AIM:To investigate cell cycle proteins in chronic hepatitis C virus infection in order to analyze their role in the process of hepatocyte transformation and to characterize their prognostic properties. METHODS:Subject...AIM:To investigate cell cycle proteins in chronic hepatitis C virus infection in order to analyze their role in the process of hepatocyte transformation and to characterize their prognostic properties. METHODS:Subjects of the current study included 50 cases of chronic hepatitis C(CHC) without cirrhosis,30 cases of CHC with liver cirrhosis(LC) ,and 30 cases of hepatitis C-related hepatocellular carcinoma(HCC) admitted to the Department of Hepato-Gastroenterology,Theodor Bilharz Research Institute(TBRI) ,Giza,Egypt.Fifteen wedge liver biopsies,taken during laparoscopic cholecystectomy,were also included as normal controls.Laboratory investigations including urine and stool analysis,liver function tests and prothrombin concentration;serologic markers for viral hepatitis and ultrasonography were done for all cases of the study together with immunohistochemical analysis using primary antibodies against Cyclin D1,Cyclin E,p21,p27 and Rb/p105 proteins. RESULTS:Normal wedge liver biopsies didn't express Cyclin E or Rb/p105 immunostaining but show positive staining for Cyclin D1,p21 and p27.Cyclin D1 expressed nuclear staining that was sequentially increased from CHC to LC(P<0.01) to HCC(P<0.001) cases;meanwhile,Cyclin E revealed nuclear positivity only in the case of HCCs patients that was directly correlated to Rb/p105 immuno-reactivity.The expression of p21 and p27 was significantly increased in CHC and LC cases compared to normal controls and HCCs with no significant difference between well-and poorlydifferentiated tumors.p21 showed only a nuclear pattern of staining,while,p27 presented with either cytoplasmic and/or nuclear reactivity in all studied cases.Correlation analysis revealed a direct relation between Cyclin D1 and p21 in CHC cases(P<0.001) ,between Cyclin D1 and Cyclin E in HCCs(P<0.01);however,an inverserelationship was detected between Cyclin D1 and p21 or p27(P<0.001) and between p21 and Rb/p105(P<0.05) in HCCs. CONCLUSION:Upregulation of Cyclin D1 in CHC plays a vital role in the development and differentiation of HCC;while,Cyclin E may be a useful marker for monitoring tumor behavior.p21 and p27 can be used as predictive markers for HCC.Furthermore,higher expression of Rb/p105 as well as inverse relation with p21 and histologic grades suggests its important role in hepatic carcinogenesis.展开更多
Design Approach and Spacecraft EMI Test Methodology for High Power Communication Spacecraft
摘要：针对星载高功率发电设备与其他通信有效载荷在同一平台上的干扰问题,提出了用于现代通信航天器的EMC设计和测试方法。该方法现...Design Approach and Spacecraft EMI Test Methodology for High Power Communication Spacecraft
摘要：针对星载高功率发电设备与其他通信有效载荷在同一平台上的干扰问题,提出了用于现代通信航天器的EMC设计和测试方法。该方法现已在类似的卫星设计中成功应用。展开更多
Background Recombinant human endostatin （rh-endostatin, Endostar） has been proved to be an inhibitor of angiogenesis. Docetaxel has been also considered as a common chemotherapeutic agent with inhibition of angiogen...Background Recombinant human endostatin （rh-endostatin, Endostar） has been proved to be an inhibitor of angiogenesis. Docetaxel has been also considered as a common chemotherapeutic agent with inhibition of angiogenesis of malignancies. However, their function has been seldom compared and a best synergism protocol is not determined. This study aimed to compare the effects of two drugs, investigate their combined impact on human umbilical vein endothelial cells （HUVECs）, a molecular basis and find ideal protocols to inhibit endothelial cell proliferation. Methods HUVECs on confluent growth or activated by vascular endothelial growth factor （VEGF） were treated by rh-endostatin or/and docetaxel at respective gradient concentration in following operations as cell proliferation determined by MTT assay, cell cycle distribution, apoptosis and markers of CD146, CD62E and CD105 detected by flow cytometery, the structure of the channel formed by HUVECs measured by tube formation count. Results Rh-endostatin exhibited time dependent inhibition of proliferation while docetaxel showed both time and dose dependent inhibition. HUVECs accumulated in G0-G1 with decreased numbers of cells in G2 after a single treatment of rh-endostatin or that followed by docetaxel treatment. Cells accumulated in G2 after both a single docetaxel and simultaneous administration. Both the number of cells in Go-G1 and apoptotic cells were increased by docetaxel followed by rh-endostatin treatment. The number of non-apoptotic cells at Go-G1 was increased by first administering rh-endostatin then docetaxet. Sequential treatment of docetaxel followed by rh-endostatin resulted in the greatest increase in apoptosis （34.7%） and the second highest apoptosis was seen with simultaneous administration （18.2%）. Expression of CD146 and CD105 on confluent HUVECs was reduced at certain doses of rh-endostatin and/or docetaxel. However, rh-endostatin reduced CD105 without any apparent impact on either CD146 or CD62E expression, whereas these, markers were down-regulated by docetaxel after pre-activation by VEGF. Rh-endostatin treatment maintained tube-like structures for a limited time. In contrast, docetaxel swiftly reduced tube formation. Simultaneous treatment, or docetaxel followed by rh-endostatin, exhibited a stronger inhibition on tube formation than either agent alone. Conclusions Both rh-endostatin and docetaxel can inhibit HUVEC proliferation while the high apoptotic rate after combined administration was probably owing to different sequent administration by docetaxel followed by rh-endostatin or simultaneous treatment. Both proliferation and adhesion molecules on HUVECs of confluent growth are down-regulated by the two drugs. The rh-endostatin decreased proliferation markers, but only slightly modified adhesion molecules, while both markers were down-regulated by docetaxel on HUVECs activated by VEGF. Rh-endostatin could maintain adhesion of HUVECs at first then induce cells apoptosis to damage tube formation. We hypothesize that it could lead to vascular normalization in short time. In contrast, docetaxel can suppress HUVEC proliferation, adhesion, and reduced tube formation swiftly due to its cytotoxicity. Combined treatments can induce a synergistic inhibition of tube formation.展开更多
基金Supported by Theodor Bilharz Research Institute(Grant# 74D) in collaboration with the American University of Cairo
文摘AIM:To investigate cell cycle proteins in chronic hepatitis C virus infection in order to analyze their role in the process of hepatocyte transformation and to characterize their prognostic properties. METHODS:Subjects of the current study included 50 cases of chronic hepatitis C(CHC) without cirrhosis,30 cases of CHC with liver cirrhosis(LC) ,and 30 cases of hepatitis C-related hepatocellular carcinoma(HCC) admitted to the Department of Hepato-Gastroenterology,Theodor Bilharz Research Institute(TBRI) ,Giza,Egypt.Fifteen wedge liver biopsies,taken during laparoscopic cholecystectomy,were also included as normal controls.Laboratory investigations including urine and stool analysis,liver function tests and prothrombin concentration;serologic markers for viral hepatitis and ultrasonography were done for all cases of the study together with immunohistochemical analysis using primary antibodies against Cyclin D1,Cyclin E,p21,p27 and Rb/p105 proteins. RESULTS:Normal wedge liver biopsies didn't express Cyclin E or Rb/p105 immunostaining but show positive staining for Cyclin D1,p21 and p27.Cyclin D1 expressed nuclear staining that was sequentially increased from CHC to LC(P<0.01) to HCC(P<0.001) cases;meanwhile,Cyclin E revealed nuclear positivity only in the case of HCCs patients that was directly correlated to Rb/p105 immuno-reactivity.The expression of p21 and p27 was significantly increased in CHC and LC cases compared to normal controls and HCCs with no significant difference between well-and poorlydifferentiated tumors.p21 showed only a nuclear pattern of staining,while,p27 presented with either cytoplasmic and/or nuclear reactivity in all studied cases.Correlation analysis revealed a direct relation between Cyclin D1 and p21 in CHC cases(P<0.001) ,between Cyclin D1 and Cyclin E in HCCs(P<0.01);however,an inverserelationship was detected between Cyclin D1 and p21 or p27(P<0.001) and between p21 and Rb/p105(P<0.05) in HCCs. CONCLUSION:Upregulation of Cyclin D1 in CHC plays a vital role in the development and differentiation of HCC;while,Cyclin E may be a useful marker for monitoring tumor behavior.p21 and p27 can be used as predictive markers for HCC.Furthermore,higher expression of Rb/p105 as well as inverse relation with p21 and histologic grades suggests its important role in hepatic carcinogenesis.
文摘Design Approach and Spacecraft EMI Test Methodology for High Power Communication Spacecraft
摘要：针对星载高功率发电设备与其他通信有效载荷在同一平台上的干扰问题,提出了用于现代通信航天器的EMC设计和测试方法。该方法现已在类似的卫星设计中成功应用。
文摘Background Recombinant human endostatin （rh-endostatin, Endostar） has been proved to be an inhibitor of angiogenesis. Docetaxel has been also considered as a common chemotherapeutic agent with inhibition of angiogenesis of malignancies. However, their function has been seldom compared and a best synergism protocol is not determined. This study aimed to compare the effects of two drugs, investigate their combined impact on human umbilical vein endothelial cells （HUVECs）, a molecular basis and find ideal protocols to inhibit endothelial cell proliferation. Methods HUVECs on confluent growth or activated by vascular endothelial growth factor （VEGF） were treated by rh-endostatin or/and docetaxel at respective gradient concentration in following operations as cell proliferation determined by MTT assay, cell cycle distribution, apoptosis and markers of CD146, CD62E and CD105 detected by flow cytometery, the structure of the channel formed by HUVECs measured by tube formation count. Results Rh-endostatin exhibited time dependent inhibition of proliferation while docetaxel showed both time and dose dependent inhibition. HUVECs accumulated in G0-G1 with decreased numbers of cells in G2 after a single treatment of rh-endostatin or that followed by docetaxel treatment. Cells accumulated in G2 after both a single docetaxel and simultaneous administration. Both the number of cells in Go-G1 and apoptotic cells were increased by docetaxel followed by rh-endostatin treatment. The number of non-apoptotic cells at Go-G1 was increased by first administering rh-endostatin then docetaxet. Sequential treatment of docetaxel followed by rh-endostatin resulted in the greatest increase in apoptosis （34.7%） and the second highest apoptosis was seen with simultaneous administration （18.2%）. Expression of CD146 and CD105 on confluent HUVECs was reduced at certain doses of rh-endostatin and/or docetaxel. However, rh-endostatin reduced CD105 without any apparent impact on either CD146 or CD62E expression, whereas these, markers were down-regulated by docetaxel after pre-activation by VEGF. Rh-endostatin treatment maintained tube-like structures for a limited time. In contrast, docetaxel swiftly reduced tube formation. Simultaneous treatment, or docetaxel followed by rh-endostatin, exhibited a stronger inhibition on tube formation than either agent alone. Conclusions Both rh-endostatin and docetaxel can inhibit HUVEC proliferation while the high apoptotic rate after combined administration was probably owing to different sequent administration by docetaxel followed by rh-endostatin or simultaneous treatment. Both proliferation and adhesion molecules on HUVECs of confluent growth are down-regulated by the two drugs. The rh-endostatin decreased proliferation markers, but only slightly modified adhesion molecules, while both markers were down-regulated by docetaxel on HUVECs activated by VEGF. Rh-endostatin could maintain adhesion of HUVECs at first then induce cells apoptosis to damage tube formation. We hypothesize that it could lead to vascular normalization in short time. In contrast, docetaxel can suppress HUVEC proliferation, adhesion, and reduced tube formation swiftly due to its cytotoxicity. Combined treatments can induce a synergistic inhibition of tube formation.
