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

Takeda, Shigeomi; Yamada, Suguru; Hattori, Norifumi; Nakamura, Kae; Tanaka, Hiromasa; Kajiyama, Hiroaki; Kanda, Mitsuro; Kobayashi, Daisuke; Tanaka, Chie; Fujii, Tsutomu; Fujiwara, Michitaka; Mizuno, Masaaki; Hori, Masaru; Kodera, Yasuhiro

doi:10.1245/s10434-016-5759-1

Cited by 81 publications

(52 citation statements)

References 32 publications

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“…Therefore, as a method that can extensively reach cancer cells in the peritoneal cavity, we have devised PAM and conducted basic research to utilize PAM for clinical use as an indirect plasma therapy. Interestingly, our colleagues and we have demonstrated the anti-tumor effects of PAM against several types of cancer using an in vivo model of peritoneal metastasis 8,11,19 . These findings suggest that PAM may be a novel option for the treatment of peritoneal metastasis.…”

Section: Discussionmentioning

confidence: 96%

“…Previous reports revealed that longer treatments with direct exposure of NEAPP or PAM resulted in significantly lower viability in cancer cells 8,22 . In addition, Takeda et al revealed that not only adherent cells, but also floating cells, presented a decrease in adhesion capacity 19 . When applying PAM as part of a clinical treatment to prevent peritoneal metastasis, a shorter exposure time with PAM to the intraperitoneal cavity is necessary to minimize side effects on normal cells.…”

Section: Discussionmentioning

confidence: 99%

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Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

Yoshikawa

Liu

Nakamura

et al. 2020

Sci Rep

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the biological function of non-thermal atmospheric pressure plasma has been widely accepted in several types of cancer. We previously developed plasma-activated medium (pAM) for clinical use, and demonstrated that PAM exhibits a metastasis-inhibitory effect on ovarian cancer through reduced MMP-9 secretion. However, the anti-tumor effects of PAM on endometrial cancer remain unknown. In this study, we investigated the inhibitory effect of PAM on endometrial cancer cell viability in vitro.Our results demonstrated that AMEC and HEC50 cell viabilities were reduced by PAM at a certain PAM ratio, and PAM treatment effectively increased autophagic cell death in a concentration dependent manner. in addition, we evaluated the molecular mechanism of pAM activity and found that the mtoR pathway was inactivated by pAM. Moreover, our results demonstrated that the autophagy inhibitor MHY1485 partially inhibited the autophagic cell death induced by PAM treatment. These findings indicate that pAM decreases the viability of endometrial cancer cells along with alteration of the mtoR pathway, which is critical for cancer cell viability. collectively, our data suggest that pAM inhibits cell viability while inducing autophagic cell death in endometrial cancer cells, representing a potential novel treatment for endometrial cancer.Endometrial cancer is the most common gynecologic malignancy in Japan, with an estimated 13,600 new cases diagnosed in 2015 1 . The incidence of new cases is believed to have increased over the last few decades due to increased levels of obesity, hypertension, and diabetes mellitus, particularly in South Africa and several Asian countries including Japan 1,2 . Although the majority of endometrial cancer patients are diagnosed in the early stage and outcomes are generally favorable because of the typical symptom of irregular vaginal bleeding in women of menopausal age, the prognoses of patients in advanced stages not amenable to localized therapies remain poor 1 . Indeed, a frequent pattern of progression and recurrence is peritoneal metastasis, which is often resistant to systemic chemotherapy 3 . In addition, cytotoxic agents for endometrial cancer are relatively limited compared with other gynecologic malignancies. Thus, there is an increasing demand for novel approaches to peritoneal dissemination.For the past decade, nonequilibrium atmospheric pressure plasma (NEAPP) has been studied for its clinical applications such as sterilization, wound healing, and cancer therapy 4-6 . NEAPP represents a partially ionized gas with energy mainly accumulated as free electrons 7 . Recent studies have revealed that in addition to the direct irradiation of NEAPP to bacteria or tissues, indirect plasma treatment with plasma-activated medium (PAM) and plasma-activated lactate (PAL), which are activated by NEAPP, exhibit anti-tumor activity in several types of cancer, including ovarian, pancreatic, colorectal and gastric cancers 4,8-13 . The molecular mechanism of the anti-tumor effects triggered by PAM have been investigat...

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

Yoshikawa

Liu

Nakamura

et al. 2020

Sci Rep

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“…In this regard, the ability of PAL to suppress ovarian cancer metastases when injected intraperitoneally in a mouse model was previously reported [24]. Yet, no evidence is available on the safety of PAL intraperitoneal administration in humans [41], supporting the need to shift the main focus of the plasma onco-medicine on liquids applicable to the clinical practice. This holds particularly true in OC, where spreading of the advanced stage disease within the pelvic cavity of the patient is often the case through the occurrence of micro-lesions [42], as washing the cavity with PA-RL may significantly reduce tumor burden, while sparing the non-cancer component.…”

Section: Discussionmentioning

confidence: 99%

Plasma-activated Ringer’s Lactate Solution Displays a Selective Cytotoxic Effect on Ovarian Cancer Cells

Bisag

Bucci

Coluccelli

et al. 2020

Cancers

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Epithelial Ovarian Cancer (EOC) is one of the leading causes of cancer-related deaths among women and is characterized by the diffusion of nodules or plaques from the ovary to the peritoneal surfaces. Conventional therapeutic options cannot eradicate the disease and show low efficacy against resistant tumor subclones. The treatment of liquids via cold atmospheric pressure plasma enables the production of plasma-activated liquids (PALs) containing reactive oxygen and nitrogen species (RONS) with selective anticancer activity. Thus, the delivery of RONS to cancer tissues by intraperitoneal washing with PALs might be an innovative strategy for the treatment of EOC. In this work, plasma-activated Ringer’s Lactate solution (PA-RL) was produced by exposing a liquid substrate to a multiwire plasma source. Subsequently, PA-RL dilutions are used for the treatment of EOC, non-cancer and fibroblast cell lines, revealing a selectivity of PA-RL, which induces a significantly higher cytotoxic effect in EOC with respect to non-cancer cells.

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“…In a xenograft mouse model, PAM inhibited the growth of ovarian and pancreatic cancer tumor cells [10,41]. Intraperitoneal injection of PAM/plasma-activated Ringer's lactate (PAL) inhibited the metastasis of ovarian, gastric, and pancreatic cancer tumors in disease model mouse experiments examining peritoneal metastasis [46][47][48]. However, in apoptosis induced by PAL, less ROS are produced in comparison with PAM [49], suggesting that components generated in PAM control the redox balance.…”

Section: Indirect Treatment: Pammentioning

confidence: 99%

New Hopes for Plasma-Based Cancer Treatment

Tanaka

Mizuno

Ishikawa

et al. 2018

Plasma

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

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

Cited by 81 publications

References 32 publications

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

Plasma-activated Ringer’s Lactate Solution Displays a Selective Cytotoxic Effect on Ovarian Cancer Cells

New Hopes for Plasma-Based Cancer Treatment

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