{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T13:54:31Z","timestamp":1773150871682,"version":"3.50.1"},"reference-count":71,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T00:00:00Z","timestamp":1633824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 CA100730"],"award-info":[{"award-number":["P01 CA100730"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 OD010429"],"award-info":[{"award-number":["T32 OD010429"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Adult T-cell leukemia\/lymphoma (ATL) is an intractable disease affecting nearly 4% of Human T-cell Leukemia Virus Type 1 (HTLV-1) carriers. Acute ATL has a unique interaction with bone characterized by aggressive bone invasion, osteolytic metastasis, and hypercalcemia. We hypothesized that dual tumor and bone-targeted therapies would decrease tumor burden in bone, the incidence of metastasis, and ATL-associated osteolysis. Our goal was to evaluate dual targeting of both ATL bone tumors and the bone microenvironment using an anti-tumor HDACi (AR-42) and an osteoclast inhibitor (zoledronic acid, Zol), alone and in combination. Our results showed that AR-42, Zol, and AR-42\/Zol significantly decreased the viability of multiple ATL cancer cell lines in vitro. Zol and AR-42\/Zol decreased tumor growth in vivo. Zol \u00b1 AR-42 significantly decreased ATL-associated bone resorption and promoted new bone formation. AR-42-treated ATL cells had increased mRNA levels of PTHrP, ENPP2 (autotaxin) and MIP-1\u03b1, and TAX viral gene expression. AR-42 alone had no significant effect on tumor growth or osteolysis in mice. These findings indicate that Zol adjuvant therapy has the potential to reduce growth of ATL in bone and its associated osteolysis.<\/jats:p>","DOI":"10.3390\/cancers13205066","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T21:19:32Z","timestamp":1633900772000},"page":"5066","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Effect of a Histone Deacetylase Inhibitor (AR-42) and Zoledronic Acid on Adult T-Cell Leukemia\/Lymphoma Osteolytic Bone Tumors"],"prefix":"10.3390","volume":"13","author":[{"given":"Said M.","family":"Elshafae","sequence":"first","affiliation":[{"name":"Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Pathology, Faculty of Veterinary Medicine, Benha University, Kalyubia  13736, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole A.","family":"Kohart","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin T.","family":"Breitbach","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4631-1117","authenticated-orcid":false,"suffix":"III","given":"Blake E.","family":"Hildreth","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Rosol","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1128\/CMR.00063-09","article-title":"Epidemiology, Treatment, and Prevention of Human T-Cell Leukemia Virus Type 1-Associated Diseases","volume":"23","author":"Proietti","year":"2010","journal-title":"Clin. 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