AIM: To investigate the mRNA expressions of bFGF and MMP-9 in gastric carcinomas so as to reveal their correlations with tumor microvascular density (MVD), invasion, metastasis, and prognosis.METHODS: In situ hybridiz...AIM: To investigate the mRNA expressions of bFGF and MMP-9 in gastric carcinomas so as to reveal their correlations with tumor microvascular density (MVD), invasion, metastasis, and prognosis.METHODS: In situ hybridization and immunohistochemical techniques were used to detect the expressions of bFGFmRNA and MMP-9mRNA and the proteins of CD34 in 105 specimens of gastric carcinomas.RESULTS: In situ hybridization study showed that positive rates of bFGF mRNA and MMP-9mRNA expressions were 60.95% and 59.19%; the mean MVD was 46.09±11.52 and 43.75±13.41, respectively in piece/0.72 mm2 in tumors with bFGFmRNA and MMP-9mRNA positive expressions,which were significantly higher than those with negative expression (29.41±12.47; 33.45±13.92 piece/0.72 mm2,respectively). The positive expression rates of bFGFmRNA and MMP-9mRNA were correlated to the tumor invasion depth (rs = 0.211, P= 0.031; rs = 0.335, P= 0.001), growing pattern (rs= 0.324, P= 0.001; rs= 0.267, P= 0.006), vessel invasion (rs = 0.579, P = 0.001; rs = 0.209, P = 0.032),lymph node metastasis (rs = 0.405, P = 0.001; rs= 0.343,P = 0.001) and distant metastasis (rs= 0.474, P = 0.001;rs = 0.468, P = 0.001), but not correlated to tumortype (rs= 0.134, P= 0.173; rs= 0.103, P= 0.145) anddifferentiations (rs = 0.096, P= 0.332; rs = 0.102, P= 0.298).The mean MVD was much higher in the tumors withinfiltrating growth at stage T3-T4, with vessel invasion, lymph node metastasis and distant metastasis than those with expanding growth type (t = 10.105, P= 0.001) at stage T1-T2 (t = 5.961, P = 0.001), with non-vessel invasion (t= 7.394, P= 0.001), non-lymph node metastasis (t= 3.819, P= 0.01) and non-distant metastasis (t= 10.578, P = 0.001). Positive correlation was observed between MVD and the expressions of bFGFmRNA and MMP-9mRNA(t= 3.207, P= 0.002; t= 7.035, P= 0.001, respectively). The mean survival time and 5-year survival rate werelower in cases with MVD over 39.5 and the positive expressions of bFGFmRNA and MMP-9mRNA than those with MVD less than 39.5 and the negative expressions of bFGFmRNA and MMP-9mRNA.CONCLUSION: bFGF and MMP-9 promote the angiogenesis of the gastric cancers. Detection of the expressions of bF-GF and MMP-9 can serve as a useful index to determine the angiogenesis, invasion, metastasis, and prognosis of gastric cancers.展开更多
AIM: To investigate the relationship between the staging by endoscopic ultrasonography (EUS) and the expression of carcinoma metastasis associated gene in the patients with gastric carcinoma. METHODS: Sixty-three pati...AIM: To investigate the relationship between the staging by endoscopic ultrasonography (EUS) and the expression of carcinoma metastasis associated gene in the patients with gastric carcinoma. METHODS: Sixty-three patients with gastric cancer were diagnosed by electric gastroscopy and EUS. The preoperative staging of gastric cancer was measured by EUS and compared with pathologic staging and MMP-9 expression. Peripheral serum level of MMP-9 was measured with enzyme-linked immunosorbent assay (ELISA), while the expression of MMP-9 protein was tested with immunohistochemistry and hybridization in situ in the gastric carcinoma tissues. RESULTS: The total accuracy of EUS in estimating invasive depth of gastric cancer was 80.95%, while that in estimating lymphatic metastasis was 73.02%. Serum MMP-9 levels were consistent with the expression of MMP-9 protein and MMP-9 mRNA in tissue, a result closely correlated with invasive degree, staging with EUS and lymphatic metastasis in gastric cancer (P < 0.05). The total accuracy of estimating invasive depth in gastric cancer was 95.22% using both EUS and MMP-9. CONCLUSION: The MMP-9 level of preoperative serum presents the reference value for preoperative staging by EUS in the patients with gastric cancer. When serum MMP-9 level in gastric cancer is significantly high, physicians should pay closer attention to the metastasis which reaches the serosa or beyond. Combining EUS and MMP-9 improves the accuracy in deciding the invasion and metastasis in the patients with gastric carcinoma.展开更多
The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of...The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia （HGPIN） to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 （MMP-26） promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 （TIMP-4） is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher （p〈0.0001） MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer （p〈0.001 for each） in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.展开更多
AIM： To investigate DNA ploidy and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma and to explore the mechanism of invasion and metastasis of gastric carcinoma. METHODS： Immunohistochemical methods ...AIM： To investigate DNA ploidy and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma and to explore the mechanism of invasion and metastasis of gastric carcinoma. METHODS： Immunohistochemical methods were used to detect the expressions of MMP-9, TIMP-2, and E-cadherin in 156 cases, including 99 cases of gastric carcinoma, 16 cases of adjacent noncancerous mucosa, 16 cases of distant metastases and 25 cases of metastatic lymph node （LN） from gastric carcinoma. Flow cytometry DNA ploidy and S-phase fraction （SPF） analysis were performed on 57 cases, including 47 cases of gastric cancer, 6 cases of adjacent noncancerous mucosa, and 4 cases of distant metastatic cancer. RESULTS： The expression of MMP-9 was significantly correlated with Lauren＇s classification, Borrmann＇s classification, LN metastasis, tumor metastasis, and TNM stage, as well as depth of invasion （all P〈0.05）. The positive rate was lower in noncarcinoma than in carcinoma （31.3% vs 66.7%, P〈0.01）. The expression of TIMP-2 was significantly correlated with Borrmann＇s classification, LN metastasis, and the depth of invasion （all P〈0.05）. The expression of E-cadherin was significantly correlated with differentiation, Lauren＇s classification, Borrmann＇s classification, and LN metastasis, as well as the depth of invasion （P〈0.01 or P〈0.05）. E-cadherin was less expressed in carcinoma than in noncarcinoma （42.4% vs 87.5%, P〈0.01）. There was a positive correlation between MMP-9and TIMP-2 and a negative correlation between MMP-9 and E-cadherin, but no correlation between TIMP-2 and E-cadherin. Also there was a positive correlation between DNA aneuploid rate and differentiation and LN metastasis. SPF that was higher than 15% was positively correlated with tumor size, differentiation and LN metastasis. And there was a significant difference between carcinoma and noncarcinoma in DNA aneuploid rate and SPF. CONCLUSION： With tumor progression and development of heterogeneity, the abnormal expressions of MMP-9, TIMP-2, and E-cadherin or DNA aneuploid rate or high SPF gradually increases, suggesting that they play a crucial role in gastric carcinoma progression. 2005 The WJG Press and Elsevier Inc. All rights reserved展开更多
AIM: To investigate the changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer. METHODS: One hundred and seventy-seven gastric cancer patients with lymph node and/or distal m...AIM: To investigate the changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer. METHODS: One hundred and seventy-seven gastric cancer patients with lymph node and/or distal metastasis between 1997 and 2001 were reviewed. Differences in histology of the primary and metastatic gastric cancer were assessed. MMP-2 and nm23-H1 immunoreactivity was compared in 44 patients with tumor infiltration to the serosa layer. RESULTS: Poorly and moderately differentiated metastatic gastric cancer was found in 88.7% (157/177) and primary gastric cancer in 75.7% (134/177) of the patients. The histological type of metastatic gastric cancer that was not completely in accordance with the preponderant histology of primary gastric cancer was observed in 25 patients (14.1%). MMP-2 immunoreactivity in metastatic gastric cancer was significantly stronger than that in primary gastric cancer, while nm23-H1 immunoreactivity showed no difference in primary and metastatic gastric cancer. CONCLUSION: Metastatic gastric cancer presents more aggressive histological morphology and higher MMP-2 immunoreactivity than primary gastric cancer. This heterogeneity may elicit a possible mechanism of gastric cancer metastasis.展开更多
Objective To study the expressions of MMP-2 and TIMP-2 mRNA on cultured rat mesangial cells (MsC) and in human diseased glomeruli, and to explore their significance in the development of glomerulosclerosis. Methods Th...Objective To study the expressions of MMP-2 and TIMP-2 mRNA on cultured rat mesangial cells (MsC) and in human diseased glomeruli, and to explore their significance in the development of glomerulosclerosis. Methods The expressions of MMP-2, TIMP-2, and Col ⅣmRNA on cultured rat MsC stimulated by IL-1 or/and TGF-β1were investigated through Northern blot analysis. The levels of MMP-2 and TIMP-2 mRNA expressions and immunoreacti-vity of PCNA and Col Ⅳin human diseased glomeruli from renal biopsies of lupus nephritis (LN) patients were examined by insituhybridization and immunohistochemistry, respectively. Results The levels of MMP-2, TIMP-2, and Col ⅣmRNA expressions were markedly increased on cultured rat MsC stimulated by IL-1 or/and TGF-β1. Meanwhile, upregulation of MMP-2 and TIMP-2 mRNA expressions was confirmed in diseased glomeruli from patients with various subtypes of LN, and was closely related to the positive cell number of PCNA presentation and deposition of Col Ⅳin glomeruli. Conclusion The results suggest that the over-expressions of MMP-2 and TIMP-2 mRNA on glomerular cells might play a critical role in the development of glomerulosclerosis.展开更多
Objective:To detect the expression of RECK gene in the highly and low metastatic cell sublines of human osteosarcoma cell HOS and explore its possible roles on the occurrence and metastasis of osteosarcoma.Methods:RT-...Objective:To detect the expression of RECK gene in the highly and low metastatic cell sublines of human osteosarcoma cell HOS and explore its possible roles on the occurrence and metastasis of osteosarcoma.Methods:RT-PCR, gelatin zymography, and matrigel invasion assay were respectively used to evaluate the endogenous expression of RECK mRNA, MMP-2 activation ratio and invasive capacity in the two osteosarcoma cell sublines.Results:The highly metastatic cell group expressed significantly lower mRNA level of RECK than the low metastatic cell group(P < 0.05), but showed higher MMP-2 activation ratio and invasive capacity(P < 0.05 and P < 0.01, respectively).Conclusion:The abnormal low expression of RECK may participate in osteosarcoma invasion and metastasis, and may be a new therapeutic target for osteosarcoma.展开更多
文摘AIM: To investigate the mRNA expressions of bFGF and MMP-9 in gastric carcinomas so as to reveal their correlations with tumor microvascular density (MVD), invasion, metastasis, and prognosis.METHODS: In situ hybridization and immunohistochemical techniques were used to detect the expressions of bFGFmRNA and MMP-9mRNA and the proteins of CD34 in 105 specimens of gastric carcinomas.RESULTS: In situ hybridization study showed that positive rates of bFGF mRNA and MMP-9mRNA expressions were 60.95% and 59.19%; the mean MVD was 46.09±11.52 and 43.75±13.41, respectively in piece/0.72 mm2 in tumors with bFGFmRNA and MMP-9mRNA positive expressions,which were significantly higher than those with negative expression (29.41±12.47; 33.45±13.92 piece/0.72 mm2,respectively). The positive expression rates of bFGFmRNA and MMP-9mRNA were correlated to the tumor invasion depth (rs = 0.211, P= 0.031; rs = 0.335, P= 0.001), growing pattern (rs= 0.324, P= 0.001; rs= 0.267, P= 0.006), vessel invasion (rs = 0.579, P = 0.001; rs = 0.209, P = 0.032),lymph node metastasis (rs = 0.405, P = 0.001; rs= 0.343,P = 0.001) and distant metastasis (rs= 0.474, P = 0.001;rs = 0.468, P = 0.001), but not correlated to tumortype (rs= 0.134, P= 0.173; rs= 0.103, P= 0.145) anddifferentiations (rs = 0.096, P= 0.332; rs = 0.102, P= 0.298).The mean MVD was much higher in the tumors withinfiltrating growth at stage T3-T4, with vessel invasion, lymph node metastasis and distant metastasis than those with expanding growth type (t = 10.105, P= 0.001) at stage T1-T2 (t = 5.961, P = 0.001), with non-vessel invasion (t= 7.394, P= 0.001), non-lymph node metastasis (t= 3.819, P= 0.01) and non-distant metastasis (t= 10.578, P = 0.001). Positive correlation was observed between MVD and the expressions of bFGFmRNA and MMP-9mRNA(t= 3.207, P= 0.002; t= 7.035, P= 0.001, respectively). The mean survival time and 5-year survival rate werelower in cases with MVD over 39.5 and the positive expressions of bFGFmRNA and MMP-9mRNA than those with MVD less than 39.5 and the negative expressions of bFGFmRNA and MMP-9mRNA.CONCLUSION: bFGF and MMP-9 promote the angiogenesis of the gastric cancers. Detection of the expressions of bF-GF and MMP-9 can serve as a useful index to determine the angiogenesis, invasion, metastasis, and prognosis of gastric cancers.
文摘AIM: To investigate the relationship between the staging by endoscopic ultrasonography (EUS) and the expression of carcinoma metastasis associated gene in the patients with gastric carcinoma. METHODS: Sixty-three patients with gastric cancer were diagnosed by electric gastroscopy and EUS. The preoperative staging of gastric cancer was measured by EUS and compared with pathologic staging and MMP-9 expression. Peripheral serum level of MMP-9 was measured with enzyme-linked immunosorbent assay (ELISA), while the expression of MMP-9 protein was tested with immunohistochemistry and hybridization in situ in the gastric carcinoma tissues. RESULTS: The total accuracy of EUS in estimating invasive depth of gastric cancer was 80.95%, while that in estimating lymphatic metastasis was 73.02%. Serum MMP-9 levels were consistent with the expression of MMP-9 protein and MMP-9 mRNA in tissue, a result closely correlated with invasive degree, staging with EUS and lymphatic metastasis in gastric cancer (P < 0.05). The total accuracy of estimating invasive depth in gastric cancer was 95.22% using both EUS and MMP-9. CONCLUSION: The MMP-9 level of preoperative serum presents the reference value for preoperative staging by EUS in the patients with gastric cancer. When serum MMP-9 level in gastric cancer is significantly high, physicians should pay closer attention to the metastasis which reaches the serosa or beyond. Combining EUS and MMP-9 improves the accuracy in deciding the invasion and metastasis in the patients with gastric carcinoma.
文摘The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia （HGPIN） to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 （MMP-26） promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 （TIMP-4） is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher （p〈0.0001） MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer （p〈0.001 for each） in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.
基金Supported by the Bureau of Education of Shandong Province, No. 03K02
文摘AIM： To investigate DNA ploidy and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma and to explore the mechanism of invasion and metastasis of gastric carcinoma. METHODS： Immunohistochemical methods were used to detect the expressions of MMP-9, TIMP-2, and E-cadherin in 156 cases, including 99 cases of gastric carcinoma, 16 cases of adjacent noncancerous mucosa, 16 cases of distant metastases and 25 cases of metastatic lymph node （LN） from gastric carcinoma. Flow cytometry DNA ploidy and S-phase fraction （SPF） analysis were performed on 57 cases, including 47 cases of gastric cancer, 6 cases of adjacent noncancerous mucosa, and 4 cases of distant metastatic cancer. RESULTS： The expression of MMP-9 was significantly correlated with Lauren＇s classification, Borrmann＇s classification, LN metastasis, tumor metastasis, and TNM stage, as well as depth of invasion （all P〈0.05）. The positive rate was lower in noncarcinoma than in carcinoma （31.3% vs 66.7%, P〈0.01）. The expression of TIMP-2 was significantly correlated with Borrmann＇s classification, LN metastasis, and the depth of invasion （all P〈0.05）. The expression of E-cadherin was significantly correlated with differentiation, Lauren＇s classification, Borrmann＇s classification, and LN metastasis, as well as the depth of invasion （P〈0.01 or P〈0.05）. E-cadherin was less expressed in carcinoma than in noncarcinoma （42.4% vs 87.5%, P〈0.01）. There was a positive correlation between MMP-9and TIMP-2 and a negative correlation between MMP-9 and E-cadherin, but no correlation between TIMP-2 and E-cadherin. Also there was a positive correlation between DNA aneuploid rate and differentiation and LN metastasis. SPF that was higher than 15% was positively correlated with tumor size, differentiation and LN metastasis. And there was a significant difference between carcinoma and noncarcinoma in DNA aneuploid rate and SPF. CONCLUSION： With tumor progression and development of heterogeneity, the abnormal expressions of MMP-9, TIMP-2, and E-cadherin or DNA aneuploid rate or high SPF gradually increases, suggesting that they play a crucial role in gastric carcinoma progression. 2005 The WJG Press and Elsevier Inc. All rights reserved
文摘AIM: To investigate the changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer. METHODS: One hundred and seventy-seven gastric cancer patients with lymph node and/or distal metastasis between 1997 and 2001 were reviewed. Differences in histology of the primary and metastatic gastric cancer were assessed. MMP-2 and nm23-H1 immunoreactivity was compared in 44 patients with tumor infiltration to the serosa layer. RESULTS: Poorly and moderately differentiated metastatic gastric cancer was found in 88.7% (157/177) and primary gastric cancer in 75.7% (134/177) of the patients. The histological type of metastatic gastric cancer that was not completely in accordance with the preponderant histology of primary gastric cancer was observed in 25 patients (14.1%). MMP-2 immunoreactivity in metastatic gastric cancer was significantly stronger than that in primary gastric cancer, while nm23-H1 immunoreactivity showed no difference in primary and metastatic gastric cancer. CONCLUSION: Metastatic gastric cancer presents more aggressive histological morphology and higher MMP-2 immunoreactivity than primary gastric cancer. This heterogeneity may elicit a possible mechanism of gastric cancer metastasis.
基金Supported by Shanghai Municipal Science and Technology Develop-ment Funds (01JC14018).
文摘Objective To study the expressions of MMP-2 and TIMP-2 mRNA on cultured rat mesangial cells (MsC) and in human diseased glomeruli, and to explore their significance in the development of glomerulosclerosis. Methods The expressions of MMP-2, TIMP-2, and Col ⅣmRNA on cultured rat MsC stimulated by IL-1 or/and TGF-β1were investigated through Northern blot analysis. The levels of MMP-2 and TIMP-2 mRNA expressions and immunoreacti-vity of PCNA and Col Ⅳin human diseased glomeruli from renal biopsies of lupus nephritis (LN) patients were examined by insituhybridization and immunohistochemistry, respectively. Results The levels of MMP-2, TIMP-2, and Col ⅣmRNA expressions were markedly increased on cultured rat MsC stimulated by IL-1 or/and TGF-β1. Meanwhile, upregulation of MMP-2 and TIMP-2 mRNA expressions was confirmed in diseased glomeruli from patients with various subtypes of LN, and was closely related to the positive cell number of PCNA presentation and deposition of Col Ⅳin glomeruli. Conclusion The results suggest that the over-expressions of MMP-2 and TIMP-2 mRNA on glomerular cells might play a critical role in the development of glomerulosclerosis.
文摘Objective:To detect the expression of RECK gene in the highly and low metastatic cell sublines of human osteosarcoma cell HOS and explore its possible roles on the occurrence and metastasis of osteosarcoma.Methods:RT-PCR, gelatin zymography, and matrigel invasion assay were respectively used to evaluate the endogenous expression of RECK mRNA, MMP-2 activation ratio and invasive capacity in the two osteosarcoma cell sublines.Results:The highly metastatic cell group expressed significantly lower mRNA level of RECK than the low metastatic cell group(P < 0.05), but showed higher MMP-2 activation ratio and invasive capacity(P < 0.05 and P < 0.01, respectively).Conclusion:The abnormal low expression of RECK may participate in osteosarcoma invasion and metastasis, and may be a new therapeutic target for osteosarcoma.
