP-2) in gastric cancer and pericancerous tissues, in gastric cancers.with and without lymph node metastasis, and to analyze the effects of LOX and MMP-2 on tumor invasion and metastasis.Methods Gastric cancer and pericancerous tissues were collected from 46 patients who underwent surgery.Levels of LOX and MMP-2 mRNA were detected by RT-PCR.Protein abundance of LOX and MMP-2 was examined using Western blot.Results Expressions of LOX and MMP-2 mRNA, and protein in 46 gastric cancers were significantly higher than that in 46 pericancerous tissues.In gastric cancer with lymph node metastasis, the levels of LOX and MMP-2 mRNA and protein were higher than those in gastric cancers without lymph node metastasis ( P < 0.05 ).In the groups of gastric cancer with lymph node metastasis, expression of LOX was positively correlated with MMP-2 protein expression ( P < 0.01 ).Conclusions Expressions of LOX and MMP-2 in gastric cancer tissues are significantly higher than that in pericancerous tissues.The expressions of LOX and MMP-2 in gastric cancer with lymph node metastasis are higher than that in gastric cancer without lymph node metastasis.Expressions of LOX and MMP-2 are positively correlated.The results suggest that LOX and MMP-2 may promote the growth and metastasis of gastric cancer.     

基质金属蛋白酶-3和骨桥蛋白在子宫颈癌组织中的表达及其临床意义

目的 探讨基质金属蛋白酶-3(MMP-3)和骨桥蛋白(OPN)在子宫颈癌组织中的表达及与子宫颈癌浸润转移的关系.方法 采用免疫组织化学SP法检测54例子宫颈癌组织中MMP-3和OPN的表达,并对其与临床病理特征的关系进行分析,以15例正常子宫颈组织为对照.结果 MMP-3和OPN在子宫颈癌组织中的阳性表达率分别为70.37%、66.7%,高于正常子宫颈组织的20%、0;子宫颈间质浸润深度>1/2的阳性表达率显著高于间质浸润深度≤1/2者(P<0.05);子宫颈癌有淋巴结转移者MMP-3和OPN的阳性表达率显著高于无转移者(P<0.05),其表达与浸润深度、淋巴结转移相关.MMP-3与OPN的表达呈显著正相关(r=0.401,P<0.05).结论 MMP-3和OPN与子宫颈癌的浸润转移有关.

Abstract：

Objective To study the expressions of matrix metalloproteinase-3 (MMP-3) and osteopontin (OPN) in cervical carcinoma and their relationship with invasion and metastasis. Methods The expression of MMP-3 and OPN were detected in 54 cases of cervical cancer tissues by immunohistochemical SP method. Compared with 15 cases of normal cervical tissues, the relationship was analyzed between both protein expressions and clinical pathology. Results The expression positive rates of MMP-3 and OPN in cervical cancer tissues (70.37 % and 66.7 %, respectively) were significantly higher than those of normal cervical tissues (20 % and 0, respectively), were significantly higher with infiltration depth >1/2 and lymph node metastasis than those with depth≤1/2 and without metastasis , respectively(P <0.05). The expressions of MMP-3 and OPN were related with depth of cervical infiltration and lymph node metastasis of cervical cancer.Expressions between MMP-3 and OPN were significantly positively correlation(r =0.401, P<0.05). Conclusion The expressions of MMP-3 and OPN are correlated with invasion and metastasis of cervical carcinoma.     

NF-κB and MMP-2 expression regulated by Lrig1 through the MEK-ERK signaling pathway in Hazaks' esophageal squamous cell carcinoma北大核心CSCD

Objective: This work aimed to investigate the expression levels of Lrig1, NF-κB, and MMP-2 in Hazak's esophageal squamous cell carcinoma (ESCC), as well as to explore the relationship of Lrig1 expression through the PI3K-AKT and MEK-ERK signaling pathways with clinicopathological indices. Methods: First, RT-PCR analysis was performed to study the expression levels of Lrig1, NF-κB, and MMP-2 in 48 ESCC and noncancerous specimens. Second, some key genes of the PI3K and MEK signaling pathways such as PI3K, AKT1, MEK1, MEK2, MEK5, ERK1, and ERK2 were detected in Lrig1-positive and -negative tissues to identify the possible signaling pathway of Lrig1-regulated NF-κB and MMP-2 expression. Results: The expression of NF-κB (P<0.001, P=0.014) and MMP-2 (P=0.003, P=0.045) was significantly correlated with Lrig1 in cancer and distal normal tissues. Lrig1 may be negatively correlated with NF-κB and MMP-2 at the protein level. MEK5 (P<0.001) and ERK2 (P=0.009) expression was associated with Lrig1 in cancer tissues. PI3K expression was correlated with Lrig1 in the distal normal tissues (P<0.001). The coordinate expression ratio of Lrig1 to NF-κB and MMP2 reached 52.1% (25/48). This co-expression may be related to lymph node metastasis (P=0.020) but not to other clinicopathological features. Conclusions: These findings suggest that MMP-2 and NF-κB expression is related to Lrig1 in Hazak's ESCC, and that MEK and ERK2 mRNA expression are related to Lrig1. The co-expression of NF-κB, MMP-2, and Lrig1 may promote lymph node metastasis in ESCC among Hazak people. Lrig1 may regulate the expression of target genes not through the PI3K-AKT pathway but through the MEK-ERK signaling pathway. Further related studies are needed in the future.     

甲状腺癌钠、碘转运蛋白与血清β2-MG变化的相关性分析（英文）

Objective: The aim of our study was to investigate the correlation between the expression of sodium/iodide symporter, serum levels of β2-MG and prognosis of thyroid carcinoma patients. Methods: Ninty-five cases with thyroid carcinoma, using enzyme-linked immunosorbent assay with double-antibody sandwich to detect the serum β2-MG levels and immunohistochemistry to detect NIS expression of thyroid cancer tissue. Results: Thirty-seven cases showed positive expression of sodium/iodide symporter (38.9%) and 30 cases showed positive expression of β2-MG (31.57%). There were significant differences of NIS expression (χ2=8.207, P=0.017) and β2-MG expression (χ2=10.121, P=0.006) between different pathological types of thyroid carcinoma, but there was no correlation between the positive rate of the two research groups (r=-0.546, P=0.633). The significant differences was observed in expression of sodium/iodide symporter (χ2 = 9.272, P=0.002) and expression of β2-MG (χ2=4.441, P=0.035) between the group with neck lymph node metastasis and the group without neck lymph node metastasis and both positive rate was significantly negatively correlated (r=1.000, P=0.000). The significant differences was observed in expression of sodium/iodide symporter (χ2=9.272, P=0.002) and expression of β2-MG (χ2 = 3.867, P=0.043) between the group with distant organ metastasis and the group without distant organ metastasis (χ2=11.985, P=0.001) and both positive rate was significantly negatively correlated (r=-1.000, P=0.000). Conclusion: There are significantly negatively correlated between neck lymph node metastasis, distant organ metastasis and expression of sodium/iodide symporter and expression of β2-MG. Thyroid cancer lymph node and distant organ metastasis, the tumor tissue NIS expression and serum levels of β2-MG is significantly negatively correlated. The detection of serum β2-MG provides clinical reference value for the effects on radionuclide therapy and prognosis assessment of thyroid carcinoma. Serum β2-MG levels is negatively correlated with prognosis in thyroid cancer patients.