{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T17:30:23Z","timestamp":1701970223731},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,5,21]],"date-time":"2012-05-21T00:00:00Z","timestamp":1337558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2012,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mantle cell lymphoma (MCL) is one of the most aggressive B\u2010cell lymphomas with a median patient survival of only 5\u20137 years. The failure of existing therapies is mainly due to disease relapse when therapy\u2010resistant tumor cells remain after chemotherapy. Therefore, development and testing of novel therapeutic strategies to target these therapy\u2010resistant MCL are needed. Here, we developed an <jats:italic>in vivo<\/jats:italic> model of therapy\u2010resistant MCL by transplanting a patient\u2010derived MCL cell line (Granta 519) into NOD\/SCID mice followed by treatment with combination chemotherapy. Cytomorphologic, immunophenotypic, <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> growth analyses of these therapy\u2010resistant MCL cells confirm their MCL origin and resistance to chemotherapy. Moreover, quantitative real\u2010time PCR revealed the upregulation of GLI transcription factors, which are mediators of the hedgehog signaling pathway, in these therapy\u2010resistant MCL cells. Therefore, we developed an effective therapeutic strategy for resistant MCL by treating the NOD\/SCID mice bearing Granta 519 MCL with CHOP chemotherapy to reduce tumor burden combined with GLI\u2010antisense oligonucleotides or bortezomib, a proteosome inhibitor, to target therapy\u2010resistant MCL cells that remained after chemotherapy. This regimen was followed by treatment with MCL\u2010specific cytotoxic T lymphocytes to eliminate all detectable leftover minimal residual disease. Mice treated with this strategy showed a significantly increased survival and decreased tumor burden compared to the mice in all other groups. Such therapeutic strategies that combine chemotherapy with targeted therapy followed by tumor\u2010specific immunotherapy are effective and have excellent potential for clinical application to provide long\u2010term, disease\u2010free survival in MCL patients.<\/jats:p>","DOI":"10.1002\/ijc.27602","type":"journal-article","created":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T11:56:43Z","timestamp":1334663803000},"page":"2951-2960","source":"Crossref","is-referenced-by-count":11,"title":["Novel therapy for therapy\u2010resistant mantle cell lymphoma: Multipronged approach with targeting of hedgehog signaling"],"prefix":"10.1002","volume":"131","author":[{"given":"Ganapati V.","family":"Hegde","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara M.","family":"Nordgren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corey M.","family":"Munger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit K.","family":"Mittal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip J.","family":"Bierman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis D.","family":"Weisenburger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie M.","family":"Vose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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