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postgraduate thesis: The effects of a methionine aminopepitdase inhibitor fumagillin on leukemia cell growth in-vitro

TitleThe effects of a methionine aminopepitdase inhibitor fumagillin on leukemia cell growth in-vitro
Authors
Issue Date2013
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Mak, W. J. C. [麥允齡]. (2013). The effects of a methionine aminopepitdase inhibitor fumagillin on leukemia cell growth in-vitro. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5091367
AbstractAcute Myeloid Leukaemia (AML) is a disease normally found in elderly patients, with the median age of presentation at about 68 years. At this age, many of the patients are frail and unlikely to respond well to intensive chemotherapy treatments. Conventional chemotherapy eradicates the proliferating leukaemic progenitors while leaving the quiescent leukaemic stem cells undisturbed. These quiescent LSCs are able to then bring about leukaemic relapse. Fumagillin is a natural metabolite from Asperigillus fumigatus that is generally used as an anti-microbial agent but it is also known to bind to intracellular MetAP-II and inhibit endothelial cell growth. Many cancers are found to have an over expression of MetAP-II. In the past, MetAP-II inhibitors have been tested and shown success in angiogenesis inhibition and tumor reduction. The aim of this study is to observe whether methionine aminopeptidase-2 inhibitors can be used in the treatment of acute myeloid leukemia. The investigation included a dose response comparison of various AML cell lines to fumagillin treatment, cell proliferation assay, a colony forming unit assay, and cell cycle analysis of KG-1 cells following three days of fumagillin treatment. I have determined that fumagillin does indeed decrease the cellular proliferation of KG-1 in vivo and at 10μM, prevents colony formation in methylcellulose plating. There is an increase in cells found in the sub-G1 phase with fumagillin treatment, as analyzed by flow cytometry. It is interpolated that fumagillin treatment increases AML cell apoptosis, in addition to hindering its ability to grow in culture.
DegreeMaster of Medical Sciences
SubjectAcute myeloid leukemia - Treatment
Dept/ProgramMedicine
Persistent Identifierhttp://hdl.handle.net/10722/193534

 

DC FieldValueLanguage
dc.contributor.authorMak, Wan-ling, Justina Crystaline-
dc.contributor.author麥允齡-
dc.date.accessioned2014-01-13T23:10:35Z-
dc.date.available2014-01-13T23:10:35Z-
dc.date.issued2013-
dc.identifier.citationMak, W. J. C. [麥允齡]. (2013). The effects of a methionine aminopepitdase inhibitor fumagillin on leukemia cell growth in-vitro. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5091367-
dc.identifier.urihttp://hdl.handle.net/10722/193534-
dc.description.abstractAcute Myeloid Leukaemia (AML) is a disease normally found in elderly patients, with the median age of presentation at about 68 years. At this age, many of the patients are frail and unlikely to respond well to intensive chemotherapy treatments. Conventional chemotherapy eradicates the proliferating leukaemic progenitors while leaving the quiescent leukaemic stem cells undisturbed. These quiescent LSCs are able to then bring about leukaemic relapse. Fumagillin is a natural metabolite from Asperigillus fumigatus that is generally used as an anti-microbial agent but it is also known to bind to intracellular MetAP-II and inhibit endothelial cell growth. Many cancers are found to have an over expression of MetAP-II. In the past, MetAP-II inhibitors have been tested and shown success in angiogenesis inhibition and tumor reduction. The aim of this study is to observe whether methionine aminopeptidase-2 inhibitors can be used in the treatment of acute myeloid leukemia. The investigation included a dose response comparison of various AML cell lines to fumagillin treatment, cell proliferation assay, a colony forming unit assay, and cell cycle analysis of KG-1 cells following three days of fumagillin treatment. I have determined that fumagillin does indeed decrease the cellular proliferation of KG-1 in vivo and at 10μM, prevents colony formation in methylcellulose plating. There is an increase in cells found in the sub-G1 phase with fumagillin treatment, as analyzed by flow cytometry. It is interpolated that fumagillin treatment increases AML cell apoptosis, in addition to hindering its ability to grow in culture.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.lcshAcute myeloid leukemia - Treatment-
dc.titleThe effects of a methionine aminopepitdase inhibitor fumagillin on leukemia cell growth in-vitro-
dc.typePG_Thesis-
dc.identifier.hkulb5091367-
dc.description.thesisnameMaster of Medical Sciences-
dc.description.thesislevelMaster-
dc.description.thesisdisciplineMedicine-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5091367-
dc.date.hkucongregation2013-

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