Special Issue "Comparative Oncology: Integrating Naturally Occurring Cancers of Dogs into Investigations of Cancer Biology and Therapy"

A special issue of Veterinary Sciences (ISSN 2306-7381).

Deadline for manuscript submissions: closed (28 February 2019).

Special Issue Editors

A/Prof. Dr. Chiara Palmieri
E-Mail Website
Guest Editor
Faculty of Science,School of Veterinary Science,University of Queensland,Gatton campus, Gatton 4343,Australia
Interests: comparative oncology; dog; prostate cancer; osteosarcoma
A/Prof. Dr. Rachel Allavena
E-Mail Website
Co-Guest Editor
Faculty of Science,School of Veterinary Science,University of Queensland,Gatton campus, Gatton 4343,Australia
Interests: comparative oncology; translational medicine; animal models

Special Issue Information

Dear Colleagues,

Comparative Oncology has attracted considerable attention from the scientific community as a multidisciplinary approach for a better understanding, diagnosis and therapy of cancer in both humans and animals.

Cancer in dogs share may features with human cancer, including genetics, biological behaviour, histological features, molecular pathways and response to therapies. Osteosarcoma, lymphoma, haemangiosarcoma, prostate carcinoma, mammary carcinoma, soft tissue sarcoma, melanoma are just few examples of canine cancers offering a unique opportunity as models for translational therapeutics.  

Despite increasingly productive outcomes in the identification of cancer-associated genes, the study of tumour progression and the evaluation of novel cancer strategies, the complete biology and molecular pathology of many canine cancers still need to be revealed.

Further, as our understanding of cancer biology in dog models grows, promotion of the value of canine companions as research models needs to be continued. Communication of the value of dogs in research to the general public, veterinary practitioners and research scientists will improve trial recruitment, research and treatment outcomes for both human and canine patients.

This Special Issue on “Comparative Oncology: Integrating Naturally Occurring Cancers of Dogs into Investigations of Cancer Biology and Therapy” includes reviews and research articles on different and latest aspects of comparative oncology, from cancer pathogenesis to new treatment options.

We believe that the information provided in this issue will fill knowledge gaps and further stimulate research collaborations between scientists across different disciplines for advances in cancer prevention and cute in both medical and veterinary oncology.

A/Prof. Dr. Chiara Palmieri
A/Prof. Dr. Rachel Allavena
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Veterinary Sciences is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • comparative oncology
  • dog
  • cancer
  • animal model
  • translational medicine
  • cancer biology
  • cancer therapy

Published Papers (9 papers)

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Research

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Open AccessArticle
Correlation of BRAF Variant V595E, Breed, Histological Grade and Cyclooxygenase-2 Expression in Canine Transitional Cell Carcinomas
Vet. Sci. 2019, 6(1), 31; https://doi.org/10.3390/vetsci6010031 - 19 Mar 2019
Abstract
The presence of BRAF variant V595E, as well as an increased cyclooxygenase-2 (COX-2) expression in canine transitional cell carcinoma (TCC) are well-described in the literature. The aim of the present study was to investigate the correlation between breed (terrier versus non-terrier dogs), histological [...] Read more.
The presence of BRAF variant V595E, as well as an increased cyclooxygenase-2 (COX-2) expression in canine transitional cell carcinoma (TCC) are well-described in the literature. The aim of the present study was to investigate the correlation between breed (terrier versus non-terrier dogs), histological grade, COX-2 expression, and BRAF mutation in canine TCC. Therefore, transmural TCC biopsies from 65 dogs (15 terriers, 50 non-terriers) were graded histologically into low- and high-grade. Immunohistochemical evaluation of the intensity of COX-2 expression was performed using an immunoreactive score (IRS). Exon 15 of chromosome 16 was examined for the BRAF variant c.1799T>A by TaqMan® SNP assay. TCC was low-grade in 20 cases (one terrier, 19 non-terriers) and high-grade in 45 cases (14 terriers, 31 non-terriers). Contrary to humans, histological grade was not significantly correlated to the intensity of COX-2 expression. BRAF mutation was detected in 11/15 (73%) TCC of terriers and in 18/50 (36%) TCC of non-terriers. Histological grade and BRAF mutation were not correlated significantly (p = 0.2912). Terriers had a considerably higher prevalence of high-grade tumors (p < 0.0001), as well as of BRAF mutation (p ≤ 0.05) compared to non-terriers. In non-terriers, neoplasms with BRAF mutation showed a significantly higher intensity of COX-2 expression than those without BRAF mutation (p ≤ 0.05). In conclusion, in contrast to humans, testing for BRAF mutation in canine TCC is a sensitive diagnostic method especially in terriers (73%) and may be recommended as a screening test. However, evidence of BRAF mutation in canine TCC is not a predictor for the histological grade. Moreover, a positive correlation between histological grade and the intensity of COX-2 expression was not found. Further studies are necessary to clarify the clinical and prognostic relevance of the elevated intensity of COX-2 expression of TCC with BRAF mutation detected in non-terriers. Full article
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Open AccessArticle
Characterization of Collagen Fibers (I, III, IV) and Elastin of Normal and Neoplastic Canine Prostatic Tissues
Vet. Sci. 2019, 6(1), 22; https://doi.org/10.3390/vetsci6010022 - 02 Mar 2019
Abstract
This study aimed to investigate collagen (Coll-I, III, IV) and elastin in canine normal prostate and prostate cancer (PC) using Picrosirius red (PSR) and Immunohistochemical (IHC) analysis. Eight normal prostates and 10 PC from formalin-fixed, paraffin-embedded samples were used. Collagen fibers area was [...] Read more.
This study aimed to investigate collagen (Coll-I, III, IV) and elastin in canine normal prostate and prostate cancer (PC) using Picrosirius red (PSR) and Immunohistochemical (IHC) analysis. Eight normal prostates and 10 PC from formalin-fixed, paraffin-embedded samples were used. Collagen fibers area was analyzed with ImageJ software. The distribution of Coll-I and Coll-III was approximately 80% around prostatic ducts and acini, 15% among smooth muscle, and 5% surrounding blood vessels, in both normal prostate and PC. There was a higher median area of Coll-III in PC when compared to normal prostatic tissue (p = 0.001 for PSR and p = 0.05 for IHC). Immunostaining for Coll-IV was observed in the basal membrane of prostate acini, smooth muscle, blood vessels, and nerve fibers of normal and PC samples. Although there was no difference in Coll-IV area between normal tissue and PC, tumors with Gleason score 10 showed absence of Coll-IV, when compared to scores 6 and 8 (p = 0.0095). Elastic fibers were found in the septa dividing the lobules and around the prostatic acini of normal samples and were statistically higher in PC compared to normal tissue (p = 0.00229). Investigation of ECM components brings new information and should be correlated with prognosis in future studies. Full article
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Open AccessArticle
Tumor–Microenvironment Interaction: Analysis of Mast Cell Populations in Normal Tissue and Proliferative Disorders of the Canine Prostate
Vet. Sci. 2019, 6(1), 16; https://doi.org/10.3390/vetsci6010016 - 13 Feb 2019
Abstract
Mast cells (MCs) are involved in angiogenesis, tissue remodeling and immunomodulation in several human and animal tumors, although their exact role is still controversial. Since no information is available in canine prostate carcinoma (PC) and normal prostate tissues, the aims of this study [...] Read more.
Mast cells (MCs) are involved in angiogenesis, tissue remodeling and immunomodulation in several human and animal tumors, although their exact role is still controversial. Since no information is available in canine prostate carcinoma (PC) and normal prostate tissues, the aims of this study were to evaluate the possible correlations between MC distribution, molecular expression and microvessel density (MVD) in normal prostatic tissue and proliferative disorders of the canine prostate. All samples (6 normal, 15 benign prostate hyperplasia-BPH, 8 PC) were stained with Toluidine Blue and immunohistochemically evaluated for tryptase, c-Kit (CD117) and CD31. Mast cell density (MCD) and MVD were quantified by the hot-spot method. MCD was significantly increased in periglandular/peritumoral areas, when compared with intraglandular/intratumoral areas, in all groups (p = 0.03). C-Kit expression was strongly associated with PC (ρ = 0.75 p = 0.03), whereas positive correlation between tryptase and c-Kit expression (ρ = 0.64 p = 0.01) was observed in periglandular areas of BPH. MVD showed a correlation with MCD in BPH (ρ = 0.54 p = 0.04). Our data support the importance of c-Kit in regulating MC proliferation. The predominant location of MCs in peritumoral areas of canine PC was similar to the human counterpart, in which PC cells are supposed to produce substances attracting MCs to the tumor microenvironment. Full article
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Open AccessArticle
Deregulation of VEGFR-2 and PDGFR Expression and Microvascular Density in a Triple-Negative Model of Canine Malignant Mammary Tumors with Lymph Node or Lung Metastasis
Vet. Sci. 2019, 6(1), 3; https://doi.org/10.3390/vetsci6010003 - 09 Jan 2019
Cited by 1
Abstract
Canine mammary tumors (CMT) represent the most common cancer in noncastrated female dogs. Interestingly, triple-negative tumors are the most common molecular subtype in female dogs. In this study, we proposed to evaluate the expression of vascular endothelial growth factor receptor 2 (VEGFR-2), Platelet-derived [...] Read more.
Canine mammary tumors (CMT) represent the most common cancer in noncastrated female dogs. Interestingly, triple-negative tumors are the most common molecular subtype in female dogs. In this study, we proposed to evaluate the expression of vascular endothelial growth factor receptor 2 (VEGFR-2), Platelet-derived growth factor receptor (PDGFR), and microvascular density (MVD) in a group of metastatic and nonmetastatic triple-negative CMT and compare the expression based on clinical parameters. Twenty-six female dogs with triple-negative mammary tumors were divided into three groups: nonmetastatic tumors (NMT) (n = 11), tumors with lymph node metastasis (LNM) (n = 10), and tumors with lung metastasis (LM) (n = 5). We observed increased VEGFR-2 expression in LNM compared with NMT and a positive correlation between tumor grade and VEGFR-2 expression. A positive correlation was noted between VEGFR-2 and PDGFR expression. Regarding microvascular density (MVD), we identified a higher number of vessels in primary tumors with lymph node metastasis and lung metastasis compared with tumors with no metastasis. The primary tumors with lung metastasis exhibited an increased MVD compared with carcinoma with lymph node metastasis. Overall, our results suggest a deregulation of VEGFR-2 and PDGFR and high MVD in metastatic tumors, indicating a role for angiogenesis in tumor progression. Full article
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Review

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Open AccessReview
Risk Factors for Development of Canine and Human Osteosarcoma: A Comparative Review
Vet. Sci. 2019, 6(2), 48; https://doi.org/10.3390/vetsci6020048 - 25 May 2019
Cited by 1
Abstract
Osteosarcoma is the most common primary tumor of bone. Osteosarcomas are rare in humans, but occur more commonly in dogs. A comparative approach to studying osteosarcoma has highlighted many clinical and biologic aspects of the disease that are similar between dogs and humans; [...] Read more.
Osteosarcoma is the most common primary tumor of bone. Osteosarcomas are rare in humans, but occur more commonly in dogs. A comparative approach to studying osteosarcoma has highlighted many clinical and biologic aspects of the disease that are similar between dogs and humans; however, important species-specific differences are becoming increasingly recognized. In this review, we describe risk factors for the development of osteosarcoma in dogs and humans, including height and body size, genetics, and conditions that increase turnover of bone-forming cells, underscoring the concept that stochastic mutational events associated with cellular replication are likely to be the major molecular drivers of this disease. We also discuss adaptive, cancer-protective traits that have evolved in large, long-lived mammals, and how increasing size and longevity in the absence of natural selection can account for the elevated bone cancer risk in modern domestic dogs. Full article
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Open AccessReview
Cytokine Expression in Canine Lymphoma, Osteosarcoma, Mammary Gland Tumour and Melanoma: Comparative Aspects
Vet. Sci. 2019, 6(2), 37; https://doi.org/10.3390/vetsci6020037 - 02 Apr 2019
Abstract
Cytokines released in the tumour microenvironment play a major role in cancer pathogenesis. In human cancers and corresponding animal models, cytokine expression contributes to tumour growth and progression, as well as regulation of the host anti-tumour response. The elucidation of the function and [...] Read more.
Cytokines released in the tumour microenvironment play a major role in cancer pathogenesis. In human cancers and corresponding animal models, cytokine expression contributes to tumour growth and progression, as well as regulation of the host anti-tumour response. The elucidation of the function and importance of cytokines in canine cancers is still in an early stage, although relevant data have been obtained in classical examples of comparative models of human cancers, such as osteosarcoma, melanoma, mammary tumour and lymphoma. A deeper understanding of the cytokine signature may advance diagnosis, prevention and treatment of canine cancers. Full article
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Open AccessReview
Use of Minimally Invasive Surgery in the Diagnosis and Treatment of Cancer in Dogs and Cats
Vet. Sci. 2019, 6(1), 33; https://doi.org/10.3390/vetsci6010033 - 20 Mar 2019
Abstract
Surgical management of neoplastic disease is common in veterinary medicine. Minimally invasive surgery (MIS) has gained widespread acceptance by veterinary surgeons and is experiencing rapid growth and frequency of use. Many neoplastic diseases in the abdomen and thorax of dogs and cats can [...] Read more.
Surgical management of neoplastic disease is common in veterinary medicine. Minimally invasive surgery (MIS) has gained widespread acceptance by veterinary surgeons and is experiencing rapid growth and frequency of use. Many neoplastic diseases in the abdomen and thorax of dogs and cats can be treated as effectively with MIS as with traditional open surgery. Additionally, MIS allows for less invasive options for organ biopsy in cancer patients either for initial diagnosis or for staging to inform prognosis and treatment. Despite the recent increase in MIS, additional research is required to further characterize the benefits to oncology patients and to ensure that surgical oncologic principles and patient outcomes are not compromised by the use of MIS. Full article
Open AccessReview
A Review of Immunotherapeutic Strategies in Canine Malignant Melanoma
Vet. Sci. 2019, 6(1), 15; https://doi.org/10.3390/vetsci6010015 - 12 Feb 2019
Cited by 1
Abstract
In dogs, melanomas are relatively common tumors and the most common form of oral malignancy. Biological behavior is highly variable, usually aggressive, and frequently metastatic, with reported survival times of three months for oral or mucosal melanomas in advanced disease stages. Classical clinical [...] Read more.
In dogs, melanomas are relatively common tumors and the most common form of oral malignancy. Biological behavior is highly variable, usually aggressive, and frequently metastatic, with reported survival times of three months for oral or mucosal melanomas in advanced disease stages. Classical clinical management remains challenging; thus, novel and more efficacious treatment strategies are needed. Evidence-based medicine supports the role of the immune system to treat neoplastic diseases. Besides, immunotherapy offers the possibility of a precise medicinal approach to treat cancer. In recent years, multiple immunotherapeutic strategies have been developed, and are now recognized as a pillar of treatment. In addition, dogs represent a good model for translational medicine purposes. This review will cover the most relevant immunotherapeutic strategies for the treatment of canine malignant melanoma, divided among five different categories, namely, monoclonal antibodies, nonspecific immunotherapy activated by bacteria, vaccines, gene therapy, and lymphokine-activated killer cell therapy. Full article
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Open AccessReview
Lower Urinary Tract Neoplasia
Vet. Sci. 2018, 5(4), 96; https://doi.org/10.3390/vetsci5040096 - 27 Nov 2018
Abstract
Lower urinary tract neoplasia in companion animals is a debilitating and often life-threatening disease. Tumors of the bladder, urethra, and prostate often occur independently, although extension of these tumors into adjacent regions of the lower urinary tract is documented frequently. The most common [...] Read more.
Lower urinary tract neoplasia in companion animals is a debilitating and often life-threatening disease. Tumors of the bladder, urethra, and prostate often occur independently, although extension of these tumors into adjacent regions of the lower urinary tract is documented frequently. The most common lower urinary tract tumor in dogs and cats is transitional cell carcinoma (TCC). In both dogs and cats, TCC affecting the urinary bladder is generally considered to be highly aggressive with both local and metastatic disease potential, and this disease poses unique treatment challenges. Whereas much literature exists regarding the TCC disease process, treatment options, and prognosis in dogs, relatively few studies on feline TCC have been published due to the lower incidence of TCC in this species. Prostate tumors, most commonly adenocarcinomas, occur less commonly in dogs and cats but serve an important role as a comparative model for prostate neoplasia in humans. This article serves as a review of the current information regarding canine and feline lower urinary tract neoplasia as well as the relevance of these diseases with respect to their human counterparts. Full article
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