Promising abscopal effect of combination therapy with thermal tumour ablation and intratumoural OK-432 injection in the rat osteosarcoma model
Treatment options for metastatic osteosarcoma are limited. The present study aimed to evaluate whether radiofrequency ablation (RFA) combined with intratumoural OK-432 injection induces systemic anti-tumour immunity in rat osteosarcoma model. Eighty of 145 rats were assigned to four groups to evalua...
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description | Treatment options for metastatic osteosarcoma are limited. The present study aimed to evaluate whether radiofrequency ablation (RFA) combined with intratumoural OK-432 injection induces systemic anti-tumour immunity in rat osteosarcoma model. Eighty of 145 rats were assigned to four groups to evaluate overall survival and tumour size: control (no treatment), RFA-only, OK-432, and RFA-OK-432. The remaining 65 were assigned for histological examination. Maximum diameters of tibial and lung tumours were determined. Tumour samples were histologically examined using haematoxylin-eosin and immunohistochemical staining. Overall survival was significantly prolonged in the RFA-OK-432 group compared to the RFA-only and OK-432 groups. Only rats in the RFA-OK-432 group exhibited significant decreases in maximum tumour diameter after treatment. Ki-67-positive tumour cells in the RFA-OK-432 group were significantly stained negative on immunohistochemical analysis as opposed to those in the RFA-only and OK-432 groups. The number of CD11c+, OX-62+, CD4+, and CD8 + cells significantly increased in the RFA-OK-432 group compared to the RFA-only group. RFA with intratumoural OK-432 injection resulted in distant tumour suppression, prolonged survival, and increased dendritic cells, cytotoxic T cells, IFN-γ, and TNF-α, whereas RFA or OK-432 alone did not produce this effect. This combination may induce an abscopal effect in human osteosarcoma. |
doi_str_mv | 10.1038/s41598-020-66934-6 |
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The present study aimed to evaluate whether radiofrequency ablation (RFA) combined with intratumoural OK-432 injection induces systemic anti-tumour immunity in rat osteosarcoma model. Eighty of 145 rats were assigned to four groups to evaluate overall survival and tumour size: control (no treatment), RFA-only, OK-432, and RFA-OK-432. The remaining 65 were assigned for histological examination. Maximum diameters of tibial and lung tumours were determined. Tumour samples were histologically examined using haematoxylin-eosin and immunohistochemical staining. Overall survival was significantly prolonged in the RFA-OK-432 group compared to the RFA-only and OK-432 groups. Only rats in the RFA-OK-432 group exhibited significant decreases in maximum tumour diameter after treatment. Ki-67-positive tumour cells in the RFA-OK-432 group were significantly stained negative on immunohistochemical analysis as opposed to those in the RFA-only and OK-432 groups. The number of CD11c+, OX-62+, CD4+, and CD8 + cells significantly increased in the RFA-OK-432 group compared to the RFA-only group. RFA with intratumoural OK-432 injection resulted in distant tumour suppression, prolonged survival, and increased dendritic cells, cytotoxic T cells, IFN-γ, and TNF-α, whereas RFA or OK-432 alone did not produce this effect. This combination may induce an abscopal effect in human osteosarcoma.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-66934-6</identifier><identifier>PMID: 32541941</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67 ; 692/4028 ; Ablation ; Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; Bone cancer ; Bone Neoplasms - pathology ; Bone Neoplasms - therapy ; CD11c antigen ; CD4 antigen ; CD8 antigen ; Cell Line, Tumor ; Combination therapy ; Combined Modality Therapy ; Cytotoxicity ; Dendritic cells ; Humanities and Social Sciences ; Injection ; Lymphocytes T ; Metastases ; multidisciplinary ; Osteosarcoma ; Osteosarcoma - pathology ; Osteosarcoma - therapy ; Picibanil - administration & dosage ; Picibanil - pharmacology ; Radiofrequency Ablation - methods ; Rats ; Sarcoma ; Science ; Science (multidisciplinary) ; Treatment Outcome ; Tumor Burden ; Tumor necrosis factor-α ; Tumors ; Xenograft Model Antitumor Assays ; γ-Interferon</subject><ispartof>Scientific reports, 2020-06, Vol.10 (1), p.9679-9679, Article 9679</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-c4e249aae39f5a5306d627ded557d481e84930173d9a4a534226584ff7a2c6fc3</citedby><cites>FETCH-LOGICAL-c474t-c4e249aae39f5a5306d627ded557d481e84930173d9a4a534226584ff7a2c6fc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296025/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296025/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32541941$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iwai, Tadashi</creatorcontrib><creatorcontrib>Oebisu, Naoto</creatorcontrib><creatorcontrib>Hoshi, Manabu</creatorcontrib><creatorcontrib>Orita, Kumi</creatorcontrib><creatorcontrib>Yamamoto, Akira</creatorcontrib><creatorcontrib>Hamamoto, Shinichi</creatorcontrib><creatorcontrib>Kageyama, Ken</creatorcontrib><creatorcontrib>Nakamura, Hiroaki</creatorcontrib><title>Promising abscopal effect of combination therapy with thermal tumour ablation and intratumoural OK-432 injection in the rat osteosarcoma model</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Treatment options for metastatic osteosarcoma are limited. The present study aimed to evaluate whether radiofrequency ablation (RFA) combined with intratumoural OK-432 injection induces systemic anti-tumour immunity in rat osteosarcoma model. Eighty of 145 rats were assigned to four groups to evaluate overall survival and tumour size: control (no treatment), RFA-only, OK-432, and RFA-OK-432. The remaining 65 were assigned for histological examination. Maximum diameters of tibial and lung tumours were determined. Tumour samples were histologically examined using haematoxylin-eosin and immunohistochemical staining. Overall survival was significantly prolonged in the RFA-OK-432 group compared to the RFA-only and OK-432 groups. Only rats in the RFA-OK-432 group exhibited significant decreases in maximum tumour diameter after treatment. Ki-67-positive tumour cells in the RFA-OK-432 group were significantly stained negative on immunohistochemical analysis as opposed to those in the RFA-only and OK-432 groups. The number of CD11c+, OX-62+, CD4+, and CD8 + cells significantly increased in the RFA-OK-432 group compared to the RFA-only group. RFA with intratumoural OK-432 injection resulted in distant tumour suppression, prolonged survival, and increased dendritic cells, cytotoxic T cells, IFN-γ, and TNF-α, whereas RFA or OK-432 alone did not produce this effect. This combination may induce an abscopal effect in human osteosarcoma.</description><subject>631/67</subject><subject>692/4028</subject><subject>Ablation</subject><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Bone cancer</subject><subject>Bone Neoplasms - pathology</subject><subject>Bone Neoplasms - therapy</subject><subject>CD11c antigen</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Cell Line, Tumor</subject><subject>Combination therapy</subject><subject>Combined Modality Therapy</subject><subject>Cytotoxicity</subject><subject>Dendritic cells</subject><subject>Humanities and Social Sciences</subject><subject>Injection</subject><subject>Lymphocytes T</subject><subject>Metastases</subject><subject>multidisciplinary</subject><subject>Osteosarcoma</subject><subject>Osteosarcoma - pathology</subject><subject>Osteosarcoma - therapy</subject><subject>Picibanil - 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administration & dosage</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Bone cancer</topic><topic>Bone Neoplasms - pathology</topic><topic>Bone Neoplasms - therapy</topic><topic>CD11c antigen</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>Cell Line, Tumor</topic><topic>Combination therapy</topic><topic>Combined Modality Therapy</topic><topic>Cytotoxicity</topic><topic>Dendritic cells</topic><topic>Humanities and Social Sciences</topic><topic>Injection</topic><topic>Lymphocytes T</topic><topic>Metastases</topic><topic>multidisciplinary</topic><topic>Osteosarcoma</topic><topic>Osteosarcoma - pathology</topic><topic>Osteosarcoma - therapy</topic><topic>Picibanil - administration & dosage</topic><topic>Picibanil - pharmacology</topic><topic>Radiofrequency Ablation - methods</topic><topic>Rats</topic><topic>Sarcoma</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Treatment Outcome</topic><topic>Tumor Burden</topic><topic>Tumor necrosis factor-α</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iwai, Tadashi</creatorcontrib><creatorcontrib>Oebisu, Naoto</creatorcontrib><creatorcontrib>Hoshi, Manabu</creatorcontrib><creatorcontrib>Orita, Kumi</creatorcontrib><creatorcontrib>Yamamoto, Akira</creatorcontrib><creatorcontrib>Hamamoto, Shinichi</creatorcontrib><creatorcontrib>Kageyama, Ken</creatorcontrib><creatorcontrib>Nakamura, Hiroaki</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</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 (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database (ProQuest)</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iwai, Tadashi</au><au>Oebisu, Naoto</au><au>Hoshi, Manabu</au><au>Orita, Kumi</au><au>Yamamoto, Akira</au><au>Hamamoto, Shinichi</au><au>Kageyama, Ken</au><au>Nakamura, Hiroaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Promising abscopal effect of combination therapy with thermal tumour ablation and intratumoural OK-432 injection in the rat osteosarcoma model</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-06-15</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>9679</spage><epage>9679</epage><pages>9679-9679</pages><artnum>9679</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Treatment options for metastatic osteosarcoma are limited. The present study aimed to evaluate whether radiofrequency ablation (RFA) combined with intratumoural OK-432 injection induces systemic anti-tumour immunity in rat osteosarcoma model. Eighty of 145 rats were assigned to four groups to evaluate overall survival and tumour size: control (no treatment), RFA-only, OK-432, and RFA-OK-432. The remaining 65 were assigned for histological examination. Maximum diameters of tibial and lung tumours were determined. Tumour samples were histologically examined using haematoxylin-eosin and immunohistochemical staining. Overall survival was significantly prolonged in the RFA-OK-432 group compared to the RFA-only and OK-432 groups. Only rats in the RFA-OK-432 group exhibited significant decreases in maximum tumour diameter after treatment. Ki-67-positive tumour cells in the RFA-OK-432 group were significantly stained negative on immunohistochemical analysis as opposed to those in the RFA-only and OK-432 groups. The number of CD11c+, OX-62+, CD4+, and CD8 + cells significantly increased in the RFA-OK-432 group compared to the RFA-only group. RFA with intratumoural OK-432 injection resulted in distant tumour suppression, prolonged survival, and increased dendritic cells, cytotoxic T cells, IFN-γ, and TNF-α, whereas RFA or OK-432 alone did not produce this effect. This combination may induce an abscopal effect in human osteosarcoma.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32541941</pmid><doi>10.1038/s41598-020-66934-6</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 631/67 692/4028 Ablation Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology Bone cancer Bone Neoplasms - pathology Bone Neoplasms - therapy CD11c antigen CD4 antigen CD8 antigen Cell Line, Tumor Combination therapy Combined Modality Therapy Cytotoxicity Dendritic cells Humanities and Social Sciences Injection Lymphocytes T Metastases multidisciplinary Osteosarcoma Osteosarcoma - pathology Osteosarcoma - therapy Picibanil - administration & dosage Picibanil - pharmacology Radiofrequency Ablation - methods Rats Sarcoma Science Science (multidisciplinary) Treatment Outcome Tumor Burden Tumor necrosis factor-α Tumors Xenograft Model Antitumor Assays γ-Interferon |
title | Promising abscopal effect of combination therapy with thermal tumour ablation and intratumoural OK-432 injection in the rat osteosarcoma model |
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