ABSTRACT
Feline primary hypertrophic cardiomyopathy (HCM) is an intrinsic myocardial disease characterized by concentric hypertrophy of the left ventricle. In the present study, we investigated the microRNA-mRNA regulatory network in feline myocardial tissue affected by primary (HCMI) and secondary HCM (HCMII). MRNA expression levels of sarcomeric genes, including, TNNT2, TNNI3, MYH7, MYBPC3, TPM1 and ACTC1 were assessed in the FFPE myocardial tissues. FFPE tissues from healthy cats were sequenced by the NGS, to explore, in the entire non-deposited miRNome, the expression level of microRNAs targeting the complementary sequences of selected sarcomeric mRNAs. The sarcomeric genes TNNT2, MYH7, MYBPC3 and TPM1 showed a statistically significant upregulation in HCMI compared to HCMII (p < .01), except ACTC1 which was downregulated (p < .01); TNNI3 showed no statistically significant difference. In HCMII miR-122-5p, miR-338-3p, miR-484, miR-370-3p, miR-92b-3p, miR-375 and miR-370-3p showed a significant upregulation (p < .01) compared to control. The exception was miR-30a-5p which showed downregulation. Worthy of note is the 4-fold higher expression of miR-370-3p, a key regulator of MYBPC3, in HMCI compared to HMCII. This research does not solve the aetiological mystery of HCM, but it may help to find a way to help diagnose and define the prognosis of HCM in cats.
ABSTRACT
Since the discovery of the endocannabinoid system and due to the empirical evidence of the therapeutic effects on several illnesses both in humans and animals that follow the administration of exogenous cannabinoids (i.e., phytocannabinoids), numerous studies have been conducted. These investigations aimed to identify the expression and distribution of cannabinoid receptors in healthy and pathologic organs and tissues of different animal species and to define the interactions of phytocannabinoids with these receptors. In the last decade, pharmacokinetics, efficacy and tolerability of many Cannabis derivatives formulations, mainly containing cannabidiol, in the main species of veterinary interest, have been also investigated. This manuscript summarizes the findings reported by the scientific studies published so far on the molecular mode of action of the main phytocannabinoids, the localization of cannabinoid receptors in organs and tissues, as well as the pharmacokinetics, efficacy and tolerability of Cannabis derivatives in dogs, cats, horses and other species of veterinary interest. A deep knowledge of these issues is crucial for the use of phytocannabinoids for therapeutic purposes in animal species.
ABSTRACT
Local anaesthetics (LAs) can have detrimental effects on rat, bovine, canine, and human tendon tissues and cells. Currently, there has been no available data on the impact of these drugs on equine tenocytes. Even if LA injection for managing painful tendon conditions in horses is limited, it is usually used via intra-articular, intrasynovial, perineural, and intrathecal as well as for lameness examinations. In this in vitro study, the cytotoxic effects of LAs, including lidocaine, mepivacaine, and bupivacaine on equine tenocytes, in the presence and absence of platelet rich plasma (PRP), were investigated. PRP accelerates tissue healing and can exert cytoprotective effects on different cell types exposed to different stressful conditions, including drugs. Results indicated that the exposure to LAs significantly reduced tenocytes viability in dose- and time-dependent manners while PRP was able to counteract their cytotoxic effects. Furthermore, microscopy and flow cytometry analyses revealed apoptosis and necrosis in equine tenocytes exposed to these drugs, that were both reduced when PRP was in the medium. These findings highlight the importance of considering the tenocyte toxicity associated with intrathecal and intraneural LA injections, as they might affect tenocytes or reduce the efficacy of associated therapies. Moreover, this study also highlights the protective effects of PRP, which could make LA injections safer.
Subject(s)
Anesthetics, Local , Bupivacaine , Lidocaine , Mepivacaine , Platelet-Rich Plasma , Tenocytes , Animals , Horses , Tenocytes/drug effects , Anesthetics, Local/pharmacology , Anesthetics, Local/toxicity , Bupivacaine/toxicity , Lidocaine/pharmacology , Cell Survival/drug effects , Cells, Cultured , Apoptosis/drug effectsABSTRACT
Tumor cells can induce important cellular and molecular modifications in the tissue or host where they grow. The idea that the host and tumor interact with each other has led to the concept of a tumor microenvironment, composed of immune cells, stromal cells, blood vessels, and extracellular matrix, representing a unique environment participating and, in some cases, promoting cancer progression. The study of the tumor immune microenvironment, particularly focusing on the role of tumor-infiltrating lymphocytes (TILs), is highly relevant in oncology due to the prognostic and therapeutic significance of TILs in various tumors and their identification as targets for therapeutic intervention. Canine splenic hemangiosarcoma (HSA) is a common tumor; however, its immune microenvironment remains poorly understood. This retrospective study aimed to characterize the histological and immunohistochemical features of 56 cases of canine splenic HSA, focusing particularly on tumor-infiltrating lymphocytes (TILs). We assessed the correlations between the lymphocytic response, the macroscopic and histological characteristics of the tumor, and the survival data. Our study demonstrated that FoxP3 distribution was associated with tumor-related death and survival, while the CD20 count was associated with metastasis. This study provides an in-depth characterization of the tumor immune microenvironment in canine splenic HSA and describes potential prognostic factors.
ABSTRACT
In felines, ocular and nonocular melanomas are uncommon tumors that represent a diagnostic challenge for pathologists, especially when amelanotic. To date, the immunohistochemical diagnostic panel in cats is based on specific melanocytic markers (Melan-A and PNL2) and a nonspecific but sensitive marker (S100). In human medicine, SOX-10 is reported to be a sensitive antibody for the detection of melanoma micrometastasis in the lymph node. TRP-1, an enzyme involved in melanogenesis, has recently been used in humans and dogs as a specific melanocyte marker. The aim of this study was to evaluate the cross-reactivity and the expression of SOX-10 and TRP-1 antibodies in feline normal tissue and melanocytic tumors. Thirty-one cases of ocular, cutaneous, and oral melanomas were retrospectively evaluated and confirmed by histopathological examination and by immunolabeling with Melan-A and/or PNL2. SOX-10 nuclear expression in normal tissues was localized in epidermal, subepidermal, hair bulb, and iridal stromal melanocytes and dermal nerves. In melanomas, nuclear expression of SOX-10 was detected in ocular (11/12; 92%), oral (6/7; 86%), and cutaneous sites (12/12; 100%). TRP-1 cytoplasmic immunolabeling in normal tissue was observed in epidermal and bulbar melanocytes and in the lining pigmented epithelium of the iris and in its stroma. Its expression was positively correlated to the degree of pigmentation in the tumor and was observed in 75% of ocular (9/12), 43% of oral (3/7), and 33% of cutaneous melanomas (4/12). This study demonstrated the cross-reactivity of SOX-10 and TRP-1 antibodies in feline non-neoplastic melanocytes and their expression in ocular and nonocular melanomas.
ABSTRACT
Dirofilaria repens is a paradigmatic example of an emerging vector-borne pathogen (VBP) in both human and veterinary fields. The spatial expansion and the increasing zoonotic impact of this VBP can be related to several drivers including the genetic structure of parasite populations. Italy is one of the European countries traditionally endemic with the highest incidence of canine and human cases of subcutaneous dirofilariosis. The present study aimed to assess the genetic identity and variability of D. repens isolates of human and canine origin from areas of Central Italy, compared with those isolated from different areas of Europe by sequence analysis of mtDNA genes (i.e., 12 S rDNA and cox1). A total of twenty isolates of D. repens were obtained from biopsies of subcutaneous and ocular cases of dirofilariosis occurring in 10 dogs and 10 humans. The sequence analysis of 12 S rDNA showed that all the sequences obtained clustered as a monophyletic group with a strong nodal support, indicating that all sequence types represented D. repens. The cox1 and the 12 S sequence analysis did not show host-related polymorphisms between human and dog-derived specimens. The sequence analysis of cox1 was performed including 8 additional sequences previously obtained from human and canine isolates in the same areas. Out of the 28 sequences analyzed, 20 were grouped in a haplogroup comprising 15 haplotypes (i.e., DR1, DR2, DR4, DR5, DR7, DR8, DR10-DR18), 2 sequences matched to DR9, reported for the first time in Italy, and 6 showed peculiar polymorphisms that were not previously described. The results obtained have implications for a better understanding of the epidemiology and phylogeography of this emerging vector-borne zoonotic parasite.
Subject(s)
Dirofilaria immitis , Dirofilaria repens , Dirofilariasis , Dog Diseases , Humans , Animals , Dogs , Dirofilaria repens/genetics , Italy/epidemiology , Dirofilariasis/epidemiology , Dirofilariasis/parasitology , Europe/epidemiology , DNA, Ribosomal , Dog Diseases/epidemiology , Dog Diseases/parasitologyABSTRACT
BACKGROUND: Melanoblasts originate in the neural crest from where they migrate to peripheral tissues and differentiate into melanocytes. Alteration during melanocyte development and life can cause different diseases, ranging from pigmentary disorders and decreased visual and auditory functions, to tumours such as melanoma. Location and phenotypical features of melanocytes have been characterised in different species, yet data on dogs are lacking. OBJECTIVE: This study investigates the expression of melanocytic markers Melan A, PNL2, TRP1, TRP2, SOX-10 and MITF in melanocytes of selected cutaneous and mucosal surfaces of dogs. ANIMALS: At necropsy, samples from five dogs were harvested from oral mucosa, mucocutaneous junction, eyelid, nose and haired skin (abdomen, back, pinna, head). MATERIALS AND METHODS: Immunohistochemical and immunofluorescence analyses were performed to assess marker expression. RESULTS: Results showed variable expression of melanocytic markers in different anatomical sites, particularly within epidermis of haired skin and dermal melanocytes. Melan A and SOX-10 were the most specific and sensitive melanocytic markers. PNL2 was less sensitive, while TRP1 and TRP2 were seldomly expressed by intraepidermal melanocytes in haired skin. MITF had a good sensitivity, yet the expression often was weak. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate a variable expression of melanocytic markers in different sites, suggesting the presence of subpopulations of melanocytes. These preliminary results pave the way to understanding the pathogenetic mechanisms involved in degenerative melanocytic disorders and melanoma. Furthermore, the possible different expression of melanocyte markers in different anatomical sites could influence their sensitivity and specificity when used for diagnostic purposes.
Subject(s)
Dog Diseases , Melanoma , Skin Neoplasms , Dogs , Animals , MART-1 Antigen/metabolism , Immunohistochemistry , Melanocytes/pathology , Melanoma/veterinary , Melanoma/diagnosis , Epidermis/pathology , Skin Neoplasms/pathology , Skin Neoplasms/veterinary , Dog Diseases/diagnosisABSTRACT
The tumor microenvironment is a complex system, where neoplastic cells interact with immune and stromal cells. Tumor-associated macrophages (TAMs) are considered among the most numerically and biologically noteworthy cellular components in tumors and the attention on this cellular population has been growing during the last decade, both for its prognostic role and as a potential future therapeutic target. Melanoma, particularly the oral form, despite being one of the most immunogenic tumors, bears a poor prognosis in dogs and humans, due to its highly aggressive biological behavior and limited therapeutic options. The aims of this study are to characterize and quantify TAMs (using CD163, CD204, Iba1, and MAC387) in canine melanocytic tumors and to evaluate the association of these markers with diagnosis, histologic prognostic features, presence of metastases, and outcome, and to provide preliminary data for possible future therapies targeting TAMs. Seventy-two melanocytic tumors (27 oral melanomas, 25 cutaneous melanomas, 14 cutaneous melanocytomas, and 6 oral melanocytomas) were retrospectively selected and submitted to immunohistochemistry and double immunofluorescence. Double immunolabeling revealed that most CD163+ and CD204+cells co-expressed Iba1, which labeled also dendritic cells. Iba1 was instead rarely co-expressed with MAC387. Nevertheless, the expression of macrophagic markers showed a mild to moderate association among the four markers, except for CD204 and MAC387. The number of CD163+, CD204+, and MAC387+ cells was significantly higher in oral melanomas compared to oral melanocytomas (p < 0.001; p < 0.05 and p < 0.01, respectively), whereas Iba1 was differentially expressed in cutaneous melanomas and melanocytomas (p < 0.05). Moreover, CD163, IBA1 and MAC387 expression was associated with nuclear atypia and mitotic count. The number of CD163+cells was associated with the presence of metastases and tumor-related death in oral melanocytic tumors (p < 0.05 and p = 0.001, respectively).
ABSTRACT
Paenibacilli are gram-variable, endospore-forming bacteria that occupy various ecologic niches. These microorganisms have been known to infect humans occasionally at various anatomic sites. However, in humans, as well as in other vertebrate animals, the relationship between disease and isolation of Paenibacillus spp. remains poorly understood. We report here a case of infection in an adult Poodle dog. The animal had nodules in the lungs and multifocal osteolytic expansile bone lesions. From bone, Paenibacillus amylolyticus was recovered by culture and identified by MALDI-TOF mass spectroscopy and 16S rDNA sequencing; pyogranulomatous inflammation was observed in lung and bone specimens. The microorganism was resistant to clindamycin and imipenem. Four-month treatment with amoxicillin-clavulanate resulted in clinical resolution of disease in this dog. Nevertheless, therapy for more prolonged periods should be considered because recurrent infections can occur as a result of the transition of Paenibacillus spores to vegetative cells. Disease caused by a Paenibacillus species has not been reported previously in dogs, to our knowledge.
Subject(s)
Dog Diseases , Osteomyelitis , Paenibacillus , Animals , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Dog Diseases/drug therapy , Dogs , Osteomyelitis/drug therapy , Osteomyelitis/veterinary , Paenibacillus/genetics , Phylogeny , RNA, Ribosomal, 16S/geneticsABSTRACT
Background: In Italy, an autogenous registered vaccine, adjuvanted with aluminum hydroxide, can be administrated to contrast Salmonella enterica subsp. enterica serovar abortus equi infection, coupled to a specific antimicrobial treatment. Case Description: Here, we report the case of an abortion outbreak by Salmonella abortus equi in Central Italy where mares were vaccinated but immediately developed a strong local reaction, maybe due to the adjuvant. Promptly, another autogenous vaccine, substituting the aluminum hydroxide with a new generation adjuvant (Montanide™ Seppic IMS1313), was produced and administrated. The new formulated vaccine did not cause any adverse outcome and conferred high protection titers against the infection. To the best of our knowledge, this is the first reported case of immunization by a vaccine adjuvanted with Montanide™ Seppic IMS1313 in horses. Conclusion: This approach may be used as a preventive strategy for further outbreaks in association with the application of recommended biosafety principles.
Subject(s)
Autovaccines , Salmonella enterica , Adjuvants, Immunologic , Adjuvants, Pharmaceutic , Aluminum Hydroxide , Animals , Disease Outbreaks/prevention & control , Disease Outbreaks/veterinary , Female , Horses , Pregnancy , Salmonella , SerogroupABSTRACT
Introduction: In the last few years, different formulations containing cannabidiol (CBD) were tested with regard to its efficacy on chronic pain, refractory epilepsy, anxiety, aggressive behavior and atopic dermatitis in dogs. CBD is generally administered orally, but its low bioavailability, probably due to a first-pass metabolism, represents a great limitation. The aim of this study was to evaluate if CBD bioavailability increases after oral transmucosal administration (OTM) compared to oral treatment. Methods: Twelve dogs diagnosed with mild chronic pain were enrolled in the study and treated once orally or OTM (6 dogs/group) with a pure CBD in oil formulation at a dosing rate of 1 mg/kg b.w. At prefixed time points, blood samples were collected to define CBD plasma concentrations vs. time profiles, and the main pharmacokinetics parameters were obtained by non-compartmental model. Results: CBD Cmax, Tmax, terminal half-life and AUC0 - t were 206.77 ± 167 and 200.33 ± 158.33 ng/mL, 2.17 ± 0.98 and 1.92 ± 1.11 h, 2.67 ± 0.53 and 2.62 ± 0.64 h, 647.51 ± 453.17, and 536.05 ± 370.21 h*ng/mL, following oral and OTM administration, respectively. No significant difference in pharmacokinetic parameters were observed between treatments. Discussion: The OTM administration did not increase cannabidiol bioavailability compared to oral treatment. The almost perfectly superimposable mean plasma concentrations of cannabidiol following the two treatments suggests that CBD is not able to be adsorbed by the oral mucosa or that its absorption is very scarce, and that CBD is swallowed and absorbed in the gastrointestinal tract.
ABSTRACT
The presence and the role of tumor-infiltrating lymphocytes (TILs) in different types of tumors, but particularly in melanoma, has become more and more investigated during the last decade, both in human and veterinary medicine. Melanocytic tumors are quite rare in cats, with diffuse iris melanoma being the most commonly diagnosed in this species. The aim of this study was to characterize the lymphocytic infiltration in feline melanocytic tumors and to analyze their association with the histological features of malignancy recognized in these tumors, as well as with the expression of the most commonly used immunohistochemical markers. Thirty-eight feline melanocytic tumors were retrospectively selected; histological and immunohistochemical characterization of the tumors (histologic criteria of malignancy; S100, Melan A, and PNL2 expression) and of TILs (presence/absence, density, distribution, and grade; CD3, CD20 expression) were performed and associations between them tested. Results showed that TILs grade increased with cellular pleomorphism (P < 0.05) and, within the group of cutaneous melanocytic tumors, also with the mitotic count (P < 0.05). On the other hand, TILs grade was inversely associated with the percentage of neoplastic cells positive for Melan A (P < 0.05) and PNL2 (P < 0.05). Both CD3+ and CD20+ lymphocytes increased significantly with TILs grade and in association with mitotic count, when stratified in low/high quantity. This preliminary study suggests that TILs in feline melanoma may be associated with histologic features of malignancy and loss of melanocytic-specific markers, such as Melan A and PNL2. Further studies, with a larger cohort and follow-up information, are recommended.
Subject(s)
Cat Diseases , Lymphocytes, Tumor-Infiltrating/immunology , Melanoma , Skin Neoplasms , Animals , Antigens, Neoplasm , Biomarkers, Tumor , Cat Diseases/immunology , Cats , MART-1 Antigen , Melanoma/immunology , Melanoma/veterinary , Retrospective Studies , Skin Neoplasms/immunology , Skin Neoplasms/veterinaryABSTRACT
A 10-year-old Koninklijk Warmbloed Paardenstamboek Nederland (KWPN, Netherlands-based organization for registration of the Dutch Warmblood horses) mare was evaluated three times over four months because of recurrent colic. At every referral, a physical examination revealed a small colon impaction, which partially responded to food deprivation and oral administration of water and magnesium sulphate. Due to the recurrent nature of the small colon impaction, several differential diagnoses were considered: inflammatory bowel disease (IBD), chronic salmonellosis and myenteric ganglionopathies. At first admission, an exploratory laparotomy was proposed, but the owner declined. On the second hospitalisation, the mare underwent a standing exploratory laparoscopy, but no abnormality related to the small colon was detected and resolved with a soap-based enema. At the third hospitalisation, the owner agreed to the exploratory laparotomy, which allowed surgical biopsies of the caecum and the large and small colon. Lymphomonocytic enteritis and mild myenteric ganglionitis were diagnosed. After laparotomy, the mare regularly fed and defecated, but a few days later, tachycardia, fever and abundant gastric reflux occurred. As the clinical condition rapidly deteriorated, the owner elected for euthanasia. A post-mortem histological examination showed severe chronic lymphocytic enterocolitis and typhlitis associated with the marked depletion of myenteric ganglion bodies. Small colon impaction is a very common disorder of the small colon in horses. In the presence of myenteric ganglionopathies, this case proposes the controversial matter of primary or secondary disorders of enteric neuromuscular function as the base of repeated small colon impactions of the horse. In this mare, recurrent small colon impaction was considered secondary to severe myenteric ganglionopathy associated with chronic intestinal pseudo-obstruction.
Subject(s)
Colic , Colonic Diseases , Horse Diseases , Animals , Colic/diagnosis , Colic/veterinary , Colonic Diseases/diagnosis , Colonic Diseases/veterinary , Female , Horse Diseases/diagnosis , Horses , NetherlandsABSTRACT
Although numerous animal models, especially mouse models, have been established for the study of melanoma, they often fail to accurately describe the mechanisms of human disease because of their anatomic, physiological, and immune differences. The dog, as a spontaneous model of melanoma, is nowadays considered one of the most valid alternatives due to the heterogeneity of clinical presentations and of histological and genetic similarities of canine melanoma with the human counterpart. The aim of the study was to optimize a protocol for the isolation and cultivation of healthy and neoplastic canine melanocytes derived from the same animal and obtained from cutaneous and mucosal (oral) sites. We obtained five primary tumor cell cultures (from 2 cutaneous melanoma, 2 mucosal melanoma and 1 lymph node metastasis) and primary normal melanocyte cell cultures (from normal skin and mucosa) from the same dogs. Immunocytochemical characterization with Melan A, PNL2 and S100 antibodies confirmed the melanocytic origin of the cells. This work contributes to expanding the case record of studies on canine melanoma cell cultures as suitable model to study human and canine melanoma. To the authors' knowledge, this is the first report of isolation of normal skin and mucosal canine melanocytes.
ABSTRACT
HER2 is overexpressed, amplified, and mutated in a subset of human lung cancer. The aim of this study was to investigate HER2 protein overexpression and gene amplification in feline pulmonary carcinomas. Thirteen pulmonary carcinomas were selected and TTF-1 and HER2 expression was evaluated by immunohistochemistry. Fluorescence in situ hybridization (FISH) was performed with a HER2 probe and a BAC probe for the feline chromosome E1p1.12-p1.11 region. Twelve adenocarcinomas and 1 squamous cell carcinoma were diagnosed. TTF-1 was positive in 7 carcinomas (58%). HER2 was overexpressed in 2 (15%), equivocal in 5 (38%), and negative in 6 cases (46%). FISH analysis of HER2 was indeterminate in 2 cases. Three pulmonary carcinomas (27%) had HER2 amplification and 8 cases were not amplified (73%). The significant correlation between HER2 protein overexpression and gene amplification are promising preliminary data, but study of additional cases is needed to confirm HER2 as a target for possible innovative treatments.
Subject(s)
Carcinoma, Squamous Cell , Cat Diseases , Lung Neoplasms , Animals , Carcinoma, Squamous Cell/veterinary , Cat Diseases/genetics , Cats , Gene Amplification , In Situ Hybridization, Fluorescence/veterinary , Lung Neoplasms/genetics , Lung Neoplasms/veterinary , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolismABSTRACT
Despite promising immunotherapy strategies in human melanoma, there are few studies on the immune environment of canine melanocytic tumors. In humans, the activation of immunosuppressive cell subpopulations, such as regulatory T cells (Tregs) that express forkhead box protein P3 (FoxP3), the engagement of immunosuppressive surface receptors like cytotoxic T lymphocyte antigen (CTLA-4), and the secretion of molecules inhibiting lymphocyte activation, such as indoleamine-pyrrole 2,3-dioxygenase (IDO), are recognized as immunoescape mechanisms that allow tumor growth and progression. The aim of our study was to investigate the expression of these immunosuppression markers in canine melanocytic tumors and to postulate their possible role in melanoma biology and progression. Fifty-five formalin-fixed, paraffin-embedded canine melanocytic tumors (25 oral melanomas; 20 cutaneous melanomas; 10 cutaneous melanocytomas) were selected to investigate the expression of FoxP3, CTLA-4, and IDO by immunohistochemistry and RT-qPCR (real-time quantitative polymerase chain reaction). All of the tested markers showed high gene and protein expression in oral melanomas and were differently expressed in cutaneous melanomas when compared to their benign counterpart. IDO expression was associated with an increased hazard of death both in univariable and multivariable analyses (P < .05). FoxP3 protein expression >6.9 cells/HPF (high-power field) was an independent predictor of death (P < .05). CTLA-4 gene and protein expressions were associated with a worse prognosis, but only in the univariable analysis (P < .05). FoxP3, CTLA-4, and IDO likely play a role in canine melanoma immunoescape. Their expression, if supported by future studies, could represent a prognostic tool in canine melanoma and pave the way to future immunotherapeutic approaches in dogs.
Subject(s)
Dog Diseases , Melanoma , Mouth Neoplasms , Animals , CTLA-4 Antigen , Dogs , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Melanoma/veterinary , Mouth Neoplasms/veterinary , T-Lymphocytes, Cytotoxic , T-Lymphocytes, RegulatoryABSTRACT
Canine testicular tumors account for about 90 % of tumors affecting the male genitalia. Seminomas (SEM), Sertoli cell tumors (SCT), and interstitial cell tumors (ICT) are the most common histological diagnoses, but their incidence shows high variability among studies. Our aim is to report the results on the analysis of testicular tumors recorded by the population-based Umbria Canine Cancer Registry (CCR) for a 5-year time period and to assess the value of tumor major diameter, measured during trimming, in discriminating neoplastic from non-neoplastic lesions. The study was conducted on 388 testicular tumors (on 1969 total male tumors) diagnosed in 355 dogs from 2014 to 2018. The median incidence was 35 cases/100,000 dogs, with a proportion equal to 19,7 % of all tumors. The incidence on neutered male dogs was 352/100,000. Most tumors were ICTs (50 %), with fewer SEMs and SCTs (29 % and 17 %, respectively). Only 3 % of tumors were mixed germ cell-sex cord-stromal tumors (MGC-SCST). Ten percent of cases had multiple tumors in the same testicle, with SEM-ICT being prevalent (69.2 %). Tumors in cryptorchid testes were 5.9 % of the total, mostly SCT (60.9 %). Mean age at diagnosis was 10.7 ± 2.7, with similar values for different tumor types. Significant incidence ratios (IRR) were found in Golden retriever (IRR 7.18, CI95 % 4.72-10.92) and in English cocker spaniel (IRR 2.30, CI95 % 1.28-4.13) when compared with mixed breed dogs. A value of 0.3 cm (major diameter) of lesions at the moment of trimming was helpful in discriminating a final tumor histological diagnosis from a non-tumor lesion. Since the number of tumors included in this evaluation was limited, further studies to confirm the diagnostic value of this measure are recommended. Our results provided information on the incidence of canine testicular tumors in Umbria region that can be compared with future results and incidence from other geographical areas if provided with reliable data on the total population, can offer solid information on the incidence and proportion of different tumor types in specific territories, contributing also to the supervision of its inhabitants' health. Moreover, pathological data such as the major diameter of tumors can be obtained and contribute to diagnostic routine and standardization.
Subject(s)
Dog Diseases/epidemiology , Leydig Cell Tumor/veterinary , Seminoma/veterinary , Sertoli Cell Tumor/veterinary , Testicular Neoplasms/veterinary , Animals , Cohort Studies , Dogs , Incidence , Italy/epidemiology , Leydig Cell Tumor/epidemiology , Male , Registries , Seminoma/epidemiology , Sertoli Cell Tumor/epidemiology , Testicular Neoplasms/epidemiologyABSTRACT
Osteochondrosis is a developmental orthopedic disease affecting growing cartilage in young horses. In this study we compared the proteomes of equine chondrocytes obtained from healthy and osteochondrotic cartilage using a label-free mass spectrometry approach. Quantitative changes of some proteins selected for their involvement in different functional pathways highlighted by the bioinformatics analysis, were validated by western blotting, while biochemical alterations of extracellular matrix were confirmed via Raman spectroscopy analysis. In total 1637 proteins were identified, of which 59 were differentially abundant. Overall, the results highlighted differentially represented proteins involved in metabolic and functional pathways that may be related to the failure of the endochondral ossification process occurring in osteochondrosis. In particular, we identified proteins involved in extracellular matrix degradation and organization, vitamin metabolism, osteoblast differentiation, apoptosis, protein folding and localization, signalling and gene expression modulation and lysosomal activities. These results provide valuable new insights to elucidate the underlying molecular mechanisms associated with the development and progression of osteochondrosis. SIGNIFICANCE: Osteochondrosis is a common articular disorder in young horses mainly due to defects in endochondral ossification. The pathogenesis of osteochondrosis is still poorly understood and only a limited number of proteomic studies have been conducted. This study provides a comprehensive characterization of proteomic alterations occurring in equine osteochondrotic chondrocytes, the only resident cell type that modulates differentiation and maturation of articular cartilage. The results evidenced alterations in abundance of proteins involved in functional and metabolic pathways and in extracellular matrix remodelling. These findings could help clarify some molecular aspects of osteochondrosis and open new fields of research for elucidating the pathogenesis of this disease.
Subject(s)
Cartilage, Articular , Osteochondrosis , Animals , Chondrocytes , Horses , Osteochondrosis/veterinary , Proteome , ProteomicsABSTRACT
E-cadherin, a glycoprotein involved in cell-cell adhesion, has a pivotal role in epithelial-mesenchymal transition, a process through which neoplastic epithelial cells develop an invasive phenotype. In human cutaneous melanomas, decreased E-cadherin expression is associated with shorter survival and increased Breslow thickness, whereas in the dog its role is poorly understood. Tumor thickness and modified Clark level were recently proposed as useful features to assess canine melanocytic tumors, but no studies investigated their association with E-cadherin expression. We performed immunohistochemistry on 77 formalin-fixed, paraffin-embedded primary canine melanocytic tumors. A 3-tier and a 2-tier classification system for assessing E-cadherin expression were tested, with the latter being more informative for the assessment of canine melanocytic tumors. E-cadherin expression was lower in cutaneous melanomas than melanocytomas, as well as in amelanotic tumors compared to pigmented tumors. In amelanotic melanomas, absent E-cadherin expression was associated with an unfavorable outcome, suggesting a potential use of this marker in defining the prognosis of amelanotic melanomas. E-cadherin expression was lower in tumors with greater tumor thickness and modified Clark level ≥IV, suggesting its possible utility in identifying the most invasive tumors. The expression of E-cadherin in oral melanomas was heterogeneous, but was associated with pigmentation and clinical outcome; thus, E-cadherin evaluation could be advantageous to detect the most aggressive neoplasms. However, cutaneous melanomas without E-cadherin expression frequently had a favorable clinical outcome. Hence, its importance as prognostic factor should be carefully considered depending on the tumor origin.