AIM:To investigate the relationship between late SV40 factor(LSF)and Notch signaling in the development and progress of hepatocellular carcinoma(HCC).METHODS:Liver cancer tissue specimens from 25 patients were analyze...AIM:To investigate the relationship between late SV40 factor(LSF)and Notch signaling in the development and progress of hepatocellular carcinoma(HCC).METHODS:Liver cancer tissue specimens from 25 patients were analyzed for Notch-1 and LSF expression by immunohistochemistry.The correlation between expression and the biological effects of Notch-1 and LSF were analyzed using genetic and pharmacological strategies in HCC cell lines and human normal cell lines,including hepatic stellate cells(HSC)and human embryonic kidney epithelial cells(HEK).RESULTS:Immunohistochemistry showed that both Notch-1 and LSF were significantly upregulated in HCC samples(76%,19/25,P<0.0001 and 84%,21/25,P<0.0001,respectively)compared with non-cancer samples.Activation of Notch-1 by exogenous transfection of Notch1 intracellular domain increased LSF expression in HSC and HEK cells to levels similar to those seen in HepG2 cells.Furthermore,blocking Notch-1 activation with aγ-secretase inhibitor,DAPT,downregulated LSF expression in HepG2 cells.Additionally,a biological behavior assay showed that forced overexpression of LSF promoted HepG2 cell proliferation and invasion.CONCLUSION:LSF is a key mediator of the Notch signaling pathway,suggesting that it might be a novel therapeutic target for the treatment of HCC.展开更多
The mast cell is an enigmatic cell type whose physiological function has preoccupied large numbers of investigators for decadest. Some have concluded that the absence of mast cells is incompatible with life, at least ...The mast cell is an enigmatic cell type whose physiological function has preoccupied large numbers of investigators for decadest. Some have concluded that the absence of mast cells is incompatible with life, at least in humans, because no human conditions have been documented where these cells are absent from the body. On the other hand, mice harboring specific mutations in certain growth factors, or their receptors, that展开更多
Background： Thermothempy has already been proved effective for the treatment of various tumors, including glioma. This study was performed to determine whether tumor necrosis factor-alpha was involved in the regulati...Background： Thermothempy has already been proved effective for the treatment of various tumors, including glioma. This study was performed to determine whether tumor necrosis factor-alpha was involved in the regulation of this biological process. Methods： RT-PCR and immunocytochemistry were used to investigate the levels of tumor necrosis factor-alpha mRNA and heat shock factor-1 protein, respectively, in glioma cells. Radioimmunoassay was used to dynamically monitor contents of TNF-α in nutrient fluid for C6 cells after hyperthermia treatment. Crystal violet staining method was used to detect glioma invasiveness. Results： The most obvious increase of heat shock factor-1 protein and tumor necrosis factor -alpha mRNA in C6 cells were observed at 30 min and 60 min after hyperthermia, respectively. In addition, the radioactivity of tumor necrosis factor-alpha in C6 cells＇ culture fluid also reached peak at 120 min of hyperthermia. The glioma invasiveness decreases and the concentration of tumor necrosis factor-alpha reached the maximum at 120 min of hyperthermia. Conclusion： Our results showed that the hyperthermia-mediated glioma invasiveness decreases was due to accelerated release of tumor necrosis factor-alpha,which could cause the decreases of glioma invasiveness by promoting the release heat shock factor-1 from neurospongioma cells .展开更多
The native extracellular matrix （ECM） and the cells that comprise human tissues are together engaged in a complex relationship; cells alter the composition and structure of the ECM to regulate the material and biolo...The native extracellular matrix （ECM） and the cells that comprise human tissues are together engaged in a complex relationship; cells alter the composition and structure of the ECM to regulate the material and biologic properties of the surrounding environment while the composition and structure of the ECM modulates cellular processes that maintain healthy tissue and repair diseased tissue. This reciprocal relationship occurs via cell adhesion molecules （CAMs） such as integrins, selectins, cadherins and IgSF adhesion molecules. To study these celI-ECM interactions, researchers use two-dimensional substrates or three-dimensional matrices composed of native proteins or bioactive peptide sequences to study single cell function. While two-dimensional snbstrates provide valuable information about cell-ECM interactions, three-dimensional matrices more closely mimic the native ECM; cells cultured in three-dimensional matrices have demonstrated greater cell movement and increased integrin expression when compared to cells cultured on two-dimensional substrates. In this article we review a number of cellular processes （adhesion, motility, phagocytosis, differentiation and survival） and examine the cell adhesion molecules and ECM proteins （or bioactive peptide sequences） that mediate cell functionality.展开更多
基金Supported by The National Natural Science Foundation of China,No.30470780
文摘AIM:To investigate the relationship between late SV40 factor(LSF)and Notch signaling in the development and progress of hepatocellular carcinoma(HCC).METHODS:Liver cancer tissue specimens from 25 patients were analyzed for Notch-1 and LSF expression by immunohistochemistry.The correlation between expression and the biological effects of Notch-1 and LSF were analyzed using genetic and pharmacological strategies in HCC cell lines and human normal cell lines,including hepatic stellate cells(HSC)and human embryonic kidney epithelial cells(HEK).RESULTS:Immunohistochemistry showed that both Notch-1 and LSF were significantly upregulated in HCC samples(76%,19/25,P<0.0001 and 84%,21/25,P<0.0001,respectively)compared with non-cancer samples.Activation of Notch-1 by exogenous transfection of Notch1 intracellular domain increased LSF expression in HSC and HEK cells to levels similar to those seen in HepG2 cells.Furthermore,blocking Notch-1 activation with aγ-secretase inhibitor,DAPT,downregulated LSF expression in HepG2 cells.Additionally,a biological behavior assay showed that forced overexpression of LSF promoted HepG2 cell proliferation and invasion.CONCLUSION:LSF is a key mediator of the Notch signaling pathway,suggesting that it might be a novel therapeutic target for the treatment of HCC.
基金Supported by the grants from the National Institutes of Health,USA (DK33491 and AT01180) and the Crohn's and Colitis Foundation of America
文摘The mast cell is an enigmatic cell type whose physiological function has preoccupied large numbers of investigators for decadest. Some have concluded that the absence of mast cells is incompatible with life, at least in humans, because no human conditions have been documented where these cells are absent from the body. On the other hand, mice harboring specific mutations in certain growth factors, or their receptors, that
基金Supported by the Scientific Research Foundation of Hebei Provincial Department of Healththe Project of Science and Technology Research andDevelopment Plan of Tangshan City,Hebei Province(NO.20110165,20120144)(10140201A-15)
文摘Background： Thermothempy has already been proved effective for the treatment of various tumors, including glioma. This study was performed to determine whether tumor necrosis factor-alpha was involved in the regulation of this biological process. Methods： RT-PCR and immunocytochemistry were used to investigate the levels of tumor necrosis factor-alpha mRNA and heat shock factor-1 protein, respectively, in glioma cells. Radioimmunoassay was used to dynamically monitor contents of TNF-α in nutrient fluid for C6 cells after hyperthermia treatment. Crystal violet staining method was used to detect glioma invasiveness. Results： The most obvious increase of heat shock factor-1 protein and tumor necrosis factor -alpha mRNA in C6 cells were observed at 30 min and 60 min after hyperthermia, respectively. In addition, the radioactivity of tumor necrosis factor-alpha in C6 cells＇ culture fluid also reached peak at 120 min of hyperthermia. The glioma invasiveness decreases and the concentration of tumor necrosis factor-alpha reached the maximum at 120 min of hyperthermia. Conclusion： Our results showed that the hyperthermia-mediated glioma invasiveness decreases was due to accelerated release of tumor necrosis factor-alpha,which could cause the decreases of glioma invasiveness by promoting the release heat shock factor-1 from neurospongioma cells .
文摘The native extracellular matrix （ECM） and the cells that comprise human tissues are together engaged in a complex relationship; cells alter the composition and structure of the ECM to regulate the material and biologic properties of the surrounding environment while the composition and structure of the ECM modulates cellular processes that maintain healthy tissue and repair diseased tissue. This reciprocal relationship occurs via cell adhesion molecules （CAMs） such as integrins, selectins, cadherins and IgSF adhesion molecules. To study these celI-ECM interactions, researchers use two-dimensional substrates or three-dimensional matrices composed of native proteins or bioactive peptide sequences to study single cell function. While two-dimensional snbstrates provide valuable information about cell-ECM interactions, three-dimensional matrices more closely mimic the native ECM; cells cultured in three-dimensional matrices have demonstrated greater cell movement and increased integrin expression when compared to cells cultured on two-dimensional substrates. In this article we review a number of cellular processes （adhesion, motility, phagocytosis, differentiation and survival） and examine the cell adhesion molecules and ECM proteins （or bioactive peptide sequences） that mediate cell functionality.
