ABSTRACT
The epithelial-mesenchymal transition (EMT) is one mechanism by which cells with mesenchymal features can be generated and is a fundamental event in morphogenesis. Recently, invasion and metastasis of cancer cells from the primary tumor are now thought to be initiated by the developmental process termed the EMT, whereby epithelial cells lose cell polarity and cell-cell interactions, and gain mesenchymal phenotypes with increased migratory and invasive properties. The EMT is believed to be an important step in metastasis and is implicated in cancer progression, although the influence of the EMT in clinical specimens has been debated. This review presents the recent results of two cell surface proteins, the functions and underlying mechanisms of which have recently begun to be demonstrated, as novel regulators of the molecular networks that induce the EMT and cancer progression.
Subject(s)
Cell Polarity , Epithelial Cells , Epithelial-Mesenchymal Transition , Membrane Proteins , Membranes , Morphogenesis , Neoplasm Metastasis , PhenotypeABSTRACT
PURPOSE: Evaluation of the effects of a vehicle's movement/ operation on fluid flow regulators during patient transport. To determine whether or not vehicle trembling during idling and movement during patient transport are factors affecting the velocity of fluid injection. METHODS: The volume of fluid, as measured in an idling or moving vehicle, was evaluated using three different types of marketed flow regulators at three different injection speeds: 10, 20 and 40 ml/hr. RESULTS: In all cases, when the vehicle was idling or in motion, discrepancies were observed between the pre-calculated amount of fluid and the actual amount of fluid injected. However, a greater discrepancy was observed to exist in a moving vehicle. CONCLUSION: The trembling and movement of a vehicle during patient transport affects fluid injection results.
Subject(s)
Humans , Fluid Therapy , Infusion Pumps , Transportation of PatientsABSTRACT
PURPOSE: Evaluation of the effects of a vehicle's movement/ operation on fluid flow regulators during patient transport. To determine whether or not vehicle trembling during idling and movement during patient transport are factors affecting the velocity of fluid injection. METHODS: The volume of fluid, as measured in an idling or moving vehicle, was evaluated using three different types of marketed flow regulators at three different injection speeds: 10, 20 and 40 ml/hr. RESULTS: In all cases, when the vehicle was idling or in motion, discrepancies were observed between the pre-calculated amount of fluid and the actual amount of fluid injected. However, a greater discrepancy was observed to exist in a moving vehicle. CONCLUSION: The trembling and movement of a vehicle during patient transport affects fluid injection results.
Subject(s)
Humans , Fluid Therapy , Infusion Pumps , Transportation of PatientsABSTRACT
Tumor migration/invasion is the main cause of tumor progression and STAT3 is needed to enhance tumor migration/invasion by up-regulating MMP-9. Thus, agents that inhibit STAT3 activation may be used as an anticancer drug. We present herein that 6-methyl-2-propylimino-6, 7-dihydro-5H-benzo [1, 3]-oxathiol- 4-one (LYR71) , a derivative of trimeric resveratrol, has an anticancer activity through inhibition of STAT3 activation. We found that LYR71 suppressed STAT3 activation and inhibited the expression and activity of MMP-9 in RANTES-stimulated breast cancer cells. In addition, LYR71 reduced RANTES-induced MMP-9 transcripts by blocking STAT3 recruitment, dissociating p300 and deacetylating histone H3 and H4 on the MMP-9 promoter. Furthermore, LYR71 inhibited tumor migration/invasion in RANTES-treated breast cancer cells and consequently blocked tumor progression in tumor-bearing mice. Taken together, the results of this study suggest that LYR71 can be therapeutically useful due to the inhibition effect of STAT3-mediated MMP-9 expression in breast cancer cells.
Subject(s)
Animals , Female , Humans , Mice , Antineoplastic Agents/chemistry , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Blotting, Western , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Chromatin Immunoprecipitation , Gene Expression/drug effects , Imines/chemistry , Immunohistochemistry , Mammary Neoplasms, Experimental/pathology , Matrix Metalloproteinase 9/genetics , Mice, Inbred BALB C , Mice, Nude , Molecular Structure , Phosphorylation/drug effects , Reverse Transcriptase Polymerase Chain Reaction , STAT3 Transcription Factor/genetics , Stilbenes/chemistry , Xenograft Model Antitumor Assays/methodsABSTRACT
We previously reported that trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, induced DLC-1 mRNA expression and accumulated acetylated histones H3 and H4 associated with the DLC-1 promoter in DLC-1 non-expressing gastric cancer cells. In this study, we demonstrated the molecular mechanisms by which TSA induced the DLC-1 gene expression. Treatment of the gastric cancer cells with TSA activates the DLC-1 promoter activity through Sp1 sites located at -219 and -174 relative to the transcription start site. Electrophoretic mobility-shift assay (EMSA) revealed that Sp1 and Sp3 specifically interact with these Sp1 sites and showed that TSA did not change their binding activities. The ectopic expression of Sp1, but not Sp3, enhances the DLC-1 promoter responsiveness by TSA. Furthermore, the TSA-induced DLC-1 promoter activity was increased by p300 expression and reduced by knockdown of p300. These results demonstrated the requirement of specific Sp1 sites and dependence of Sp1 and p300 for TSA-mediated activation of DLC-1 promoter.