Item – Theses Canada

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OCLC number
1019461714
Link(s) to full text
LAC copy
Author
Fasih, Aisha.
Title
Indium-111-labeled nimotuzumab modified with nuclear localization sequences (NLS) : an Auger electron-emitting radiotherapeutic agent for EGFR-overexpressing and trastuzumab-resistant breast cancer.
Degree
M. Sc. -- University of Toronto, 2011
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, 2012.
Description
1 online resource
Notes
Includes bibliographical references.
Abstract
<?Pub Inc> Objective: The cytotoxic property of anti-EGFR-1 monoclonal-antibody nimotuzumab modified with nuclear localization sequence and radiolabeled with 111In was evaluated in trastuzumab-resistant breast cancer cells. Methods: 111In-nimotuzumab-NLS was constructed and its immunoreactivity was determined. Cellular and nuclear uptake was evaluated by cell fractionation. Finally, the cytotoxicity of conjugates (111In-nimotuzumab/ 111In-nimotuzumab-NLS) was studied by clonogenic assays. Results: The immunoreactivity of 111In-nimotuzumab-NLS was conserved. 111In-nimotuzumab-NLS exhibited 2-fold higher nuclear translocation as compared to 111In-nimotuzumab in MDA-MB-468 cells. Nuclear importation of 111In-nimotuzumab-NLS in MDA-MB-468 cells was 4-fold and 6-fold higher than moderate and low EGFR expressing cell lines, respectively. Clonogenic survival (CS) for MDA-MB-468 cells showed 111In-nimotuzumab-NLS to be 10-folds and 60-folds more potent than 111In-nimotuzumab and nimotuzumab, respectively. Moderate killing for TrR1 and MDA-MB-231 was observed. 111In-hEGF showed significantly higher cytotoxicity and 2-fold higher [gamma]-H2AX foci integrated density/nuclear-area as compared to 111In-nimotuzumab-NLS. Preserved selectivity of 111In-nimotuzumab-NLS makes it an excellent drug for treating cancers.
ISBN
9780494760505
0494760508