Item – Theses Canada

OCLC number
1032995687
Link(s) to full text
LAC copy
LAC copy
Author
Fasih, Aisha.
Title
111In-labeled Nimotuzumab Modified with Nuclear Localization Sequences (NLS) : an Auger Electron-emitting Radiotherapeutic Agent for EGFR-overexpressing and Trastuzumab-resistant Breast Cancer.
Degree
MAST -- University of Toronto, 2011
Publisher
Toronto : University of Toronto, 2011.
Description
1 online resource
Notes
Includes bibliographical references.
Abstract
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.
Other link(s)
hdl.handle.net
tspace.library.utoronto.ca
Subject
Herceptin resistant breast cancer.
Auger eletron radiotherapy.
Nimotuzumab (mAb of EGFR)
Indium-111.
0572.