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
The action mechanism of matrix metalloproteinases-2 （MMP-2） and tissue inhibitor of metalloproteinases-2 （TIMP-2） in the genesis, development and degeneration of haemangioma was investigated by detecting their exp...The action mechanism of matrix metalloproteinases-2 （MMP-2） and tissue inhibitor of metalloproteinases-2 （TIMP-2） in the genesis, development and degeneration of haemangioma was investigated by detecting their expression in the tissue of haemangioma in different phases by using the immunohistochemistry. Fifty paraffin-embedded specimens of skin capillary haemangioma were collected, which were documented in the Department of Pathology, Renmin Hospital of Wuhan University from 2000 to 2006. All samples were stained by regular HE method, and proliferative cell nuclear antigen （PCNA） was tested by immunohistochemical S-P method. The samples were classified according to the Mulliken criteria and the expression pattern of PCNA. Immunohistochemical S-P method was ap- plied to detect the expression of MMP-2 and TIMP-2 in proliferative and degenerative phases of cutaneous capillary haemangioma, and in normal skin tissues. In combination with the detection of the expression of factor Ⅷ-related antigen, it was verified that in haemangioma tissues, the cells expressing MMP-2 and TIMP-2 were vascular endothelial cells. The MMP-2 and TIMP-2 expression was quantitatively analyzed by image analysis system （HPIAS-1000）, and one-way ANOVA（107） and SNK（q） test were done to analyze average absorbance （A） and positive area rate of immunohistochemically positive particles by using SPSS11.5. The results showed： （1） Among 50 samples of haemangioma, there were 26 proliferative haemangiomas, and 24 degenerative haemangiomas, respectively; （2） The expression of MMP-2 was weak in normal vascular endothelial cells, cytoplasm of connective tissues and extracellular matrix around blood vessels. The expression of MMP-2 in proliferative group was significantly higher than in degenerative group and control group （normal skin） （P〈0.05）, but there was no statistically significant difference between the latter two groups; （3） TIMP-2 was highly expressed in normal tissues, degenerative vascular endothelial cells, cytoplasm of connective tissues and extracellular matrix around blood vessels. The expression level of TIMP-2 in proliferative phase was significantly lower than in degenerative phase （P〈0.05）, and the expression of TIMP-2 in proliferative phase was significantly different from that in degenerative phase and normal tissues （P〈0.05）. It was concluded that in proliferative phase of haemangioma, MMP-2 may promote over-proliferation of endothelial cells of haemangioma, and in degenerative phase, TIMP-2 can inhibit the proliferation of endothelial cells of haemangioma. The two substances play important roles in the genesis, development and degeneration of haemangiomas.展开更多
In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cereb...In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy （control group）. Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy. The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations. Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed. These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-I, resulting in a relative overabundance of matrix metalloproteinase-9, might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations.展开更多
In this study, genes of two distinct tissue inhibitors of metalloproteinases-2 (TIMP-2) from Japanese puffer fishFugu rubripes, Fugu TIMP-2a and TIMP-2b, were cloned. The open reading frames of Fugu TIMP-2a and TIMP-2...In this study, genes of two distinct tissue inhibitors of metalloproteinases-2 (TIMP-2) from Japanese puffer fishFugu rubripes, Fugu TIMP-2a and TIMP-2b, were cloned. The open reading frames of Fugu TIMP-2a and TIMP-2b cDNAsare composed of 660 and 657 nucleotides and 220 and 219 amino acids, respectively. Both Fugu TIMP-2s contain 12 cysteineresidues, which might form six disulfide bonds as in other animals’ TIMP-2s. Reverse-transcribed polymerase chain reactionanalysis showed the mRNAs of Fugu TIMP-2a and TIMP-2b to be expressed in some tissues examined with different expres-sion patterns. These findings suggest that the two distinct Fugu TIMP-2s might perform different functions in Fugu tissues.展开更多
目的探讨2型糖尿病(T2DM)患者血清血管生成抑制蛋白-1(VASH-1)、金属蛋白酶组织抑制物1(TIMP-1)与糖尿病视网膜病变的关系。方法选取2020年1月至2021年1月陕西省商洛眼科医院收治的79例T2DM患者作为研究对象。根据眼底荧光血管造影结果...目的探讨2型糖尿病(T2DM)患者血清血管生成抑制蛋白-1(VASH-1)、金属蛋白酶组织抑制物1(TIMP-1)与糖尿病视网膜病变的关系。方法选取2020年1月至2021年1月陕西省商洛眼科医院收治的79例T2DM患者作为研究对象。根据眼底荧光血管造影结果将患者分为无视网膜病变组、视网膜病变组。另选取40例同期健康体检者作为对照组。采用酶联免疫吸附试验检测血清VASH-1、TIMP-1水平。绘制受试者工作特征(ROC)曲线评估血清VASH-1、TIMP-1水平对T2DM患者发生视网膜病变的预测价值。采用多因素Logistic回归分析T2DM患者发生视网膜病变的危险因素。结果无视网膜病变组纳入45例患者、视网膜病变组纳入34例患者。无视网膜病变组与视网膜病变组FPG、2 h PG、HbA1c、UACR水平均高于对照组,且视网膜病变组均高于无视网膜病变组,差异均有统计学意义(P<0.05)。视网膜病变组T2DM病程长于无视网膜病变组,差异有统计学意义(P<0.05)。无视网膜病变组与视网膜病变组血清VASH-1水平均高于对照组,TIMP-1水平均低于对照组,且视网膜病变组血清VASH-1水平高于无视网膜病变组,视网膜病变组血清TIMP-1水平低于无视网膜病变组,差异均有统计学意义(P<0.05)。ROC曲线分析结果显示,血清VASH-1、TIMP-1预测T2DM患者发生视网膜病变的曲线下面积分别为0.807、0.847。多因素Logistic回归分析结果显示,病程长、血清VASH-1高水平、TIMP-1低水平为T2DM患者发生视网膜病变的危险因素(P<0.05)。结论发生视网膜病变的T2DM患者血清VASH-1水平升高、TIMP-1水平降低。血清VASH-1、TIMP-1为T2DM患者发生视网膜病变的影响因素,二者有望作为临床诊治T2DM患者发生视网膜病变的生物标志物。展开更多
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supported by a grant from the National Natural Sciences Foundation of China (No.30872688)
文摘The action mechanism of matrix metalloproteinases-2 （MMP-2） and tissue inhibitor of metalloproteinases-2 （TIMP-2） in the genesis, development and degeneration of haemangioma was investigated by detecting their expression in the tissue of haemangioma in different phases by using the immunohistochemistry. Fifty paraffin-embedded specimens of skin capillary haemangioma were collected, which were documented in the Department of Pathology, Renmin Hospital of Wuhan University from 2000 to 2006. All samples were stained by regular HE method, and proliferative cell nuclear antigen （PCNA） was tested by immunohistochemical S-P method. The samples were classified according to the Mulliken criteria and the expression pattern of PCNA. Immunohistochemical S-P method was ap- plied to detect the expression of MMP-2 and TIMP-2 in proliferative and degenerative phases of cutaneous capillary haemangioma, and in normal skin tissues. In combination with the detection of the expression of factor Ⅷ-related antigen, it was verified that in haemangioma tissues, the cells expressing MMP-2 and TIMP-2 were vascular endothelial cells. The MMP-2 and TIMP-2 expression was quantitatively analyzed by image analysis system （HPIAS-1000）, and one-way ANOVA（107） and SNK（q） test were done to analyze average absorbance （A） and positive area rate of immunohistochemically positive particles by using SPSS11.5. The results showed： （1） Among 50 samples of haemangioma, there were 26 proliferative haemangiomas, and 24 degenerative haemangiomas, respectively; （2） The expression of MMP-2 was weak in normal vascular endothelial cells, cytoplasm of connective tissues and extracellular matrix around blood vessels. The expression of MMP-2 in proliferative group was significantly higher than in degenerative group and control group （normal skin） （P〈0.05）, but there was no statistically significant difference between the latter two groups; （3） TIMP-2 was highly expressed in normal tissues, degenerative vascular endothelial cells, cytoplasm of connective tissues and extracellular matrix around blood vessels. The expression level of TIMP-2 in proliferative phase was significantly lower than in degenerative phase （P〈0.05）, and the expression of TIMP-2 in proliferative phase was significantly different from that in degenerative phase and normal tissues （P〈0.05）. It was concluded that in proliferative phase of haemangioma, MMP-2 may promote over-proliferation of endothelial cells of haemangioma, and in degenerative phase, TIMP-2 can inhibit the proliferation of endothelial cells of haemangioma. The two substances play important roles in the genesis, development and degeneration of haemangiomas.
文摘In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy （control group）. Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy. The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations. Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed. These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-I, resulting in a relative overabundance of matrix metalloproteinase-9, might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations.
基金partially supported by a grant from the Ministry of Education,Culture,Sports,Science and Technology of Japan.
文摘In this study, genes of two distinct tissue inhibitors of metalloproteinases-2 (TIMP-2) from Japanese puffer fishFugu rubripes, Fugu TIMP-2a and TIMP-2b, were cloned. The open reading frames of Fugu TIMP-2a and TIMP-2b cDNAsare composed of 660 and 657 nucleotides and 220 and 219 amino acids, respectively. Both Fugu TIMP-2s contain 12 cysteineresidues, which might form six disulfide bonds as in other animals’ TIMP-2s. Reverse-transcribed polymerase chain reactionanalysis showed the mRNAs of Fugu TIMP-2a and TIMP-2b to be expressed in some tissues examined with different expres-sion patterns. These findings suggest that the two distinct Fugu TIMP-2s might perform different functions in Fugu tissues.
文摘目的探讨2型糖尿病(T2DM)患者血清血管生成抑制蛋白-1(VASH-1)、金属蛋白酶组织抑制物1(TIMP-1)与糖尿病视网膜病变的关系。方法选取2020年1月至2021年1月陕西省商洛眼科医院收治的79例T2DM患者作为研究对象。根据眼底荧光血管造影结果将患者分为无视网膜病变组、视网膜病变组。另选取40例同期健康体检者作为对照组。采用酶联免疫吸附试验检测血清VASH-1、TIMP-1水平。绘制受试者工作特征(ROC)曲线评估血清VASH-1、TIMP-1水平对T2DM患者发生视网膜病变的预测价值。采用多因素Logistic回归分析T2DM患者发生视网膜病变的危险因素。结果无视网膜病变组纳入45例患者、视网膜病变组纳入34例患者。无视网膜病变组与视网膜病变组FPG、2 h PG、HbA1c、UACR水平均高于对照组,且视网膜病变组均高于无视网膜病变组,差异均有统计学意义(P<0.05)。视网膜病变组T2DM病程长于无视网膜病变组,差异有统计学意义(P<0.05)。无视网膜病变组与视网膜病变组血清VASH-1水平均高于对照组,TIMP-1水平均低于对照组,且视网膜病变组血清VASH-1水平高于无视网膜病变组,视网膜病变组血清TIMP-1水平低于无视网膜病变组,差异均有统计学意义(P<0.05)。ROC曲线分析结果显示,血清VASH-1、TIMP-1预测T2DM患者发生视网膜病变的曲线下面积分别为0.807、0.847。多因素Logistic回归分析结果显示,病程长、血清VASH-1高水平、TIMP-1低水平为T2DM患者发生视网膜病变的危险因素(P<0.05)。结论发生视网膜病变的T2DM患者血清VASH-1水平升高、TIMP-1水平降低。血清VASH-1、TIMP-1为T2DM患者发生视网膜病变的影响因素,二者有望作为临床诊治T2DM患者发生视网膜病变的生物标志物。
