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A úlcera de abomaso, classicamente definida como um processo de autodigestão da mucosa abomasal, é uma das abomasopatias mais comuns no gado leiteiro. É uma doença multifatorial em que o principal fator desencadeante nem sempre é identificado; estando na maioria das vezes, relacionado com fatores predisponentes. No interesse de fomentar o acervo de informações sobre a ocorrência de abomasopatias, este manuscrito teve como objetivo descrever os aspectos clínicos, epidemiológicos e patológicos dos casos de úlceras de abomaso em bovinos leiteiros diagnosticados na área coberta pela Universidade Federal de Fronteira Sul, Realeza, PR. Foram avaliados 98 casos de bovinos leiteiros do sudoeste do Paraná a partir dos dados de necropsias registrados entre abril de 2009 e dezembro de 2019, de forma retrospectiva, sendo essa lesão relatada em 87,50% dentre os animais que apresentavam algum tipo de enfermidade digestória ou metabólica. A mediana de vida foi a de 60 meses, sendo apenas 9,52% criados em sistema intensivo. A ocorrência de úlcera abomasal foi determinante para a morte de 54,17% dos animais necropsiados que apresentavam enfermidade digestória e/ou metabólica, evidenciando a importância de informação sobre a ocorrência dessa enfermidade, que acomete principalmente o gado leiteiro, podendo levar ao óbito do animal.

Made available in DSpace on 2019-10-06T16:06:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-02-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The mTOR/4E-BP1/eIF4E pathway plays important roles in the neoplastic transformation process and in tumour growth. In men, the mTOR/4E-BP1/eIF4E pathway was described as altered in different tumours, including prostate cancer (PC). Apart from humans, the dog is the only species that develops PC with high frequency and is considered a good model for comparative oncology initiatives. Due to limited information on this pathway in canine tumours, this study aimed to investigate mTOR, 4E-BP1 and eIF4E gene and protein expression in canine PC, as well as in metastatic and normal prostatic tissues, and to evaluate the correlations between gene/protein expression and Gleason score (GS) in PC. A total of 35 formalin-fixed paraffin-embedded (FFPE) samples, including 13 of normal prostatic tissue, 17 PC samples and 5 metastasis samples, were evaluated by immunohistochemistry and qPCR. mTOR gene mutation in the kinase domain was also investigated. We identified higher p-mTOR and eIF4E protein levels in canine PC with higher GS values (≥ 8) and a significant positive correlation in expression between these proteins. eIF4E overexpression was observed in metastasis relative to expression in normal samples. Our data suggest that p-mTOR and eIF4E expression is positively correlated with GS in canine PC, similar to the pattern in humans. More studies of the mTOR/4EBP1/eIF4E pathway should be performed to identify possible correlations of the proteins involved with clinical and pathologic findings in canine PC and the roles of these proteins as therapeutic targets for the treatment of canine PC. Department of Veterinary Pathology School of Agricultural and Veterinarian Sciences São Paulo State University (Unesp) Department of Veterinary Clinic School of Veterinary Medicine and Animal Science São Paulo State University (Unesp) Department of Veterinary Pathology School of Agricultural and Veterinarian Sciences São Paulo State University (Unesp) Department of Veterinary Clinic School of Veterinary Medicine and Animal Science São Paulo State University (Unesp) CNPq: 443884/2014-5

Made available in DSpace on 2022-04-29T08:31:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background: Vascular endothelial growth factor-A (VEGF-A) and its receptor, VEGF receptor-2 (VEGFR-2), represent a complex family of angiogenic molecules consisting of different ligands and receptors. Due to the importance of VEGF-A/VEGFR-2 signaling in tumor proliferation and angiogenesis, this study aimed to evaluate the protein and gene expression levels of VEGF-A and VEGFR-2 in canine prostate cancer (PC). Methods: We analyzed VEGF-A and VEGFR-2 expression in 87 PC samples by immunohistochemistry and quantitative-polymerase chain reaction. PC samples were graded according to the Gleason score and the immunohistochemical staining for VEGF-A and VEGFR-2 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 VEGF-A and VEGFR-2 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. Results: Negative to weakly positive expression levels of VEGF-A and VEGFR-2 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-A (p

Made available in DSpace on 2019-10-06T16:22:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01. Added 1 bitstream(s) on 2019-10-09T18:35:19Z : No. of bitstreams: 1 S0100-736X2019000100040.pdf: 2621138 bytes, checksum: aa859149f83aebb38f1b4c7f4dd8d6b8 (MD5) Canine prostate gland is a hormonal dependent organ and its imbalance of estrogen and androgen receptor expressions are directly associated with the development of different diseases. Due to the lack of information regarding the behavior of the aforementioned receptors in canine prostate cancer (PC), this study aimed to identify estrogen receptor alpha (ERα), androgen receptor (AR), Ki67 and phosphatase and tensin homolog (PTEN) protein expressions in canine PC by immunohistochemistry. We found nuclear expression of ERα and AR in the epithelial cells of normal canine samples and a loss of protein expression in PC samples. Normal samples showed Ki67 expression in a few basal cells and the PC samples showed the highest mean of positive cells (253.1). Canine prostate cancer showed a high proliferative index, which was associated with independence of hormonal actuation. PTEN showed positive nuclear and cytoplasmic expression in normal canine samples and a loss in PC. Loss of ERα, AR and PTEN indicated that canine PC exhibits the same immunohistochemical phenotype as in human patients with PC resistant to hormonal therapy. Therefore, canine PC should be considered as a model to study human PC resistant to hormonal therapy. Departamento de Clínica Veterinária Faculdade de Medicina Veterinária e Zootecnia (FMVZ) Universidade Estadual Paulista (Unesp), Rua Prof. Dr. Walter Mauricio Correra s/n, Rubião Junior Departamento de Anestesiologia Faculdade de Medicina de Botucatu, Av. Prof. Montenegro s/n Instituto de Ciências Biomédicas Abel Salazar (ICBAS) Universidade do Porto (UP), Rua Jorge de Viterbo Ferreira 228 Departamento de Clínica Veterinária Faculdade de Medicina Veterinária e Zootecnia (FMVZ) Universidade Estadual Paulista (Unesp), Rua Prof. Dr. Walter Mauricio Correra s/n, Rubião Junior Departamento de Anestesiologia Faculdade de Medicina de Botucatu, Av. Prof. Montenegro s/n

A espécie canina apresenta semelhanças com a espécie humana com relação às lesõesprostáticas, sendo a única espécie a apresentar tumores espontâneos e com frequência, dessemodo representa um importante modelo para estudo comparativo de afecções desta glândula.O desenvolvimento das neoplasias prostáticas é multifatorial e dentre eles, alteraçõesgenéticas e epigenéticas estão envolvidas, portanto o cão pode ser um modelo natural eespontâneo para o estudo das lesões pré neoplásicas e neoplásicas da próstata, com futuro altopotencial de ser utilizado como modelo em testes pré-clínicos de medicamentos. Uma das viasimportantes para o desenvolvimento dos carcinomas prostáticos é a WNT canônica,dependente da proteína β-catenina. Nesta revisão, abordaremos o papel desta via e suaparticipação na carcinogênese prostática, importante em humanos e cães, além de algumasproteínas envolvidas na regulação da mesma

Mammary neoplasms affect a population of uncastrated and elderly female dogs and most of these neoplasms are malignant. In order to study this disease cell culture presents itself as a promising preclinical model, creating the opportunity to deposit cell lines at a cell bank, allowing a great repetition of the assays and making the validation of the results more reliable. Including, in vitro experiments for vasculogenic mimicry (VM) evaluation. VM is related to cancer cells capable of generate vascular-like structures without endothelial cells, mimicking the vasculogenic process. The aim of this study was to establish and characterize ten cell lines from canine mammary gland tumour according to immunophenotype and tumorigenicity, and with its ability to form vasculogenic mimicry-like structures in vitro. Fifteen samples from canine mammary gland carcinoma were collected and cultured in vitro and ten cell lines were established and characterized. Cells were evaluated for morphology, phenotype, vascular mimicry and tumorigenicity. All cell lines presented spindle shape morphology and expressed concomitant pan-cytokeratin and CK8/18. Four cell lines had vasculogenic mimicry ability and two cell showed in vivo tumorigenic potential. Cell characterization of those lines will help to create a database for more knowledge of mammary gland carcinomas in dogs, including studies of tumor behavior and new therapeutic targets.

Made available in DSpace on 2020-12-12T01:51:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-11-29 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) E-cadherin is a transmembrane glycoprotein responsible for cell-to-cell adhesion, and its loss has been associated with metastasis development. Although E-cadherin downregulation was previously reported in canine prostate cancer (PC), the mechanism involved in this process is unclear. It is well established that dogs, besides humans, spontaneously develop PC with high frequency; therefore, canine PC is an interesting model to study human PC. In human PC, CDH1 methylation has been associated with E-cadherin downregulation. However, no previous studies have described the methylation pattern of CDH1 promoter in canine PC. Herein, we evaluated the E-cadherin protein and gene expression in canine PC compared to normal tissues. DNA methylation pattern was investigated as a regulatory mechanism of CDH1 silencing. Our cohort is composed of 20 normal prostates, 20 proliferative inflammatory atrophy (PIA) lesions, 20 PC, and 11 metastases from 60 dogs. The E-cadherin protein expression was assessed by immunohistochemistry and western blotting and gene expression by qPCR. Bisulfite- pyrosequencing assay was performed to investigate the CDH1 promoter methylation pattern. Membranous E-cadherin expression was observed in all prostatic tissues. A higher number of E-cadherin negative cells was detected more frequently in PC compared to normal and PIA samples. High-grade PC showed a diffuse membranous positive immunostaining. Furthermore, PC patients with a higher number of E-cadherin negative cells presented shorter survival time and higher Gleason scores. Western blotting and qPCR assays confirmed the immunohistochemical results, showing lower E-cadherin protein and gene expression levels in PC compared to normal samples. We identified CDH1 promoter hypermethylation in PIA and PC samples. An in vitro assay with two canine prostate cancer cells (PC1 and PC2 cell lines) was performed to confirm the methylation as a regulatory mechanism of E-cadherin expression. PC1 cell line presented CDH1 hypermethylation and after 5-Aza-dC treatment, a decreased CDH1 methylation and increased gene expression levels were observed. Positive E-cadherin cells were massively found in metastases (mean of 90.6%). In conclusion, low levels of E-cadherin protein, gene downregulation and CDH1 hypermethylation was detected in canine PC. However, in metastatic foci occur E-cadherin re-expression confirming its relevance in these processes. Institute of Health Sciences Paulista University—UNIP Department of Veterinary Surgery and Anesthesiology School of Veterinary Medicine and Animal Science Sao Paulo State University—UNESP Department of Veterinary Clinic School of Veterinary Medicine and Animal Science Sao Paulo State University—UNESP Department of Veterinary Medicine Università degli studi di Milano International Center for Research (CIPE) AC Camargo Cancer Center Department of Clinical Genetics University Hospital of Southern Denmark Institute of Regional Health Research University of Southern Denmark Department of Veterinary Surgery and Anesthesiology School of Veterinary Medicine and Animal Science Sao Paulo State University—UNESP Department of Veterinary Clinic School of Veterinary Medicine and Animal Science Sao Paulo State University—UNESP

Made available in DSpace on 2018-12-11T17:01:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-06-01 The PTEN, AR, MDM2 and p53 protein network plays a central role in the development of many human cancers, thus eliciting the development of targeted cancer therapeutics. Dogs spontaneously develop tumours, and they are considered a good model for comparative oncology initiatives. Due to the limited information on these proteins in canine tumours, this study aimed to investigate gene and protein alterations in PTEN, AR, MDM2 and p53 in canine prostate cancer (PC). Protein expression was evaluated by immunohistochemistry (15 normal, 22 proliferative inflammatory atrophy (PIA) and 19 PC samples) and Western blotting (2 normal prostate tissue, 2 BPH, 2 PIA samples and 2 PC samples) and gene expression by RT-qPCR (10 normal, 10 PIA and 15 PC samples) of formalin-fixed tissue. We identified nuclear and cytoplasmic expression of PTEN and p53 in all samples, with only nuclear staining found for MDM2 and AR. Our results revealed high expression of MDM2 in PC and PIA samples compared to normal samples, whereas PTEN, P53 and AR expression was down-regulated in PC compared to normal tissue. All tumour samples (n = 19) showed loss of nuclear PTEN expression, and all cancer mimickers showed positive nuclear staining. Therefore, nuclear PTEN staining could be a good diagnostic marker for differentiating between malignant lesions and mimickers. Canine prostate carcinogenesis involves increased expression of MDM2 in association with decreased expression of PTEN, p53 and AR, such as occurs in hormone refractory PC in men. Thus, dogs may be an important model for studying advanced stage PC. Faculdade de Ciências Agronômicas Univ. Estadual Paulista - UNESP Department of Veterinary Clinic School of Veterinary Medicine and Animal Science Univ. Estadual Paulista - UNESP Department of Urology Botucatu Medical School - FMB Univ. Estadual Paulista - UNESP Faculdade de Ciências Agronômicas Univ. Estadual Paulista - UNESP Department of Veterinary Clinic School of Veterinary Medicine and Animal Science Univ. Estadual Paulista - UNESP Department of Urology Botucatu Medical School - FMB Univ. Estadual Paulista - UNESP

The epithelial-mesenchymal transition (EMT) is a fundamental event responsible for the invasiveness and metastasis of epithelial tumours. The EMT has been described in many human cancers, but there are few reports of this phenomenon in veterinary oncology. Due to the importance of this process, the current study evaluated mesenchymal and epithelial marker protein expression in prostate lesions from dogs. Our results indicate both a loss of E-cadherin and translocation of β-catenin from the membrane to the cytoplasm and nucleus in the tumour group. Vimentin expression in the tumour group was higher than in normal tissue. All of the metastases were positive for prostate-specific antigen, pan-cytokeratin and E-cadherin, although fewer positive cells were present than in the primary tumours. The immunohistochemical results showed a loss of epithelial markers and a gain of a mesenchymal marker among metastatic cells, suggesting that the EMT occurs during the metastatic process of canine prostate carcinoma.

Made available in DSpace on 2018-12-11T17:19:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-06-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) NKX3.1/C-MYC cross-regulation has been reported in the normal human prostate, and loss of NKX3.1 and gain of C-MYC seem to be important events in prostate cancer development and progression. The dog can be an interesting model for human prostatic disease, and yet only one previous research study has shown deregulation of NKX3.1 and MYC in the canine prostate. To address the expression of NKX3.1 and C-MYC in different canine prostatic lesions, this study verified the gene and protein expression of NKX3.1 and C-MYC in normal canine prostatic tissues. We identified a 26 kDa band that corresponded to the NKX3.1 protein, while C-MYC showed a 50 kDa band on Western blotting analysis of all prostatic tissues. We observed that NKX3.1 protein and transcript were down-regulated in prostate cancer (PC) samples compared with non-neoplastic samples. We also observed that C-MYC protein was overexpressed in PC samples compared with normal (P =.001) and proliferative inflammatory atrophy (PIA) samples (P =.003). We found a positive correlation between NKX3.1 and C-MYC protein expression in normal and PIA samples. Interestingly, a negative correlation (NKX3.1 downregulation and MYC overexpression) was observed between NKX3.1 and MYC transcripts in PC. Thus, samples with higher C-MYC expression also exhibited higher NKX3.1 expression, which indicates the regulation of C-MYC by NKX3.1 protein. As in humans, these two genes and proteins were found to be related to canine prostate cancer. However, in contrast from what is observed in humans, in canine PC samples, the downregulation of NKX3.1 cannot be explained by DNA hypermethylation. Department of Veterinary Clinic School of Veterinary Medicine and Animal Science São Paulo State University – UNESP Department of Veterinary Clinic School of Veterinary Medicine and Animal Science São Paulo State University – UNESP FAPESP: CNPq 306055/2011-2 FAPESP: FAPESP 2010/13774-6 FAPESP: FAPESP 2012/16068-0 FAPESP: FAPESP 2012/18426-1

Made available in DSpace on 2018-12-11T17:21:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01 Saúde Animal Veterinary Hospital Department of Veterinary Clinic School of Veterinary Medicine and Animal Science São Paulo State University - UNESP College of Veterinary Medicine Western University of Health Sciences Department of Veterinary Clinic School of Veterinary Medicine and Animal Science São Paulo State University - UNESP