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

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...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Darwich, Manal El. (author)
التنسيق: masterThesis
منشور في: 2016
الموضوعات:
الوصول للمادة أونلاين:http://hdl.handle.net/10725/3598
https://doi.org/10.26756/th.2015.53
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author Darwich, Manal El.
author_facet Darwich, Manal El.
author_role author
dc.creator.none.fl_str_mv Darwich, Manal El.
dc.date.none.fl_str_mv 2016-04-18T12:00:43Z
2016-04-18T12:00:43Z
2016-04-18
9/14/2015
dc.identifier.none.fl_str_mv http://hdl.handle.net/10725/3598
https://doi.org/10.26756/th.2015.53
dc.language.none.fl_str_mv en
dc.publisher.none.fl_str_mv Lebanese American University
dc.rights.*.fl_str_mv info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Acute Myeloid Leukemia
Lebanese American University -- Dissertations
Dissertations, Academic
dc.title.none.fl_str_mv Potency and selectivity of a urokinase activated recombinant anthrax toxin to acute myeloid leukemia (AML) cells. (c2015)
dc.type.none.fl_str_mv Thesis
info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/masterThesis
description 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.
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network_name_str Lebanese American University repository
oai_identifier_str oai:laur.lau.edu.lb:10725/3598
publishDate 2016
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spelling Potency and selectivity of a urokinase activated recombinant anthrax toxin to acute myeloid leukemia (AML) cells. (c2015)Darwich, Manal El.Acute Myeloid LeukemiaLebanese American University -- DissertationsDissertations, AcademicAcute 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.N/A1 hard copy: xiii, 52 leaves; ill. (some col.); 30 cm. available at RNL.Includes bibliographical references (leaves 47-52).Lebanese American University2016-04-18T12:00:43Z2016-04-18T12:00:43Z9/14/20152016-04-18Thesisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttp://hdl.handle.net/10725/3598https://doi.org/10.26756/th.2015.53eninfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/35982023-02-28T09:00:05Z
spellingShingle Potency and selectivity of a urokinase activated recombinant anthrax toxin to acute myeloid leukemia (AML) cells. (c2015)
Darwich, Manal El.
Acute Myeloid Leukemia
Lebanese American University -- Dissertations
Dissertations, Academic
status_str publishedVersion
title Potency and selectivity of a urokinase activated recombinant anthrax toxin to acute myeloid leukemia (AML) cells. (c2015)
title_full Potency and selectivity of a urokinase activated recombinant anthrax toxin to acute myeloid leukemia (AML) cells. (c2015)
title_fullStr Potency and selectivity of a urokinase activated recombinant anthrax toxin to acute myeloid leukemia (AML) cells. (c2015)
title_full_unstemmed Potency and selectivity of a urokinase activated recombinant anthrax toxin to acute myeloid leukemia (AML) cells. (c2015)
title_short Potency and selectivity of a urokinase activated recombinant anthrax toxin to acute myeloid leukemia (AML) cells. (c2015)
title_sort Potency and selectivity of a urokinase activated recombinant anthrax toxin to acute myeloid leukemia (AML) cells. (c2015)
topic Acute Myeloid Leukemia
Lebanese American University -- Dissertations
Dissertations, Academic
url http://hdl.handle.net/10725/3598
https://doi.org/10.26756/th.2015.53