Solid Carcinoma of the Canine Mammary Gland: a Histological Type or Tumour Cell Arrangement?

Nakagaki, Karen YR.; Nunes, Maíra; Garcia, Ana Paula V; Nunes, Fernanda Camargo; Schmitt, Fernando; Cassali, Geovanni Dantas

doi:10.1016/j.jcpa.2021.10.011

Cited by 7 publications

(8 citation statements)

References 34 publications

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“…The in ammatory score was performed with hematoxylin and eosin (H&E) stained slides and evaluated airway, vascular and parenchymal in ammation [47,48]. For immunohistochemistry analysis, lung tissue slides from controls, and post-COVID HM GF mice were immune-stained as described before [49]. Brie y, the slides were incubated with primary anti-α-actin antibodies (human, 1:500) (DAKO, USA) overnight at 4ºC.…”

Section: Histopathology and Immunohistochemistry Analysismentioning

confidence: 99%

Gut microbiota from patients with mild COVID-19 cause alterations in mice that resemble post-COVID syndrome

Almeida

Engel

Ricci

et al. 2022

Preprint

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Background There is mounting evidence that SARS-CoV-2 targets tissues beyond the respiratory tract. Long-term sequelae after COVID-19 are frequent and of major concern. Prolonged virus detection in the gut has been particularly intriguing. Of note, SARS-CoV-2 infection also disturbs the gut microbiota composition, a finding linked with disease severity in patients with COVID-19. Here, we aimed to characterize the functional role of the gut microbiota in the long-term consequences of COVID-19. To this end, we characterized the gut microbiota from COVID-19 human subjects and followed the effects of human fecal transfer to germ-free mice. Results The gut microbiota of post-COVID subjects (up to 4 months from the initial positive test) revealed a remarkable predominance of Enterobacteriaceae strains with multidrug-resistance phenotype compared to healthy controls. After fecal transfer to germ-free mice, animals receiving samples from post-COVID subjects displayed higher lung inflammation and increased susceptibility to pulmonary infection caused by an antimicrobial resistant Klebsiella pneumoniae strain. These mice also showed poorer cognitive performance associated with increased expression of TNF-α, reduced levels of brain-derived neurotrophic factor-BDNF and postsynaptic density protein-PSD-95 in the brain, as well as alterations of several biochemical pathways. These alterations were observed in the absence of SARS-CoV-2, suggesting that alterations in the gut microbiota caused them. Consistent with this hypothesis, brain dysfunctions induced in a mouse model of coronavirus infection were partially prevented by modulation of the microbiota via treatment with the commensal probiotic bacteria Bifidobacterium longum 51A. Conclusions Our results show prolonged impact of SARS-CoV-2 infection in the gut microbiota that persists even after the individuals have cleared the virus. Increased Enterobacteriaceae with antimicrobial resistance phenotype were of particular concern. Moreover, microbiota transfer from post-COVID subjects induced loss of brain cognitive functions and impaired lung defense in mice. Altogether, our work emphasizes the importance of microbiota as a target for therapies to help treat post-COVID sequelae.

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Section: Histopathology and Immunohistochemistry Analysismentioning

confidence: 99%

Gut microbiota from patients with mild COVID-19 cause alterations in mice that resemble post-COVID syndrome

Almeida

Engel

Ricci

et al. 2022

Preprint

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“…Mammary gland tumors are the most prevalent neoplasm in intact female dogs, but the incidence can vary and be as high as 83% in a study population [ 1 , 2 ]. Comparatively, in 2022, Brazil’s public health system reported 73,610 new diagnoses of breast cancer in women, 30.1% of all newly diagnosed neoplasias, which is more than three times what ranked second in statistics [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic effects of crotoxin from Crotalus durissus terrificus snake in canine mammary tumor cell lines

Pedro,

Brasileiro,

Macedo

et al. 2024

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: Mammary gland tumors are the most prevalent neoplasm in intact female dogs, and they are good natural models to study comparative oncology. Most canine mammary malignancies, as in women, are commonly refractory to conventional therapies and demand continuous new therapeutic approaches. Crotalus durissus terrificus , also called rattlesnake, has more than 60 different proteins in its venom with multiple pharmaceutical uses, such as antitumor, antiviral, and antimicrobial action. Crotoxin, a potent β-neurotoxin formed by the junction of two subunits, a basic subunit (CB-PLA 2 ) and an acidic subunit (crotapotin), has already been reported to have anticancer properties in different types of cancers. Methods: In this work, we describe the cytotoxic potential of crotoxin and its subunits compared to doxorubicin (drug of choice) in two canine mammary carcinoma cell lines. Results: Crotoxin, CB-PLA 2 , crotalic venom, and doxorubicin decreased cell viability and the ability to migrate in a dose-dependent manner, and crotapotin did not present an antitumoral effect. For all compounds, the predominant cell death mechanism was apoptosis. In addition, crotoxin did not show toxicity in normal canine mammary gland cells. Conclusion: Therefore, this work showed that crotoxin and CB-PLA 2 had cytotoxic activity, migration inhibition, and pro-apoptotic potential in canine mammary gland carcinoma cell lines, making their possible use in cancer research.

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“…Another difference is histology. About 50% of canine mammary tumors are complex or mixed, with multiple cell lineages (e.g., epithelial and myoepithelial cells) proliferating [ 14 , 19 , 20 ]. These histologies (e.g., adenomyoepithelioma) are, however, are very rare (< 1%) in human breast cancers [ 14 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…The same as human breast cancers, spontaneous canine mammary cancers are heterogeneous and consist of distinct subtypes [ 19 , 20 ]. Thus, subtype-level dog–human comparison is needed to evaluate the dog–human homology.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, subtype-level dog–human comparison is needed to evaluate the dog–human homology. Canine mammary cancers have been histopathologically and clinically subtyped, as well as molecularly subtyped with immunohistochemical markers established for human breast cancer (anti-ER, PR, HER2, -CK 5/6 and -CK14) [ 19 , 20 , 23 , 24 ]. However, to our knowledge, canine mammary tumors have not been independently subtyped by genome-wide molecular studies.…”

Section: Introductionmentioning

confidence: 99%

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Human basal-like breast cancer is represented by one of the two mammary tumor subtypes in dogs

Watson,

Wang,

et al. 2023

Breast Cancer Res

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Background About 20% of breast cancers in humans are basal-like, a subtype that is often triple-negative and difficult to treat. An effective translational model for basal-like breast cancer is currently lacking and urgently needed. To determine whether spontaneous mammary tumors in pet dogs could meet this need, we subtyped canine mammary tumors and evaluated the dog–human molecular homology at the subtype level. Methods We subtyped 236 canine mammary tumors from 3 studies by applying various subtyping strategies on their RNA-seq data. We then performed PAM50 classification with canine tumors alone, as well as with canine tumors combined with human breast tumors. We identified feature genes for human BLBC and luminal A subtypes via machine learning and used these genes to repeat canine-alone and cross-species tumor classifications. We investigated differential gene expression, signature gene set enrichment, expression association, mutational landscape, and other features for dog–human subtype comparison. Results Our independent genome-wide subtyping consistently identified two molecularly distinct subtypes among the canine tumors. One subtype is mostly basal-like and clusters with human BLBC in cross-species PAM50 and feature gene classifications, while the other subtype does not cluster with any human breast cancer subtype. Furthermore, the canine basal-like subtype recaptures key molecular features (e.g., cell cycle gene upregulation, TP53 mutation) and gene expression patterns that characterize human BLBC. It is enriched in histological subtypes that match human breast cancer, unlike the other canine subtype. However, about 33% of canine basal-like tumors are estrogen receptor negative (ER−) and progesterone receptor positive (PR+), which is rare in human breast cancer. Further analysis reveals that these ER−PR+ canine tumors harbor additional basal-like features, including upregulation of genes of interferon-γ response and of the Wnt-pluripotency pathway. Interestingly, we observed an association of PGR expression with gene silencing in all canine tumors and with the expression of T cell exhaustion markers (e.g., PDCD1) in ER−PR+ canine tumors. Conclusions We identify a canine mammary tumor subtype that molecularly resembles human BLBC overall and thus could serve as a vital translational model of this devastating breast cancer subtype. Our study also sheds light on the dog–human difference in the mammary tumor histology and the hormonal cycle.

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Solid Carcinoma of the Canine Mammary Gland: a Histological Type or Tumour Cell Arrangement?

Cited by 7 publications

References 34 publications

Gut microbiota from patients with mild COVID-19 cause alterations in mice that resemble post-COVID syndrome

Gut microbiota from patients with mild COVID-19 cause alterations in mice that resemble post-COVID syndrome

Cytotoxic effects of crotoxin from Crotalus durissus terrificus snake in canine mammary tumor cell lines

Human basal-like breast cancer is represented by one of the two mammary tumor subtypes in dogs

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