Title details Help Title The effect of N-(4-hydroxyphenyl) retinamide on HTLV-I associated Adult T-Cell leukemia/lymphoma using SCID ATL mouse models / by Georgette Georges Francis Thesis Name(s) Francis, Georgette Georges (Main Author) American University of Beirut. Faculty of Arts and Sciences. Department of Biology (Related name) Publication 2009 Link(s) Click for full-text Physical Details xvi, 88 leaves; col. ill.; 30 cm. Subjects Adult T-cell leukemia HTLV-I (Virus) Lymphomas--Animal models Leukemia--Animal models Mice as laboratory animals Retinoids Classmarks T:005301 Notes Dissertation: Thesis (M.S.)--American University of Beirut, Dept. of Biology, 2009. Dissertation: Advisor : Dr. Nadine Darwiche, Professor, Biology Co-Advisor : Dr. Ali Bazarbachi, Professor, Internal Medicine Member of Committee : Dr. Sawsan Kreydiyyeh, Professor, Biology Member of Committee : Dr. Khouzama Knio, Professor, Biology Bib. & Index: Bibliography : leaves 71-88. Abstract Adult T-cell leukemia-lymphoma (ATL) is an aggressive peripheral T-cell malignancy caused by human T-cell lymphotropic virus type I (HTLV-I). ATL carries a poor prognosis with a mean survival time of less than eight months, in the acute form, mainly due to acquired resistance to chemotherapy. The viral transactivator protein Tax plays a critical role in HTLV-I-induced transformation and apoptosis resistance. N-(4-hydroxyphenyl)retinamide (HPR) is a synthetic retinoid that inhibits growth and induces apoptosis in many human cell lines including those that are resistant to natural retinoids. Using ATL mouse models, we aim at evaluating the efficacy of a new targeted therapy mediated by HPR for the treatment of HTLV-I associated ATL. We reproduced the SCID ATL Tax transgenic mouse model described by Hasegawa et al. (Nature Medicine 2006). Then, we determined the toxicity of HPR on SCID mice as well as the effect of HPR as a potential chemopreventive and/or chemotherapeutic agent on SCID ATL mouse models. Finally, we reproduced an ATL animal model using NOD/SCID and NOG/SCID mice inoculated by HTLV-I infected cell lines, thus expressing the whole virus not just the Tax oncogene as in the SCID ATL Tax transgenic model. We were able to successfully reproduce the SCID ATL Tax transgenic mouse model with the gross pathological and histological features that characterize the ATL disease. Toxicity studies showed that HPR in the concentrations used has no toxic effect on normal SCID mice. The treatment with HPR resulted in the lengthening of SCID ATL mice survival from one to three weeks compared to untreated mice. However, HPR does not seem to have any chemopreventive effect on SCID ATL mice survival. NOD/SCID and NOG/SCID ATL models, expressing the whole HTLV-I virus, were successfully reproduced with the gross pathological and histological characteristics of ATL. ATL animal models are crucial to develop prior to any drug clinical trials. This research may support a potential therapeutic role for HPR in ATL and T-cell lymphomas, especially in these leukemic cells that are resistant to all-trans retinoic acid and other therapeutic agents. Availability Barcode Location Shelf Shelfmark Status Category   Jafet Archives and Special Collections Thesis T:5301:c.1 ASC-Binding Building Use

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