{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T14:23:40Z","timestamp":1782743020960,"version":"3.54.5"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T00:00:00Z","timestamp":1296518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>A strong link has been established between exposure to asbestos and increased risk for pleural malignant mesothelioma (MM). Adenosine plays a key role in inflammatory processes and cancer, where it is involved in the regulation of cell death and proliferation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The primary aim of this study was to investigate the presence of adenosine receptors (ARs) in human MM pleura (MMP) and healthy mesothelial pleura (HMP). To shed some light on the interaction between adenosine and MM, the presence and functionality of ARs were explored in human healthy mesothelial cells (HMC) and in malignant mesothelioma cells (MMC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>ARs were analyzed by using reverse transcriptase\u2013polymerase chain reaction, Western blotting, and saturation binding assays. HMC were treated with crocidolite asbestos, which is the principal risk factor for MM. The role of A3ARs on these cellular models, evaluating cAMP production, Akt phosphorylation, and nuclear factor (NF)-\u03baB activation, was investigated. The dual effect of A3AR stimulation on healthy and cancer cell growth was studied by means of proliferation, apoptosis, and cytotoxicity assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>A3AR was up-regulated by 2.5-fold (P &amp;lt; 0.01) in MMP when compared with HMP. Stimulation of A3ARs decreased proliferation and exerted a cytotoxic and proapoptotic effect on MMC and on HMC exposed to asbestos and tumor necrosis factor-\u03b1, but not on HMC with an involvement of the deregulation of Akt\/NF-\u03baB cell survival pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These new findings suggest that A3AR could represent a pharmacological target to prevent tumor development after asbestos exposure and to treat full-blown MM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201006-0980oc","type":"journal-article","created":{"date-parts":[[2010,9,24]],"date-time":"2010-09-24T22:50:44Z","timestamp":1285368644000},"page":"522-530","source":"Crossref","is-referenced-by-count":48,"title":["A3 Receptors Are Overexpressed in Pleura from Patients with Mesothelioma and Reduce Cell Growth via Akt\/Nuclear Factor-\u03baB Pathway"],"prefix":"10.1093","volume":"183","author":[{"given":"Katia","family":"Varani","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Section of Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Maniero","sequence":"additional","affiliation":[{"name":"Department of Morphology and Embryology, Section of Cell Biology and Molecular Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Vincenzi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Section of Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Targa","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Section of Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Stefanelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Section of Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pio","family":"Maniscalco","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Radiological Sciences, Section of General and Thoracic Surgery, University of Ferrara, Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Martini","sequence":"additional","affiliation":[{"name":"Department of Morphology and Embryology, Section of Cell Biology and Molecular Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Tognon","sequence":"additional","affiliation":[{"name":"Department of Morphology and Embryology, Section of Cell Biology and Molecular Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Andrea","family":"Borea","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Section of Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,2,15]]},"reference":[{"key":"2026032504243963300_BIB1","first-page":"1086","volume-title":"Eur Respir J","year":"2006"},{"key":"2026032504243963300_BIB2","first-page":"1741","volume-title":"Cancer Epidemiol Biomarkers Prev","year":"2005"},{"key":"2026032504243963300_BIB3","first-page":"10397","volume-title":"Proc Natl Acad Sci USA","year":"2006"},{"key":"2026032504243963300_BIB4","first-page":"1454","volume-title":"Cancer","year":"2007"},{"key":"2026032504243963300_BIB5","first-page":"123","volume-title":"Pharmacol Ther","year":"2008"},{"key":"2026032504243963300_BIB6","first-page":"297","volume-title":"Handb Exp 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