Recent Advances in Canine Mammary Tumors

A special issue of Animals (ISSN 2076-2615). This special issue belongs to the section "Companion Animals".

Deadline for manuscript submissions: closed (10 December 2023) | Viewed by 20244

Special Issue Editors


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Laboratório de Investigação Molecular no Câncer (LIMC), Faculdade de Medicina de São José do Rio Preto (FAMERP), Avenida Brigadeiro Faria Lima, 5416, São José do Rio Preto 15090-000, Brazil
Interests: immunohistochemical evaluation of mammary cancer biomarkers; tumor biomarkers in liquid biopsy; extracellular vesicles as diagnostic and prognostic tools for cancer; antioxidant action of melatonin and its potential use in mammary cancer treatment
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Department of Structural and Functional Biology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu 18618-689, Brazil
Interests: effects of melatonin and its MT2/MT2 receptors on cancer cells; potential therapeutic use of melatonin; paclitaxel; P-MAPA immunomodulator associated with interleukin-12 in ovarian cancer
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Instituto de Ciências da Saúde (ICS), Universidade Federal de Mato Grosso (UFMT), Campo Grande 78550-000, Brazil
Interests: immunohematology; canine blood groups; extracellular vesicles as tumor biomarkers in liquid biopsy and their role as diagnostic and prognostic tools in mammary tumors

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Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Giuseppe Máximo Scolfaro Street, 10.000, Campinas 13083-970, Brazil
Interests: tumor metabolism and metabolic reprogramming; lipid metabolism in cancer; diet as a preventive and therapeutic approach; mitochondria in cancer, tumor immunology and comparative oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Canine mammary tumors (CMTs) are the most common neoplasm in intact female dogs, and about 50% of them are considered malignant. A CMT is a good spontaneous animal model of human breast cancer (HBC) research because it shares many similarities, such as epidemiologic, clinical, genetical, biological and pathological characteristics; additionally, their histological and molecular patterns are very heterogeneous. Different hormones and growth factors influence the occurrence of CMTs, but the pathological mechanisms remain unclear. In addition to circulating hormones, their receptors play a central role in mammary tumor formation (estrogen and progesterone receptors). Surgery is still the frontline treatment, but other therapies can be beneficial regarding patients’ survival. Advances in molecular pathways associated with cancer progression have highlighted several aspects in the field, and the development of new treatments may be promising for comparative and translational oncology.

This Special Issue aims to publish original research papers or reviews about canine mammary tumors, concerning their diagnosis, prognosis and therapeutics.

Areas of interest: CMT histological and molecular classification for diagnosis and prognosis; biomarkers; therapeutic approaches; experimental models suitable for CMTs; angiogenesis; metastasis and invasion; the role of the immune system and molecular pathways associated with CMT development and progression; and comparative and translational oncology.

We invite you to share your recent findings through this Special Issue.

Prof. Dr. Debora Aparecida Pires de Campos Zuccari
Prof. Dr. Luiz Gustavo de Almeida Chuffa
Prof. Dr. Adriana Alonso Novais
Prof. Dr. Guilherme Henrique Tamarindo
Guest Editors

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Keywords

  • dogs
  • cancer
  • biomarkers
  • diagnosis
  • prognosis
  • extracellular vesicles
  • therapeutics
  • liquid biopsy
  • comparative oncology
  • translational models

Published Papers (11 papers)

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Research

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14 pages, 1475 KiB  
Article
Effect of Melatonin on Chemoresistance Exhibited by Spheres Derived from Canine Mammary Carcinoma Cells
by Dania Cataldo, Guillermo Aravena, Alejandro Escobar, Julio C. Tapia, Oscar A. Peralta and Cristian G. Torres
Animals 2024, 14(8), 1229; https://doi.org/10.3390/ani14081229 - 19 Apr 2024
Viewed by 573
Abstract
Mammary cancer is a frequent disease in female dogs, where a high proportion of cases correspond to malignant tumors that may exhibit drug resistance. Within the mammary tumor microenvironment, there is a cell subpopulation called cancer stem cells (CSCs), which are capable of [...] Read more.
Mammary cancer is a frequent disease in female dogs, where a high proportion of cases correspond to malignant tumors that may exhibit drug resistance. Within the mammary tumor microenvironment, there is a cell subpopulation called cancer stem cells (CSCs), which are capable of forming spheres in vitro and resisting anti-tumor treatments, partly explaining the recurrence of some tumors. Previously, it has been described that spheres derived from canine mammary carcinoma cells CF41.Mg and REM 134 exhibit stemness characteristics. Melatonin has shown anti-tumor effects on mammary tumor cells; however, its effects have been poorly evaluated in canine mammary CSCs. This study aimed to analyze the effect of melatonin on the chemoresistance exhibited by stem-like neoplastic cells derived from canine mammary carcinoma to cytotoxic drugs such as doxorubicin and mitoxantrone. CF41.Mg and REM 134 cells were cultured in high-glucose DMEM supplemented with fetal bovine serum and L-glutamine. The spheres were cultured in ultra-low attachment plates in DMEM/F12 medium without fetal bovine serum and with different growth factors. The CD44+/CD24−/low phenotype was analyzed by flow cytometry. The viability of sphere-derived cells (MTS reduction) was studied in the presence of melatonin (0.1 or 1 mM), doxorubicin, mitoxantrone, and luzindole. In addition, the gene (RT-qPCR) of the multidrug resistance bombs MDR1 and ABCG2 were analyzed in the presence of melatonin. Both cell types expressed the MT1 gene, which encodes the melatonin receptor MT1. Melatonin 1 mM does not modify the CD44+/CD24−/low phenotype; however, the hormone reduced viability (p < 0.0001) only in CF41.Mg spheres, without inducing an additive effect when co-incubated with cytotoxic drugs. These effects were independent of the binding of the hormone to its receptor MT1, since, by pharmacologically inhibiting them, the effect of melatonin was not blocked. In CF41.Mg spheres, the relative gene expression of ABCG2 and MDR1 was decreased in response to the hormone (p < 0.001). These results indicate that melatonin negatively modulates the cell survival of spheres derived from CF41.Mg cells, in a way that is independent of its MT1 receptor. These effects did not counteract the resistance to doxorubicin and mitoxantrone, even though the hormone negatively regulates the gene expression of MDR1 and ABCG2. Full article
(This article belongs to the Special Issue Recent Advances in Canine Mammary Tumors)
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13 pages, 8461 KiB  
Article
Sirtuin 1 Expression in Canine Mammary Tumors: A Pilot Study
by Mariafrancesca Sgadari, Nunzio Antonio Cacciola, Karen Power, Manuela Martano and Brunella Restucci
Animals 2023, 13(16), 2609; https://doi.org/10.3390/ani13162609 - 13 Aug 2023
Viewed by 1759
Abstract
Sirtuin 1 (SIRT1) is a protein involved in aging, cell protection, and energy metabolism in mammals. Recently, SIRT1 has been intensively studied in medical oncology, but the role of SIRT1 is still controversial, as it has been proposed as both an oncogene and [...] Read more.
Sirtuin 1 (SIRT1) is a protein involved in aging, cell protection, and energy metabolism in mammals. Recently, SIRT1 has been intensively studied in medical oncology, but the role of SIRT1 is still controversial, as it has been proposed as both an oncogene and a tumor suppressor. The aim of this study is to investigate the expression of SIRT1 by immunohistochemistry in canine mammary tissues, and by Western blot and immunofluorescence analysis in different canine mammary cell lines. Our results showed a decrease in SIRT1 expression from normal mammary gland tissue, and from benign and well-differentiated malignant tumors (G1) to less differentiated ones (G2–G3). Furthermore, a shift in the subcellular localization of SIRT1 from the nucleus to the cytoplasm was observed in less differentiated malignant tumors. However, further studies are needed to investigate the subcellular localization of SIRT1 in canine cancer cells and the role it may play in oncogenesis in animals. Full article
(This article belongs to the Special Issue Recent Advances in Canine Mammary Tumors)
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12 pages, 2172 KiB  
Article
In Silico and In Vitro Evaluation of Bevacizumab Biosimilar MB02 as an Antitumor Agent in Canine Mammary Carcinoma
by Georgina A. Cardama, Paula L. Bucci, Jesús S. Lemos, Candela Llavona, Micaela A. Benavente, Eva Hellmén, María Laura Fara, Eduardo Medrano, Eduardo Spitzer, Ignacio A. Demarco, Patricia Sabella, Juan Garona and Daniel F. Alonso
Animals 2023, 13(15), 2507; https://doi.org/10.3390/ani13152507 - 3 Aug 2023
Viewed by 1460
Abstract
Canine mammary carcinomas (CMC) are associated with major aggressive clinical behavior and high mortality. The current standard of care is based on surgical resection, without an established effective treatment scheme, highlighting the urgent need to develop novel effective therapies. Vascular endothelial growth factor [...] Read more.
Canine mammary carcinomas (CMC) are associated with major aggressive clinical behavior and high mortality. The current standard of care is based on surgical resection, without an established effective treatment scheme, highlighting the urgent need to develop novel effective therapies. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis and progression in the majority of solid cancers, including human and canine mammary carcinomas. The first therapy developed to target VEGF was bevacizumab, a recombinant humanized monoclonal antibody, which has already been approved as an anticancer agent in several human cancers. The goal of this work was to establish the therapeutic value of MB02 bevacizumab biosimilar in CMC. First, through different in silico approaches using the MUSCLE multiple-sequence alignment tool and the FoldX protein design algorithm, we were able to predict that canine VEGF is recognized by bevacizumab, after showing an extremely high sequence similarity between canine and human VEGF. Further, by using an ELISA-based in vitro binding assay, we confirmed that MB02 biosimilar was able to recognize canine VEGF. Additionally, canine VEGF-induced microvascular endothelial cell proliferation was inhibited in a concentration-dependent manner by MB02 biosimilar. These encouraging results show a high potential for MB02 as a promising therapeutic agent for the management of CMC. Full article
(This article belongs to the Special Issue Recent Advances in Canine Mammary Tumors)
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11 pages, 466 KiB  
Article
Protective Effect of HER2 Gene Polymorphism rs24537331 in the Outcome of Canine Mammary Tumors
by Ana Canadas-Sousa, Marta Santos and Patrícia Dias-Pereira
Animals 2023, 13(8), 1384; https://doi.org/10.3390/ani13081384 - 18 Apr 2023
Viewed by 1503
Abstract
The role of HER2 in canine mammary tumors is not completely elucidated, and the contradictory results published so far may be, in part, explained by the genetic variability recognized in the canine HER2 gene. Single nucleotide polymorphism (SNPs) in HER2 were recently associated [...] Read more.
The role of HER2 in canine mammary tumors is not completely elucidated, and the contradictory results published so far may be, in part, explained by the genetic variability recognized in the canine HER2 gene. Single nucleotide polymorphism (SNPs) in HER2 were recently associated with less aggressive canine mammary tumor histotypes. This study assesses the relationship between SNPs rs24537329 and rs24537331 in canine HER2 gene and clinicopathological characteristics and outcome of mammary tumors in a group of 206 female dogs. Allelic variants were observed in 69.8% and 52.7% of the dogs for SNP rs24537329 and rs24537331, respectively. Our results demonstrated that SNP rs24537331 was associated with decreased tumoral necrosis (HR: 3.09; p = 0.012) and with longer disease-specific overall survival (HR: 2.59; p = 0.013). However, no statistically significant associations were found between SNP rs24537329 and the tumors’ clinicopathological characteristics or survival. Our data suggest that SNP rs24537331 may have a protective effect in canine mammary tumors, allowing the identification of a subgroup of animals prone to develop less aggressive forms of the disease. This study emphasizes the importance of the genetic tests associated with clinical images and histological examinations when assessing CMT outcomes. Full article
(This article belongs to the Special Issue Recent Advances in Canine Mammary Tumors)
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18 pages, 2567 KiB  
Article
Parameters of Metabolic Response to Surgical Trauma Induced via Unilateral Total Mastectomy Associated or Not to Ovariohysterectomy in Dogs
by Sabrina Marin Rodigheri, Felipe Noleto de Paiva, Bruna Fernanda Firmo, Taise Fuchs, Cynthia Bueno Mani and Andrigo Barboza de Nardi
Animals 2023, 13(5), 926; https://doi.org/10.3390/ani13050926 - 3 Mar 2023
Cited by 1 | Viewed by 1782
Abstract
Surgical excision of solid tumors is required for local control of neoplasms. However, surgical trauma can stimulate the release of proangiogenic growth factors, suppressing cell-mediated immunity and favoring the development of micrometastases and progression of residual disease. The present study aimed to evaluate [...] Read more.
Surgical excision of solid tumors is required for local control of neoplasms. However, surgical trauma can stimulate the release of proangiogenic growth factors, suppressing cell-mediated immunity and favoring the development of micrometastases and progression of residual disease. The present study aimed to evaluate the intensity of the metabolic response to trauma induced via unilateral mastectomy in bitches with mammary neoplasia, the consequences of its joint performance with ovariohysterectomy, and their respective effects on the organic response. Two groups of animals were evaluated in seven perioperative moments, namely, unilateral mastectomy (G1) and unilateral mastectomy associated with ovariohysterectomy (G2). Thirty-two female dogs were selected, ten clinically healthy, and twenty-two diagnosed with mammary neoplasia. Surgical trauma reduced serum concentrations of albumin and interleukin-2 but increased blood levels of glucose and interleukin-6 in the postoperative of G1 and G2 patients. Moreover, serum cortisol levels increased after unilateral mastectomy associated with ovariohysterectomy. Our findings allowed us to conclude that unilateral mastectomy induces significant metabolic alterations in female dogs with mammary neoplasms and its joint performance with ovariohysterectomy increases the organic response to trauma. Full article
(This article belongs to the Special Issue Recent Advances in Canine Mammary Tumors)
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10 pages, 1039 KiB  
Article
Confirmation of the Prognostic Value of Foxp3+ Cells in Canine Mammary Tumors
by Francesca Parisi, Francesca Millanta, Marika Nicastro, Iacopo Vannozzi and Alessandro Poli
Animals 2023, 13(3), 505; https://doi.org/10.3390/ani13030505 - 31 Jan 2023
Viewed by 1234
Abstract
Foxp3+ cell counts were evaluated by immunohistochemistry in 59 canine mammary tumors, 20 adenomas, and 39 carcinomas in three different compartments: intratumoral, within the adjacent stroma, and in the distant stroma. Foxp3+ lymphocyte counts were compared with histotype, grading, presence of lymphatic invasion, [...] Read more.
Foxp3+ cell counts were evaluated by immunohistochemistry in 59 canine mammary tumors, 20 adenomas, and 39 carcinomas in three different compartments: intratumoral, within the adjacent stroma, and in the distant stroma. Foxp3+ lymphocyte counts were compared with histotype, grading, presence of lymphatic invasion, immunohistochemical expression of estrogen and progesterone receptors, expression of c-erbB-2, and the overall survival (OS). Our findings confirmed that Foxp3+ cells were significantly higher in canine mammary carcinomas compared to adenomas. A significantly higher number of Foxp3+ cells were detected in grade III carcinomas compared to grade II carcinomas, as well as in tumors with lymphatic invasion and loss of ER-expression. Finally, a high number of Foxp3+ cells was associated with poor prognosis. In conclusion, our findings highlighted the association of Foxp3+ lymphocytes with negative clinicopathological features and shorter overall survival (OS), thus confirming the role of Tregs as a negative prognostic marker in canine mammary carcinomas. Full article
(This article belongs to the Special Issue Recent Advances in Canine Mammary Tumors)
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12 pages, 271 KiB  
Article
Proof-of-Concept Study of an Alpha-Fetoprotein-Derived Peptide for the Management of Canine Mammary Cancer
by James A. Bennett, Ann Hohenhaus and Thomas T. Andersen
Animals 2023, 13(3), 403; https://doi.org/10.3390/ani13030403 - 25 Jan 2023
Viewed by 1315
Abstract
Novel, well-tolerated drugs are needed for the management of canine mammary cancer. Many of these cancers are promoted in their growth by estrogen. Alpha-fetoprotein (AFP) is a ubiquitous mammalian protein that has anti-estrogenic properties. AFPep (the anti-estrogenic site of AFP) has been developed [...] Read more.
Novel, well-tolerated drugs are needed for the management of canine mammary cancer. Many of these cancers are promoted in their growth by estrogen. Alpha-fetoprotein (AFP) is a ubiquitous mammalian protein that has anti-estrogenic properties. AFPep (the anti-estrogenic site of AFP) has been developed into a readily synthesizable drug. AFPep has been shown to have anti-mammary cancer activity in several models of this disease, both in cell culture and in rodents. The purpose of the study reported herein was to determine the tolerability of AFPep in normal and tumor-bearing dogs. AFPep was given to dogs via both parenteral and oral routes in a single application and in repeated daily doses. Full clinical chemistry and hematology values were determined before and after drug administration. Blood levels of the drug were achieved in dogs that had been previously found to be oncostatic in rodents. No changes in clinical chemistry, hematology, and clinical behaviors were found in dogs following drug administration. The data support the further development of AFPep for clinical use against canine mammary cancer. Full article
(This article belongs to the Special Issue Recent Advances in Canine Mammary Tumors)
14 pages, 1656 KiB  
Article
Pharmacokinetics of Carboplatin in Combination with Low-Dose Cyclophosphamide in Female Dogs with Mammary Carcinoma
by Marília Carneiro Machado, Priscila Akemi Yamamoto, Leandro Francisco Pippa, Natália Valadares de Moraes, Fabiane Maria Fernandes Neves, Ricardo Dias Portela, Stella Maria Barrouin-Melo, Anna Hielm-Björkman, Ana Leonor Pardo Campos Godoy and Alessandra Estrela-Lima
Animals 2022, 12(22), 3109; https://doi.org/10.3390/ani12223109 - 10 Nov 2022
Cited by 3 | Viewed by 2779
Abstract
This prospective study aimed to evaluate the effect of metronomic cyclophosphamide on carboplatin’s tolerability, efficacy, and pharmacokinetics in dogs with mammary carcinoma. Sixteen female dogs with mammary carcinoma were divided into groups: 300 mg/m2 intravenous (i.v.) carboplatin therapy (G1 = 8) or [...] Read more.
This prospective study aimed to evaluate the effect of metronomic cyclophosphamide on carboplatin’s tolerability, efficacy, and pharmacokinetics in dogs with mammary carcinoma. Sixteen female dogs with mammary carcinoma were divided into groups: 300 mg/m2 intravenous (i.v.) carboplatin therapy (G1 = 8) or 300 mg/m2 i.v. carboplatin which was associated with 12.5 mg/m2 oral cyclophosphamide in a metronomic regimen (G2 = 8). The investigated animals underwent a clinical evaluation, a mastectomy, a carboplatin chemotherapy, and serial blood sampling for the pharmacokinetic analysis. The adverse events and survival rates were monitored. A non-compartmental analysis was applied to calculate the pharmacokinetic parameters of carboplatin in the 2nd and 4th chemotherapy cycles. Carboplatin PK showed high interindividual variability with a 10-fold variation in the area under the plasma concentration–time curve (AUC) in G1. The systemic plasma exposure to carboplatin was equivalent in both of the treatments considering the AUC and maximum plasma concentration (Cmax) values. Although the red blood cells (p < 0.0001), platelets (p = 0.0005), total leukocytes (p = 0.0002), and segmented neutrophils (p = 0.0007) were reduced in G2, the survival rate increased (p = 0.0044) when it was compared to G1. In conclusion, adding low daily doses of cyclophosphamide to a carboplatin therapy showed promising outcomes in female dogs with mammary tumors. Full article
(This article belongs to the Special Issue Recent Advances in Canine Mammary Tumors)
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14 pages, 2370 KiB  
Article
The Analysis of E-Cadherin, N-Cadherin, Vimentin, HER-2, CEA, CA15-3 and SF Expression in the Diagnosis of Canine Mammary Tumors
by Chao Yu, Huihua Zheng, Xiangyu Liu and Guanghong Xie
Animals 2022, 12(21), 3050; https://doi.org/10.3390/ani12213050 - 6 Nov 2022
Cited by 6 | Viewed by 2077
Abstract
Canine mammary tumors (CMTs) are one of the most common tumors in female dogs, and they are associated with a poor prognosis owing to their high rate of recurrence and metastasis rates, which make their diagnosis especially important in clinical veterinary medicine. In [...] Read more.
Canine mammary tumors (CMTs) are one of the most common tumors in female dogs, and they are associated with a poor prognosis owing to their high rate of recurrence and metastasis rates, which make their diagnosis especially important in clinical veterinary medicine. In this study, the characteristics of tumors were observed in dogs suffering from CMTs, and clinical diagnosis and histopathology were used to identify tumors. Furthermore, the expression levels of tumor markers for CMTs were analyzed by enzyme-linked immunosorbent assay (ELISA) and quantitative PCR (qPCR). Upon clinical examination, dogs with CMTs displayed a distinct and irregular mass in the mammary gland, and X-ray (Latero-lateral and ventro-dorsal views) and ultrasonography of the abdomen revealed a moderately echogenic mass at the mammary gland with slightly stronger density than the surrounding tissue. A total of 30 tumors were identified by histopathology, 11 benign and 19 malignant. Changes in some indicators in dogs suffering from CMTs and healthy dogs suggested that there were multiple direct or paraneoplastic changes associated with tumors that could be detected/suspected by hematological examination, and ELISA revealed the HER-2 serum concentrations were significantly different between healthy animals and those with malignant tumors. qPCR indicated that tumor markers N-cadherin, Vimentin, HER-2, CEA, CA15-3 and SF were higher in dogs with malignant tumors than healthy dogs, with a low level of E-cadherin in malignant tumors. This study verified that serological tests and molecular biological tests were essential to the early diagnosis, treatment and prognosis of dogs with tumors. Full article
(This article belongs to the Special Issue Recent Advances in Canine Mammary Tumors)
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Review

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15 pages, 1160 KiB  
Review
Metabolic Alterations in Canine Mammary Tumors
by Guilherme Henrique Tamarindo, Adriana Alonso Novais, Luiz Gustavo Almeida Chuffa and Debora Aparecida Pires Campos Zuccari
Animals 2023, 13(17), 2757; https://doi.org/10.3390/ani13172757 - 30 Aug 2023
Cited by 1 | Viewed by 2764
Abstract
Canine mammary tumors (CMTs) are among the most common diseases in female dogs and share similarities with human breast cancer, which makes these animals a model for comparative oncology studies. In these tumors, metabolic reprogramming is known as a hallmark of carcinogenesis whereby [...] Read more.
Canine mammary tumors (CMTs) are among the most common diseases in female dogs and share similarities with human breast cancer, which makes these animals a model for comparative oncology studies. In these tumors, metabolic reprogramming is known as a hallmark of carcinogenesis whereby cells undergo adjustments to meet the high bioenergetic and biosynthetic demands of rapidly proliferating cells. However, such alterations are also vulnerabilities that may serve as a therapeutic strategy, which has mostly been tested in human clinical trials but is poorly explored in CMTs. In this dedicated review, we compiled the metabolic changes described for CMTs, emphasizing the metabolism of carbohydrates, amino acids, lipids, and mitochondrial functions. We observed key factors associated with the presence and aggressiveness of CMTs, such as an increase in glucose uptake followed by enhanced anaerobic glycolysis via the upregulation of glycolytic enzymes, changes in glutamine catabolism due to the overexpression of glutaminases, increased fatty acid oxidation, and distinct effects depending on lipid saturation, in addition to mitochondrial DNA, which is a hotspot for mutations. Therefore, more attention should be paid to this topic given that targeting metabolic fragilities could improve the outcome of CMTs. Full article
(This article belongs to the Special Issue Recent Advances in Canine Mammary Tumors)
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15 pages, 1648 KiB  
Review
The Importance of Ultrasonography in the Evaluation of Mammary Tumors in Bitches
by Marcus Antônio Rossi Feliciano, Brenda dos Santos Pompeu de Miranda, Luiz Paulo Nogueira Aires, Bruna Bressianini Lima, Ana Paula Luiz de Oliveira, Giovanna Serpa Maciel Feliciano and Ricardo Andrés Ramirez Uscategui
Animals 2023, 13(11), 1742; https://doi.org/10.3390/ani13111742 - 24 May 2023
Cited by 1 | Viewed by 1731
Abstract
The high incidence of mammary tumors in small animals is concerning. Patient history, clinical examination, physical evaluation, and imaging studies are important for clinical staging. Ultrasonography is commonly applied to investigate the presence of abdominal metastasis. However, it has been shown to provide [...] Read more.
The high incidence of mammary tumors in small animals is concerning. Patient history, clinical examination, physical evaluation, and imaging studies are important for clinical staging. Ultrasonography is commonly applied to investigate the presence of abdominal metastasis. However, it has been shown to provide important information regarding mammary tumors’ architecture and advanced sonographic techniques can provide information regarding neovascularization, stiffness, and perfusion. Different techniques have been investigated to determine accuracy to predict the lesions’ histological classification. This paper reviews the information regarding each sonographic technique in the evaluation of mammary tumors, describing the most common findings and their potential to accurately assess and predict malignancy. Even though the gold standard for the diagnosis of mammary lesions is the histopathological examination, some ultrasonographic features described can predict the potential of a lesion being malignant. Among the different sonographic techniques, elastography can be considered the most reliable modality to accurately differentiate benign from malignant tumors when malignant lesions present increased stiffness. However, the combination of all sonographic techniques can provide important information that can lead to a better therapeutic approach and clinical staging. Furthermore, the potential of the sonographic study, especially CEUS to monitor therapeutic progression, demonstrate the need of further studies. Full article
(This article belongs to the Special Issue Recent Advances in Canine Mammary Tumors)
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