Prognostic Factors and Immune Response in Small Animal Oncology and Surgery

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

Deadline for manuscript submissions: closed (30 December 2023) | Viewed by 8428

Special Issue Editors


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Guest Editor
Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, Italy
Interests: veterinary pathology; veterinary oncology; cancer immunology; oncogenic viruses; immunuohistochemistry/fluorescence

E-Mail Website
Guest Editor
Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, Italy
Interests: veterinary pathology; tumor biology; veterinary dermatopathology; melanoma; cell culture

Special Issue Information

Dear Colleagues,

Veterinary oncology, with particular attention to small animals, is rapidly becoming one of the main and most dynamic branches of veterinary medicine. Clinicians, surgeons, pathologists, and researchers in the field are therefore called to refine the knowledge and the instruments to improve the life of pets and humans experiencing cancer by identifying solid prognostic factors in animal tumors and by investigating the spontaneous models of cancer that our pets provide us with. To develop veterinary and comparative oncology, the provision of deeper knowledge on the role of the immune response in small animals’ tumors is an essential goal that deserves our attention and efforts.

We are pleased to invite you to contribute to this Special Issue which will focus on topics relevant to both veterinary and comparative oncology.

This Special Issue aims to gather information from the latest studies and research, providing brand new tools for a better understanding of our pets’ oncological diseases, focusing on both prognostic features and deepening our knowledge on the immune response to cancer, with a “one health” approach.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Prognostic tools in veterinary oncology from a clinical, surgical, and pathological point of view;
  • The role and the prognostic value of immune response in veterinary and comparative oncology.

We look forward to receiving your contributions.

Dr. Ilaria Porcellato
Dr. Chiara Brachelente
Guest Editors

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Keywords

  • prognostic factors
  • cancer immune response
  • veterinary oncology
  • small animals
  • spontaneous models
  • comparative oncology
  • one health
  • canine oncology
  • feline oncology

Published Papers (4 papers)

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Research

19 pages, 6451 KiB  
Article
Clinical Implications of Immune Checkpoints and the RANK/RANK-L Signaling Pathway in High-Grade Canine Mast Cell Tumors
by Noelia C. Talavera Guillén, Andrigo Barboza de Nardi, Felipe Noleto de Paiva, Queila Cristina Dias, Alexandra Pinheiro Fantinatti and Wagner José Fávaro
Animals 2023, 13(12), 1888; https://doi.org/10.3390/ani13121888 - 6 Jun 2023
Cited by 1 | Viewed by 2510
Abstract
Mast cell tumors (MCTs) are the most common malignant cutaneous tumors in dogs, and they present extremely variable biological behavior. The interaction between RANK, RANK-L, and immune checkpoints is frequently detected in the tumor microenvironment, and, together, they participate in every stage of [...] Read more.
Mast cell tumors (MCTs) are the most common malignant cutaneous tumors in dogs, and they present extremely variable biological behavior. The interaction between RANK, RANK-L, and immune checkpoints is frequently detected in the tumor microenvironment, and, together, they participate in every stage of cancer development. Thus, the aim of this study was to characterize the molecular profiles of PD-L1, CTLA-4, RANK/RANK-L signaling pathway, and IFN-γ in primary tumors and lymph node metastases. Formalin-fixed, paraffin-embedded slides of MCTs and metastatic lymph nodes of ten dogs were submitted to immunohistochemical investigations. The results demonstrated that the tumor microenvironment of the high-grade mast cell tumors showed moderate or intense immunolabeling of all proteins, and the lymph node metastases also showed moderate or intense immunolabeling of checkpoint proteins. In addition, MCTs larger than 3 cm were associated with intensified PD-L1 (p = 0.03) in metastatic lymph nodes and RANK-L (p = 0.049) immunoreactivity in the tumor. Furthermore, dogs with a survival time of less than 6 months showed higher PD-L1 immunoreactivity (p = 0.042). In conclusion, high-grade MCT is associated with an immunosuppressive microenvironment that exhibits elevated RANK/RANK-L signaling and enhanced immune checkpoint immunoreactivity, potentially facilitating intratumorally immune escape. These biomarkers show promise as clinical indicators of disease progression and might response to immunotherapy in dogs with high-grade MCTs, thus emphasizing their importance for guiding treatment decisions and improving outcomes. Full article
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16 pages, 3504 KiB  
Article
Epithelial-to-Mesenchymal Transition and Phenotypic Marker Evaluation in Human, Canine, and Feline Mammary Gland Tumors
by Alessandro Sammarco, Chiara Gomiero, Giorgia Beffagna, Laura Cavicchioli, Silvia Ferro, Silvia Michieletto, Enrico Orvieto, Marco Patruno and Valentina Zappulli
Animals 2023, 13(5), 878; https://doi.org/10.3390/ani13050878 - 28 Feb 2023
Cited by 2 | Viewed by 1959
Abstract
Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties. EMT has been closely associated with cancer cell aggressiveness. The aim of this study was to evaluate the mRNA and protein expression of EMT-associated markers in mammary tumors of humans [...] Read more.
Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells acquire mesenchymal properties. EMT has been closely associated with cancer cell aggressiveness. The aim of this study was to evaluate the mRNA and protein expression of EMT-associated markers in mammary tumors of humans (HBC), dogs (CMT), and cats (FMT). Real-time qPCR for SNAIL, TWIST, and ZEB, and immunohistochemistry for E-cadherin, vimentin, CD44, estrogen receptor (ER), progesterone receptor (PR), ERBB2, Ki-67, cytokeratin (CK) 8/18, CK5/6, and CK14 were performed. Overall, SNAIL, TWIST, and ZEB mRNA was lower in tumors than in healthy tissues. Vimentin was higher in triple-negative HBC (TNBC) and FMTs than in ER+ HBC and CMTs (p < 0.001). Membranous E-cadherin was higher in ER+ than in TNBCs (p < 0.001), whereas cytoplasmic E-cadherin was higher in TNBCs when compared with ER+ HBC (p < 0.001). A negative correlation between membranous and cytoplasmic E-cadherin was found in all three species. Ki-67 was higher in FMTs than in CMTs (p < 0.001), whereas CD44 was higher in CMTs than in FMTs (p < 0.001). These results confirmed a potential role of some markers as indicators of EMT, and suggested similarities between ER+ HBC and CMTs, and between TNBC and FMTs. Full article
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13 pages, 1933 KiB  
Article
RT-qPCR Expression Profiles of Selected Oncogenic and Oncosuppressor miRNAs in Formalin-Fixed, Paraffin-Embedded Canine Mammary Tumors
by Jessica Maria Abbate, Alessia Giannetto, Francesca Arfuso, Barbara Brunetti and Giovanni Lanteri
Animals 2022, 12(21), 2898; https://doi.org/10.3390/ani12212898 - 22 Oct 2022
Cited by 2 | Viewed by 1548
Abstract
MicroRNAs (miRNAs) can act as oncogenes or oncosuppressor genes, and their involvement in nearly all cancer-associated processes makes these small molecules promising diagnostic and prognostic biomarkers in cancer, as well as specific targets for cancer therapy. This study aimed to investigate the expression [...] Read more.
MicroRNAs (miRNAs) can act as oncogenes or oncosuppressor genes, and their involvement in nearly all cancer-associated processes makes these small molecules promising diagnostic and prognostic biomarkers in cancer, as well as specific targets for cancer therapy. This study aimed to investigate the expression of 7 miRNAs (miR-18a, miR-18b, miR-22, miR-124, miR-145, miR-21, miR-146b) in formalin-fixed, paraffin-embedded canine mammary tumors (CMTs) by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Twenty-six mammary samples were selected, including 22 CMTs (7 benign; 15 malignant) and 4 control samples (3 normal mammary gland and 1 case of lobular hyperplasia). Oncogenic miR-18a, miR-18b and miR-21 were significantly upregulated in malignant tumors compared with control tissues (p < 0.05). Conversely, oncosuppressor miR-146b was significantly downregulated in benign and malignant mammary tumors compared with control samples (p < 0.05) while, no group-related differences in the expression levels of miR-22, miR-124 and miR-145 were found (p > 0.05). Upregulated miRNAs found here, may regulate genes involved in receptor-mediated carcinogenesis and proteoglycan remodeling in cancer; while miRNA with reduced expression can regulate genes involved in Toll-like receptor and MAPK signaling pathways. According to the results obtained in the current study, the oncogenic and oncosuppressor miRNAs analyzed here are dysregulated in CMTs and the dysregulation of miRNA targets may lead to specific altered cellular processes and key pathways involved in carcinogenesis. Of note, since oncogenic miRNAs predicted to regulate neoplastic cell proliferation and hormonal activities, they may play an active role in neoplastic transformation and/or progression, having mechanistic and prognostic relevance in CMTs. Full article
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15 pages, 2801 KiB  
Article
The Implication of Serum Autoantibodies in Prognosis of Canine Mammary Tumors
by Stephen Hsien-Chi Yuan, Shih-Chieh Chang, Pei-Yi Chou, Youngsen Yang and Hao-Ping Liu
Animals 2022, 12(18), 2463; https://doi.org/10.3390/ani12182463 - 18 Sep 2022
Viewed by 1688
Abstract
Canine mammary tumor (CMT) is the most prevalent neoplasm in female dogs. Tumor recurrence and metastasis occur in malignant CMT (MMT) dogs after surgery. Identification of serum prognostic biomarkers holds the potential to facilitate prediction of disease outcomes. We have identified CMT-associated autoantibodies [...] Read more.
Canine mammary tumor (CMT) is the most prevalent neoplasm in female dogs. Tumor recurrence and metastasis occur in malignant CMT (MMT) dogs after surgery. Identification of serum prognostic biomarkers holds the potential to facilitate prediction of disease outcomes. We have identified CMT-associated autoantibodies against thymidylate synthetase (TYMS), insulin-like growth factor-binding protein 5 (IGFBP5), hyaluronan and proteoglycan link protein 1 (HAPLN1), and anterior gradient 2 (AGR2), i.e., TYMS-AAb, IGFBP5-AAb, HAPLN1-AAb, and AGR2-AAb, respectively, by conducting serological enzyme-linked immunosorbent assays (ELISA). Herein we assessed serum AAb levels in 11 MMT dogs before and after surgery, demonstrating that IGFBP5-AAb and HAPLN1-AAb significantly decrease at 3- and 12-months post-surgery (p < 0.05). We evaluated the correlation between the presurgical AAb level and overall survival (OS) of 90 CMT dogs after surgery. Kaplan-Meier survival analysis reveals that IGFBP5-AAbHIgh and TYMS-AAbHigh are significantly correlated with worse OS (p = 0.017 and p = 0.029, respectively), while AGR2-AAbLow is correlated with somewhat poorer OS (p = 0.086). Areas under a time-dependent receiver operating characteristic curve (AUC) of IGFBP5-AAb and TYMS-AAb in predicting OS of MMT dogs are 0.611 and 0.616, respectively. Notably, MMT dogs presenting TYMS-AAbHigh/IGFBP5-AAbHigh/AGR2-AAbLow have worst OS (p = 0.0004). This study reveals an association between the serum AAb level and CMT prognosis. Full article
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