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Microarray analysis of gene expression profiles of cardiac myo-cytes and fibroblasts after mechanical stress, ionising or ultravio-let radiation
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
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2005 In: BMC Genomics, Vol. 6, no 1, 6- p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2005. Vol. 6, no 1, 6- p.
URN: urn:nbn:se:uu:diva-94916OAI: oai:DiVA.org:uu-94916DiVA: diva2:168936
Available from: 2006-09-29 Created: 2006-09-29Bibliographically approved
In thesis
1. Systematic Modular Approaches to Reveal DNA Damage Responses in Mammalian Cells
Open this publication in new window or tab >>Systematic Modular Approaches to Reveal DNA Damage Responses in Mammalian Cells
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cancer therapy operates by inflicting damage in malignant cells. The most lethal target is the genomic DNA. As a single double strand DNA break has the potential to kill the cell, mechanisms have evolved to detect and block propagation of the damage. Genes and their products function in a highly connected network-structure with ample cross-talk between different pathways. This interplay can be studied by genome-wide experiments, such as expression profiling. The aim of this thesis is to study the cellular effects of DNA damaging agents.

A theoretical framework is explored to improve understanding of expression profiling results. To analyse large datasets, computational methods were developed to model the data. Further, the response to DNA damage was investigated in different cellular systems. As late radiation toxicity is a severe limitation of radiotherapy of cancer patients, patients were enrolled in a study to search for a molecular signature to identify high-risk patients. Ex vivo irradiation of lymphocytes revealed a signature of functionally related gene sets that were capable to separate patients with regard to toxicity status.

The gene set analysis was also applied to a dataset where mouse embryonic stem cells had been exposed to various doses of cisplatin. At several time-points after administration of the drug, expression profiles were determined. In addition to the expected increase of genes related to apoptosis and cell cycle progression, damaged cells also seemed to have embarked upon a p53-dependent differentiation programme. Finally, in a study of cardiac rodent cells, the genotoxic treatment with irradiation was compared to the mechanical stress induced in heart tissue.

In conclusion, this thesis presents evidence for the advantage of using functionally related sets of genes in analysis and interpretation of genome-wide experiments. This strategy may improve clinical understanding of the effects of DNA damaging agents used for cancer therapeutics.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 70 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 176
Molecular biology, gene expression profiling, DNA damage, network, cancer, ionizing radiation, cisplatin, Molekylärbiologi
urn:nbn:se:uu:diva-7163 (URN)91-554-6667-2 (ISBN)
Public defence
2006-10-21, Auditorium Minus, Gustavianum, Akademigatan 3, Uppsala, 09:15
Available from: 2006-09-29 Created: 2006-09-29Bibliographically approved

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