Nakamura Kae, Yoshikawa Nobuhisa, Mizuno Yuko, Ito Miwa, Tanaka Hiromasa, Mizuno Masaaki, Toyokuni Shinya, Hori Masaru, Kikkawa Fumitaka, Kajiyama Hiroaki
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan.
Center for Low-Temperature Plasma Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
Cancers (Basel). 2021 Mar 7;13(5):1141. doi: 10.3390/cancers13051141.
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The major cause of EOC's lethality is that intraperitoneal recurrence occurs with high frequency due to occult metastasis. We had demonstrated that plasma-activated medium (PAM) exerts a metastasis-inhibitory effect on ovarian cancer in vitro and in vivo. Here we investigated how PAM inhibits intraperitoneal metastasis. We studied PAM's inhibition of micro-dissemination onto the omentum by performing in vivo imaging in combination with a sequential histological analysis. The results revealed that PAM induced macrophage infiltration into the disseminated lesion. The iNOS-positive signal was co-localized at the macrophages in the existing lesion, indicating that PAM might induce M1-type macrophages. This may be another mechanism of the antitumor effect through a PAM-evoked immune response. Intraperitoneal lavage with plasma-activated lactate Ringer's solution (PAL) significantly improved the overall survival rate in an ovarian cancer mouse model. Our results demonstrated the efficiency and practicality of aqueous plasma for clinical applications.
上皮性卵巢癌（EOC）是最致命的妇科恶性肿瘤。EOC致死的主要原因是由于隐匿性转移导致腹腔内复发频繁发生。我们已经证明，血浆激活介质（PAM）在体外和体内对卵巢癌均具有转移抑制作用。在此，我们研究了PAM如何抑制腹腔转移。我们通过结合序贯组织学分析进行体内成像，研究了PAM对大网膜微播散的抑制作用。结果显示，PAM诱导巨噬细胞浸润至播散性病变中。iNOS阳性信号在现有病变中的巨噬细胞处共定位，表明PAM可能诱导M1型巨噬细胞。这可能是通过PAM诱发的免疫反应产生抗肿瘤作用的另一种机制。在卵巢癌小鼠模型中，用血浆激活乳酸林格氏液（PAL）进行腹腔灌洗可显著提高总体生存率。我们的结果证明了水性血浆在临床应用中的有效性和实用性。
