Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma

Fluorescence-guided cancer has not yet been shown to be curative due to residual microscopic disease. Human fibrosarcoma HT1080 expressing red fluorescent protein (RFP) was implanted orthotopically in the quadriceps femoris muscle of nude mice. The tumor-bearing mice were injected with high and low-...

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Main Authors:	Yano, Shuya, Miwa, Shinji, Kishimoto, Hiroyuki, Uehara, Fuminari, Tazawa, Hiroshi, Toneri, Makoto, Hiroshima, Yukihiko, Yamamoto, Mako, Urata, Yasuo, Kagawa, Shunsuke, Bouvet, Michael, Fujiwara, Toshiyoshi, Hoffman, Robert M.
Format:	Online
Language:	English
Published:	Impact Journals LLC 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537004/

id	pubmed-4537004
recordtype	oai_dc
spelling	pubmed-45370042015-08-26 Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma Yano, Shuya Miwa, Shinji Kishimoto, Hiroyuki Uehara, Fuminari Tazawa, Hiroshi Toneri, Makoto Hiroshima, Yukihiko Yamamoto, Mako Urata, Yasuo Kagawa, Shunsuke Bouvet, Michael Fujiwara, Toshiyoshi Hoffman, Robert M. Research Paper Fluorescence-guided cancer has not yet been shown to be curative due to residual microscopic disease. Human fibrosarcoma HT1080 expressing red fluorescent protein (RFP) was implanted orthotopically in the quadriceps femoris muscle of nude mice. The tumor-bearing mice were injected with high and low-dose telomerase-dependent, green fluorescent protein (GFP)-containing adenovirus OBP-401, which labeled the tumor with GFP. Fluorescence-guided surgery (FGS) or bright light surgery (BLS) was then performed. OBP-401 could label soft-tissue sarcoma (STS) with GFP in situ, concordant with RFP. OBP-401-based FGS resulted in superior resection of STS in the orthotopic model of soft-tissue sarcoma, compared to BLS. High-dose administration of OBP-401 enabled FGS without residual sarcoma cells or local or metastatic recurrence, due to its dual effect of cancer-cell labeling with GFP and killing. High-dose OBP-401 based-FGS improved disease free survival (p = 0.00049) as well as preserved muscle function compared with BLS. High-dose OBP-401-based FGS could cure STS, a presently incurable disease. Since the parent virus of OBP-401, OBP-301, has been previously proven safe in a Phase I clinical trial, it is expected the OBP-401-FGS technology described in the present report should be translatable to the clinic in the near future. Impact Journals LLC 2015-04-14 /pmc/articles/PMC4537004/ /pubmed/26033451 Text en Copyright: © 2015 Yano et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yano, Shuya Miwa, Shinji Kishimoto, Hiroyuki Uehara, Fuminari Tazawa, Hiroshi Toneri, Makoto Hiroshima, Yukihiko Yamamoto, Mako Urata, Yasuo Kagawa, Shunsuke Bouvet, Michael Fujiwara, Toshiyoshi Hoffman, Robert M.
spellingShingle	Yano, Shuya Miwa, Shinji Kishimoto, Hiroyuki Uehara, Fuminari Tazawa, Hiroshi Toneri, Makoto Hiroshima, Yukihiko Yamamoto, Mako Urata, Yasuo Kagawa, Shunsuke Bouvet, Michael Fujiwara, Toshiyoshi Hoffman, Robert M. Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma
author_facet	Yano, Shuya Miwa, Shinji Kishimoto, Hiroyuki Uehara, Fuminari Tazawa, Hiroshi Toneri, Makoto Hiroshima, Yukihiko Yamamoto, Mako Urata, Yasuo Kagawa, Shunsuke Bouvet, Michael Fujiwara, Toshiyoshi Hoffman, Robert M.
author_sort	Yano, Shuya
title	Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma
title_short	Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma
title_full	Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma
title_fullStr	Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma
title_full_unstemmed	Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma
title_sort	targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma
description	Fluorescence-guided cancer has not yet been shown to be curative due to residual microscopic disease. Human fibrosarcoma HT1080 expressing red fluorescent protein (RFP) was implanted orthotopically in the quadriceps femoris muscle of nude mice. The tumor-bearing mice were injected with high and low-dose telomerase-dependent, green fluorescent protein (GFP)-containing adenovirus OBP-401, which labeled the tumor with GFP. Fluorescence-guided surgery (FGS) or bright light surgery (BLS) was then performed. OBP-401 could label soft-tissue sarcoma (STS) with GFP in situ, concordant with RFP. OBP-401-based FGS resulted in superior resection of STS in the orthotopic model of soft-tissue sarcoma, compared to BLS. High-dose administration of OBP-401 enabled FGS without residual sarcoma cells or local or metastatic recurrence, due to its dual effect of cancer-cell labeling with GFP and killing. High-dose OBP-401 based-FGS improved disease free survival (p = 0.00049) as well as preserved muscle function compared with BLS. High-dose OBP-401-based FGS could cure STS, a presently incurable disease. Since the parent virus of OBP-401, OBP-301, has been previously proven safe in a Phase I clinical trial, it is expected the OBP-401-FGS technology described in the present report should be translatable to the clinic in the near future.
publisher	Impact Journals LLC
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537004/
_version_	1613259868714565632

Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma

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