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Published in: Annals of Surgical Oncology 1/2018

01-01-2018 | Pancreatic Tumors

Effect of Plasma-Activated Lactated Ringer’s Solution on Pancreatic Cancer Cells In Vitro and In Vivo

Authors: Yusuke Sato, MD, Suguru Yamada, MD, PhD, FACS, Shigeomi Takeda, MD, Norifumi Hattori, MD, PhD, Kae Nakamura, PhD, Hiromasa Tanaka, PhD, Masaaki Mizuno, MD, PhD, Masaru Hori, PhD, Yasuhiro Kodera, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Issue 1/2018

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Abstract

Background

The medical applications of nonequilibrium atmospheric pressure plasma in cancer therapy have attracted attention. We previously reported on the antitumor effect of plasma-activated medium. However, this approach requires plasma-activated liquids that are administrable to the human body. In this study, we produced plasma-activated lactated Ringer’s solution (PAL) and evaluated its antitumor effect and mechanism. Furthermore, we evaluated the effect of the intraperitoneal administration of PAL using a peritoneal dissemination mouse tumor model.

Methods

The antitumor effect of PAL on pancreatic cancer cell lines was evaluated using proliferation and apoptosis assays. In addition, cellular reactive oxygen species (ROS) generation was examined. The role of ROS was assessed using a proliferation assay with N-acetyl cysteine (NAC). An adhesion assay was performed to evaluate the effect of PAL on cell adhesion. Finally, pancreatic cancer cells stably expressing luciferase (AsPC-1/CMV-Luc) were injected intraperitoneally into mice, followed by intraperitoneal injection of PAL. Peritoneal dissemination was monitored using in vivo bioluminescent imaging.

Results

The antitumor effect of PAL was shown in all cell lines in vitro. The TUNEL assay showed that PAL induced apoptosis. ROS uptake was observed in PAL-treated cells, and the antitumor effect was inhibited by NAC. Cell adhesion also was suppressed by PAL. The intraperitoneal administration of PAL suppressed the formation of peritoneal nodules in vivo.

Conclusions

Our study demonstrated the antitumor effects of PAL in vitro and in vivo. Intraperitoneal administration of PAL may be a novel therapeutic option for peritoneal metastases.
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Metadata
Title
Effect of Plasma-Activated Lactated Ringer’s Solution on Pancreatic Cancer Cells In Vitro and In Vivo
Authors
Yusuke Sato, MD
Suguru Yamada, MD, PhD, FACS
Shigeomi Takeda, MD
Norifumi Hattori, MD, PhD
Kae Nakamura, PhD
Hiromasa Tanaka, PhD
Masaaki Mizuno, MD, PhD
Masaru Hori, PhD
Yasuhiro Kodera, MD, PhD, FACS
Publication date
01-01-2018
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 1/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-017-6239-y

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