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Intraperitoneal Administration of Plasma-Activated Medium: Proposal of a Novel Treatment Option for Peritoneal Metastasis From Gastric Cancer

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The administration of fluid irradiated with non-equilibrium atmospheric pressure plasma (NEAPP) has attracted much interest as a novel therapeutic method for cancer. The authors previously reported on the efficacy of plasma-activated medium (PAM) for treating cancer cell lines through the induction of apoptosis. In this study, the therapeutic effect of PAM was evaluated in vivo using a peritoneal metastasis mouse model.

Methods

Two gastric cancer cell lines were used in proliferation assays performed to optimize the production of PAM by changing the distance between the plasma source and the medium surface and by altering the volume of irradiated medium. Wound-healing and adhesion assays were conducted to determine the effect of PAM therapy on cell migration and adhesion capacity in vitro. Finally, a mouse model established by the intraperitoneal injection of enhanced green fluorescent protein-tagged gastric cancer cells was used to explore the efficacy of PAM administered intraperitoneally in inhibiting peritoneal metastasis formation.

Results

Shorter distances between the plasma source and the medium surface and smaller volumes of treated medium increased the anti-tumor effect of PAM. The PAM treatment attenuated gastric cancer cell migration and adhesion in vitro. The intraperitoneal administration of PAM decreased the formation of peritoneal metastatic nodules by 60% in the mouse model, and no adverse events were observed.

Conclusions

Plasma-activated liquids may represent a novel therapeutic method for the treatment of peritoneal metastases in gastric cancer.

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Disclosures

There are no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan

    Shigeomi Takeda MD, Suguru Yamada MD, PhD, FACS, Norifumi Hattori MD, Mitsuro Kanda MD, PhD, FACS, Daisuke Kobayashi MD, PhD, Chie Tanaka MD, PhD, Tsutomu Fujii MD, PhD, FACS, Michitaka Fujiwara MD, PhD & Yasuhiro Kodera MD, PhD, FACS

  2. Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Kae Nakamura PhD & Hiroaki Kajiyama MD, PhD

  3. Institutes of Innovation for Future Society, Nagoya University, Nagoya, Japan

    Hiromasa Tanaka PhD & Masaru Hori PhD

  4. Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Masaaki Mizuno MD, PhD

Authors
  1. Shigeomi Takeda MD
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  2. Suguru Yamada MD, PhD, FACS
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  3. Norifumi Hattori MD
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  4. Kae Nakamura PhD
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  5. Hiromasa Tanaka PhD
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  6. Hiroaki Kajiyama MD, PhD
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  7. Mitsuro Kanda MD, PhD, FACS
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  8. Daisuke Kobayashi MD, PhD
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  9. Chie Tanaka MD, PhD
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  10. Tsutomu Fujii MD, PhD, FACS
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  11. Michitaka Fujiwara MD, PhD
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  12. Masaaki Mizuno MD, PhD
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  13. Masaru Hori PhD
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  14. Yasuhiro Kodera MD, PhD, FACS
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Corresponding author

Correspondence to Suguru Yamada MD, PhD, FACS.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10434_2016_5759_MOESM1_ESM.ppt

Supplementary material 1 (PPT 845 kb) Experimental system for producing PAM. (a) Photograph of our device. (b) Schematics of PAM production.

10434_2016_5759_MOESM2_ESM.pptx

Supplementary material 2 (PPTX 73 kb)Effect of repeated PAM exposure. A total of 3×103 cells were seeded into a 96-well plate, and the medium was replaced as follows. Untreated: The medium was replaced every 24 h with RPMI-1640. 1: At 24 h after seeding, the medium was replaced with PAM, and after another 24 h and 48 h, the medium was replaced with RPMI-1640. 2: At 24 h and 48 h after seeding, the medium was replaced with PAM, and after another 24 h, the medium was replaced with RPMI-1640. 3: At 24 h, 48 h and 72 h after seeding, the medium was replaced with PAM. Finally, at 96 h after seeding, an MTS assay was performed, and the proliferation rates were calculated. Each column represents the mean of three replicates, and the error bars represent standard deviation.

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Takeda, S., Yamada, S., Hattori, N. et al. Intraperitoneal Administration of Plasma-Activated Medium: Proposal of a Novel Treatment Option for Peritoneal Metastasis From Gastric Cancer. Ann Surg Oncol 24, 1188–1194 (2017). https://doi.org/10.1245/s10434-016-5759-1

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  • DOI: https://doi.org/10.1245/s10434-016-5759-1

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