Benzoporphyrin derivative and the photodynamic extracorporeal treatment of leukemia
department or school: Science, Faculty of
department or school: Microbiology and Immunology, Department of
data provider: DSpace
degree campus: UBCV
creator: Jamieson, Catriona Helen Macleod
issued: 2008-12-16T23:27:01Z
issued: 1992
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: The main question that was addressed in this thesis was whether benzoporphyrin derivative (BPD), a potent photosensitizer, could be used to photodynamically purge residual leukemic cells from bone marrow prior to autologous bone marrow transplantation (ABMT). The ultimate aim was to design a new purging regimen that would selectively eliminate leukemic stem cells while sparing normal stem cells and thereby, provide for better engraftment and a greater log reduction in leukemic cells resulting in prolonged disease free survival or cure. Five systems were used to test this hypothesis. 1) Fluorescence activated cell sorting (FACS) analysis was used to analyze and sort normal and leukemic cells incubated with BPD, which emitted a characteristic red fluorescent signal (Chapter 2). These studies showed that BPD-uptake by leulcemic cells was significantly greater than by normal cells. Differences in BPD fluorescence between normal and leukemic cells facilitated sorting of leukemic from normal cells via FACS thus, providing a novel diagnostic method for assessing leukemic cell burden within bone marrow and possibly a new adjunct to purging regimens based on the use of small volumes of CD34+ cells that could be further purged of leukemic cells via FACS based on BPD fluorescence differences between normal and leukemic cells. 2) Clonogenic and hemopoietic progenitor cell (HPC) assays were used to assess normal or leukemic peripheral blood (PBL) or bone marrow progenitor cell survival subsequent to treatment with BPD and light (Chapters 3 and 4). Clonogenic assays revealed that approximately four logs of leukemic cells derived from the leukemic cell lines EM-2 and K562 could be eliminated at concentrations that eliminated less than one log of normal peripheral blood (PBL) progenitors. Similarly, chronic myelogenous leukemic (CML) PBL progenitors were markedly inhibited by treatment with 10 ng BPD/ml and light while, more than 70% of normal PBL progenitors survived treatment wit…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/2993
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note: BENZOPORPHYRIN DERiVATIVE AND THE PHOTODYNAMICEXTRACORPOREAL TREATMENT OF LEUKEMIAbyCATRIONA HELEN MACLEOD JAMIESONB. Sc., The University of British Columbia, 1987A THESIS SUBMITTED IN PARTIAL FULFILLMENT OFTHE REQUIREMENTS FOR THE DEGREE OFDOCTOR OF PHILOSOPHYinTHE FACULTY OF GRADUATE STUDIESDEPARTMENT OF MICROBIOLOGYWe accept this thesis as conformingto the required standardTHE UNIVERSITY OF BRITISH COLUMBIAAUGUST, 1992© Catriona Helen Macleod Jamieson, 1992Signature(s) removed to protect privacyIn presenting this thesis in partial fulfilment of the requirements for an advanceddegree at the University of British Columbia, I agree that the Library shall make itfreely available for reference and study. I further agree that permission for extensivecopying of this thesis for scholarly purposes may be granted by the head of mydepartment or by his or her representatives. It is understood that copying orpublication of this thesis for financial gain shall not be allowed without my writtenpermission.Department of /L’( ìThe University of British ColumbiaVancouver, CanadaDate Oc4-f,c.v /LL1(Signature)DE-6 (2/88)Signature(s) removed to protect privacyABSTRACTThe main question that was addressed in this thesis was whether benzoporphyrin derivative(BPD), a potent photosensitizer, could be used to photodynamically purge residualleukemic cells from bone marrow prior to autologous bone marrow transplantation(ABMT). The ultimate aim was to design a new purging regimen that would selectivelyeliminate leukemic stem cells while sparing normal stem cells and thereby, provide forbetter engraftment and a greater log reduction in leukemic cells resulting in prolongeddisease free survival or cure. Five systems were used to test this hypothesis. 1)Fluorescence activated cell sorting (FACS) analysis was used to analyze and sort normaland leukemic cells incubated with BPD, which emitted a characteristic red fluorescentsignal (Chapter 2). These studies showed that BPD-uptake by leulcemic cells…
has type: Thesis/Dissertation
date issued: 1992-11
is shown at: 10.14288/1.0086572
language: eng
degree discipline: Microbiology and Immunology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/2993