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...
محفوظ في:
| المؤلف الرئيسي: | |
|---|---|
| التنسيق: | masterThesis |
| منشور في: |
2016
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| الموضوعات: | |
| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/3598 https://doi.org/10.26756/th.2015.53 |
| الوسوم: |
إضافة وسم
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| _version_ | 1864513461657010176 |
|---|---|
| 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. |
| eu_rights_str_mv | openAccess |
| format | masterThesis |
| id | LAURepo_fecd795932eec9862987f463e4809d32 |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/3598 |
| publishDate | 2016 |
| publisher.none.fl_str_mv | Lebanese American University |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| 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 |