{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:33:03Z","timestamp":1790922783571,"version":"4.1.0"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2017,1,20]],"date-time":"2017-01-20T00:00:00Z","timestamp":1484870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0170186","type":"journal-article","created":{"date-parts":[[2017,1,20]],"date-time":"2017-01-20T13:31:39Z","timestamp":1484919099000},"page":"e0170186","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Apoptosis Induction and Gene Expression Profile Alterations of Cutaneous T-Cell Lymphoma Cells following Their Exposure to Bortezomib and Methotrexate"],"prefix":"10.1371","volume":"12","author":[{"given":"Vassiliki","family":"Mpakou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia","family":"Papadavid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frieda","family":"Kontsioti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Konsta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Vikentiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aris","family":"Spathis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotiris","family":"Papageorgiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diamantina","family":"Vasilatou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Gkontopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efthimia","family":"Mpazani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petros","family":"Karakitsos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Rigopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Dimitriadis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0421-9424","authenticated-orcid":true,"given":"Vasiliki","family":"Pappa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,1,20]]},"reference":[{"issue":"19","key":"ref1","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1056\/NEJMra032810","article-title":"The pathogenesis of mycosis fungoides","volume":"350","author":"M Girardi","year":"2004","journal-title":"N Engl J Med"},{"key":"ref2","article-title":"Cutaneous T-Cell Lymphoma: A Review with a Focus on Targeted Agents","author":"S Devata","year":"2016","journal-title":"Am J Clin Dermatol"},{"issue":"10","key":"ref3","doi-asserted-by":"crossref","first-page":"3768","DOI":"10.1182\/blood-2004-09-3502","article-title":"WHO-EORTC classification for cutaneous lymphomas","volume":"105","author":"R Willemze","year":"2005","journal-title":"Blood"},{"issue":"7","key":"ref4","first-page":"857","article-title":"Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression","volume":"139","author":"YH Kim","year":"2003","journal-title":"Arch Dermatol"},{"key":"ref5","first-page":"75","article-title":"Management of cutaneous T cell lymphoma: new and emerging targets and treatment options","volume":"4","author":"JY Li","year":"2012","journal-title":"Cancer Manag Res"},{"issue":"33","key":"ref6","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1200\/JCO.2012.44.5650","article-title":"Emerging treatment options for advanced-stage mycosis fungoides","volume":"30","author":"RE Drews","year":"2012","journal-title":"J Clin Oncol"},{"issue":"5","key":"ref7","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1001\/archdermatol.2011.98","article-title":"The Stanford University experience with conventional-dose, total skin electron-beam therapy in the treatment of generalized patch or plaque (T2) and tumor (T3) mycosis fungoides","volume":"147","author":"D Navi","year":"2011","journal-title":"Arch Dermatol"},{"issue":"4","key":"ref8","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1007\/s11899-015-0293-y","article-title":"Cutaneous T cell Lymphoma: an Update on Pathogenesis and Systemic Therapy","volume":"10","author":"CG Chung","year":"2015","journal-title":"Curr Hematol Malig Rep"},{"issue":"7","key":"ref9","first-page":"3071","article-title":"The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells","volume":"61","author":"T Hideshima","year":"2001","journal-title":"Cancer Res"},{"issue":"11","key":"ref10","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1038\/leu.2009.173","article-title":"Proteasome inhibitors in the treatment of multiple myeloma","volume":"23","author":"JJ Shah","year":"2009","journal-title":"Leukemia"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1756-8722-5-24","article-title":"Novel therapeutic agents for cutaneous T-Cell lymphoma","volume":"5","author":"S Jain","year":"2012","journal-title":"J Hematol Oncol"},{"issue":"22","key":"ref12","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.2174\/1381612811319220012","article-title":"From bortezomib to other inhibitors of the proteasome and beyond","volume":"19","author":"D Buac","year":"2013","journal-title":"Curr Pharm Des"},{"issue":"6","key":"ref13","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1158\/1078-0432.CCR-07-2218","article-title":"Proteasome inhibitors in cancer therapy: lessons from the first decade","volume":"14","author":"RZ Orlowski","year":"2008","journal-title":"Clin Cancer Res"},{"issue":"14","key":"ref14","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1200\/JCO.2007.14.0152","article-title":"Bortezomib with or without irinotecan in relapsed or refractory colorectal cancer: results from a randomized phase II study","volume":"26","author":"PS Kozuch","year":"2008","journal-title":"J Clin Oncol"},{"issue":"6","key":"ref15","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1016\/j.juro.2007.08.015","article-title":"A phase II trial of bortezomib and prednisone for castration resistant metastatic prostate cancer","volume":"178","author":"MJ Morris","year":"2007","journal-title":"J Urol"},{"issue":"5","key":"ref16","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1093\/annonc\/mdm569","article-title":"A phase I\/II study of bortezomib and capecitabine in patients with metastatic breast cancer previously treated with taxanes and\/or anthracyclines","volume":"19","author":"P Schmid","year":"2008","journal-title":"Ann Oncol"},{"issue":"6","key":"ref17","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/j.1600-0609.2009.01239.x","article-title":"Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in cutaneous T cell lymphoma","volume":"82","author":"U Heider","year":"2009","journal-title":"Eur J Haematol"},{"issue":"Suppl 5","key":"ref18","doi-asserted-by":"crossref","first-page":"S187","DOI":"10.3816\/CLM.2008.s.015","article-title":"Novel therapies for cutaneous T-cell lymphomas","volume":"8","author":"SM Horwitz","year":"2008","journal-title":"Clin Lymphoma Myeloma"},{"issue":"17","key":"ref19","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.1016\/j.ejca.2012.06.003","article-title":"Bortezomib in combination with CHOP as first-line treatment for patients with stage III\/IV peripheral T-cell lymphomas: a multicentre, single-arm, phase 2 trial","volume":"48","author":"SJ Kim","year":"2012","journal-title":"Eur J Cancer"},{"issue":"27","key":"ref20","doi-asserted-by":"crossref","first-page":"4293","DOI":"10.1200\/JCO.2007.11.4207","article-title":"Phase II trial of proteasome inhibitor bortezomib in patients with relapsed or refractory cutaneous T-cell lymphoma","volume":"25","author":"PL Zinzani","year":"2007","journal-title":"J Clin Oncol"},{"issue":"3","key":"ref21","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1111\/bjd.12071","article-title":"Proteasome inhibition as a novel mechanism of the proapoptotic activity of gamma-secretase inhibitor I in cutaneous T-cell lymphoma","volume":"168","author":"E Biskup","year":"2013","journal-title":"Br J Dermatol"},{"issue":"2","key":"ref22","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1158\/1535-7163.MCT-08-0759","article-title":"Dihydrofolate reductase amplification and sensitization to methotrexate of methotrexate-resistant colon cancer cells","volume":"8","author":"C Morales","year":"2009","journal-title":"Mol Cancer Ther"},{"issue":"8","key":"ref23","first-page":"2036","article-title":"Accumulation of DNA strand breaks in cells exposed to methotrexate or N10-propargyl-5,8-dideazafolic acid","volume":"48","author":"A Lorico","year":"1988","journal-title":"Cancer Res"},{"issue":"3","key":"ref24","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1517\/14656566.2.3.409","article-title":"The pharmacology of methotrexate","volume":"2","author":"K Barnhart","year":"2001","journal-title":"Expert Opin Pharmacother"},{"issue":"2","key":"ref25","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/0190-9622(91)70199-C","article-title":"The pharmacology of methotrexate","volume":"25","author":"EA Olsen","year":"1991","journal-title":"J Am Acad Dermatol"},{"issue":"6","key":"ref26","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1089\/cbr.2007.0402","article-title":"Interferon and low dose methotrexate improve outcome in refractory mycosis fungoides\/Sezary syndrome","volume":"22","author":"A Aviles","year":"2007","journal-title":"Cancer Biother Radiopharm"},{"issue":"9","key":"ref27","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1179\/1607845415Y.0000000002","article-title":"Interferon and low doses of methotrexate versus interferon and retinoids in the treatment of refractory\/relapsed cutaneous T-cell lymphoma","volume":"20","author":"A Aviles","year":"2015","journal-title":"Hematology"},{"issue":"3","key":"ref28","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1080\/09546630802562427","article-title":"Evaluation of the efficacy of the combination of oral bexarotene and methotrexate for the treatment of early stage treatment-refractory cutaneous T-cell lymphoma","volume":"20","author":"AP Kannangara","year":"2009","journal-title":"J Dermatolog Treat"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1002\/1097-0142(196408)17:8<1045::AID-CNCR2820170811>3.0.CO;2-S","article-title":"Observations on the Use of Cancer Chemotherapeutic Agents in Patients with Mycosis Fungoides","volume":"17","author":"JC Wright","year":"1964","journal-title":"Cancer"},{"issue":"4","key":"ref30","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S0190-9622(96)80062-4","article-title":"Low-dose methotrexate to treat erythrodermic cutaneous T-cell lymphoma: results in twenty-nine patients","volume":"34","author":"HS Zackheim","year":"1996","journal-title":"J Am Acad Dermatol"},{"issue":"5","key":"ref31","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S0190-9622(03)01591-3","article-title":"Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients","volume":"49","author":"HS Zackheim","year":"2003","journal-title":"J Am Acad Dermatol"},{"issue":"2","key":"ref32","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.leukres.2012.10.011","article-title":"Dasatinib inhibits proliferation and induces apoptosis in the KASUMI-1 cell line bearing the t(8;21)(q22;q22) and the N822K c-kit mutation","volume":"37","author":"VE Mpakou","year":"2013","journal-title":"Leukemia research"},{"issue":"1","key":"ref33","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1182\/blood-2014-07-588236","article-title":"Lack of durable disease control with chemotherapy for mycosis fungoides and Sezary syndrome: a comparative study of systemic therapy","volume":"125","author":"CF Hughes","year":"2015","journal-title":"Blood"},{"issue":"5","key":"ref34","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1038\/jid.2008.309","article-title":"Low FAS\/CD95 expression by CTCL correlates with reduced sensitivity to apoptosis that can be restored by FAS upregulation","volume":"129","author":"J Wu","year":"2009","journal-title":"J Invest Dermatol"},{"issue":"4","key":"ref35","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1001\/archdermatol.2010.376","article-title":"Reduction of Fas\/CD95 promoter methylation, upregulation of Fas protein, and enhancement of sensitivity to apoptosis in cutaneous T-cell lymphoma","volume":"147","author":"J Wu","year":"2011","journal-title":"Arch Dermatol"},{"issue":"2","key":"ref36","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1158\/1541-7786.MCR-10-0368","article-title":"Bortezomib induces nuclear translocation of IkappaBalpha resulting in gene-specific suppression of NF-kappaB\u2014dependent transcription and induction of apoptosis in CTCL","volume":"9","author":"A Juvekar","year":"2011","journal-title":"Mol Cancer Res"},{"issue":"6","key":"ref37","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1182\/blood-2005-06-2536","article-title":"Down-regulating constitutive activation of the NF-kappaB canonical pathway overcomes the resistance of cutaneous T-cell lymphoma to apoptosis","volume":"107","author":"A Sors","year":"2006","journal-title":"Blood"},{"issue":"11","key":"ref38","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1016\/j.bbamcr.2014.07.012","article-title":"Bcl3 regulates pro-survival and pro-inflammatory gene expression in cutaneous T-cell lymphoma","volume":"1843","author":"TP Chang","year":"2014","journal-title":"Biochim Biophys Acta"},{"issue":"6","key":"ref39","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.4049\/jimmunol.1402610","article-title":"Bortezomib inhibits expression of TGF-beta1, IL-10, and CXCR4, resulting in decreased survival and migration of cutaneous T cell lymphoma cells","volume":"194","author":"TP Chang","year":"2015","journal-title":"J Immunol"},{"key":"ref40","article-title":"Candidate driver genes in Sezary syndrome: frequent perturbations of genes involved in genome maintenance and DNA repair","author":"WJ Woollard","year":"2016","journal-title":"Blood"},{"issue":"1","key":"ref41","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/exd.12567","article-title":"Characterization of the novel Sezary lymphoma cell line BKP1","volume":"24","author":"J Boudjarane","year":"2015","journal-title":"Exp Dermatol"},{"issue":"17","key":"ref42","doi-asserted-by":"crossref","first-page":"3886","DOI":"10.1200\/JCO.2005.11.353","article-title":"Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73","volume":"23","author":"R van Doorn","year":"2005","journal-title":"J Clin Oncol"},{"issue":"2","key":"ref43","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.beha.2012.04.007","article-title":"Proteasome inhibitors in mantle cell lymphoma","volume":"25","author":"B Holkova","year":"2012","journal-title":"Best Pract Res Clin Haematol"},{"issue":"6","key":"ref44","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.molcel.2004.11.033","article-title":"Proteasome involvement in the repair of DNA double-strand breaks","volume":"16","author":"NJ Krogan","year":"2004","journal-title":"Mol Cell"},{"issue":"1","key":"ref45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2008.12.030","article-title":"The vital link between the ubiquitin-proteasome pathway and DNA repair: impact on cancer therapy","volume":"283","author":"A Motegi","year":"2009","journal-title":"Cancer Lett"},{"issue":"15","key":"ref46","doi-asserted-by":"crossref","first-page":"7395","DOI":"10.1158\/0008-5472.CAN-07-1015","article-title":"Proteasome function is required for DNA damage response and fanconi anemia pathway activation","volume":"67","author":"C Jacquemont","year":"2007","journal-title":"Cancer Res"},{"issue":"5","key":"ref47","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s00280-009-0961-5","article-title":"Perturbation of DNA repair pathways by proteasome inhibitors corresponds to enhanced chemosensitivity of cells to DNA damage-inducing agents","volume":"64","author":"T Takeshita","year":"2009","journal-title":"Cancer Chemother Pharmacol"},{"issue":"1","key":"ref48","doi-asserted-by":"crossref","first-page":"e1004943","DOI":"10.1371\/journal.pgen.1004943","article-title":"DNA damage response factors from diverse pathways, including DNA crosslink repair, mediate alternative end joining","volume":"11","author":"SM Howard","year":"2015","journal-title":"PLoS Genet"},{"issue":"5","key":"ref49","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s00432-011-1132-8","article-title":"Methotrexate-mediated inhibition of RAD51 expression and homologous recombination in cancer cells","volume":"138","author":"LQ Du","year":"2012","journal-title":"J Cancer Res Clin Oncol"},{"issue":"6754","key":"ref50","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/44385","article-title":"Two subsets of memory T lymphocytes with distinct homing potentials and effector functions","volume":"401","author":"F Sallusto","year":"1999","journal-title":"Nature"},{"issue":"5","key":"ref51","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1182\/blood-2009-11-251926","article-title":"Sezary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors","volume":"116","author":"JJ Campbell","year":"2010","journal-title":"Blood"},{"issue":"5","key":"ref52","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1038\/jid.2012.10","article-title":"MDM2 inhibitor nutlin-3a induces apoptosis and senescence in cutaneous T-cell lymphoma: role of p53","volume":"132","author":"V Manfe","year":"2012","journal-title":"J Invest Dermatol"},{"issue":"7","key":"ref53","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/nrm4007","article-title":"p53 in survival, death and metabolic health: a lifeguard with a licence to kill","volume":"16","author":"F Kruiswijk","year":"2015","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"4","key":"ref54","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nrm2147","article-title":"p53 in health and disease","volume":"8","author":"KH Vousden","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"3","key":"ref55","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.cell.2009.04.037","article-title":"Blinded by the Light: The Growing Complexity of p53","volume":"137","author":"KH Vousden","year":"2009","journal-title":"Cell"},{"issue":"20","key":"ref56","doi-asserted-by":"crossref","first-page":"12893","DOI":"10.1074\/jbc.272.20.12893","article-title":"p53-dependent induction of apoptosis by proteasome inhibitors","volume":"272","author":"UG Lopes","year":"1997","journal-title":"J Biol Chem"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jprot.2014.09.010","article-title":"A proteomic analysis of p53-independent induction of apoptosis by bortezomib in 4T1 breast cancer cell line","volume":"113","author":"A Yerlikaya","year":"2015","journal-title":"J Proteomics"},{"issue":"5","key":"ref58","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1007\/s13277-012-0386-3","article-title":"The p53-independent induction of apoptosis in breast cancer cells in response to proteasome inhibitor bortezomib","volume":"33","author":"A Yerlikaya","year":"2012","journal-title":"Tumour Biol"},{"issue":"4","key":"ref59","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s10238-004-0055-y","article-title":"Relationship between dose of methotrexate, apoptosis, p53\/p21 expression and intestinal crypt proliferation in the rat","volume":"4","author":"RJ Gibson","year":"2005","journal-title":"Clin Exp Med"},{"issue":"4","key":"ref60","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.bcp.2010.11.014","article-title":"Methotrexate induces apoptosis through p53\/p21-dependent pathway and increases E-cadherin expression through downregulation of HDAC\/EZH2","volume":"81","author":"WY Huang","year":"2011","journal-title":"Biochem Pharmacol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0170186","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T04:24:52Z","timestamp":1540268692000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0170186"}},"subtitle":[],"editor":[{"given":"Peiwen","family":"Fei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,1,20]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,1,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0170186","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,20]]}}}