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NTNU Open
Master thesis . 2012
Data sources: NTNU Open
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Differentially Regulated pathways of Potential Importance for Treatment Response and Cardiac Toxicity after Administration of Doxorubicine to BC Patients

Authors: Olsen, Tone;

Differentially Regulated pathways of Potential Importance for Treatment Response and Cardiac Toxicity after Administration of Doxorubicine to BC Patients

Abstract

Doxorubicin is a topoisomerase-targeting anthracycline that is one of the most effective anticancer drugs currently known. However, its clinical use is restricted by cardiotoxicity and the development of drug resistance. The main goal of this thesis has been to increase the knowledge of doxorubicin mechanism in addition to evaluate if predictive biomarkers for doxorubicin response could be identified. A total of 128 tumor samples collected from breast cancer patients before and after neoadjuvant treatment with doxorubicin were studied. mRNA expression level in tumor tissue was assessed using whole-genome mRNA microarray analysis (Agilent Human GE 4x44K microarray).More than 5000 genes were found to be up- and down regulated following doxorubicin treatment. The molecular and cellular functions as well as canonical pathways found to be enriched in the list of genes up regulated after doxorubicin exposure were involved in among other cardiovascular system development and function, cellular movement and immune responses. p53 was found to be the transcription factor regulating the highest number of target molecules within the list of up regulated genes. RNA processing, splicing and translation were shown to be overrepresented in the list of down regulated genes. The association between doxorubicin response and changes in gene expression revealed several genes such as CTGF, ITGB4 and IGF1 to be up regulated in the samples collected from patients characterized with a partial response to doxorubicin compared to those with minimal change and/or stable disease following treatment. In addition, the gene expression profiles between samples having wild type compared to mutated TP53 were studied, and a lower induction of expression were found for several genes such as FGF9 and COL11A2 in the samples having a mutated p53. This study showed that the gene expression profile in breast cancer tumors is altered as a response to doxorubicin exposure. Identifying genes significantly altered after therapy and associate their change with response to treatment may help identify the subgroup of patients benefitting from doxorubicin treatment. Patients with little or no effect of treatment could receive alternative therapy and be spared unnecessary treatment and risk of side effects.

Country
Norway
Keywords

Molekylærbiologi, MBIOT5 Bioteknologi (5 årig), ntnudaim:6939

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
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Related to Research communities
Cancer Research