{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:10:41Z","timestamp":1760145041969,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Massey University Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>The renin\u2013angiotensin 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.<\/jats:p>","DOI":"10.3390\/vetsci11060275","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T06:29:43Z","timestamp":1718605783000},"page":"275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multimodal Blockade of the Renin\u2013Angiotensin System in the Treatment of Cancer in Dogs Has Mild Adverse Effects in Some Dogs"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1813-2197","authenticated-orcid":false,"given":"Keren E.","family":"Dittmer","sequence":"first","affiliation":[{"name":"School of Veterinary Science, Massey University, Palmerston North 4410, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9064-5459","authenticated-orcid":false,"given":"Sarah","family":"Wetzel","sequence":"additional","affiliation":[{"name":"School of Veterinary Science, Massey University, Palmerston North 4410, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Odom","sequence":"additional","affiliation":[{"name":"School of Veterinary Science, Massey University, Palmerston North 4410, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4769-5247","authenticated-orcid":false,"given":"John S.","family":"Munday","sequence":"additional","affiliation":[{"name":"School of Veterinary Science, Massey University, Palmerston North 4410, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Flatt","sequence":"additional","affiliation":[{"name":"Vet South, Winton Clinic, Winton 9720, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid J.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Parkhill Vet Hospital, Birkenhead, Auckland 0626, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Hughes","sequence":"additional","affiliation":[{"name":"Shirley Vet Clinic, 15 Marshland Road, Shirley, Christchurch 8061, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0695-453X","authenticated-orcid":false,"given":"Swee T.","family":"Tan","sequence":"additional","affiliation":[{"name":"Gillies McIndoe Research Institute, Wellington 7184, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/j.1365-2796.2008.01981.x","article-title":"Renin-Angiotensin System Revisited","volume":"264","author":"Fyhrquist","year":"2008","journal-title":"J. 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