{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:04:04Z","timestamp":1792015444786,"version":"4.4.0"},"reference-count":45,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Open Access Publication Fund of the University of Veterinary Medicine Hannover, Foundation"},{"name":"Brigitte und Prof. Dr. Reiner M\u00fcller-Peddinghaus Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oncolytic viruses and morbilliviruses in particular, represent an interesting therapeutic approach for tumors with a poor prognosis and frequent resistance to conventional therapies. Canine histiocytic sarcomas (HS) exemplify such a neoplasm in need for new curative approaches. Previous investigations demonstrated a limited success of an acute intratumoral application of canine distemper virus (CDV) on xenotransplanted canine histiocytic sarcoma cells (DH82 cells), while persistently CDV-infected DH82 cell transplants exhibited a complete spontaneous regression. Therefore, the present study focuses on an intratumoral application of persistently CDV vaccine strain Onderstepoort-infected DH82 (DH82 Ond p.i.) cells into non-infected subcutaneous DH82 cell transplants in a murine model. DH82 cell transplants that received 10 applications, two days apart, showed a transient growth retardation as well as larger areas of intratumoral necrosis, lower mitotic rates, and a decreased intratumoral vascularization compared to controls. Viral mRNA was detected in all neoplasms following application of DH82 Ond p.i. cells until 66 days after the last injection. Furthermore, infectious virus was present until 62 days after the last injection. Although complete regression was not achieved, the present application regimen provides promising results as a basis for further treatments, particularly with genetically modified viruses, to enhance the observed effects.<\/jats:p>","DOI":"10.3390\/ijms25158297","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T17:08:34Z","timestamp":1722359314000},"page":"8297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Persistence of Infectious Canine Distemper Virus in Murine Xenotransplants of Canine Histiocytic Sarcoma Cells after Intratumoral Application"],"prefix":"10.3390","volume":"25","author":[{"given":"Mara Sophie","family":"Lombardo","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2578-4409","authenticated-orcid":false,"given":"Federico","family":"Armando","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany"},{"name":"Pathology Unit, Veterinary Medicine Department, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Marek","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, 30559 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, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8151-5644","authenticated-orcid":false,"given":"Wolfgang","family":"Baumg\u00e4rtner","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2592-6868","authenticated-orcid":false,"given":"Christina","family":"Puff","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.1182\/blood.V84.9.2840.2840","article-title":"Histiocytes and histiocytosis","volume":"84","author":"Cline","year":"1994","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/(SICI)1096-911X(199709)29:3<157::AID-MPO1>3.0.CO;2-C","article-title":"Contemporary classification of histiocytic disorders. The WHO committee on histiocytic\/reticulum cell proliferations. Reclassification working group of the histiocyte society","volume":"29","author":"Favara","year":"1997","journal-title":"Med. Pediatr. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1177\/0300985813510413","article-title":"A review of histiocytic diseases of dogs and cats","volume":"51","author":"Moore","year":"2014","journal-title":"Vet. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1354\/vp.43-5-632","article-title":"Canine hemophagocytic histiocytic sarcoma: A proliferative disorder of CD11d+ macrophages","volume":"43","author":"Moore","year":"2006","journal-title":"Vet. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1159\/000340066","article-title":"Histiocytic sarcoma\u2014Targeted therapy: Novel therapeutic options? A series of 4 cases","volume":"35","author":"Schlick","year":"2012","journal-title":"Onkologie"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1476-5810.2006.00090.x","article-title":"Histiocytic sarcomas in flat-coated retrievers: A summary of 37 cases (November 1998-March 2005)","volume":"4","author":"Fidel","year":"2006","journal-title":"Vet. Comp. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/scientificamerican1114-54","article-title":"Can viruses treat cancer?","volume":"311","author":"Mahoney","year":"2014","journal-title":"Sci. Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00005-008-0047-9","article-title":"Natural and genetically engineered viral agents for oncolysis and gene therapy of human cancer","volume":"56","author":"Sinkovics","year":"2008","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0140-6736(71)91186-X","article-title":"Hodgkin\u2019s disease: Remission after measles","volume":"297","author":"Zygiert","year":"1971","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.molmed.2013.02.008","article-title":"Mounting a strategic offense: Fighting tumor vasculature with oncolytic viruses","volume":"19","author":"Angarita","year":"2013","journal-title":"Trends Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cytogfr.2010.02.007","article-title":"Double trouble for tumours: Exploiting the tumour microenvironment to enhance anticancer effect of oncolytic viruses","volume":"21","author":"Atkins","year":"2010","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_12","first-page":"571","article-title":"Oncolytic viruses & their specific targeting to tumour cells","volume":"139","author":"Singh","year":"2012","journal-title":"Indian J. Med. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1111\/jcmm.13023","article-title":"Reduced angiogenic gene expression in morbillivirus-triggered oncolysis in a translational model for histiocytic sarcoma","volume":"21","author":"Pfankuche","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s40336-017-0231-1","article-title":"Molecular mechanisms of hypoxia in cancer","volume":"5","author":"Challapalli","year":"2017","journal-title":"Clin. Transl. Imaging"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/ncponc0736","article-title":"Clinical trial results with oncolytic virotherapy: A century of promise, a decade of progress","volume":"4","author":"Liu","year":"2007","journal-title":"Nat. Clin. Pract. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.ctrv.2010.12.003","article-title":"The emerging role of viruses in the treatment of solid tumours","volume":"37","author":"Bourke","year":"2011","journal-title":"Cancer Treat. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1517\/14712598.1.3.525","article-title":"Oncolytic virotherapy for cancer with the adenovirus dl1520 (Onyx-015): Results of phase I and phase II trials","volume":"1","author":"Kirn","year":"2001","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1200\/JCO.2016.67.1529","article-title":"Talimogene Laherparepvec in combination with Ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma","volume":"34","author":"Puzanov","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/jnci\/djj111","article-title":"China appoves world\u2019s first oncolytic virus therapy for cancer treatment","volume":"98","author":"Garber","year":"2006","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3746","DOI":"10.1182\/blood.V97.12.3746","article-title":"Live attenuated measles virus induces regression of human lymphoma xenografts in immunodeficient mice","volume":"97","author":"Grote","year":"2001","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vetimm.2008.09.023","article-title":"Pathogenesis and immunopathology of systemic and nervous canine distemper","volume":"127","author":"Beineke","year":"2009","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1158\/1078-0432.CCR-04-1944","article-title":"In vitro canine distemper virus infection of canine lymphoid cells: A prelude to oncolytic therapy for lymphoma","volume":"11","author":"Suter","year":"2005","journal-title":"Clin. Caner Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1046\/j.1439-0442.1999.00184.x","article-title":"Characterization of a canine CD44 specific monoclonal antibody","volume":"46","author":"Alldinger","year":"1999","journal-title":"Zentralbl. Veterinarmed."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1476-5829.2012.00349.x","article-title":"The growth of the canine glioblastoma cell line D-GBM and the canine histiocytic sarcoma cell line DH82 is inhibited by the resveratrol oligomers hopeaphenol and r2-viniferin","volume":"12","author":"Empl","year":"2014","journal-title":"Vet. Comp. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.vetimm.2003.08.005","article-title":"Down-regulation of MHC class II receptors of DH82 cells, following infection with Ehrlichia canis","volume":"96","author":"Harrus","year":"2003","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.tvjl.2008.03.026","article-title":"Influence of persistent canine distemper virus infection on expression of RECK, matrix-metalloproteinases and their inhibitors in a canine macrophage\/monocytic tumour cell line (DH82)","volume":"182","author":"Puff","year":"2009","journal-title":"Vet. J."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Armando, F., Fayyad, A., Arms, S., Barthel, Y., Schaudien, D., Rohn, K., Gambini, M., Lombardo, M.S., Beineke, A., and Baumg\u00e4rtner, W. (2021). Intratumoral canine distemper virus infection inhibits tumor growth by modulation of the tumor microenvironment in a murine xenograft model of canine histiocytic sarcoma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073578"},{"key":"ref_28","unstructured":"Lapp, S. (2013). In Vivo Untersuchungen \u00fcber die Onkolytische Wirkung des Staupevirus bei dem Disseminierten Histiozyt\u00e4ren Sarkom des Hundes in Einem Mausmodell, University of Veterinary Medicine Hannover."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kirn, D.H., Wang, Y., Le Boeuf, F., Bell, J., and Thorne, S.H. (2007). Targeting of interferon-beta to produce a specific, multi-mechanistic oncolytic vaccinia virus. PLoS Med., 4.","DOI":"10.1371\/journal.pmed.0040353"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1002\/ijc.29068","article-title":"GMCSF-armed vaccinia virus induces an antitumor immune response","volume":"136","author":"Parviainen","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/sj.cgt.7700799","article-title":"Widespread intratumoral virus distribution with fractionated injection enables local control of large human rhabdomyosarcoma xenografts by oncolytic herpes simplex viruses","volume":"12","author":"Currier","year":"2005","journal-title":"Cancer Gene Ther."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Boisgerault, N., Guillerme, J.B., Pouliquen, D., Mesel-Lemoine, M., Achard, C., Combredet, C., Fonteneau, J.F., Tangy, F., and Gregoire, M. (2013). Natural oncolytic activity of live-attenuated measles virus against human lung and colorectal adenocarcinomas. Biomed. Res. Int., 2013.","DOI":"10.1155\/2013\/387362"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Armando, F., Gambini, M., Corradi, A., Giudice, C., Pfankuche, V.M., Brogden, G., Attig, F., von K\u00f6ckritz-Blickwede, M., Baumg\u00e4rtner, W., and Puff, C. (2020). Oxidative stress in canine histiocytic sarcoma cells induced by an infection with canine distemper virus led to a dysregulation of HIF-1alpha downstream pathway resulting in a reduced expression of VEGF-B in vitro. Viruses, 12.","DOI":"10.3390\/v12020200"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/vco.12466","article-title":"Oncolytic activity of canine distemper virus in canine mammary tubular adenocarcinoma cells","volume":"17","author":"Li","year":"2019","journal-title":"Vet. Comp. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/vco.12468","article-title":"Anti-tumour activity of oncolytic reovirus against canine histiocytic sarcoma cells","volume":"17","author":"Igase","year":"2019","journal-title":"Vet. Comp. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/0167-5699(92)90008-U","article-title":"The origin and function of tumor-associated macrophages","volume":"13","author":"Mantovani","year":"1992","journal-title":"Immunol. Today"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.vetimm.2018.03.002","article-title":"Matrix metalloproteinases expression in spontaneous canine histiocytic sarcomas and its xenograft model","volume":"198","author":"Fayyad","year":"2018","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1002\/jcp.24260","article-title":"Tumor associated macrophages and neutrophils in tumor progression","volume":"228","author":"Galdiero","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.coi.2010.01.009","article-title":"Macrophages, innate immunity and cancer: Balance, tolerance, and diversity","volume":"22","author":"Mantovani","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Marek, K., Armando, F., Asawapattanakul, T., Nippold, V.M., Plattet, P., Gerold, G., Baumg\u00e4rtner, W., and Puff, C. (2023). Functional granulocyte\u2013macrophage colony-stimulating factor (GM-CSF) delivered by canine histiocytic sarcoma cells persistently infected with engineered attenuated canine distemper virus. Pathogens, 12.","DOI":"10.3390\/pathogens12070877"},{"key":"ref_41","first-page":"6463","article-title":"Neutrophils contribute to the measles virus-induced antitumor effect: Enhancement by granulocyte macrophage colony-stimulating factor expression","volume":"63","author":"Grote","year":"2003","journal-title":"Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1002\/cncr.20434","article-title":"Oncolysis by viral replication and inhibition of angiogenesis by a replication-conditional herpes simplex virus that expresses mouse endostatin","volume":"101","author":"Mullen","year":"2004","journal-title":"Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Marek, K., Armando, F., Nippold, V.M., Rohn, K., Plattet, P., Brogden, G., Gerold, G., Baumg\u00e4rtner, W., and Puff, C. (2022). Persistent infection of a canine histiocytic sarcoma cell line with attenuated canine distemper virus expressing vasostatin or granulocyte-macrophage colony-stimulating factor. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116156"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.virusres.2009.04.027","article-title":"Distinct cell tropism of canine distemper virus strains to adult olfactory ensheathing cells and Schwann cells in vitro","volume":"144","author":"Techangamsuwan","year":"2009","journal-title":"Virus Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8297\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:26:13Z","timestamp":1760109973000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,30]]},"references-count":45,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158297"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158297","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,30]]}}}