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UBC Theses and Dissertations
Marker analysis for the detection of metastatic breast cancer Hornby, Ann Elizabeth
Abstract
The main objective of this thesis was to examine the possibility of transferring the current immunologic methods of detecting metastatic breast cancer to a more specific, more sensitive, and less subjective nucleic acid-based technology. The rational was two-fold: (1) early detection of metastatic disease may be useful in determining treatment protocols for breast cancer patients; and (2) the ability to detect small numbers of tumor cells in blood or bone marrow may help in monitoring the effectiveness of treatment. Chronic myelogenous leukemia (CML) was successfully used as a model system for the development of PCR for the detection of rare mRNAs expressed in blood or bone marrow. The level of sensitivity achieved was 1/10⁶ cells. Once the PCR technology was established CML bone marrow was then used to study the effect of Benzoporphyrin derivative mono acid-A (BPD-MA) on the enzymatic activity of Taq polymerase. BPD-MA is a photoactive drug being developed by Quadra Logic Technologies Ltd., with potential use as a bone marrow purging agent for patients with metastatic breast cancer undergoing autologous bone marrow transplantation. BPD-MA did not interfere with the ability of Taq polymerase to detect rare mRNA expression in bone marrow, therefore PCR technology could be used to monitor the effectiveness of treatment after bone marrow purging and autologous bone marrow transplantation. Using RNA PCR technology the expression of three genes currently used for the detection of metastatic breast cancer by immunological methods was studied. Polymorphic epithelial mucin gene expression was analyzed in breast cancer cell lines, and normal blood and bone marrow. No expression was detected in bone marrow; however, expression was detected in peripheral blood. This may account for reports of cross-reactivity of mAbs directed against epithelial mucins detected in peripheral blood. Keratin 18 and 8 expression was analyzed in a similar manner. Keratin 18 expression was detected in both blood and bone marrow, whereas, keratin 8 expression was detected in blood only. The expression of both keratins appeared to be the result of transcriptionally active processed pseudogenes. Keratin 8 pseudogene expression also appeared to be differentially regulated in breast versus peripheral blood cells.
Item Metadata
Title |
Marker analysis for the detection of metastatic breast cancer
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
1993
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Description |
The main objective of this thesis was to examine the possibility of
transferring the current immunologic methods of detecting metastatic
breast cancer to a more specific, more sensitive, and less subjective
nucleic acid-based technology. The rational was two-fold: (1) early
detection of metastatic disease may be useful in determining treatment
protocols for breast cancer patients; and (2) the ability to detect
small numbers of tumor cells in blood or bone marrow may help in
monitoring the effectiveness of treatment. Chronic myelogenous leukemia
(CML) was successfully used as a model system for the development of PCR
for the detection of rare mRNAs expressed in blood or bone marrow. The
level of sensitivity achieved was 1/10⁶ cells. Once the PCR technology
was established CML bone marrow was then used to study the effect of
Benzoporphyrin derivative mono acid-A (BPD-MA) on the enzymatic activity
of Taq polymerase. BPD-MA is a photoactive drug being developed by
Quadra Logic Technologies Ltd., with potential use as a bone marrow
purging agent for patients with metastatic breast cancer undergoing
autologous bone marrow transplantation. BPD-MA did not interfere with
the ability of Taq polymerase to detect rare mRNA expression in bone
marrow, therefore PCR technology could be used to monitor the
effectiveness of treatment after bone marrow purging and autologous bone
marrow transplantation. Using RNA PCR technology the expression of
three genes currently used for the detection of metastatic breast cancer
by immunological methods was studied. Polymorphic epithelial mucin gene
expression was analyzed in breast cancer cell lines, and normal blood
and bone marrow. No expression was detected in bone marrow; however,
expression was detected in peripheral blood. This may account for
reports of cross-reactivity of mAbs directed against epithelial mucins
detected in peripheral blood. Keratin 18 and 8 expression was analyzed
in a similar manner. Keratin 18 expression was detected in both blood
and bone marrow, whereas, keratin 8 expression was detected in blood
only. The expression of both keratins appeared to be the result of
transcriptionally active processed pseudogenes. Keratin 8 pseudogene
expression also appeared to be differentially regulated in breast versus
peripheral blood cells.
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Extent |
9406782 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-04-08
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Provider |
Vancouver : University of British Columbia Library
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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.
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DOI |
10.14288/1.0088207
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
1994-05
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Item Media
Item Citations and Data
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.