High <scp>COX</scp>‐2 expression in canine mast cell tumours is associated with proliferation, angiogenesis and decreased overall survival

Gregório, Hugo; Raposo, Teresa P; Queiroga, Felisbina L.; Pires, Isabel; Peña, Laura; Prada, Justina

doi:10.1111/vco.12280

Cited by 18 publications

(21 citation statements)

References 51 publications

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“…Furthermore, known correlations between lymphocyte phenotypes and specific functions have been used to elucidate other prognostically significant lymphocyte subsets such as Th1, Th2, Th17, γ/δ‐T cells, CD8 + CD103 + T cells, and lymphocyte memory subsets, in addition to prognostic markers of T cell exhaustion, in a variety of human tumours . Indeed, the variability of CD3+ infiltrates in predicting prognosis in certain canine tumour types may be explained by the heterogeneity of TILs function that exists, emphasizing the need for more detailed phenotypic analyses of lymphocyte subsets in future studies …”

Section: Discussionmentioning

confidence: 99%

Association of macrophage and lymphocyte infiltration with outcome in canine osteosarcoma

Withers

Skorupski

York

et al. 2018

Vet Comparative Oncology

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Immunotherapeutic strategies have shown promise for the treatment of canine osteosarcoma (cOSA). Very little is known about the immune microenvironment within cOSA, however, limiting our ability to identify potential immune targets and biomarkers of therapeutic response. We therefore prospectively assessed the disease-free interval (DFI) and overall survival time (ST) of 30 dogs with cOSA treated with amputation and six doses of adjuvant carboplatin. We then quantified lymphocytic (CD3+, FOXP3+) and macrophage (CD204+) infiltrates within the primary tumours of this cohort using immunohistochemistry, and evaluated their association with outcome. Overall, the median DFI and ST were 392 and 455 days, respectively. The median number of CD3+ and FOXP3+ infiltrates were 45.8 cells/mm (4.6-607.6 cells/mm ) and 8.5 mm (0-163.1 cells/mm ), respectively. The median area of CD204+ macrophages was 4.7% (1.3%-23.3%), and dogs with tumours containing greater than 4.7% CD204+ macrophages experienced a significantly longer DFI (P = 0.016). Interestingly, a significantly lower percentage of CD204+ macrophages was detected in cOSA arising from the proximal humerus compared to other appendicular bone locations (P = 0.016). Lymphocytic infiltrates did not appear to correlate with outcome in cOSA. Overall, our findings suggest that macrophages may play a role in inhibiting cOSA progression, as has been suggested in human osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Association of macrophage and lymphocyte infiltration with outcome in canine osteosarcoma

Withers

Skorupski

York

et al. 2018

Vet Comparative Oncology

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“…Some studies showed the relationship of COX-2 overexpression with shorter OS and/or PFS (62, 66), however in others no such relationship was found (32). Contradictory data concerning any connection between increased COX-2 expression and a bad prognosis, shorter OS and a worse response to treatment were also obtained in the studies of some tumours in dogs and cats (11, 37, 80).…”

Section: Clinical Significance Of Cox-2 Expressionmentioning

confidence: 96%

Significance of cyclooxygenase-2 in oncogenesis

Szweda

Rychlik

Babińska

et al. 2019

Journal of Veterinary Research

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The cyclooxygenase-2 (COX-2) enzyme catalyses the first stage of biosynthesis of prostanoids, proteins that are implicated in various physiological and pathological processes in humans and animals. The expression of COX-2 increases significantly during pathological processes accompanied by inflammation, pain and fever. Overexpression of COX-2 was determined in tumour tissues, which suggests that this enzyme participates in oncogenesis. In this paper the topics discussed are mechanisms regulating COX-2 expression, COX isoforms, their role in the body and the oncogenic mechanisms triggered by the overexpression of COX-2, including inhibition of apoptosis, intensification of neoangiogenesis, increased metastatic capacity, and weakening of the immune system. The significance of and the mechanisms by which COX-2 participates in oncogenesis have been studied intensively in recent years. The results are highly promising, and they expand our understanding of the complex processes and changes at the molecular, cellular and tissue level that promote oncogenesis and cancer progression. Notwithstanding the knowledge already gleaned, many processes and mechanisms have not yet been elucidated in human medicine and, in particular, in veterinary medicine. Further research is required to develop effective tumour diagnostic methods and treatment procedures for humans and animals.

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“…However, neither system predicts metastasis. It worth to note that COX-2 overexpression is associated with decreased overall survival and higher grades of malignancy according to Patnaik and Kiupel grading systems [46].…”

Section: Mast Cell Tumorsmentioning

confidence: 99%

Molecular Mechanisms of Canine Cancers

Cao¹,

Kouznetsova²,

Tsigelny³

2019

obm genet

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Cancer is the leading cause of death in dogs, and 50 percent of dogs over the age of 10 develop cancer at some point. The most common cancers in dogs include lymphoma, mast cell tumors, osteosarcoma, mammary gland tumors, and melanoma, and many of them share marked similarities with their human counterparts. Although canines are afflicted with many of the same types of cancers as humans, the genetic basis behind these cancers are not as well understood. Thus, the aim of this study is to elucidate some of the molecular mechanisms behind canine cancers. Canine lymphoma mutation patterns generally vary with the type of lymphoma afflicted-B-cell lymphomas have mutations in the alternative NF-kB pathway including MAP3K14, whereas in T-cell lymphomas the mTOR pathway in boxers and cellular metabolism genes in golden retrievers are affected. Mast cell tumors are largely traced to internal tandem duplications and deletions in the juxtamembrane domain of the proto-oncogene c-KIT. In osteosarcoma, mutations in RB1 and TP53 (especially G: C->A:T transitions in exons 4 and 5), as well as CDK4 inhibitors CDKN2A/B are common. Mammary gland tumors are associated with BRCA2 underexpression due to reading frame shift and mutations in BRC repeat 3. Lastly, deletion or underexpression of p16 and PTEN and altered expression of cell-cell adhesion molecules are common factors in the development of melanoma. The genes identified were then studied to identify more key amino acid mutations that changed protein products and promoted tumorigenesis. Genes that altered expression levels of proteins were analyzed separately. Both sets of candidate genes were then analyzed with the Database for Annotation, Visualization, and Integrated Discovery (DAVID) in order to elucidate the molecular pathways involved in canine cancers and identify more genes possibly involved in tumorigenesis. The proposition of this review is that treatments for both canine and human cancers would be enhanced by comparative genomic studies.

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High COX‐2 expression in canine mast cell tumours is associated with proliferation, angiogenesis and decreased overall survival

Cited by 18 publications

References 51 publications

Association of macrophage and lymphocyte infiltration with outcome in canine osteosarcoma

Association of macrophage and lymphocyte infiltration with outcome in canine osteosarcoma

Significance of cyclooxygenase-2 in oncogenesis

Molecular Mechanisms of Canine Cancers

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