Journal Articles

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    Papillomaviruses and Papillomaviral Disease in Dogs and Cats: A Comprehensive Review.
    (MDPI (Basel, Switzerland), 2024-12-01) Munday JS; Knight CG; Materniak-Kornas M; Rola-Łuszczak M; Woźniakowski G
    Papillomaviruses (PVs) frequently infect humans as well as non-human species. While most PV infections are asymptomatic, PVs can also cause hyperplastic papillomas (warts) as well as pre-neoplastic and neoplastic lesions. In this review, the life cycle of PVs is discussed, along with the mechanisms by which PVs cause hyperplastic and neoplastic diseases. The humoral and cell-mediated immune responses to PVs are reviewed, giving context to the later discussion on the use of vaccines to reduce canine and feline PV-associated disease. Both dogs and cats are infected by numerous different PV types classified into multiple different PV genera. The taxonomic classification of PVs is reviewed, along with the significance of this classification. The PV-associated diseases of dogs and cats are then described. These descriptions include the clinical presentation of the disease, the causative PV types, the histological features that allow diagnosis, and, where appropriate, possible treatment options. The review is comprehensive and contains the latest information about PVs and the diseases they cause in dogs and cats.
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    Multimodal Blockade of the Renin-Angiotensin System in the Treatment of Cancer in Dogs Has Mild Adverse Effects in Some Dogs.
    (MDPI (Basel, Switzerland), 2024-06-17) Dittmer KE; Wetzel S; Odom T; Munday JS; Flatt EA; Wilson IJ; Hughes C; Tan ST; Ferreira F; Sparger EE
    The renin-angiotensin system (RAS) is increasingly being recognized to play a role in the tumor microenvironment, promoting tumor growth. Studies blocking a single part of the RAS have shown mixed results, possibly due to the existence of different bypass pathways and redundancy within the RAS. As such, multimodal blockade of the RAS has been developed to exert more complete inhibition of the RAS. The aim of the present study was to assess the safety of multimodal RAS blockade in dogs. Five dogs (four with appendicular osteosarcoma, one with oral malignant melanoma) were treated with atenolol, benazepril, curcumin, meloxicam, and metformin. The dogs underwent clinical examination, blood pressure measurement, and hematology and serum biochemistry tests performed at 0, 1, 3, 6, 9, and 12 weeks, then every 3 months thereafter. End-of-life decisions were made by the owners. None of the dogs developed hypotension. One dog had intermittent vomiting during the 64 weeks it was on the trial. One dog had a one-off increase in serum SDMA(symmetrical dimethylarginine) concentration. Dogs were euthanized at weeks 3 (osteosarcoma), 10 (osteosarcoma), 17 (osteosarcoma), and 26 (oral malignant melanoma), and one dog was still alive at the end of the trial at 64 weeks (osteosarcoma). This is the first assessment of multimodal blockade of the RAS in dogs, and the results suggest it causes only mild adverse effects in some animals. The efficacy of the treatment was not assessed due to the small number of dogs. This pilot study allows for future larger studies assessing multimodal RAS blockade for the treatment of canine cancer.
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    Papillomaviruses in Domestic Cats
    (MDPI (Basel, Switzerland), 2021-08-22) Munday JS; Thomson NA; Beatty JA; Tasker S
    Papillomaviruses (PVs) are well established to cause hyperplastic papillomas (warts) in humans and animals. In addition, due to their ability to alter cell regulation, PVs are also recognized to cause approximately 5% of human cancers and these viruses have been associated with neoplasia in a number of animal species. In contrast to other domestic species, cats have traditionally been thought to less frequently develop disease due to PV infection. However, in the last 15 years, the number of viruses and the different lesions associated with PVs in cats have greatly expanded. In this review, the PV life cycle and the subsequent immune response is briefly discussed along with methods used to investigate a PV etiology of a lesion. The seven PV types that are currently known to infect cats are reviewed. The lesions that have been associated with PV infections in cats are then discussed and the review finishes with a brief discussion on the use of vaccines to prevent PV-induced disease in domestic cats.
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    Detection of a Novel Papillomavirus Type within a Feline Cutaneous Basal Cell Carcinoma
    (MDPI (Basel, Switzerland), 2022-12-01) Munday JS; Hunt H; Orbell G; Pfeffer H; Bennett P
    A 4 cm diameter exophytic mass was excised from the left flank of a 10-year-old domestic short-haired cat. Histology of the superficial aspects of the mass revealed epidermal cells arranged in nests and trabeculae while the deeper parts of the mass consisted of small round cells arranged in sheets or bundles of elongate spindle-shaped cells. A diagnosis of basal cell carcinoma (BCC) was made. Approximately 40% of the cells throughout the neoplasm contained prominent papillomaviral (PV)-induced cell changes. The BCC recurred three months after excision and grew rapidly. At this time a smaller mass was observed on the thorax. Due to the rapid recurrence of the BCC, the cat was euthanatized. As in the initial mass, histology of the recurrent mass revealed pleomorphic cells that often contained PV-induced cell changes. In contrast, the thoracic mass appeared as a more typical BCC and contained no histological evidence of PV infection. A novel PV DNA sequence was amplified from the flank BCC. While the sequence was most (75.1%) similar to Felis catus papillomavirus (FcaPV) 6, the level of similarity between the sequences is consistent with a novel PV type. No PV DNA was amplifiable from the thoracic mass. The case is unique due to the histological features of the BCC and the presence of a putative novel PV type. Observations from the present case add to the number of PV types associated with disease in cats as well as increasing the spectrum of PV-induced lesions in this species.
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    Multimodal Blockade of the Renin-Angiotensin System Is Safe and Is a Potential Cancer Treatment for Cats
    (MDPI (Basel, Switzerland), 2022-08-05) Munday JS; Odom T; Dittmer KE; Wetzel S; Hillmer K; Tan ST
    The role of the renin-angiotensin system (RAS) in cancer growth and progression is well recognized in humans. However, studies on RAS inhibition with a single agent have not shown consistent anticancer effects, potentially due to the neoplastic cells utilizing alternative pathways for RAS activation. To achieve more complete RAS inhibition, multimodal therapy with several medications that simultaneously block multiple steps in the RAS has been developed for use in humans. In the present study, the safety of multimodal RAS inhibition using atenolol, benazepril, metformin, curcumin, and meloxicam was assessed in six cats with squamous cell carcinomas. Cats were treated for 8 weeks, with blood pressure measured and blood sampled five times during the treatment period. None of the cats developed hypotension, azotemia, or increased serum liver enzyme concentrations. The packed cell volume of one cat decreased to just below the reference range during treatment. One cat was reported to have increased vomiting, although this occurred infrequently. One cat was withdrawn from the study due to difficulties administering the medications, and another cat died of an unrelated cause. Two cats were euthanatized during the study period due to cancer progression. Two cats completed the 8-week study period. One was subsequently euthanized due to cancer progression while the other cat is still alive 32 weeks after entering the study and is still receiving the multimodal blockade of the RAS. This is the first evaluation of multimodal blockade of the RAS in veterinary species. The study showed that the treatment is safe, with only mild adverse effects observed in two treated cats. Due to the small number of cats, the efficacy of treatment could not be evaluated. However, evidence from human studies suggests that a multimodal blockade of RAS could be a safe and cost-effective treatment option for cancer in cats.