{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T03:39:04Z","timestamp":1764905944948,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T00:00:00Z","timestamp":1594857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/135871\/2018","UIDB\/00511\/2020","UID\/AGR\/04033\/2019"],"award-info":[{"award-number":["SFRH\/BD\/135871\/2018","UIDB\/00511\/2020","UID\/AGR\/04033\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011776","name":"Instituto Portugu\u00eas de Oncologia do Porto","doi-asserted-by":"publisher","award":["PI86-CI-IPOP-66-2017","PI127-CI-IPOP-118-2019"],"award-info":[{"award-number":["PI86-CI-IPOP-66-2017","PI127-CI-IPOP-118-2019"]}],"id":[{"id":"10.13039\/501100011776","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011733","name":"Liga Portuguesa Contra o Cancro","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100011733","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cancer cachexia is a multifactorial syndrome characterized by general inflammation, weight loss and muscle wasting, partly mediated by ubiquitin ligases such as atrogin-1, encoded by Fbxo32. Cancers induced by high-risk human papillomavirus (HPV) include anogenital cancers and some head-and-neck cancers and are often associated with cachexia. The aim of this study was to assess the presence of cancer cachexia in HPV16-transgenic mice with or without exposure to the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). Male mice expressing the HPV16 early region under the control of the cytokeratin 14 gene promoter (K14-HPV16; HPV+) and matched wild-type mice (HPV\u2212) received DMBA (or vehicle) topically over 17 weeks of the experiment. Food intake and body weight were assessed weekly. The gastrocnemius weights and Fbxo32 expression levels were quantified at sacrifice time. HPV-16-associated lesions in different anatomic regions were classified histologically. Although unexposed HPV+ mice showed higher food intake than wild-type matched group (p &lt; 0.01), they presented lower body weights (p &lt; 0.05). This body weight trend was more pronounced when comparing DMBA-exposed groups (p &lt; 0.01). The same pattern was observed in the gastrocnemius weights (between the unexposed groups: p &lt; 0.05; between the exposed groups: p &lt; 0.001). Importantly, DMBA reduced body and gastrocnemius weights (p &lt; 0.01) when comparing the HPV+ groups. Moreover, the Fbxo32 gene was overexpressed in DMBA-exposed HPV+ compared to control mice (p &lt; 0.05). These results show that K14-HPV16 mice closely reproduce the anatomic and molecular changes associated with cancer cachexia and may be a good model for preclinical studies concerning the pathogenesis of this syndrome.<\/jats:p>","DOI":"10.3390\/ijms21145020","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T10:54:46Z","timestamp":1594896886000},"page":"5020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Human Papillomavirus 16-Transgenic Mice as a Model to Study Cancer-Associated Cachexia"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2030-6368","authenticated-orcid":false,"given":"Sara","family":"Peixoto da Silva","sequence":"first","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-524X","authenticated-orcid":false,"given":"Joana M. O.","family":"Santos","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"given":"Ver\u00f3nica F.","family":"Mestre","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal"},{"name":"Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5001-911 Vila Real, Portugal"}]},{"given":"Beatriz","family":"Medeiros-Fonseca","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal"},{"name":"Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5001-911 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9519-4044","authenticated-orcid":false,"given":"Paula A.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal"},{"name":"Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5001-911 Vila Real, Portugal"}]},{"given":"Margarida","family":"M. S. M. Bastos","sequence":"additional","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2151-2449","authenticated-orcid":false,"given":"Rui M.","family":"Gil da Costa","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5001-911 Vila Real, Portugal"},{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"},{"name":"Postgraduate Programme in Adult Health (PPGSAD), Tumour and DNA Biobank, Federal University of Maranh\u00e3o (UFMA), 65080-805 S\u00e3o Lu\u00eds, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal"},{"name":"Virology Service, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"CEBIMED, Faculty of Health Sciences of the Fernando Pessoa University, 4249-004 Porto, Portugal"},{"name":"Research Department of the Portuguese League Against Cancer\u2014Regional Nucleus of the North (Liga Portuguesa Contra o Cancro\u2014N\u00facleo Regional do Norte), 4200-177 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.bbagrm.2019.01.001","article-title":"Hallmarks of HPV carcinogenesis: The role of E6, E7 and E5 oncoproteins in cellular malignancy","volume":"1862","author":"Estevao","year":"2019","journal-title":"Biochim. 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