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ABSTRACT: Colon cancer is a type of malignant tumor that causes considerable mortality worldwide. Epithelial cellular adhesion molecule (EpCAM), a tumor-associated antigen of colon tumors, is a target for colon cancer therapy. EpCAM-specific monoclonal antibodies (mAbs) have been applied in human colon cancer since the 1990 s; however, the therapeutic effects are limited. EpCAM activates nuclear signaling pathways by releasing its intracellular domain (EpICD). The released EpICD stimulates the Wnt/β-catenin signaling pathway, which is also strongly associated with tumorigenesis. EpCAM is also a target gene of the Wnt/β-catenin signaling pathway. EpCAM and the Wnt/β-catenin signaling pathway form a functional interaction cycle in colon cancer. Thus, we propose a new therapeutic drug for colon cancer: an EpCAM single-chain fragment variable antibody (scFv)-truncated protamine (tp)-siRNA. EpCAM scFv can recognize and bind colon cancer cells through its EpCAM antigen activity. Furthermore, the specific siRNA transferred into colon cancer cells specifically inhibits Wnt/β-catenin signal transmission. Therefore, this new drug may efficiently interrupt the functional cycle between EpCAM and Wnt/β-catenin signaling and be an effective therapeutic strategy for colon cancer.
Cell Biology International 04/2013; · 1.48 Impact Factor
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ABSTRACT: Subarachnoid hemorrhage (SAH) is a frequent occurrence in cerebrovascular accidents, and inflammation occurs in the subarachnoid space after SAH. Arachnoid cells have the capability to present antigens and active T-lymphocytes after stimulation by cerebrospinal fluid (CSF). However, the effect of CSF on T-lymphocytes and arachnoid cell adhesion was not clearly understood. In this study, we used ELISA to detected tumor necrosis factor-α (TNF-α) content in CSF of SAH patients. CSF or recombinant TNF-α were applied on arachnoid cells and T-lymphoctes, and RT-PCR and western blotting were performed to determine the expression of intercellular adhesion molecule-1 (ICAM-1) in arachnoid cells and Lymphocyte Function-Associated Antigen-1 (LFA-1) in T-lymphocytes, respectively. Meanwhile, the Matrix Metal Proteinase-9 (MMP-9) expression in these cells was also determined. We found that the content of TNF-α in the CSF was significantly increased in the CSF of SAH patients (from 22±8pg/mL of healthy people to 436-450pg/mL of SAH patients). Treatement with CSF could increase the expression of ICAM-1in arachnoid cells and that of LFA-1 in T-lymphocytes, mainly through the increased levels of TNF-α. We also found that the co-culture of arachnoid cells and T-lymphocytes increased the expression of MMP-9 in both cells through the interaction of ICAM-1 of and LFA-1. All of these results suggested that arachnoid cells are involved in the T-lymphocytes invasion in the subarachnoid space after SAH.
Brain research 03/2013; · 2.46 Impact Factor
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ABSTRACT: The development of bone tissue engineering has provided new solutions for bone defects. However, the cell-scaffold-based approaches currently in use have several limitations, including low cell seeding rates and poor bone formation capacity. In the present study, we developed a novel strategy to engineer bone grafts using mesenchymal stem cell sheets and coral particles. Rabbit bone marrow mesenchymal stem cells were continuously cultured to form a cell sheet with osteogenic potential and coral particles were integrated into the sheet. The composite sheet was then wrapped around a cylindrical mandrel to fabricate a tubular construct. The resultant tubular construct was cultured in a spinner-flask bioreactor and subsequently implanted into a subcutaneous pocket in a nude mouse for assessment of its histological characteristics, radiological density and mechanical property. A similar construct assembled from a cell sheet alone acted as a control. In vitro observations demonstrated that the composite construct maintained its tubular shape, and exhibited higher radiological density, compressive strength and greater extracellular matrix deposition than did the control construct. In vivo experiments further revealed that new bone formed ectopically on the composite constructs, so that the 8-week explants of the composite sheets displayed radiological density similar to that of native bone. These results indicate that the strategy of using a combination of a cell sheet and coral particles has great potential for bone tissue engineering and repairing bone defects.
Biochemical and Biophysical Research Communications 03/2013; · 2.48 Impact Factor
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ABSTRACT: The transcription factors (Oct4, Sox2, c-Myc, and Klf4) play an important role in the generation of induced pluripotent stem cells. These factors are expressed in metaphase II oocytes and embryonic stem cells (ESCs). The mechanisms responsible for the reprogramming of ooplasm during nuclear transfer are expected to be associated with the four factors. Here, we show that different paternal genetic backgrounds are able to influence the in vitro development of parthenogenetic and cloned embryos. Using real- time polymerase chain reaction (PCR) we found that the expression level of Oct4 in oocytes was less than that of ESCs, whereas oocytes from KM x C3H females showed the highest expression level of Sox2 than the other strains tested or in G1 ESCs. c-Myc mRNA levels in oocytes from KM mice were greater than those found in ESCs or oocytes of KM x C3H mice. These data demonstrate that the expression of the four transcription factors was different among the oocytes, which may be a contributing factor for the different efficiencies of parthenogenesis and the development of cloned embryos in vitro.
Cellular reprogramming. 10/2010; 12(5):565-70.
