{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T22:44:53Z","timestamp":1770158693642,"version":"3.49.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":3870,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001458","name":"AKC Canine Health Foundation","doi-asserted-by":"publisher","award":["1759"],"award-info":[{"award-number":["1759"]}],"id":[{"id":"10.13039\/100001458","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001458","name":"AKC Canine Health Foundation","doi-asserted-by":"publisher","award":["2081-A"],"award-info":[{"award-number":["2081-A"]}],"id":[{"id":"10.13039\/100001458","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH Comprehensive Cancer Center","award":["P30 CA077598"],"award-info":[{"award-number":["P30 CA077598"]}]},{"name":"Lipidomics Shared Resource"},{"DOI":"10.13039\/100006806","name":"Hollings Cancer Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006806","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006942","name":"Medical University of South Carolina","doi-asserted-by":"publisher","award":["P30 CA138313"],"award-info":[{"award-number":["P30 CA138313"]}],"id":[{"id":"10.13039\/100006942","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lipidomics Core in the SC Lipidomics and Pathobiology COBRE"},{"name":"Department Biochemistry, MUSC","award":["P20 RR017677"],"award-info":[{"award-number":["P20 RR017677"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sphingosine-1-phosphate (S1P) is a key biolipid signaling molecule that regulates cell growth and survival, but it has not been studied in tumors from dogs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis\/Objectives<\/jats:title>\n                    <jats:p>S1P\/S1P1 signaling will contribute to the progression of hemangiosarcoma (HSA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Thirteen spontaneous HSA tissues, 9 HSA cell lines, 8 nonmalignant tissues, including 6 splenic hematomas and 2 livers with vacuolar degeneration, and 1 endothelial cell line derived from a dog with splenic hematoma were used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a retrospective case series and in\u00a0vitro study. Samples were obtained as part of medically necessary diagnostic procedures. Microarray, qRT-PCR, immunohistochemistry, and immunoblotting were performed to examine S1P1 expression. S1P concentrations were measured by high-performance liquid chromatography\/mass spectrometry. S1P signaling was evaluated by intracellular Ca2+ mobilization; proliferation and survival were evaluated using the MTS assay and Annexin V staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Canine HSA cells expressed higher levels of S1P1 mRNA than nonmalignant endothelial cells. S1P1 protein was present in HSA tissues and cell lines. HSA cells appeared to produce low levels of S1P, but they selectively consumed S1P from the culture media. Exogenous S1P induced an increase in intracellular calcium as well as increased proliferation and viability of HSA cells. Prolonged treatment with FTY720, an inhibitor of S1P1, decreased S1P1 protein expression and induced apoptosis of HSA cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and clinical importance<\/jats:title>\n                    <jats:p>S1P\/S1P1 signaling pathway functions to maintain HSA cell viability and proliferation. The data suggest that S1P1 or the S1P pathway in general could be targets for therapeutic intervention for dogs with HSA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.13570","type":"journal-article","created":{"date-parts":[[2015,6,25]],"date-time":"2015-06-25T04:39:29Z","timestamp":1435207169000},"page":"1088-1097","source":"Crossref","is-referenced-by-count":14,"title":["Association of Sphingosine-1-phosphate (S1P)\/S1P Receptor-1 Pathway with Cell Proliferation and Survival in Canine Hemangiosarcoma"],"prefix":"10.1093","volume":"29","author":[{"given":"A.M.","family":"Rodriguez","sequence":"first","affiliation":[{"name":"The Potomac School , McLean, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.J.","family":"Graef","sequence":"additional","affiliation":[{"name":"Animal Cancer Care and Research Program, University of Minnesota , St. Paul, MN"},{"name":"College of Veterinary Medicine, University of Minnesota Department of Veterinary Clinical Science, , St. Paul, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.N.","family":"LeVine","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Iowa State University Department of Veterinary Clinical Sciences, , Ames, IA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.R.","family":"Cohen","sequence":"additional","affiliation":[{"name":"The Potomac School , McLean, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.F.","family":"Modiano","sequence":"additional","affiliation":[{"name":"Animal Cancer Care and Research Program, University of Minnesota , St. Paul, MN"},{"name":"College of Veterinary Medicine, University of Minnesota Department of Veterinary Clinical Science, , St. Paul, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, 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