Preclinical Verification of the Efficacy and Safety of Aqueous Plasma for Ovarian Cancer Therapy
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 o...
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Veröffentlicht in: | Cancers 2021-03, Vol.13 (5), p.1141 |
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creator | Nakamura, Kae Yoshikawa, Nobuhisa Mizuno, Yuko Ito, Miwa Tanaka, Hiromasa Mizuno, Masaaki Toyokuni, Shinya Hori, Masaru Kikkawa, Fumitaka Kajiyama, Hiroaki |
description | 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. |
doi_str_mv | 10.3390/cancers13051141 |
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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.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13051141</identifier><identifier>PMID: 33799991</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Abdomen ; Antitumor activity ; Cancer therapies ; Chemotherapy ; Immune response ; Lactic acid ; Lethality ; Lymphatic system ; Macrophages ; Malignancy ; Medical prognosis ; Metastases ; Metastasis ; Nitric-oxide synthase ; Omentum ; Ovarian cancer ; Plasma</subject><ispartof>Cancers, 2021-03, Vol.13 (5), p.1141</ispartof><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-4a3ad7a95efd1a78339756702ed6f50c1626bf52f968887d981acf4f135d4c03</citedby><cites>FETCH-LOGICAL-c487t-4a3ad7a95efd1a78339756702ed6f50c1626bf52f968887d981acf4f135d4c03</cites><orcidid>0000-0003-0493-1825 ; 0000-0003-0105-6017 ; 0000-0001-6576-9417 ; 0000-0001-8662-9421 ; 0000-0002-5757-1109</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962102/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962102/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33799991$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nakamura, Kae</creatorcontrib><creatorcontrib>Yoshikawa, Nobuhisa</creatorcontrib><creatorcontrib>Mizuno, Yuko</creatorcontrib><creatorcontrib>Ito, Miwa</creatorcontrib><creatorcontrib>Tanaka, Hiromasa</creatorcontrib><creatorcontrib>Mizuno, Masaaki</creatorcontrib><creatorcontrib>Toyokuni, Shinya</creatorcontrib><creatorcontrib>Hori, Masaru</creatorcontrib><creatorcontrib>Kikkawa, Fumitaka</creatorcontrib><creatorcontrib>Kajiyama, Hiroaki</creatorcontrib><title>Preclinical Verification of the Efficacy and Safety of Aqueous Plasma for Ovarian Cancer Therapy</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>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. 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Yoshikawa, Nobuhisa ; Mizuno, Yuko ; Ito, Miwa ; Tanaka, Hiromasa ; Mizuno, Masaaki ; Toyokuni, Shinya ; Hori, Masaru ; Kikkawa, Fumitaka ; Kajiyama, Hiroaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-4a3ad7a95efd1a78339756702ed6f50c1626bf52f968887d981acf4f135d4c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Abdomen</topic><topic>Antitumor activity</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Immune response</topic><topic>Lactic acid</topic><topic>Lethality</topic><topic>Lymphatic system</topic><topic>Macrophages</topic><topic>Malignancy</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Nitric-oxide synthase</topic><topic>Omentum</topic><topic>Ovarian cancer</topic><topic>Plasma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nakamura, Kae</creatorcontrib><creatorcontrib>Yoshikawa, Nobuhisa</creatorcontrib><creatorcontrib>Mizuno, Yuko</creatorcontrib><creatorcontrib>Ito, Miwa</creatorcontrib><creatorcontrib>Tanaka, Hiromasa</creatorcontrib><creatorcontrib>Mizuno, Masaaki</creatorcontrib><creatorcontrib>Toyokuni, Shinya</creatorcontrib><creatorcontrib>Hori, Masaru</creatorcontrib><creatorcontrib>Kikkawa, Fumitaka</creatorcontrib><creatorcontrib>Kajiyama, Hiroaki</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nakamura, Kae</au><au>Yoshikawa, Nobuhisa</au><au>Mizuno, Yuko</au><au>Ito, Miwa</au><au>Tanaka, Hiromasa</au><au>Mizuno, Masaaki</au><au>Toyokuni, Shinya</au><au>Hori, Masaru</au><au>Kikkawa, Fumitaka</au><au>Kajiyama, Hiroaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preclinical Verification of the Efficacy and Safety of Aqueous Plasma for Ovarian Cancer Therapy</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2021-03-07</date><risdate>2021</risdate><volume>13</volume><issue>5</issue><spage>1141</spage><pages>1141-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33799991</pmid><doi>10.3390/cancers13051141</doi><orcidid>https://orcid.org/0000-0003-0493-1825</orcidid><orcidid>https://orcid.org/0000-0003-0105-6017</orcidid><orcidid>https://orcid.org/0000-0001-6576-9417</orcidid><orcidid>https://orcid.org/0000-0001-8662-9421</orcidid><orcidid>https://orcid.org/0000-0002-5757-1109</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Abdomen Antitumor activity Cancer therapies Chemotherapy Immune response Lactic acid Lethality Lymphatic system Macrophages Malignancy Medical prognosis Metastases Metastasis Nitric-oxide synthase Omentum Ovarian cancer Plasma |
title | Preclinical Verification of the Efficacy and Safety of Aqueous Plasma for Ovarian Cancer Therapy |
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