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Infectious laryngotracheitis (ILT) is an important upper respiratory disease of chickens. Gross and histologic lesions of ILT in chickens are compared to immunohistochemistry to evaluate the diagnostic test sensitivity. A total of 31 separate ILT-confirmed necropsy submissions (12 commercial meat-type flocks, 13 egg-type producers, and 6 backyard flocks) were arbitrarily selected. Each submission ranged from 1 to 18 birds, for a total of 246 chickens. Cases with available formalin-fixed tissues were selected to include a range of bird production types, ages, clinical histories, and severity of macroscopic and histologic lesions. Macroscopic findings in the respiratory tract varied from increased mucus (55.6%) to fibrinonecrotic exudate (20.3%) and hemorrhages in the larynx and trachea (13.0%). Syncytia with intranuclear inclusion bodies were present in the respiratory tract epithelium with or without hemorrhages. Sections of conjunctiva, sinus, larynx, trachea, lung, and air sac were analyzed by immunohistochemistry (IHC) to detect gallid alphaherpesvirus 1 (GaHV-1) antigen. Positive immunolabeling was detected in the cytoplasm and nuclei of syncytia and epithelial cells in 18/22 conjunctivae (82%), 12/13 sinuses (92%), 18/22 larynxes (82%), 23/25 tracheas (92%), 10/21 lungs (57%), and 3/8 air sacs (37%). Of the 34 tissues with no visible syncytia or inclusion bodies, 8 were positive by IHC. In conclusion, IHC was useful to study the viral antigen tissue distribution and support the diagnosis of ILT when the histopathologic interpretation was doubtful.

Developmental vitamin D (DVD)-deficiency is an epidemiologically established risk factor for autism. Emerging studies also highlight the involvement of gut microbiome/gut physiology in autism. The current study aims to examine the effect of DVD-deficiency on a broad range of autism-relevant behavioural phenotypes and gut health. Vitamin D deficient rat dams exhibited altered maternal care, DVD-deficient pups showed increased ultrasonic vocalizations and as adolescents, social behaviour impairments and increased repetitive self-grooming behaviour. There were significant impacts of DVD-deficiency on gut health demonstrated by alterations to the microbiome, decreased villi length and increased propionate levels. Overall, our animal model of this epidemiologically validated risk exposure for autism shows an expanded range of autism-related behavioural phenotypes and now alterations in gut microbiome that correlate with social behavioural deficits raising the possibility that DVD-deficiency induced ASD-like behaviours are due to alterations in gut health.

Aortic valve stenosis has become the most common valvular disease in elderly patients. Several treatments are available such as surgical aortic valve replacement and transcatheter aortic valve implantation. To date, however, there is a need to discover alternative treatments that can delay the disease progression and, therefore, the implant of a prosthetic valve. In this regard, a decalcification procedure based on the use of ultrasonic waves could represent an innovative solution in transcatheter cardiovascular therapies. In this article, we describe an innovative transcatheter debridement device (TDD) that uses low-intensity ultrasound shock waves for calcium ablation from the native aortic valve and bioprosthetic valve. Mesenchymal stem cells were seeded onto pericardium-based scaffolds and committed into an osteogenic phenotype. After treatment with TDD, cell proliferation was analyzed, as well as lactate dehydrogenase release and cell morphology. The release of calcium and inflammation events were detected. The results confirmed that the TDD was able to induce a safe decalcification without any adverse inflammatory events.

BACKGROUND: Aggressive fluid or blood component transfusion for severe hemorrhagic shock may restore macrocirculatory parameters, but not always improve microcirculatory perfusion and tissue oxygen delivery. We established an ovine model of hemorrhagic shock to systematically assess tissue oxygen delivery and repayment of oxygen debt; appropriate outcomes to guide Patient Blood Management. METHODS: Female Dorset-cross sheep were anesthetized, intubated, and subjected to comprehensive macrohemodynamic, regional tissue oxygen saturation (StO2), sublingual capillary imaging, and arterial lactate monitoring confirmed by invasive organ-specific microvascular perfusion, oxygen pressure, and lactate/pyruvate levels in brain, kidney, liver, and skeletal muscle. Shock was induced by stepwise withdrawal of venous blood until MAP was 30 mm Hg, mixed venous oxygen saturation (SvO2) 4 mM. Resuscitation with PlasmaLyte® was dosed to achieve MAP > 65 mm Hg. RESULTS: Hemorrhage impacted primary outcomes between baseline and development of shock: MAP 89 ± 5 to 31 ± 5 mm Hg (P

Cancers occur across species. Understanding what is consistent and varies across species can provide new insights into cancer initiation and evolution, with significant implications for advancing human healthcare, animal welfare, and wildlife conservation. We built the pan-species cancer digital pathology atlas (PANCAD) and conducted the first pan-species study of computational comparative pathology using a supervised convolutional neural network algorithm trained on human samples. The artificial intelligence algorithm achieves high accuracy in measuring immune response through single-cell classification for two transmissible cancers (canine transmissible venereal tumour, 0.94; Tasmanian devil facial tumour disease, 0.88). Furthermore, in 18 other vertebrate species (mammalia=11, reptilia=4, aves=2, and amphibia=1), accuracy (0.57-0.94) was influenced by cell morphological similarity preserved across different taxonomic groups, tumour sites, and variations in the immune compartment. A new metric, named morphospace overlap, was developed to guide veterinary pathologists towards rational deployment of this technology on new samples. This study provides the foundation and guidelines for transferring artificial intelligence technologies to veterinary pathology based on a new understanding of morphological conservation, which could vastly accelerate new developments in veterinary medicine and comparative oncology.

The increasing incidence of calcific aortic valve disease necessitates the elaboration of new strategies to retard the progression of the pathology with an innovative solution. While the increasing diffusion of the transcatheter aortic valve replacements (TAVRs) allows a mini-invasive approach to aortic valve substitution as an alternative to conventional surgical replacement (SAVR) in an always larger patient population, TAVR implantation still has contraindications for young patients. In addition, it is liable to undergo calcification with the consequent necessity of re-intervention with conventional valve surgery or repeated implantation in the so-called TAVR-in-TAVR procedure. Inspired by applications for non-cardiac pathologies or for vascular decalcification before stenting (i.e., coronary lithotripsy), in the present study, we show the feasibility of human valve treatment with a mini-invasive device tailored to deliver shockwaves to the calcific leaflets. We provide evidence of efficient calcium deposit ruptures in human calcified leaflets treated ex vivo and the safety of the treatment in pigs. The use of this device could be helpful to perform shockwaves valvuloplasty as an option to retard TAVR/SAVR, or as a pretreatment to facilitate prosthesis implantation and minimize the occurrence of paravalvular leak.

Made available in DSpace on 2022-04-28T19:52:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-03-01 Fundação para a Ciência e a Tecnologia Cancer registries are fundamental tools for collecting epidemiological cancer data and developing cancer prevention and control strategies. While cancer registration is common in the human medical field, many attempts to develop animal cancer registries have been launched over time, but most have been discontinued. A pivotal aspect of cancer registration is the availability of cancer coding systems, as provided by the International Classification of Diseases for Oncology (ICD-O). Within the Global Initiative for Veterinary Cancer Surveillance (GIVCS), established to foster and coordinate animal cancer registration worldwide, a group of veterinary pathologists and epidemiologists developed a comparative coding system for canine neoplasms. Vet-ICD-O-canine-1 is compatible with the human ICD-O-3.2 and is consistent with the currently recognized classification schemes for canine tumors. It comprises 335 topography codes and 534 morphology codes. The same code as in ICD-O-3.2 was used for the majority of canine tumors showing a high level of similarity to their human counterparts (n = 408). De novo codes (n = 152) were created for specific canine tumor entities (n = 126) and topographic sites (n = 26). The Vet-ICD-O-canine-1 coding system represents a user-friendly, easily accessible, and comprehensive resource for developing a canine cancer registration system that will enable studies within the One Health space. Departamento de Estudo de Populações Vet-OncoNet ICBAS Instituto de Ciências Biomédicas Abel Salazar Universidade do Porto EPIUnit—Instituto de Saúde Pública Universidade do Porto Laboratório Para a Investigação Integrativa e Translacional em Saúde Populacional (ITR) Department of Veterinary Medicine and Animal Production University of Naples Federico II Institute of Pathology School of Medicine Technical University of Munich Associate Laboratory for Animal and Veterinary Science-AL4AnimalS Animal and Veterinary Research Centre (CECAV) University of Trás-os-Montes and Alto Douro (UTAD) School of Veterinary Medicine and Animal Science São Paulo State University (UNESP), SP Division of Neurological Sciences DCR-VPH Vetsuisse Faculty University of Bern Department of Veterinary Sciences University of Turin National Disease Registration Service NHS Digital International Agency for Research on Cancer IARC Institute of Veterinary Pathology Vetsuisse Faculty University of Zurich School of Veterinary Science Gatton Campus The University of Queensland School of Veterinary Medicine and Animal Science University of São Paulo, SP School of Veterinary Medicine and Animal Science São Paulo State University (UNESP), SP Fundação para a Ciência e a Tecnologia: UIDB/CVT/00772/2020

Simple Summary Early detection of racehorses at risk of stress fracture is key to reducing the number of horses with catastrophic fractures while racing. Bone changes are often visible in the limbs of Thoroughbred racehorses in work, particularly in the fetlock region. However, it is currently unknown whether some of these changes indicate an impending fracture or are a healthy adaptation to high-speed exercise. This study looks at imaging and gross changes in a specific area (parasagittal grooves (PSGs) of the cannon bone) and the utility of X-ray, computed tomography (CT) and magnetic resonance imaging (MRI) to detect the changes. All fetlock joints were assessed from twenty horses that died during racing or training, including horses with and without fetlock fracture. Overall, X-ray was poor for detecting PSG changes. Some PSG changes on CT and MRI were common in Thoroughbred racehorses and possibly represent normal bone adaptation when seen in clinical cases. However, certain CT and MRI findings were more prevalent in horses with a fracture, possibly indicating microdamage accumulation and increased risk of fracture. Bilateral advanced imaging is recommended in clinical cases of suspected fetlock pathology. Abstract (1) Background: Parasagittal groove (PSG) changes are often present on advanced imaging of racing Thoroughbred fetlocks and have been suggested to indicate increased fracture risk. Currently, there is limited evidence differentiating the imaging appearance of prodromal changes in horses at risk of fracture from horses with normal adaptive modelling in response to galloping. This study aims to investigate imaging and gross PSG findings in racing Thoroughbreds and the comparative utility of different imaging modalities to detect PSG changes. (2) Methods: Cadaver limbs were collected from twenty deceased racing/training Thoroughbreds. All fetlocks of each horse were examined with radiography, low-field magnetic resonance imaging (MRI), computed tomography (CT), contrast arthrography and gross pathology. (3) Results: Horses with fetlock fracture were more likely to have lateromedial PSG sclerosis asymmetry and/or lateral PSG lysis. PSG lysis was not readily detected using MRI. PSG subchondral bone defects were difficult to differentiate from cartilage defects on MRI and were not associated with fractures. The clinical relevance of PSG STIR hyperintensity remains unclear. Overall, radiography was poor for detecting PSG changes. (4) Conclusions: Some PSG changes in Thoroughbred racehorses are common; however, certain findings are more prevalent in horses with fractures, possibly indicating microdamage accumulation. Bilateral advanced imaging is recommended in racehorses with suspected fetlock pathology.

Women’s participation and completion at veterinary schools has increased globally for the past few decades. However, increased female graduates have not translated into similar patterns of academic staffing. The gender distribution within each academic level at eight accredited veterinary faculties in Australia and New Zealand, 38 accredited faculties in the USA and Canada and 98 accredited faculties in Europe were analyzed. Women occupied 47.9%, 45.5% and 47.5% of the academic positions in Australia/New Zealand, the USA/Canada and Europe, respectively. Compared to their male counterparts, female academics were more likely to hold the lower ranked positions. The gender distribution is skewed toward men in the senior positions at or above associate professor level in all analyzed regions. The findings of this study confirm gender inequality in academic progression meaning there is a continued need to develop strategies to eliminate inequity in veterinary science faculties worldwide.

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

Simple Summary Prostatic diseases are important worldwide, being the prostate cancer (PC) the most common tumor in men. Among the factors associated with PC development, the preneoplastic lesions are well-recognized. Preneoplastic lesions are cellular morphological alterations, induced by different factors and present a potential to progression for PC. In this scenario, dogs are considered spontaneous models. Dogs naturally develops prostatic hyperplasia, preneoplastic lesions and PC. Among the preneoplastic lesions, the proliferative inflammatory atrophy (PIA) develops spontaneously in dogs. PIA is an epithelial lesion induced by prostatic chronic inflammation, leading to a proliferative atrophy of the prostate gland. Thus, this study aimed to perform a full PIA morphological, phenotypical and molecular characterization in dogs. After reviewing the archives of the veterinary pathology service, it was identified 171 dogs containing PIA in the prostate gland, and among the PC cases (N = 84), it was identified PIA lesions surrounding 60.7% of PC cases. Besides that, we identified loss of genes related to the maintenance of prostatic tissue and can predispose to malignant transformation. Moreover, mutations in androgen receptor gene were identified, demonstration alteration in DNA in PIA. Overall, these results support the hypothesis that PIA can be considered a preneoplastic lesion in canine prostate. Abstract Proliferative inflammatory atrophy (PIA) is an atrophic lesion of the prostate gland that occurs in men and dogs and is associated with a chronic inflammatory infiltrate. In this study, we retrospectively reviewed canine prostatic samples from intact dogs, identifying 50 normal prostates, 140 cases of prostatic hyperplasia, 171 cases of PIA, 84 with prostate cancer (PC), 14 with prostatic intraepithelial neoplasia (PIN) and 10 with bacterial prostatitis. PIA samples were then selected and classified according to the human classification. The presence of PIA lesions surrounding neoplastic areas was then evaluated to establish a morphological transition from normal to preneoplastic and neoplastic tissue. In addition, the expression of PTEN, P53, MDM2 and nuclear androgen receptor (AR) were analyzed in 20 normal samples and 20 PIA lesions by immunohistochemistry and qPCR. All PIA lesions showed variable degrees of mononuclear cell infiltration around the glands and simple atrophy was the most common histopathological feature. PIA was identified between normal glands and PC in 51 (61%) out of the 84 PC samples. PIA lesions were diffusely positive for molecular weight cytokeratin (HMWC). Decreased PTEN and AR gene and protein expression was found in PIA compared to normal samples. Overall, our results strongly suggest that PIA is a frequent lesion associated with PC. Additionally, this finding corroborates the hypothesis that in dogs, as is the case in humans, PIA is a pre neoplastic lesion that has the potential to progress into PC, indicating an alternative mechanism of prostate cancer development in dogs.

Background and Aims Carcinoma associated with perianal fistula in Crohn’s disease is a pending threat for patients. This study aimed to improve understanding and facilitate development of diagnostic and therapeutic strategies. Methods A retrospective case-control study was conducted at four German hospitals. The analysis included 40 patients with proven malignancy associated with perianal Crohn’s fistulas and 40 randomly selected controls with fistulizing perianal Crohn’s disease. Differences between groups were analysed and multivariate calculations were performed to describe risk factors for oncological outcomes. Results Histology revealed adenocarcinoma in 33/40 patients and squamous cell carcinoma in 7/40 patients. Compared to fistula patients without carcinoma, patients with malignancies associated with fistula had a diagnosis of Crohn’s disease at younger age. Crohn’s disease lasted longer in patients with malignancy [25.8 ± 9.0 vs 19.6 ± 10.4; p = 0.006]. Fistula-related findings differed significantly between the two groups. Signs of complicated and severe fistulation including complex anatomy and chronic activity occurred significantly more often in patients with malignancy associated with fistula. Significant multivariate hazard ratios for overall mortality and progression-free survival were shown for histological type of cancer, metastatic disease and R1 resection. Overall survival was 45.1 ± 28.6 months and the 5-year survival rate was 65%. Conclusions In patients with adenocarcinoma or squamous cell carcinoma associated with perianal fistula in Crohn’s disease, fistula characteristics determine the risk of malignancy. Early diagnosis influences outcomes, while treatment of chronic fistula activity may be key to preventing malignancy. Expert multimodal therapy is paramount for successful treatment of perianal fistula-associated malignancies.

Background Refractory cardiogenic shock (CS), frequently complicated by pulmonary failure, often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Currently available animal models, such as the coronary ligation model, result in highly variable injury profiles and unacceptably high levels of subsequent ventricular fibrillation, cardiac arrest, and death. As the use of ECMO increases, there is a growing need for a clinically relevant, robust, and titratable model of severe cardiopulmonary failure supported by VA-ECMO. Methods Six sheep (60 ± 6 kg) were anaesthetized, intubated and mechanically ventilated. VA-ECMO was initially carried out at a flow rate of 1 L/min. CS was induced through 1-mL left ventricle myocardial injections of 96% ethanol and confirmed when systolic blood pressure (SBP) was 4 mmol/L. Then, pulmonary failure was confirmed when PaO2 was

CD24 is a cell surface molecule anchored by glycosyl-phosphatidyl-inositol and expressed by different human cancers, including prostate cancer (PC). Some studies have demonstrated that CD24 expression is associated with poor patient outcome, however, few studies have investigated CD24 expression in spontaneous animal models of human PC, such as canine PC. This study aimed to evaluate the expression of CD24 in human PC using the in silico analysis of the data obtained from The Cancer Genome Atlas (TCGA) and comparing it with the previously published prostatic canine transcriptome data. In addition, CD24 expression was confirmed by immunohistochemistry in an independent cohort of canine prostatic samples and its prognostic significance assessed. The systematic review identified 10 publications fitting with the inclusion criteria of this study. Of the 10 manuscripts, 5 demonstrated a direct correlation between CD24 overexpression and patient prognoses. CD24 expression was also associated with PSA relapse (2/5) and tumor progression (1/5). However, the in silico analysis did not validate CD24 as a prognostic factor of human PC. Regarding canine PC, 10 out of 30 normal prostates and 27 out of 40 PC samples were positive for CD24. As in humans, there was no association with overall survival. Overall, our results demonstrated a significant CD24 overexpression in human and canine prostate cancer, although its prognostic value may be questionable. However, tumors overexpressing CD24 may be a reliable model for new target therapies and dogs could be used of a unique preclinical model for these studies.

The acute respiratory distress syndrome (ARDS) is a severe lung disorder with a high morbidity and mortality which affects all age groups. Despite active research with intense, ongoing attempts in developing pharmacological agents to treat ARDS, its mortality rate remains unaltered high and treatment is still only supportive. Over the years, there have been many attempts to identify meaningful subgroups likely to react differently to treatment among the heterogenous ARDS population, most of them unsuccessful. Only recently, analysis of large ARDS cohorts from randomized controlled trials have identified the presence of distinct biological subphenotypes among ARDS patients: a hypoinflammatory (or uninflamed; named P1) and a hyperinflammatory (or reactive; named P2) subphenotype have been proposed and corroborated with existing retrospective data. The hyperinflammatory subphenotyope was clearly associated with shock state, metabolic acidosis, and worse clinical outcomes. Core features of the respective subphenotypes were identified consistently in all assessed cohorts, independently of the studied population, the geographical location, the study design, or the analysis method. Additionally and clinically even more relevant treatment efficacies, as assessed retrospectively, appeared to be highly dependent on the respective subphenotype. This discovery launches a promising new approach to targeted medicine in ARDS. Even though it is now widely accepted that each ARDS subphenotype has distinct functional, biological, and mechanistic differences, there are crucial gaps in our knowledge, hindering the translation to bedside application. First of all, the underlying driving biological factors are still largely unknown, and secondly, there is currently no option for fast and easy identification of ARDS subphenotypes. This narrative review aims to summarize the evidence in biological subphenotyping in ARDS and tries to point out the current issues that will need addressing before translation of biological subohenotypes into clinical practice will be possible.

Anatomic pathology is a vital component of veterinary medicine but as a primarily subjective qualitative or semiquantitative discipline, it is at risk of cognitive biases. Logistic regression is a statistical technique used to explain relationships between data categories and outcomes and is increasingly being applied in medicine for predicting disease probability based on medical and patient variables. Our aims were to evaluate histologic features of canine and feline bladder diseases and explore the utility of logistic regression modeling in identifying associations in veterinary histopathology, then formulate a predictive disease model using urinary bladder as a pilot tissue. The histologic features of 267 canine and 71 feline bladder samples were evaluated, and a logistic regression model was developed to identify associations between the bladder disease diagnosed, and both patient and histologic variables. There were 102 cases of cystitis, 84 neoplasia, 42 urolithiasis and 63 normal bladders. Logistic regression modeling identified six variables that were significantly associated with disease outcome: species, urothelial ulceration, urothelial inflammation, submucosal lymphoid aggregates, neutrophilic submucosal inflammation, and moderate submucosal hemorrhage. This study demonstrated that logistic regression modeling could provide a more objective approach to veterinary histopathology and has opened the door toward predictive disease modeling based on histologic variables.

Congenital heart diseases have rarely been described in rabbits. The purpose of the present case report is to describe the clinical, radiographic, echocardiographic, and pathological features of a partial atrioventricular septal defect in a pet rabbit. A 3-month-old, 380-g male vaccinated pet rabbit was presented for decreased activity, increased respiratory rate and effort, anorexia, and decreased fecal output of 2 days duration. Total body radiographic images revealed severe cardiomegaly associated with enlarged caudal pulmonary vessels and increased interstitial to alveolar lung pattern. Echocardiographic imaging showed evidence of distended heart chambers, abnormal flow through the atria, and mitral valve regurgitation. The rabbit was treated with furosemide and an angiotensin-converting enzyme inhibitor but rapidly deteriorated and died. Necropsy confirmed the dilation of both ventricles and the presence of a partial atrioventricular septal defect associated with an ostium primum atrial septal defect just over the tricuspid valve and the mitral valve.

Studies documenting the application of ultrasonography to depict normal and pathological changes in koalas (Phascolarctos cinereus), especially in the male, are scarce. Sixty-two wild koalas were used in this study to define ultrasonographic protocols and features for the assessment of the male koala reproductive tract. Testis, epididymis and spermatic cord were examined using a hockey stick transducer. The normal koala testis showed a homogeneous echogenicity and an obvious hyper-echoic band corresponding to the tunica albuginea. The cauda epididymis was characterised by hypo- and hyper-echoic regions and was most effectively imaged in sagittal section. The koala prostate was assessed using a micro-curved transducer positioned midline, caudal to the bladder. On transverse section, it showed distinct margins and a well-defined internal structure, although the prostatic urethra was not apparent on most scans. To image the bulbourethral glands (BGs), the hockey stick transducer was placed lateral to the cloaca. BGIII was located just below the skin, while BGII was located deeper than BGIII. BGI was too small and not sufficiently echogenic to be detected. The ultrasonographic appearance of the BGs was similar to that of the testes but with more obvious hypo-echoic stippling. This comprehensive review of the ultrasonographic appearance of normal male koala reproductive tract can be used by veterinarians and others, in zoos or those working with wild koalas, during assessment of the reproductive tract of male koalas in relation to seasonal changes in accessory gland function or for the pathological investigation of reproductive lesions and infertility problems.

Made available in DSpace on 2018-12-11T17:16:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-12-06 Background: c-KIT expression has been related to bone metastasis in human prostate cancer, but whether c-KIT expression can be similarly classified in canine prostatic tissue is unknown. This study assessed c-KIT and Ki67 expression in canine prostate cancer (PC). c-KIT gene and protein expression and Ki67 expression were evaluated in forty-four canine prostatic tissues by immunohistochemistry, RT-qPCR and western blot. Additionally, we have investigated c-KIT protein expression by immunoblotting in two primary canine prostate cancer cell lines. Results: Eleven normal prostates, 12 proliferative inflammatory atrophy (PIA) prostates, 18 PC, 3 metastatic lesions and two prostate cancer cell cultures (PC1 and PC2) were analysed. The prostatic tissue exhibited varying degrees of membranous, cytoplasmic or membranous/cytoplasmic c-KIT staining. Four normal prostates, 4 PIA and 5 prostatic carcinomas showed positive c-KIT expression. No c-KIT immunoexpression was observed in metastases. Canine prostate cancer and PIA samples contained a higher number of Ki67-positive cells compared to normal samples. The median relative quantification (RQ) for c-KIT expression in normal, PIA and prostate cancer and metastatic samples were 0.6 (0.1-2.5), 0.7 (0.09-2.1), 0.7 (0.09-5.1) and 0.1 (0.07-0.6), respectively. A positive correlation between the number of Ki67-positive cells and c-KIT transcript levels was observed in prostate cancer samples. In the cell line, PC1 was negative for c-KIT protein expression, while PC2 was weakly positive. Conclusion: The present study identified a strong correlation between c-KIT expression and proliferative index, suggesting that c-KIT may influence cell proliferation. Therefore, c-KIT heterogeneous protein expression among the samples (five positive and thirteen negative prostate cancer samples) indicates a personalized approach for canine prostate cancer. Univ. Estadual Paulista - UNESP Department of Veterinary Clinic School of Veterinary Medicine and Animal Science, Rua Prof. Dr Walter Correa, s/n, Unesp, Mail box- 560 The University of Queensland Gatton Campus School of Veterinary Science Univ. Estadual Paulista - UNESP Department of Veterinary Clinic School of Veterinary Medicine and Animal Science, Rua Prof. Dr Walter Correa, s/n, Unesp, Mail box- 560

In the last decades, many research groups have experimented the synthesis of hydroxyapatite (HA) for bone tissue application obtaining products with different shapes and dimensions. This review aims to summarise and critically analyse the most used methods to prepare physiologic-like nano-HA, in the form of plates or rods, similar to the HA present in the human bones. Moreover, mesoporous HA has gained increasing interest in the biomedical field due its pecualiar structural features, such as high surface area and accessible mesoporous volume, which is known to confer enhanced biological behaviour and the possibility to act as nanocarriers of functional agents for bone-related therapies. For this reason, more recent studies related to the synthesis of mesoporous HA, with physiological-like morphology, are also considered in this review. Since a wide class of surfactant molecules plays an essential role both in the shape and size control of HA crystals and in the formation of mesoporosity, a section devoted to the mechanisms of action of several surfactants is also provided.

Cytokines released in the tumour microenvironment play a major role in cancer pathogenesis. In human cancers and corresponding animal models, cytokine expression contributes to tumour growth and progression, as well as regulation of the host anti-tumour response. The elucidation of the function and importance of cytokines in canine cancers is still in an early stage, although relevant data have been obtained in classical examples of comparative models of human cancers, such as osteosarcoma, melanoma, mammary tumour and lymphoma. A deeper understanding of the cytokine signature may advance diagnosis, prevention and treatment of canine cancers.

Made available in DSpace on 2019-10-06T16:13:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The cancer cell population is heterogeneous, and cancer stem cells (CSCs) are important for tumor growth and maintenance. The CSC population is associated with different neoplastic characteristics, such as cell migration, resistance to apoptosis, radiation therapy and chemotherapy. To increase the knowledge of CSCs in canine prostate cancer (PC), we characterized CSC markers in canine PC tissues and tumorspheres. We performed immunohistochemistry of OCT3/4, Nestin, NANOG, CD44 and CD24 in 10 normal canine prostatic tissue samples, 10 prostatic hyperplastic (PH) tissue samples and 28 PC tissue samples. Then, we established two canine prostate cancer cell cultures and characterized the CSC profile of tumorspheres grown from these cultures. Normal and PH tissues were positive for Nestin, NANOG, CD44 and CD24 only in the basal cell layer. OCT3/4 was expressed in the luminal cells of normal and PH tissues. There was no significant difference in Nestin expression among the prostatic tissues. However, we found higher expression of NANOG and CD44 in canine PC tissues than that in normal and PH tissues. Tumorspheres from canine prostate cancer cells express OCT3/4, Nestin, NANOG and CD44, indicating that these markers may be potential cancer stem cell markers in canine PC. The results obtained can be useful to better characterize the stem cell population in canine prostatic cancer and to guide future studies in comparative oncology. São Paulo State University – UNESP Department of Veterinary Surgery and Anaesthesiology School of Veterinary Medicine and Animal Science São Paulo State University – UNESP Department of Veterinary Clinic School of Veterinary Medicine and Animal Science School of Veterinary Science The University of Queensland, Gatton Campus São Paulo State University – UNESP Department of Veterinary Surgery and Anaesthesiology School of Veterinary Medicine and Animal Science São Paulo State University – UNESP Department of Veterinary Clinic School of Veterinary Medicine and Animal Science FAPESP: 2015/25400-7 FAPESP: 2017/25822-4