{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:50:20Z","timestamp":1791942620066,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2015\/25400\u20107"],"award-info":[{"award-number":["2015\/25400\u20107"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Vascular endothelial growth factor\u2010A (VEGF\u2010A) and its receptor, VEGF receptor\u20102 (VEGFR\u20102), represent a complex family of angiogenic molecules consisting of different ligands and receptors. Due to the importance of VEGF\u2010A\/VEGFR\u20102 signaling in tumor proliferation and angiogenesis, this study aimed to evaluate the protein and gene expression levels of VEGF\u2010A and VEGFR\u20102 in canine prostate cancer (PC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed VEGF\u2010A and VEGFR\u20102 expression in 87 PC samples by immunohistochemistry and quantitative\u2010polymerase chain reaction. PC samples were graded according to the Gleason score and the immunohistochemical staining for VEGF\u2010A and VEGFR\u20102 was quantified using a selected threshold from the ImageJ Software. Microvascular density was assessed by cluster of differentiation 31 staining and counting the number of positive vessels. Additionally, the homology of <jats:italic>VEGF\u2010A<\/jats:italic> and <jats:italic>VEGFR\u20102<\/jats:italic> between humans and dogs was assessed, followed by the construction of a protein structure homology model to compare the tertiary structures of these proteins in both species.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Negative to weakly positive expression levels of VEGF\u2010A and VEGFR\u20102 were observed in the epithelial cells of the normal prostate (NP) and prostatic hyperplasia samples. In contrast, the canine proliferative atrophy and PC samples exhibited higher VEGF\u2010A (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001) and VEGFR\u20102 (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001) compared to NP. Moreover, positive correlations between the expression levels of <jats:italic>VEGF\u2010A<\/jats:italic> and <jats:italic>VEGFR\u20102<\/jats:italic> (Spearman's coefficient (<jats:italic>r<\/jats:italic>)\u2009=\u2009.68, <jats:italic>p<\/jats:italic>\u2009=\u2009.013) and the expression levels of VEGF\u2010A and VEGFR\u20102 proteins (<jats:italic>r<\/jats:italic>\u2009=\u2009.8, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001) were also observed in the NP samples. Additionally, the patients with PC exhibiting higher VEGFR\u20102 expression levels experienced a shorter survival period (<jats:italic>p<\/jats:italic>\u2009=\u2009.0372). Furthermore, we found an association between the microvascular density and overall survival. Dogs with a higher number of vessels showed a shorter survival time. We further demonstrated that the <jats:italic>VEGF\u2010A<\/jats:italic> and <jats:italic>VEGFR\u20102<\/jats:italic> exhibited high homology between humans and dogs, and identified their protein structures in both species.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In conclusion, VEGFR\u20102 appears to be an independent prognostic factor in animals with PC. <jats:italic>VEGF\u2010A<\/jats:italic> and <jats:italic>VEGFR\u20102<\/jats:italic> are highly conserved between humans and dogs, which can be investigated further in future cross\u2010species studies to explore their therapeutic applications.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24199","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T17:24:06Z","timestamp":1627493046000},"page":"1021-1031","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Expression and prognostic significance of vascular endothelial growth factor\u2010A (VEGF\u2010A) and its receptor in canine prostate cancer"],"prefix":"10.1002","volume":"81","author":[{"given":"Antonio Fernando","family":"Leis\u2010Filho","sequence":"first","affiliation":[{"name":"Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science S\u00e3o Paulo State University\u2014UNESP Botucatu Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia deFaria","family":"Lainetti","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science S\u00e3o Paulo State University\u2014UNESP Botucatu Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila Emiko","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science S\u00e3o Paulo State University\u2014UNESP Botucatu Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Palmieri","sequence":"additional","affiliation":[{"name":"School of Veterinary Science The University of Queensland Gatton Campus Gatton Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9e Laufer","family":"Amorim","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science S\u00e3o Paulo State University\u2014UNESP Botucatu Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6702-6139","authenticated-orcid":false,"given":"Carlos Eduardo","family":"Fonseca\u2010Alves","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science S\u00e3o Paulo State University\u2014UNESP Botucatu Sao Paulo Brazil"},{"name":"Institute of Health Sciences Paulista University\u2014UNIP Bauru Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcpa.2019.07.005"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20071555"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0199173"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2018.04.001"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300985815574008"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20720"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20721"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9061441"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.29"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(02)00261-7"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22596"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.398"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300985814549951"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13081887"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2015.09.004"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/vr.104414"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2016.03.008"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/vetsci6010003"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/vms3.66"},{"key":"e_1_2_9_21_1","volume-title":"The BLAST sequence analysis tool. 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