Objective: To investigate the expression of matrix metalloproteinase-7 (MMP-7) and Fas ligand (FasL) in gastric cancer and explore their role in progression of gastric cancer. Methods: Formalin-fixed paraffin and emb...Objective: To investigate the expression of matrix metalloproteinase-7 (MMP-7) and Fas ligand (FasL) in gastric cancer and explore their role in progression of gastric cancer. Methods: Formalin-fixed paraffin and embedded tissues of primary gastric cancer and adjacent non-tumor mucosa from 113 cases were evaluated for MMP-7, FasL and Capase-3 expression by streptavidin-peroxidase (S-P) immunohistochemistry. The expression of the first two proteins in cancer cells of primary foci was compared with clinicopathological parameters of tumors. We also observed the correlation of MMP-7 and FasL expression with Caspase-3 expression in cancer cells of primary foci. Results: MMP-7 positive immunostaining was less frequently detected in adjacent epithelial cells than in cancer cells of primary foci of gastric cancer (P<0.05, 29.2% vs 69.0%), and so was FasL (P<0.05, 34.5% vs 54.0%). MMP-7 expression was associated with tumor size, Borrmann抯 classification, invasive depth, metastasis and TNM staging (P<0.05), but not with growth pattern, Lauren抯 classification, or histological classification (P>0.05). FasL expression was correlated with tumor size, invasive depth, metastasis, Lauren抯 classification, histological classification (P<0.05), while not with Borrmann抯 classification, TNM staging or growth pattern (P>0.05). Cancer cells of primary foci expressed less Caspase-3 than their adjacent epithelial cells (P<0.05, 32.7% vs 50.4%). There was an obvious correlation between FasL, MMP-7 and Caspase-3 expression in cancer cells of primary foci (P<0.05). Co-expression of MMP-7 and FasL paralleled with Caspase-3 expression in cancer cells of primary foci (P<0.05). Conclusion: MMP-7 and FasL expression was up-regulated in gastric carcinogenesis and was principally involved in progression of gastric cancer. FasL expression could reflect the differentiation of gastric cancer cells and underlie the molecular mechanisms of different pathways of gastric tumorigenesis. Co-expression of MMP-7 and FasL could have apoptosis-inducing effect on gastric cancer cells.展开更多
Objective. To investigate the role of matrix metalloproteinase-7 (MMP-7) expression in caricinogenesisand progression of gastric cancer.Methods. We studied MMP-7 expression and microvessel density (MVD) in adjacent mu...Objective. To investigate the role of matrix metalloproteinase-7 (MMP-7) expression in caricinogenesisand progression of gastric cancer.Methods. We studied MMP-7 expression and microvessel density (MVD) in adjacent mucosa and pri-mary foci of 113 cases of gastric cancer by streptavidin-biotin-immunoperoxidase method using anti-MMP-7 and anti-CD34 antibodies. MMP-7 expression and mean MVD were compared with clinicopatholog-ical features of gastric cancer, with the relationship between MMP-7 expression and MVD concerned in gastric cancer.Results. MMP-7 showed positive expression in adjacent mucosa of gastric cancer (29.20%, 33/113),less than that in gastric cancer (69.03%, 78/113). MMP-7 expression in primary foci of gastric cancerwas positively correlated with tumor size, invasive depth, metastasis and TNM staging (P＜0.05), but notwith differentiation or growth pattern of gastric cancer (P＞0.05). Positive correlation of mean MVD withtumor size, invasive depth, metastasis and TNM staging was found (P＜0.05), despite no relationshipbetween mean MVD and differentiation of gastric cancer (P＞0.05). Mean MVD was dependent on MMP-7expression in gastric cancer (P＜0.05).Conclusion. Up-regulated expression of MMP-7 played an important role in carcinogenesis and pro-gression by participating in growth, invasion, metastasis and angiogenesis of gastric cancer. MMP-7 ex-pression could be regarded as an effective and objective marker to reflect the biological behaviors of gas-tric cancer.展开更多
Objective:To explore the expression of matrix metalloproteinase-7 in serous ovarian tumors. Methods: Expression of MMP- 1 in 6 normal ovaries, 12 serous cystadenomas of ovary, 6 borderline cystadenomas of ovary, and 2...Objective:To explore the expression of matrix metalloproteinase-7 in serous ovarian tumors. Methods: Expression of MMP- 1 in 6 normal ovaries, 12 serous cystadenomas of ovary, 6 borderline cystadenomas of ovary, and 22 serous cystadenocarcinomas of ovary were studied by immunohistoc/temical SP staining. Results: No expression of MMP- 1 was detected in normal ovaries. In most serous ovarian tumors, expression of MMP-7 was detected in both the cytoplasm of tumor cells and stroma, although it was reported in other tumors that MMP- 7 was mainly expressed in the cytoplasm of tumor cells. The expression level of MMP-7 in the cytoplasm of tumor cells was statistically insignificant between serous cystadenomas of ovary, borderline cystadenomas of ovary, and serous cystadenocarcinomas of ovary. But in the stroma, the expression level of MMP-7 in borderline cystadenomas of ovary and serous cystadenocarcinomas of ovary was significantly higher than that in serous cystadenomas of ovary (P<0. 05). In borderline cystadenomas and serous cystadenocarcinomas of ovary, expression of MMP-7 could also be detected in the nuclei of some tumor cells. Conclusion: MMP-7 may play an important role in the progression of serous ovarian tumors.展开更多
BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found t...BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.展开更多
Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug deliv...Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.展开更多
目的:探讨子痫前期(PE)患者血清和胎盘中的肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-7(MMP-7)的表达水平。方法:选取2021年11月—2023年8月扬州大学临床医学院妇产科收治的86例PE患者,分为早发型PE(n=33)和...目的:探讨子痫前期(PE)患者血清和胎盘中的肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-7(MMP-7)的表达水平。方法:选取2021年11月—2023年8月扬州大学临床医学院妇产科收治的86例PE患者,分为早发型PE(n=33)和晚发型PE(n=53),另外选取健康孕妇(n=45)作为对照。检测所有纳入患者血清及胎盘组织中的TNF-α、MMP-1和MMP-7水平。结果:早发型PE患者(34.71±1.35周vs 40.43±0.70周)及晚发型PE患者(38.43±0.60周vs 40.43±0.70周)的孕周明显小于对照组(均P<0.05);早发型PE患者血清中TNF-α(507.92±28.99 ng/L vs 478.50±41.15 ng/L)、MMP-1(1156.67±158.07μg/L vs 1037.59±163.10μg/L)和MMP-7(211.00±18.64μg/L vs 196.32±19.87μg/L)的表达较晚发型PE患者显著增加(均P<0.05),晚发型PE患者血清中TNF-α(478.50±41.15 ng/L vs 446.90±41.52 ng/L)、MMP-1(1037.59±163.10μg/L vs 840.78±174.43μg/L)和MMP-7(196.32±19.87μg/L vs 166.01±15.09μg/L)的表达较对照组显著增加(均P<0.05);免疫组化结果显示,早发型PE患者胎盘组织中TNF-α、MMP-1和MMP-7表达水平较晚发型PE及对照组明显升高(均P<0.05)。结论:早发型PE患者及晚发型PE患者的TNF-α、MMP-1和MMP-7表达明显增加,这可能在PE的发生发展中起到重要作用。展开更多
文摘Objective: To investigate the expression of matrix metalloproteinase-7 (MMP-7) and Fas ligand (FasL) in gastric cancer and explore their role in progression of gastric cancer. Methods: Formalin-fixed paraffin and embedded tissues of primary gastric cancer and adjacent non-tumor mucosa from 113 cases were evaluated for MMP-7, FasL and Capase-3 expression by streptavidin-peroxidase (S-P) immunohistochemistry. The expression of the first two proteins in cancer cells of primary foci was compared with clinicopathological parameters of tumors. We also observed the correlation of MMP-7 and FasL expression with Caspase-3 expression in cancer cells of primary foci. Results: MMP-7 positive immunostaining was less frequently detected in adjacent epithelial cells than in cancer cells of primary foci of gastric cancer (P<0.05, 29.2% vs 69.0%), and so was FasL (P<0.05, 34.5% vs 54.0%). MMP-7 expression was associated with tumor size, Borrmann抯 classification, invasive depth, metastasis and TNM staging (P<0.05), but not with growth pattern, Lauren抯 classification, or histological classification (P>0.05). FasL expression was correlated with tumor size, invasive depth, metastasis, Lauren抯 classification, histological classification (P<0.05), while not with Borrmann抯 classification, TNM staging or growth pattern (P>0.05). Cancer cells of primary foci expressed less Caspase-3 than their adjacent epithelial cells (P<0.05, 32.7% vs 50.4%). There was an obvious correlation between FasL, MMP-7 and Caspase-3 expression in cancer cells of primary foci (P<0.05). Co-expression of MMP-7 and FasL paralleled with Caspase-3 expression in cancer cells of primary foci (P<0.05). Conclusion: MMP-7 and FasL expression was up-regulated in gastric carcinogenesis and was principally involved in progression of gastric cancer. FasL expression could reflect the differentiation of gastric cancer cells and underlie the molecular mechanisms of different pathways of gastric tumorigenesis. Co-expression of MMP-7 and FasL could have apoptosis-inducing effect on gastric cancer cells.
文摘Objective. To investigate the role of matrix metalloproteinase-7 (MMP-7) expression in caricinogenesisand progression of gastric cancer.Methods. We studied MMP-7 expression and microvessel density (MVD) in adjacent mucosa and pri-mary foci of 113 cases of gastric cancer by streptavidin-biotin-immunoperoxidase method using anti-MMP-7 and anti-CD34 antibodies. MMP-7 expression and mean MVD were compared with clinicopatholog-ical features of gastric cancer, with the relationship between MMP-7 expression and MVD concerned in gastric cancer.Results. MMP-7 showed positive expression in adjacent mucosa of gastric cancer (29.20%, 33/113),less than that in gastric cancer (69.03%, 78/113). MMP-7 expression in primary foci of gastric cancerwas positively correlated with tumor size, invasive depth, metastasis and TNM staging (P＜0.05), but notwith differentiation or growth pattern of gastric cancer (P＞0.05). Positive correlation of mean MVD withtumor size, invasive depth, metastasis and TNM staging was found (P＜0.05), despite no relationshipbetween mean MVD and differentiation of gastric cancer (P＞0.05). Mean MVD was dependent on MMP-7expression in gastric cancer (P＜0.05).Conclusion. Up-regulated expression of MMP-7 played an important role in carcinogenesis and pro-gression by participating in growth, invasion, metastasis and angiogenesis of gastric cancer. MMP-7 ex-pression could be regarded as an effective and objective marker to reflect the biological behaviors of gas-tric cancer.
基金Supported by Grant from the Natural Science Foundation of Shaanxi Province(2001K10-G4)and Scientific Research Grant of the Second Hospital of Xi'an Jiaotong University(2001YJ-22)
文摘Objective:To explore the expression of matrix metalloproteinase-7 in serous ovarian tumors. Methods: Expression of MMP- 1 in 6 normal ovaries, 12 serous cystadenomas of ovary, 6 borderline cystadenomas of ovary, and 22 serous cystadenocarcinomas of ovary were studied by immunohistoc/temical SP staining. Results: No expression of MMP- 1 was detected in normal ovaries. In most serous ovarian tumors, expression of MMP-7 was detected in both the cytoplasm of tumor cells and stroma, although it was reported in other tumors that MMP- 7 was mainly expressed in the cytoplasm of tumor cells. The expression level of MMP-7 in the cytoplasm of tumor cells was statistically insignificant between serous cystadenomas of ovary, borderline cystadenomas of ovary, and serous cystadenocarcinomas of ovary. But in the stroma, the expression level of MMP-7 in borderline cystadenomas of ovary and serous cystadenocarcinomas of ovary was significantly higher than that in serous cystadenomas of ovary (P<0. 05). In borderline cystadenomas and serous cystadenocarcinomas of ovary, expression of MMP-7 could also be detected in the nuclei of some tumor cells. Conclusion: MMP-7 may play an important role in the progression of serous ovarian tumors.
文摘BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2023MC168the National Natural Science Foundation of China,No.31670989the Key R&D Program of Shandong Province,No.2019GSF107037(all to CS).
文摘Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.
文摘目的:探讨子痫前期(PE)患者血清和胎盘中的肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-7(MMP-7)的表达水平。方法:选取2021年11月—2023年8月扬州大学临床医学院妇产科收治的86例PE患者,分为早发型PE(n=33)和晚发型PE(n=53),另外选取健康孕妇(n=45)作为对照。检测所有纳入患者血清及胎盘组织中的TNF-α、MMP-1和MMP-7水平。结果:早发型PE患者(34.71±1.35周vs 40.43±0.70周)及晚发型PE患者(38.43±0.60周vs 40.43±0.70周)的孕周明显小于对照组(均P<0.05);早发型PE患者血清中TNF-α(507.92±28.99 ng/L vs 478.50±41.15 ng/L)、MMP-1(1156.67±158.07μg/L vs 1037.59±163.10μg/L)和MMP-7(211.00±18.64μg/L vs 196.32±19.87μg/L)的表达较晚发型PE患者显著增加(均P<0.05),晚发型PE患者血清中TNF-α(478.50±41.15 ng/L vs 446.90±41.52 ng/L)、MMP-1(1037.59±163.10μg/L vs 840.78±174.43μg/L)和MMP-7(196.32±19.87μg/L vs 166.01±15.09μg/L)的表达较对照组显著增加(均P<0.05);免疫组化结果显示,早发型PE患者胎盘组织中TNF-α、MMP-1和MMP-7表达水平较晚发型PE及对照组明显升高(均P<0.05)。结论:早发型PE患者及晚发型PE患者的TNF-α、MMP-1和MMP-7表达明显增加,这可能在PE的发生发展中起到重要作用。
