{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T14:38:42Z","timestamp":1747147122382,"version":"3.40.5"},"reference-count":46,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K08714","20K08673"],"award-info":[{"award-number":["20K08714","20K08673"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Primary human herpesvirus 8 (HHV8)\u2010unrelated effusion large B\u2010cell lymphoma is a clinical disease entity distinct from HHV8\u2010positive primary effusion lymphoma (PEL). However, the lack of experimental HHV8\u2010unrelated effusion large B\u2010cell lymphoma models continues to hinder the pathophysiologic and therapeutic investigations of this disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The lymphoma cells were obtained from the pleural effusion of a patient with primary HHV8\u2010unrelated effusion large B\u2010cell lymphoma and cultured <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We established a novel HHV8\u2010unrelated effusion large B\u2010cell lymphoma cell line, designated Pell\u20101, carrying a <jats:italic>c\u2010MYC<\/jats:italic> rearrangement with features distinct from those of HHV8\u2010positive PEL. Moreover, we developed an HHV8\u2010unrelated effusion large B\u2010cell lymphoma cell line\u2010derived xenograft model. Pell\u20101 cells induced profuse lymphomatous ascites and subsequently formed intra\u2010abdominal tumors after intraperitoneal implantation into irradiated nonobese diabetic\/severe combined immunodeficient mice. Thus, this xenograft mouse model mimicked the clinical phenomena observed in patients and recapitulated the sequential stages of aggressive HHV8\u2010unrelated effusion large B\u2010cell lymphoma. The bromodomain and extraterminal domain (BET) inhibitors JQ1 and birabresib (MK\u20108628\/OTX015) reduced the proliferation of Pell\u20101 cells <jats:italic>in vitro<\/jats:italic> through the induction of cell cycle arrest and apoptosis. The antitumor effect of BET inhibition was also demonstrated <jats:italic>in vivo<\/jats:italic>, as birabresib significantly reduced ascites and suppressed tumor progression without apparent adverse effects in the xenografted mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These preclinical findings suggest the therapeutic potential of targeting c\u2010MYC through BET inhibition in HHV8\u2010unrelated effusion large B\u2010cell lymphoma.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4394","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T08:39:29Z","timestamp":1637915969000},"page":"8976-8987","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Development of a novel cell line\u2010derived xenograft model of primary herpesvirus 8\u2010unrelated effusion large B\u2010cell lymphoma and antitumor activity of birabresib <i>in vitro<\/i> and <i>in vivo<\/i>"],"prefix":"10.1002","volume":"10","author":[{"given":"Tomohiro","family":"Nishimori","sequence":"first","affiliation":[{"name":"Department of Microbiology and Infection Kochi Medical School Kochi University Nankoku Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-3040","authenticated-orcid":false,"given":"Tomonori","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infection Kochi Medical School Kochi University Nankoku Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumiko","family":"Hashida","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infection Kochi Medical School Kochi University Nankoku Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takako","family":"Ujihara","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infection Kochi Medical School Kochi University Nankoku Japan"},{"name":"Science Research Center Kochi University Nankoku Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayuko","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infection Kochi Medical School Kochi University Nankoku Japan"},{"name":"Department of Hematology Kochi Medical School Kochi University Nankoku Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiya","family":"Ogasawara","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infection Kochi Medical School Kochi University Nankoku Japan"},{"name":"Department of Hematology Kochi Medical School Kochi University Nankoku Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoya","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Kochi Medical School Kochi University Nankoku Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiro","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Pathology Kochi Medical School Kochi University Nankoku Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kensuke","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Hematology Kochi Medical School Kochi University Nankoku Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8714-2068","authenticated-orcid":false,"given":"Masanori","family":"Daibata","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infection Kochi Medical School Kochi University Nankoku Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"323","volume-title":"WHO classification of tumours of haematopoietic and lymphoid tissues","author":"Said J","year":"2017"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-1578(10)60004-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13040878"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S167392"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-852442"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPHZ3CHO4HUWET"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000097460"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318267fabc"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2008.00005.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001168"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13449"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jasc.2014.10.002"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002293"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.2.645.bloodjournal882645"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190290012100"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401160"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3283365395"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2006.12.023"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12559"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2008.15"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.169.6.2191"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26060"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5274.494"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.190157"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11389-5"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.017"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11101483"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.11.003"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-1561"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4131"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-019-0761-2"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.121616198"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-0774.2005.00007.x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11626-010-9333-z"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.5.1671.1671_1671_1679"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090349"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-03-791426"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.23324"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.2.1328-1333.1995"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(01)00169-2"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.159"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.205.2.9356629"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2008.04.012"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(16)00021-1"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(15)00247-1"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.78.2292"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.4394","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.4394","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.4394","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T05:03:26Z","timestamp":1693199006000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.4394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,24]]},"references-count":46,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1002\/cam4.4394"],"URL":"https:\/\/doi.org\/10.1002\/cam4.4394","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"type":"print","value":"2045-7634"},{"type":"electronic","value":"2045-7634"}],"subject":[],"published":{"date-parts":[[2021,11,24]]},"assertion":[{"value":"2021-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}