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Title: | A novel orally available inhibitor of focal adhesion signaling increases survival in a xenograft model of diffuse large B-cell lymphoma with central nervous system involvement |
Author: | Bosch, Rosa Moreno Jiménez, María José Diéguez González, Rebeca Céspedes, María Virtudes Gallardo, Alberto Trias, Manuel Grañena Batista, Alberto Sierra Gil, Jorge Casanova Rigat, Isolda Mangues Bafalluy, Ramon |
Keywords: | Malalties del sistema nerviós central Limfomes Central nervous system diseases Lymphomas |
Issue Date: | Aug-2013 |
Publisher: | Ferrata Storti Foundation |
Abstract: | Central nervous system dissemination is a relatively uncommon but almost always fatal complication in diffuse large B-cell lymphoma patients. Optimal therapy for central nervous involvement in this malignancy has not been established. In this paper, we aimed to evaluate the therapeutic effect of E7123, a celecoxib derivative that inhibits focal adhesion signaling, in a novel xenograft model of diffuse large B-cell lymphoma with central nervous system involvement. Cells obtained after disaggregation of HT subcutaneous tumors (HT-SC cells) were intravenously injected in NOD/SCID mice. These mice received oral vehicle or 75 mg/kg of E7123 daily until they were euthanized for weight loss or signs of sickness. The antitumor effect of E7123 was validated in an independent experiment using a bioluminescent mouse model. Intravenously injected HT-SC cells showed higher take rate and higher central nervous system tropism (associated with increased expression of beta 1-integrin and p130Cas proteins) than HT cells. The oral administration of E7123 significantly increased survival time in 2 independent experiments using mice injected with unmodified or bioluminescent HT-SC cells. We have developed a new xenograft model of diffuse large B-cell lymphoma with central nervous system involvement that can be used in the pre-clinical evaluation of new drugs for this malignancy. E7123 is a new, well-tolerated and orally available therapeutic agent that merits further investigation since it may improve current management of diffuse large B-cell lymphoma patients with central nervous system involvement. |
Note: | Reproducció del document publicat a: https://doi.org/10.3324/haematol.2012.071811 |
It is part of: | Haematologica, 2013, vol. 98, num. 8, p. 1242-1249 |
URI: | http://hdl.handle.net/2445/126453 |
Related resource: | https://doi.org/10.3324/haematol.2012.071811 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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File | Description | Size | Format | |
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BoschR.pdf | 1.89 MB | Adobe PDF | View/Open |
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