{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:04:10Z","timestamp":1792015450102,"version":"4.4.0"},"reference-count":67,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Histiocytic sarcomas refer to highly aggressive tumors with a poor prognosis that respond poorly to conventional treatment approaches. Oncolytic viruses, which have gained significant traction as a cancer therapy in recent decades, represent a promising option for treating histiocytic sarcomas through their replication and\/or by modulating the tumor microenvironment. The live attenuated canine distemper virus (CDV) vaccine strain Onderstepoort represents an attractive candidate for oncolytic viral therapy. In the present study, oncolytic virotherapy with CDV was used to investigate the impact of this virus infection on tumor cell growth through direct oncolytic effects or by virus-mediated modulation of the tumor microenvironment with special emphasis on angiogenesis, expression of selected MMPs and TIMP-1 and tumor-associated macrophages in a murine xenograft model of canine histiocytic sarcoma. Treatment of mice with xenotransplanted canine histiocytic sarcomas using CDV induced overt retardation in tumor progression accompanied by necrosis of neoplastic cells, increased numbers of intratumoral macrophages, reduced angiogenesis and modulation of the expression of MMPs and TIMP-1. The present data suggest that CDV inhibits tumor growth in a multifactorial way, including direct cell lysis and reduction of angiogenesis and modulation of MMPs and their inhibitor TIMP-1, providing further support for the concept of its role in oncolytic therapies.<\/jats:p>","DOI":"10.3390\/ijms22073578","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T09:57:04Z","timestamp":1617098224000},"page":"3578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Intratumoral Canine Distemper Virus Infection Inhibits Tumor Growth by Modulation of the Tumor Microenvironment in a Murine Xenograft Model of Canine Histiocytic Sarcoma"],"prefix":"10.3390","volume":"22","author":[{"given":"Federico","family":"Armando","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, B\u00fcnteweg 17, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Fayyad","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, B\u00fcnteweg 17, 30559 Hannover, Germany"},{"name":"Department of Veterinary Medicine, An-Najah National University, 9720061 Nablus, Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Arms","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, B\u00fcnteweg 17, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Barthel","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, B\u00fcnteweg 17, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Schaudien","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Stra\u00dfe 1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Rohn","sequence":"additional","affiliation":[{"name":"Institute for Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, B\u00fcnteweg 2, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4689-5132","authenticated-orcid":false,"given":"Matteo","family":"Gambini","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, B\u00fcnteweg 17, 30559 Hannover, Germany"},{"name":"Dipartimento di Medicina Veterinaria (DIMEVET), Universit\u00e0 degli Studi di Milano, Via dell\u2019Universit\u00e0 6, 26900 Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara Sophie","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, B\u00fcnteweg 17, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Beineke","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, B\u00fcnteweg 17, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Baumg\u00e4rtner","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, B\u00fcnteweg 17, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Puff","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, B\u00fcnteweg 17, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.tvjl.2013.09.020","article-title":"Longevity and mortality of owned dogs in England","volume":"198","author":"Church","year":"2013","journal-title":"Vet. 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