Comparative epidemiological study of breast cancer in humans and canine mammary tumors: insights from Portugal.

Dogs spontaneously develop mammary gland tumors (MGT) and exhibit striking similarities in clinical and epidemiological characteristics to human breast cancer (HBC). Descriptive and comparative analysis of HBC and canine MGT with a focus on evaluating similarities and geographical distribution were the aims of this study. HBC cases were obtained from North Regional Oncological Registry (RORENO) (2010-2015) and canine MGT cases from Vet-OncoNet (2019-2022). Analyses were performed based on published and well accepted classification systems (ICD-O-3.2 for humans and Vet-ICD-O-canine-1). Age-standardized incidence risks (ASIR) of Porto district municipalities were calculated using 2021 Portuguese census (INE) and data from the Portuguese animal registration system (SIAC). Among 7,674 HBC cases and 1,140 MGT cases, a similar age and sex distribution pattern was observed. Approximately 69.2% of HBC cases were between 40 and 69 years old, while 66.9% of MGT cases were diagnosed between 7 and 12 years old (mean age of 9.6 years, SD = 2.6). In women, Invasive breast carcinoma (8500/3) was the most common histological type (n = 5,679, 74%) while in dogs it was the Complex Carcinoma (8983.1/3) (n = 205, 39%). Cocker and Yorkshire Terriers exhibited the highest relative risks (3.2 and 1.6, p < 0.05, respectively) when compared to cross breed dogs. The municipalities' ASIR of the two species exhibited a high correlation (R = 0.85, p < 0.01) and the spatial cluster analysis revealed similar geographic hotspots. Also, higher ASIR values both in women and dogs were more frequently found in urbanized areas compared to rural areas. This research sheds light on the shared features and geographical correlation between HBC and canine MGT, highlighting the potential of cross-species environmental oncology studies.

A retrospective histopathological survey on canine lymphomas subtypes of Porto District.

Background: Lymphomas are dogs' most common hematopoietic neoplasms and represent a heterogeneous group, as occurs in humans. Considering the role of dogs as models of human lymphomas and the geographical correlation of the cases of canine and human lymphoma, it is important to continuously assess the epidemiological distribution of lymphoma subtypes in dogs. Aim: This study aimed to provide a survey of canine lymphoma subtypes diagnosed from 2005 to 2016 in the academic veterinary pathology laboratory of the University of Porto. Methods: A total of 75 canine lymphomas diagnosed by histopathology in the Porto district were included. All cases were immunophenotyped by CD3 and PAX5, classified according to the current classification WHO and coded with Vet-ICD-O-canine-1. Results: Mixed breed dogs were most common (28%), followed by Cocker Spaniels (12%), Boxers (9%), and Labrador Retrievers (6%). The mean age was 9.2 years (SD = 3.3) (10.7 years for small, 8.9 years for medium and large, and 5.7 years for giant breed dogs, p < 0.05). Regarding sex, there was no difference in frequencies or mean age. B-cell lymphomas were more common (57.4%) than T-cell lymphomas (37.3%), and 5.3% were classified as non-B/non-T-cell lymphomas. Of the cases, 49% had a multicentric distribution, followed by splenic (22%), cutaneous (12%), alimentary (12%), and extranodal (3%) forms. The most common B-cell subtypes were diffuse large B-cell lymphoma (DLBCL) (16.3%) and large immunoblastic lymphoma (14%), while T-zone lymphoma (21.4%) and intestinal lymphoma (18%) were the most common T-cell lymphoma subtypes. Conclusion: Our study shows that the Porto district follows the international trend of higher prevalence of B-cell lymphomas in dogs, especially of the DLBCL subtype.

Vet-OncoNet: Malignancy Analysis of Neoplasms in Dogs and Cats.

Analysis of canine and feline tumor malignancy data can help clinicians identify high-risk patients and make more accurate decisions. Based on a sample of 16,272 cancer records, including 3266 cats and 13,006 dogs, collected from January 2019 to December 2021 in the Vet-OncoNet Network database, this study aimed to compare the tumor malignancy profile between cats and dogs, considering animal-related factors (sex, age, and breed), topography, and geographic location using a mixed-effects logistic regression model. Cats had a higher proportion of malignant tumors (78.7%) than dogs (46.2%), and the malignancy profile was very different regarding tumors' topographies. The mean age of malignant tumors occurred eight months later than benign ones (9.1, SD = 3.4; 9.8, SD = 3.2), in general. Species (OR = 3.96, 95%CI 3.57: 4.39) and topography (MOR = 4.10) were the two most important determinants of malignancy risk. Female dogs had a higher risk than male dogs (OR = 1.19, 95%CI 1.08: 1.31), which does not appear to be the case in cats (OR = 0.98, 95%CI 0.77: 1.23). Breed contributed significantly to differences in malignancy risk in dogs (MOR = 1.56), particularly in pit bulls and boxers. District of residence was not so relevant in predicting malignancy risk (MOR = 1.14). In both species, the risk of malignancy increased by approximately 20% every three years. It could be hypothesized that species differences in genetic structure may contribute to tumor malignancy.

Cross Species Analysis and Comparison of Tumors in Dogs and Cats, by Age, Sex, Topography and Main Morphologies. Data from Vet-OncoNet.

The animal cancer burden is essential for the translational value of companion animals in comparative oncology. The present work aims to describe, analyze, and compare frequencies and associations of tumors in dogs and cats based on the Animal Cancer Registry created by Vet-OncoNet. With 9079 registries, regarding 2019 and 2020, 81% (n = 7355) belonged to dogs. In comparison, cats have a general one-year right advance in the mean age of cancer diagnosis compared to dogs. The multivariate topography group analysis shows a distinct pattern between the two species: dogs have higher odds of cancer in the genito-urinary system, spleen, soft tissue tumors and skin, while cats show higher odds for tumors in the eyes, digestive organs, nasal cavity, lymph nodes, bones and mammary glands. Regarding morphologies, dogs are overrepresented in mast cell tumors (MCT), melanomas, and hemangiosarcomas. While cats are overrepresented in fibrosarcomas, lymphomas (T and B-cell), in malignant mammary tumors, and squamous cell carcinoma (SCC). Females have greater odds only in the mammary gland, with males having greater odds in six of twelve topographies. This study is the first outcome of continuous animal cancer registration studies in Portugal.

Vet-ICD-O-Canine-1, a System for Coding Canine Neoplasms Based on the Human ICD-O-3.2.

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.

Vet-OncoNet: Developing a Network of Veterinary Oncology and Reporting a Pioneering Portuguese Experience.

Vet-OncoNet is a replicable tripartite animal cancer database with the scientific and academic purposes of collecting data and producing evidence-based knowledge for cancer science in general. Inspired by the One Health vision, Vet-OncoNet uses business intelligence tools to optimize the process of capturing, treating, and reporting animal cancer data to a national level in three interfaces: ACR (animal cancer registry, pathology-based), COR (clinical oncology registry, vet practice-based) and RFR (risk factor registry, owner-based). The first results show that skin and mammary gland are by far the most affected systems. Mast cell tumors and complex adenoma of the mammary gland are the most frequent histologic type in dogs, while in cats they are squamous cell carcinomas, tubular adenocarcinoma of the mammary gland and lymphomas. Regarding COR, it provides valuable information on the landscape of veterinary oncology practices, therapeutics options, outcomes and owners' drivers' adherence towards therapies, which range from 30% up to 80% upon vet practices. Furthermore, being aware of the role of animals within the family and as possible sentinels of environmental risks to cancer in humans, the network built an interface (Pet-OncoNet) dedicated to owners and a database (RFR) that receives information regarding pets and owners' daily habits.

In vitro inhibitory effect of trichostatin A on canine grade 3 mast cell tumor.

Mast cell tumor (MCT) is one of the most prevalent neoplasms that affect skin and soft tissue in dogs. Because mast cell tumors present a great variety of clinical appearance and behavior, their treatment becomes a challenge. Trichostatin A (TSA), an antifungal antibiotic, has shown inhibitory effects on the proliferation and induction of apoptosis in various types of cancer cells. In order to evaluate the potential of trichostatin A as a therapeutic drug, cells of grade 3 MCT were cultured and treated with concentrations of 1 nM to 400 nM of TSA. MTT assay and trypan blue exclusion assays were performed to estimate cell growth and cell viability, and cell cycle analysis was evaluated. TSA treatment showed a reduction in numbers of viable cells and an increase of cell death by apoptosis. The cell cycle analysis showed an increase of hypodiploid cells and a reduction of G0/G1 and G2/M -phases. According to these results, trichostatin A may be an interesting potential chemotherapeutic agent for the treatment of canine MCT.

Cytotoxic effects of butanolic extract from Pfaffia paniculata (Brazilian ginseng) on cultured human breast cancer cell line MCF-7.

Roots of Pfaffia paniculata have been well documented for multifarious therapeutic values and have also been used for cancer therapy in folk medicine. This study has been performed in a human breast tumor cell line, the MCF-7 cells. These are the most commonly used model of estrogen-positive breast cancer, and it has been originally established in 1973 at the Michigan Cancer Foundation from a pleural effusion taken from a woman with metastatic breast cancer. Butanolic extract of the roots of P. paniculata showed cytotoxic effect MCF-7 cell line, as determined with crystal violet assay, cellular death with acridine orange/ethidium bromide staining, and cell proliferation with immunocytochemistry of bromodeoxyuridine (BrdU). Subcellular alterations were evaluated by electron microscopy. Cells treated with butanolic extract showed degeneration of cytoplasmic components and profound morphological and nuclear alterations. The results show that this butanolic extract indeed presents cytotoxic substances, and its fractions merit further investigations.

Pfaffia paniculata (Brazilian ginseng) methanolic extract reduces angiogenesis in mice.

Pfaffia paniculata (Brazilian ginseng) roots have been indicated for the treatment of several diseases. Our studies have shown that P. paniculata roots present antineoplastic effects and cancer chemopreventive activity in a mouse hepatocarcinogenesis model. The purpose of this study was to investigate the effects of the Brazilian ginseng on corneal angiogenesis in mice. We first conducted a toxicological study employing 250, 500, or 1000mg/kg/day of the methanolic extract of P. paniculata roots by gavage to BALB/c mice. Animals did not lose weight during the treatment nor presented histopathological alterations. The effect of this root on angiogenesis in the cornea of BALB/c mice was then assessed. Male mice were treated, by gavage, once a day, with doses of 250, 500, or 1000mg/kg of methanolic extract of P. paniculata powdered root for 10 days; filtered water was used as control. Corneal cauterization was accomplished by the contact of a silver nitrate crystal on the central area of the cornea, in the 5th day of treatment with P. paniculata, which continued thereafter; the animals were euthanized on the 6th day after cauterization. Newly formed blood vessels were filled with India ink, and the corneas were routinely processed. Blood vessels were quantified in an image analysis system. A smaller total area of neovascularization in the mouse cornea was observed in animals treated with 1000mg/kg of the methanolic extract of P. paniculata. These results indicate an antiangiogenic effect of this extract. The mechanisms of this antiangiogenic activity of P. paniculata should be further investigated.

Effects of Pfaffia paniculata (Brazilian ginseng) extract on macrophage activity.

The roots of Pfaffia paniculata (Brazilian ginseng) have been indicated for the treatment of several diseases and as an analgesic and antiinflamatory drug. Treatment of mice with 200 mg/kg of the powdered root of P. paniculata reduced the Ehrlich ascitic volume [Matsuzaki, P., Akisue, G., Salgado Oloris, S.C., Gorniak, S.L., Zaidan Dagli, M.L., 2003. Effect of Pffafia paniculata (Brazilian ginseng) on the Ehrlich tumor on its ascitic form. Life Sciences, Dec 19; 74 (5), 573-579.]. One of the putative means to control the Ehrlich tumor growth is by increasing macrophage activity [Kleeb, S.R., Xavier, J.G., Frussa-Filho, R., Dagli, M.L.Z., 1997. Effect of haloperidol on the development of the solid Ehrlich tumor in mice. Life Sciences, 60 (4/5), 69-742.]. The aim of this study was to investigate experimentally the effects of the methanolic extract of P. paniculata roots on macrophage activity. Male mice received, by gavage, once a day, different doses (100, 250, or 500 mg/kg) of the methanolic extract of P. paniculata or filtered water, as control, for 10 days. Macrophage activity was evaluated through the phagocytosis index (PI), spreading index (SI), production of peroxide oxigen and nitric oxide. The peritoneal cells were activated with ip inoculation of Ehrlich ascitic cells, 24 h before the macrophage harvesting. The methanolic extract raised significantly the SI of mice from group of 500 mg/kg in comparison with the control group and group of 100 mg/kg. This raise of SI possibly induced the higher phagocytic activity observed in the experimental situation. Increased macrophage activity may be one of the effects contributing to inhibition of the Ehrlich ascitic tumor growth in mice.