A significant amount of research indicates that the cyclooxygenase/prostaglandin E2 (PGE2) pathway of inflammation contributes to the development and progression of a variety of cancers, including squamous cell carcinoma of the oral cavity and oropharynx (OSCC). Although there have been promising results from studies examining the utility of anti-inflammatory drugs in the treatment of OSCC, this strategy has been met with only variable success and these drugs are also associated with toxicities that make them inappropriate for some OSCC patients. Improved inflammation-targeting therapies require continued study of the mechanisms linking inflammation and progression of OSCC. In this review, a synopsis of OSCC biology will be provided, and recent insights into inflammation related mechanisms of OSCC pathobiology will be discussed. The roles of prostaglandin E2 and cluster of differentiation factor 147 (CD147) will be presented, and evidence for their interactions in OSCC will be explored. Through continued investigation into the protumourigenic pathways of OSCC, more treatment modalities targeting inflammation-related pathways can be designed with the hope of slowing tumour progression and improving patient prognosis in patients with this aggressive form of cancer.

Feline oral squamous cell carcinoma (OSCC) is a highly invasive form of cancer in cats. In human OSCC, cluster of differentiation 147 (CD147) contributes to inflammation and tumor invasiveness. CD147 is a potential therapeutic target, but the expression of CD147 in feline OSCC has not been examined. Immunohistochemistry was used to determine if cyclooxygenase 2 (COX-2) and CD147 expression in feline OSCC biopsies was coordinated. Tumor cells were more likely to express COX-2 (22/43 cases or 51%) compared to stroma (8/43 or 19%) and adjacent oral epithelium (9/31 cases or 29%) (p < 0.05). CD147 was also more likely to occur in tumor cells compared to stroma and adjacent mucosa, with 21/43 (49%) of cases having >50% tumor cells with mild or moderate CD147 expression, compared to 9/28 (32%) in adjacent epithelium and only 5/43 (12%) in adjacent stroma (p < 0.05). In feline OSCC cell lines (SCCF1, SCCF2, and SCCF3), CD147 gene expression was more consistently expressed compared to COX-2, which was 60-fold higher in SCCF2 cells compared to SCCF1 cells (p < 0.05). CD147 expression did not correlate with COX-2 expression and prostaglandin E2 (PGE2) secretion, indicating that they may be independently regulated. CD147 potentially represents a novel therapeutic target for the treatment of feline OSCC and further study of CD147 is warranted.

The importance of inflammation in the pathogenesis of cancer was first proposed by Rudolph Virchow over 150 years ago, and our understanding of its significance has grown over decades of biomedical research. The arachidonic acid pathway of inflammation, including cyclooxygenase (COX) enzymes, PGE2 synthase enzymes, prostaglandin E2 (PGE2) and PGE2 receptors has been extensively studied and has been associated with different diseases and different types of cancers, including oral squamous cell carcinoma (OSCC). In addition to inflammation in the tumour microenvironment, low oxygen levels (hypoxia) within tumours have also been shown to contribute to tumour progression. Understandably, most of our OSCC knowledge comes from study of this aggressive cancer in human patients and in experimental rodent models. However, domestic animals develop OSCC spontaneously and this is an important, and difficult to treat, form of cancer in veterinary medicine. The primary goal of this review article is to explore the available evidence regarding interaction between hypoxia and the arachidonic acid pathway of inflammation during malignant behaviour of OSCC. Overlapping mechanisms in hypoxia and inflammation can contribute to tumour growth, angiogenesis, and, importantly, resistance to therapy. The benefits and controversies of anti-inflammatory and anti-angiogenic therapies for human and animal OSCC patients will be discussed, including conventional pharmaceutical agents as well as natural products.

The early postnatal period is a critical neurodevelopmental stage characterized by rapid neural maturation and is adversely affected by early-life stressors. This study explored the behavioural, physiological, and epigenetic consequences of early-life stress in a population of homeless rescue kittens. This longitudinal study included 50 kittens rescued and placed into foster care by the Prince Edward Island Humane Society. They underwent behavioural testing at 8, 10, and 12 weeks of age. Hair cortisol concentration was measured at 8 weeks and served as a physiological marker of the previous 3 months’ cumulative stress response, which, for these kittens, included the late gestation period. A blood sample for relative telomere length measurement was taken at 10–12 weeks to estimate epigenetic changes as young kittens. Data were analyzed with respect to age and performance in all repeated measures tests, status as a stray or a surrender, and the presence of the dam in their foster homes. As expected, the performance of kittens in all tests changed over the 5 weeks of testing. Kittens separated from their mothers exhibited significantly higher hair cortisol concentrations (p = 0.02) and elongated relative telomere lengths (p = 0.04). No correlation was found between hair cortisol concentration and relative telomere lengths (p = 0.99). These results support the need for further study on the effects of epigenetics and early-life stress, both in kittens and across species.

A 4 month-old, 14.8 kg male Newfoundland dog was evaluated by a specialist veterinary cardiology service after a heart murmur had been detected on a routine physical examination. Cardiac auscultati...