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Human Papillomavirus 16-Transgenic Mice as a Model to Study Cancer-Associated Cachexia.

التفاصيل البيبلوغرافية
العنوان: Human Papillomavirus 16-Transgenic Mice as a Model to Study Cancer-Associated Cachexia.
المؤلفون: Peixoto da Silva S; Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal.; Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal., Santos JMO; Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal.; Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal., Mestre VF; Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal.; Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5001-911 Vila Real, Portugal., Medeiros-Fonseca B; Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal.; Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5001-911 Vila Real, Portugal., Oliveira PA; Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), 5001-801 Vila Real, Portugal.; Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5001-911 Vila Real, Portugal., M S M Bastos M; LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal., Gil da Costa RM; Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal.; Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5001-911 Vila Real, Portugal.; LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal.; Postgraduate Programme in Adult Health (PPGSAD), Tumour and DNA Biobank, Federal University of Maranhão (UFMA), 65080-805 São Luís, Brazil., Medeiros R; Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal.; Faculty of Medicine of the University of Porto (FMUP), 4200-319 Porto, Portugal.; Virology Service, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal.; CEBIMED, Faculty of Health Sciences of the Fernando Pessoa University, 4249-004 Porto, Portugal.; Research Department of the Portuguese League Against Cancer-Regional Nucleus of the North (Liga Portuguesa Contra o Cancro-Núcleo Regional do Norte), 4200-177 Porto, Portugal.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2020 Jul 16; Vol. 21 (14). Date of Electronic Publication: 2020 Jul 16.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Cachexia/*etiology , Human papillomavirus 16/*physiology , Neoplasms/*complications , Papillomavirus Infections/*complications, Animals ; Body Weight ; Cachexia/genetics ; Cachexia/pathology ; Cachexia/virology ; Disease Models, Animal ; Gene Expression ; Human papillomavirus 16/genetics ; Humans ; Male ; Mice, Transgenic ; Muscle Proteins/genetics ; Neoplasms/genetics ; Neoplasms/pathology ; Neoplasms/virology ; Papillomavirus Infections/genetics ; Papillomavirus Infections/pathology ; Papillomavirus Infections/virology ; SKP Cullin F-Box Protein Ligases/genetics
مستخلص: 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 - ) 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 < 0.01), they presented lower body weights ( p < 0.05). This body weight trend was more pronounced when comparing DMBA-exposed groups ( p < 0.01). The same pattern was observed in the gastrocnemius weights (between the unexposed groups: p < 0.05; between the exposed groups: p < 0.001). Importantly, DMBA reduced body and gastrocnemius weights ( p < 0.01) when comparing the HPV + groups. Moreover, the Fbxo32 gene was overexpressed in DMBA-exposed HPV + compared to control mice ( p < 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.
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معلومات مُعتمدة: SFRH/BD/135871/2018 Fundação para a Ciência e a Tecnologia; PI86-CI-IPOP-66-2017 Instituto Português de Oncologia do Porto; PI127-CI-IPOP-118-2019 Instituto Português de Oncologia do Porto; UIDB/00511/2020 Fundação para a Ciência e a Tecnologia; UID/AGR/04033/2019 Fundação para a Ciência e a Tecnologia; - Liga Portuguesa Contra o Cancro
فهرسة مساهمة: Keywords: DMBA; HPV16; K14-HPV16; cancer cachexia; mouse model; wasting syndrome
المشرفين على المادة: 0 (Muscle Proteins)
EC 2.3.2.27 (Fbxo32 protein, mouse)
EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases)
تواريخ الأحداث: Date Created: 20200726 Date Completed: 20210222 Latest Revision: 20210222
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7404304
DOI: 10.3390/ijms21145020
PMID: 32708666
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms21145020