Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sect...Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.展开更多
BACKGROUND A noninvasive biomarker with high diagnostic performance is urgently needed for the early diagnosis of colorectal cancer(CRC).AIM To evaluate the diagnostic value of matrix metalloproteinases(MMPs)2,7 and 9...BACKGROUND A noninvasive biomarker with high diagnostic performance is urgently needed for the early diagnosis of colorectal cancer(CRC).AIM To evaluate the diagnostic value of matrix metalloproteinases(MMPs)2,7 and 9 in urine for CRC.METHODS Of 59 healthy controls,47 patients with colon polyps and 82 patients with CRC were included in this study.Carcinoembryonic antigen(CEA)in serum and MMP2,MMP7,and MMP9 in urine were detected.The combined diagnostic model of the indicators was established by binary logistic regression.The receiver operating characteristic curve(ROC)of the subjects was used to evaluate the independent and combined diagnostic value of the indicators.RESULTS The MMP2,MMP7,MMP9,and CEA levels in the CRC group differed significantly from levels in the healthy controls(P<0.05).The levels of MMP7,MMP9,and CEA also differed significantly between the CRC group and the colon polyps group(P<0.05).The area under the curve(AUC)distinguishing between the healthy control and the CRC patients using the joint model with CEA,MMP2,MMP7 and MMP9 was 0.977,and the sensitivity and specificity were 95.10%and 91.50%,respectively.For early-stage CRC,the AUC was 0.975,and the sensitivity and specificity were 94.30%and 98.30%,respectively.For advanced stage CRC,the AUC was 0.979,and the sensitivity and specificity were 95.70%and 91.50%,respectively.Using CEA,MMP7 and MMP9 to jointly established a model distinguishing the colorectal polyp group from the CRC group,the AUC was 0.849,and the sensitivity and specificity were 84.10%and 70.20%,respectively.For early-stage CRC,the AUC was 0.818,and the sensitivity and specificity were 76.30%and 72.30%,respectively.For advanced stage CRC,the AUC was 0.875,and the sensitivity and specificity were 81.80%and 72.30%,respectively.CONCLUSION MMP2,MMP7 and MMP 9 may exhibit diagnostic value for the early detection of CRC and may serve as auxiliary diagnostic markers for CRC.展开更多
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 detec...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 expres- sions 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.展开更多
Objective:To evaluate whether the methanol extract of Codium fragile(MECF) regulates tumor necrosis factor-α(TNF-α)-induced invasion of human breast cancer MDA-MB-231 cells by suppressing matrix metalloproteinase-9(...Objective:To evaluate whether the methanol extract of Codium fragile(MECF) regulates tumor necrosis factor-α(TNF-α)-induced invasion of human breast cancer MDA-MB-231 cells by suppressing matrix metalloproteinase-9(MMP-9).Methods:Reverse transcriptionpolymerase chain reaction(RT-PCR) and western blot analysis were performed to analyze the expression of MMP-9 and nuclear factor-κB(NF-κB) subunits,p65 and p50,and IκB in MDA-MB-231 cells.3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide(MTT) assay was used for cell viability.MMP-9 activity and invasion were measured by gelatin zymography and a matrigel invasion assay,respectively.NF- κB activity was measured by an electrophoretic mobility shift assay and luciferase activity.Results:MECF had no effects on cell viability up to a concentration of 100 μg/mL in human breast cancer MDA-MB-231 cells regardless of the presence of TNF-α.MDA-MB-231 cells that were stimulated with TNF-α showed a marked increase of invasion compared to the untreated control,whereas pretreatment with MECF downregulated the TNF-α-induced invasion of MDA-MB-231 cells.Additionally,zymography,western blot analysis,and reverse transcriptase-polymerase chain reaction(RT-PCR) confirmed that MECF decreased TNF-α-induced MMP-9 expression and activity which is a key regulator for cancer invasion.According to an electrophoretic morbidity shift assay,pretreatment with MECF in MDA-MB-231 cells significantly decreased the TNF-α-induced DNA-binding activity of nuclear factor- κB(NF- κB),which is an important transcription factor for regulating cancer invasion-related genes such as MMP-9.Furthermore,treatment with MECF sustained the expression of p65 and p50 in response to TNF-α in the cytosolic compartment.The luciferase assay demonstrated that MECF attenuated TNF-α-induced NF- κB luciferase activity.Conclusion:MECF exhibited its antiinvasive capability by downregulating TNF-α-induced MMP-9 expression,resulting from the suppression of NF- κB activity in the human breast cancer cell line MDA-MB-231.展开更多
To study the expression of matrix metalloproteinase 2 and 9 in human prostate cancer, matrix metalloproteinase 2 and 9 were immunohistochemically detected in tissues of prostate cancer and benign prostatic hype...To study the expression of matrix metalloproteinase 2 and 9 in human prostate cancer, matrix metalloproteinase 2 and 9 were immunohistochemically detected in tissues of prostate cancer and benign prostatic hyperplasia (BPH). Our results showed that matrix metalloproteinase 2 and 9 levels in prostate cancer were much higher than those in tissues of BPH, with the cancer invasion being positively correlated with the expression of the metalloproteinases. It is concluded that matrix metalloproteinase 2 and 9 are better molecular markers, which are of help in the diagnosis and prediction of prognosis of prostate cancer.展开更多
AIM:To assess expression of matrix metalloproteinases 2(MMP2)and MMP9 in gastric cancer,superficial gastritis and normal mucosa,and to measure metalloproteinase activity.METHODS:MMP2 and MMP9 mRNA expression was deter...AIM:To assess expression of matrix metalloproteinases 2(MMP2)and MMP9 in gastric cancer,superficial gastritis and normal mucosa,and to measure metalloproteinase activity.METHODS:MMP2 and MMP9 mRNA expression was determined by quantitative real-time polymerase chain reaction.Normalization was carried out using three different factors.Proteins were analyzed by quantitative gelatin zymography(qGZ).RESULTS:18S ribosomal RNA(18SRNA)was very highly expressed,while hypoxanthine ribosyltransferase-1(HPRT-1)was moderately expressed.MMP2 was highly expressed,while MMP9 was not detected or lowly expressed in normal tissues,moderately or highly expressed in gastritis and highly expressed in cancer.Relative expression of 18SRNA and HPRT-1 showed no significant differences.Significant differences in MMP2 and MMP9 were found between cancer and normal tissue,but not between gastritis and normal tissue.Absolute quantification of MMP9 echoed this pattern,but differential expression of MMP2 proved conflictive.Analysis by qGZ indicated significant differences between cancer and normal tissue in MMP-2,total MMP-9,250 and 110 kDa bands.CONCLUSION:MMP9 expression is enhanced in gastric cancer compared to normal mucosa;interpretation of differential expression of MMP2 is difficult to establish.展开更多
基金supported by the Construction of Prevention and Treatment System of Geriatric Syndromes Focusing on Disability and Dementia(No.21-1-2-2-zyyd-nsh)。
文摘Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.
基金Supported by the National Key Research and Development Program of China,No.2020YFC2004604 and 2020YFC2002700.
文摘BACKGROUND A noninvasive biomarker with high diagnostic performance is urgently needed for the early diagnosis of colorectal cancer(CRC).AIM To evaluate the diagnostic value of matrix metalloproteinases(MMPs)2,7 and 9 in urine for CRC.METHODS Of 59 healthy controls,47 patients with colon polyps and 82 patients with CRC were included in this study.Carcinoembryonic antigen(CEA)in serum and MMP2,MMP7,and MMP9 in urine were detected.The combined diagnostic model of the indicators was established by binary logistic regression.The receiver operating characteristic curve(ROC)of the subjects was used to evaluate the independent and combined diagnostic value of the indicators.RESULTS The MMP2,MMP7,MMP9,and CEA levels in the CRC group differed significantly from levels in the healthy controls(P<0.05).The levels of MMP7,MMP9,and CEA also differed significantly between the CRC group and the colon polyps group(P<0.05).The area under the curve(AUC)distinguishing between the healthy control and the CRC patients using the joint model with CEA,MMP2,MMP7 and MMP9 was 0.977,and the sensitivity and specificity were 95.10%and 91.50%,respectively.For early-stage CRC,the AUC was 0.975,and the sensitivity and specificity were 94.30%and 98.30%,respectively.For advanced stage CRC,the AUC was 0.979,and the sensitivity and specificity were 95.70%and 91.50%,respectively.Using CEA,MMP7 and MMP9 to jointly established a model distinguishing the colorectal polyp group from the CRC group,the AUC was 0.849,and the sensitivity and specificity were 84.10%and 70.20%,respectively.For early-stage CRC,the AUC was 0.818,and the sensitivity and specificity were 76.30%and 72.30%,respectively.For advanced stage CRC,the AUC was 0.875,and the sensitivity and specificity were 81.80%and 72.30%,respectively.CONCLUSION MMP2,MMP7 and MMP 9 may exhibit diagnostic value for the early detection of CRC and may serve as auxiliary diagnostic markers for CRC.
文摘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 expres- sions 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.
基金supported by Basic Science Research Program(2015R1D1A1A01060538)through the National Research Foundation of Korea(NRF)funded from the Ministry of Education,Science and Technology of Korea
文摘Objective:To evaluate whether the methanol extract of Codium fragile(MECF) regulates tumor necrosis factor-α(TNF-α)-induced invasion of human breast cancer MDA-MB-231 cells by suppressing matrix metalloproteinase-9(MMP-9).Methods:Reverse transcriptionpolymerase chain reaction(RT-PCR) and western blot analysis were performed to analyze the expression of MMP-9 and nuclear factor-κB(NF-κB) subunits,p65 and p50,and IκB in MDA-MB-231 cells.3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide(MTT) assay was used for cell viability.MMP-9 activity and invasion were measured by gelatin zymography and a matrigel invasion assay,respectively.NF- κB activity was measured by an electrophoretic mobility shift assay and luciferase activity.Results:MECF had no effects on cell viability up to a concentration of 100 μg/mL in human breast cancer MDA-MB-231 cells regardless of the presence of TNF-α.MDA-MB-231 cells that were stimulated with TNF-α showed a marked increase of invasion compared to the untreated control,whereas pretreatment with MECF downregulated the TNF-α-induced invasion of MDA-MB-231 cells.Additionally,zymography,western blot analysis,and reverse transcriptase-polymerase chain reaction(RT-PCR) confirmed that MECF decreased TNF-α-induced MMP-9 expression and activity which is a key regulator for cancer invasion.According to an electrophoretic morbidity shift assay,pretreatment with MECF in MDA-MB-231 cells significantly decreased the TNF-α-induced DNA-binding activity of nuclear factor- κB(NF- κB),which is an important transcription factor for regulating cancer invasion-related genes such as MMP-9.Furthermore,treatment with MECF sustained the expression of p65 and p50 in response to TNF-α in the cytosolic compartment.The luciferase assay demonstrated that MECF attenuated TNF-α-induced NF- κB luciferase activity.Conclusion:MECF exhibited its antiinvasive capability by downregulating TNF-α-induced MMP-9 expression,resulting from the suppression of NF- κB activity in the human breast cancer cell line MDA-MB-231.
文摘To study the expression of matrix metalloproteinase 2 and 9 in human prostate cancer, matrix metalloproteinase 2 and 9 were immunohistochemically detected in tissues of prostate cancer and benign prostatic hyperplasia (BPH). Our results showed that matrix metalloproteinase 2 and 9 levels in prostate cancer were much higher than those in tissues of BPH, with the cancer invasion being positively correlated with the expression of the metalloproteinases. It is concluded that matrix metalloproteinase 2 and 9 are better molecular markers, which are of help in the diagnosis and prediction of prognosis of prostate cancer.
基金Supported by The National Council on Science and Technology (CONACYT:85675 and 79628)Institute of Public Health(POA: 2008-2010)Research Office of Veracruzana University and Public Education Secretariat(SEP-PROMEP-UV:PTC-319)
文摘AIM:To assess expression of matrix metalloproteinases 2(MMP2)and MMP9 in gastric cancer,superficial gastritis and normal mucosa,and to measure metalloproteinase activity.METHODS:MMP2 and MMP9 mRNA expression was determined by quantitative real-time polymerase chain reaction.Normalization was carried out using three different factors.Proteins were analyzed by quantitative gelatin zymography(qGZ).RESULTS:18S ribosomal RNA(18SRNA)was very highly expressed,while hypoxanthine ribosyltransferase-1(HPRT-1)was moderately expressed.MMP2 was highly expressed,while MMP9 was not detected or lowly expressed in normal tissues,moderately or highly expressed in gastritis and highly expressed in cancer.Relative expression of 18SRNA and HPRT-1 showed no significant differences.Significant differences in MMP2 and MMP9 were found between cancer and normal tissue,but not between gastritis and normal tissue.Absolute quantification of MMP9 echoed this pattern,but differential expression of MMP2 proved conflictive.Analysis by qGZ indicated significant differences between cancer and normal tissue in MMP-2,total MMP-9,250 and 110 kDa bands.CONCLUSION:MMP9 expression is enhanced in gastric cancer compared to normal mucosa;interpretation of differential expression of MMP2 is difficult to establish.
