CXC chemokine ligand 10 (CXCL10) is a CXC chemokine family protein that transmits signals by binding to its specific receptor, CXCR3. CXCL10 is also known as an interferon-γ-inducible chemokine involved in various biological phenomena, including chemotaxis of natural killer (NK) cells and cytotoxic T lymphocytes, that suppress tumor growth and inhibition of angiogenesis. In this study, we examined the effects of forced expression of CXCL10 in a murine colon carcinoma cell line (CT26) on growth and metastasis in syngeneic mice. We first established CT26 cells that were stably expressing murine CXCL10 (CT26/CXCL10) and compared their growth with their parental CT26 cells in vitro and in vivo. The in vitro growth of the CT26/CXCL10 and CT26 cells was comparable, whereas the in vivo growth of the CT26/CXCL10 cells in the skin was strongly suppressed. Liver metastasis of the CT26/CXCL10 cells was also significantly suppressed after intra-splenic implantation. Removal of NK cells by the administration of anti-asialo GM1 antibody canceled the suppression of subcutaneous growth and liver metastasis of CT26/CXCL10 cells. Immunofluorescence clearly showed that abundant NKp46-positive NK cells were recruited into the liver metastatic lesions of the CT26/CXCL10 cells, consistent with specific NK cell migration towards the culture supernatant from the CT26/CXCL10 cells in the chemotaxis assay using transwells. These findings indicate that CXCL10 prevents in vivo growth and metastasis of colon carcinoma cells by recruiting NK cells, suggesting that forced expression of CXCL10 in the colon tumors by gene delivery should lead to a favorable clinical outcome.
The numerical investigation focused on the shear behavior of prestressed concrete (PC) beams with small rectangular openings, using the software ABAQUS. Three variables, including the prestressing force, the height of the opening and its length, were considered. The numerical results exhibited a good agreement with the previous experimental outcomes, and the parametric analysis was conducted to study the local internal force distribution of two chords during the loading process. The results indicate that for RC beams with openings, the shear proportion variation of the top chord is stable as the opening size changes, while it decreases almost linearly with the increase of prestressing force for PC beams with openings. The position of contraflexure point is found to be proportional to the root of the reinforcement ratio of the chord, and it moves towards the support with the increase of the prestressing force. Furthermore, the empirical equations to determine the shear proportions and the position of contraflexure point between chords are established.
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