{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:19:03Z","timestamp":1784557143086,"version":"3.55.0"},"reference-count":49,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>\n                    Multiple myeloma (MM) is a plasma cell malignancy in which involvement of the thyroid hormone-integrin \u03b1v\u03b23 pathway was shown, and pharmacologic inhibition of this pathway is a rational approach to disease management. A thyroid hormone derivative, tetraiodothyroacetic acid (tetrac), which inhibits\n                    <jats:sc>l<\/jats:sc>\n                    -thyroxine (T\n                    <jats:sub>4<\/jats:sub>\n                    ) and 3,5,3\u2032-triiodo-\n                    <jats:sc>l<\/jats:sc>\n                    -thyronine (T\n                    <jats:sub>3<\/jats:sub>\n                    ) binding to \u03b1v\u03b23 integrin, was studied in five MM cell lines and primary bone marrow (BM) MM cells. Tetrac inhibited MM cell proliferation (absolute cell number\/viability) and induced caspase-dependent apoptosis (annexin-V\/PI and cell cycle). Activation of caspase-9 and caspase-3 was further demonstrated. Moreover, DNA damage markers, ataxia-telangiectasia-mutated (ATM) kinase, poly ADP-ribose polymerase (PARP-1) and histone \u03b3H2AX were induced by tetrac. The various tetrac-initiated effects were attenuated by Arg-Gly-Asp (RGD) peptide, suggesting integrin involvement. Primary BM mononuclear cells were harvested from MM patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200939) at various disease stages. Tetrac-induced apoptosis (12\/17 samples) and sensitized the cytotoxic action of bortezomib (6\/9 samples). Lastly, expression of plasma membrane integrin \u03b1v\u03b23 was shown not only in the malignant plasma clone, but also in other cell populations within the BM samples (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200925). Tetrac is anti-proliferative and pro-apoptotic in MM and cells may offer a therapeutic approach for this disease.\n                  <\/jats:p>","DOI":"10.1530\/erc-17-0246","type":"journal-article","created":{"date-parts":[[2017,10,10]],"date-time":"2017-10-10T20:40:25Z","timestamp":1507668025000},"page":"21-34","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":9,"title":["The induction of myeloma cell death and DNA damage by tetrac, a thyroid hormone derivative"],"prefix":"10.1530","volume":"25","author":[{"given":"Keren","family":"Cohen","sequence":"first","affiliation":[{"name":"1Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, Israel"},{"name":"2Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel"},{"name":"3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uri","family":"Abadi","sequence":"additional","affiliation":[{"name":"1Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, Israel"},{"name":"3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleck","family":"Hercbergs","sequence":"additional","affiliation":[{"name":"4Radiation Oncology, Cleveland Clinic, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"Davis","sequence":"additional","affiliation":[{"name":"5Department of Medicine, Albany Medical College, Albany, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Ellis","sequence":"additional","affiliation":[{"name":"1Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, Israel"},{"name":"3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osnat","family":"Ashur-Fabian","sequence":"additional","affiliation":[{"name":"1Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, Israel"},{"name":"2Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel"},{"name":"3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2017121817201505000_25.1.21.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2010.06.079"},{"key":"2017121817201505000_25.1.21.2","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.urolonc.2010.07.015","article-title":"The impact of sunitinib-induced hypothyroidism on progression-free survival of metastatic renal cancer patients: a prospective single-center study","volume":"30","author":"Baldazzi","year":"2010","journal-title":"Urologic Oncology"},{"key":"2017121817201505000_25.1.21.3","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0102"},{"key":"2017121817201505000_25.1.21.4","doi-asserted-by":"crossref","unstructured":"Campbell ID Humphries MJ 2011 Integrin structure, activation, and interactions. 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