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Drug-eluting scaffold inhibited in vivo pancreatic tumorigenesis by engaging murine CCR4(+)CD8(+) T cells
2019/11/27 21:20:32 admin
CCL17 is well known for its ability to engage CCR4(+)CD8(+) T cells, which have been shown to play a critical role in preventing tumorigenesis. In this study, we attempted to inhibit in vivo pancreatic tumorigenesis by engaging murine CCR4(+)CD8(+) T cells through a drug-eluting scaffold with a payload of CCL17. The drug-eluting scaffold was fabricated by electrospinning polyglyconate and porcine gelatin. The electrospun scaffold featured randomly distributed non-woven fibers with diameters ranging from 1 mu m to 4 mu m. The in vitro study confirmed that scaffolding materials were non-cytotoxic to pancreatic cancer cells. The in vivo study showed an increased presence of murine CCR4(+)CD8(+) T cells into the tumor mass treated with drug-eluting scaffold compared to those with non-eluting scaffold or the control groups. The weights of tumor masses were 132.04 mg +/- 12.25 mg in the control group, 158.12 mg +/- 18.98 mg in the NES group and 96.22 mg +/- 14.56 mg in the DES group, respectively. The volumes of tumor masses were 1035.21 mm(3) +/- 128.97 mm(3) in the control group, 978.56 mm(3) +/- 110.19 mm(3) in the NES group and 634.35 mm(3) +/- 87.12 mm(3) in the DES group, respectively. Further study showed that the increased presence of CCR4(+)CD8(+) T cells also inhibited the hepatic metastasis of pancreatic cancer cells. Our study shed a new light on the post-operative treatment of pancreatic cancer to prevent the recurrence. (C) 2017 Elsevier B.V. All rights reserved.
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