Search

Laura V Ashton,1 Barbara Graham,1 Maryam F Afzali,1 Daniel Gustafson,2 Amy L MacNeill1 1Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA; 2Departiment of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USACorrespondence: Amy L MacNeill Email amy.macneill@colostate.eduPurpose: Rhabdomyosarcomas (RMS) are difficult tumors to treat with conventional therapies. Publications indicate that oncolytic virotherapy (OV) could benefit cancer patients with tumors that are refractory to conventional treatments. It is believed that the efficacy of OV can be enhanced when used in combination with other treatments. This study evaluated the response of mice with aggressive alveolar RMS (ARMS) allografts to treatment with an OV [recombinant myxoma virus (MYXVΔserp2)] in combination with a Janus kinase (JAK) inhibitor (oclacitinib). Oclacitinib is known to inhibit JAK1 and JAK2 cell signaling pathways, which should limit the antiviral Type I interferon response. However, oclacitinib does not inhibit immune pathways that promote antigen presentation, which help stimulate an anti-cancer immune response.Materials and Methods: To determine if MYXVΔserp2 and oclacitinib could improve outcomes in animals with ARMS, nude mice were inoculated subcutaneously with murine ARMS cells to establish tumors. Immune responses, tumor growth, and clinical signs in mice treated with combination therapy were compared to mice given placebo therapy and mice treated with OV alone.Results: Combination therapy was safe; no viral DNA was detected in off-target organs, only within tumors. As predicted, viral DNA was detected in tumors of mice given oclacitinib and MYXVΔserp2 for a longer time period than mice treated with OV alone. Although tumor growth rates and median survival times were not significantly different between groups, clinical signs were less severe in mice treated with OV.Conclusion: Our data indicate that MYXVΔserp2 treatment benefits mice with ARMS by reducing clinical signs of disease and improving quality of life.Keywords: oncolytic virus, poxvirus, Janus kinase inhibitor, sarcoma

Supplemental Material, DS1_VET_10.1177_0300985818780469 for The Site of Bone Marrow Acquisition Affects the Myeloid to Erythroid Ratio in Apparently Healthy Dogs by Arnon Gal, Richard K. Burchell, Andrew J. Worth, Nicolas Lopez-Villallobos, Jonathan C. Marshall, and Amy L. MacNeill in Veterinary Pathology

Although aquatic ecologists and biogeochemists are well aware of the crucial importance of ecosystem functions, i.e., how biota drive biogeochemical processes and vice-versa, linking these fields in conceptual models is still uncommon. Attempts to explain the variability in elemental cycling consequently miss an important biological component and thereby impede a comprehensive understanding of the underlying processes governing energy and matter flow and transformation. The fate of multiple chemical elements in ecosystems is strongly linked by biotic demand and uptake; thus, considering elemental stoichiometry is important for both biogeochemical and ecological research. Nonetheless, assessments of ecological stoichiometry (ES) often focus on the elemental content of biota rather than taking a more holistic view by examining both elemental pools and fluxes (e.g., organismal stoichiometry and ecosystem process rates). ES theory holds the promise to be a unifying concept to link across hierarchical scales of patterns and processes in ecology, but this has not been fully achieved. Therefore, we propose connecting the expertise of aquatic ecologists and biogeochemists with ES theory as a common currency to connect food webs, ecosystem metabolism, and biogeochemistry, as they are inherently concatenated by the transfer of carbon, nitrogen, and phosphorous through biotic and abiotic nutrient transformation and fluxes. Several new studies exist that demonstrate the connections between food web ecology, biogeochemistry, and ecosystem metabolism. In addition to a general introduction into the topic, this paper presents examples of how these fields can be combined with a focus on ES. In this review, a series of concepts have guided the discussion: (1) changing biogeochemistry affects trophic interactions and ecosystem processes by altering the elemental ratios of key species and assemblages; (2) changing trophic dynamics influences the transformation and fluxes of matter across environmental boundaries; (3) changing ecosystem metabolism will alter the chemical diversity of the non-living environment. Finally, we propose that using ES to link nutrient cycling, trophic dynamics, and ecosystem metabolism would allow for a more holistic understanding of ecosystem functions in a changing environment.

Amy L MacNeill Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA Abstract: Over 6 million dogs are diagnosed with cancer in the USA each year. Treatment options for many of these patients are limited. It is important that the veterinary and scientific communities begin to explore novel treatment protocols for dogs with cancer. Oncolytic viral therapy is a promising treatment option that may prove to be relatively inexpensive and effective against several types of cancer. The efficacy of oncolytic virus therapies has been clearly demonstrated in murine cancer models, but the positive outcomes observed in mice are not always seen in human cancer patients. These therapies should be thoroughly evaluated in dogs with spontaneously arising cancers to provide needed information about the potential effectiveness of virus treatment for human cancers and to promote the health of our companion animals. This article provides a review of the results of oncolytic virus treatment of canine cancers. Keywords: oncolytic virus, cancer, canine