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Permanent link (DOI): https://doi.org/10.7939/R3NM4G

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Regulation of collagen type I production by ionizing radiation and transforming growth factor-β1 in primary human skin fibroblasts derived from early stage breast cancer patients in relation to acute radiation-induced toxicity Open Access

Descriptions

Other title
Subject/Keyword
Vascular endothelial growth factor
Transforming growth factor
Breast Cancer
Matrix metalloproteinase
Radiation
Radiation Therapy
Tissue inhibitor of metalloproteinase
Fibroblast
Collagen type I
Cathepsin K
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Wang, Ying Wang
Supervisor and department
Abdulkarim, Bassam (Oncology)
Examining committee member and department
Ghahary, Aziz (Surgery, University of British Columbia)
Godbout, Roseline (Oncology)
Murray, David (Oncology)
Sabri, Siham (Oncology)
Pasdar, Manijeh (Cell Biology)
Department
Department of Oncology
Specialization

Date accepted
2011-08-30T16:14:23Z
Graduation date
2011-11
Degree
Master of Science
Degree level
Master's
Abstract
Regulation of collagen type I (CI) in fibroblasts is critical for the onset and development of skin toxicities induced by radiation therapy (RT). Transforming growth factor beta-1 (TGF-β1) and vascular endothelial growth factor (VEGF) promote CI synthesis, while its degradation is modulated by matrix metalloproteinase-1 (MMP-1), tissue inhibitor of MMP-1 (TIMP-1) and cathepsin K. We investigated the effects of ionizing radiation (IR) and/or TGF-β1 on CI levels and factors involved in CI regulation in primary skin fibroblasts derived from 40 early stage breast cancer patients. We determined statistical relationships between CI levels and acute skin toxicity events in the same patients after RT. We found that inhibition of collagenolytic activity by TIMP-1 affects CI levels in response to TGF-β1 and/or IR treatment of primary human fibroblasts, and increased patient-derived fibroblast CI levels in response to ex-vivo IR could be predictive of acute RT-induced toxicities in patients.
Language
English
DOI
doi:10.7939/R3NM4G
Rights
License granted by Ying Wayne Wang (ywwang@ualberta.ca) on 2011-08-28T16:21:54Z (GMT): Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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