Potency and selectivity of a urokinase activated recombinant anthrax toxin to acute myeloid leukemia (AML) cells. (c2015)

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dc.contributor.author Darwich, Manal El.
dc.date.accessioned 2016-04-18T12:00:43Z
dc.date.available 2016-04-18T12:00:43Z
dc.date.copyright 9/14/2015 en_US
dc.date.issued 2016-04-18
dc.identifier.uri http://hdl.handle.net/10725/3598
dc.description.abstract Acute myeloid leukemia (AML) is a disorder characterized by uncontrolled mitogenetic activation and proliferation of hematopoietic precursor cells. Up to 30 % of adult patients with AML do not achieve complete remission when treated using chemotherapy. In addition, severe side effects usually limit the efficacy of available therapeutic approaches. As a result, novel tumor-selective therapeutics capable of targeting and eliminating AML blasts while sparing normal cells are urgently needed. In this study, we determine the potency and selectivity of an engineered, urokinase-activated recombinant anthrax fusion toxin (PrAgU2/FP59) on a panel of 9 AML cell lines and on normal progenitor bone marrow blasts. All 9 AML cell lines tested were sensitive to PrAgU2/FP59 while normal progenitor, bone marrow blasts were not, demonstrating the potency and selectivity of this tumor-targeted approach. Cytotoxicity of PrAgU2/FP59 appeared to be non-apoptotic and is dependent on the expression of an active cell surface urokinase plasminogen activator system (uPA/uPAR) system. Targeting the urokinase system, a protease overexpressed on AML cells, appears to be a promising approach for the development of AML-specific therapeutics. en_US
dc.language.iso en en_US
dc.subject Acute Myeloid Leukemia en_US
dc.subject Lebanese American University -- Dissertations en_US
dc.subject Dissertations, Academic en_US
dc.title Potency and selectivity of a urokinase activated recombinant anthrax toxin to acute myeloid leukemia (AML) cells. (c2015) en_US
dc.type Thesis en_US
dc.term.submitted Summer II en_US
dc.author.degree MS in Molecular Biology en_US
dc.author.school SAS en_US
dc.author.idnumber 200500528 en_US
dc.author.commembers El Sibai, Mirvat
dc.author.commembers Rizk, Sandra
dc.author.woa OA en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.description.physdesc 1 hard copy: xiii, 52 leaves; ill. (some col.); 30 cm. available at RNL. en_US
dc.author.advisor Abi Habib, Ralph
dc.keywords AML en_US
dc.keywords PrAgU2/FP59 en_US
dc.keywords Dual selectivity en_US
dc.keywords Apoptosis en_US
dc.keywords Anthrax toxin en_US
dc.description.bibliographiccitations Includes bibliographical references (leaves 47-52). en_US
dc.identifier.doi https://doi.org/10.26756/th.2015.53 en_US
dc.publisher.institution Lebanese American University en_US

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