uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Identification of molecular mechanisms for cellular drug resistance by combining drug activity and gene expression profiles.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
Show others and affiliations
2005 In: British Journal of Cancer, Vol. 93, no 4, 483-92 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2005. Vol. 93, no 4, 483-92 p.
URN: urn:nbn:se:uu:diva-94696OAI: oai:DiVA.org:uu-94696DiVA: diva2:168650
Available from: 2006-09-01 Created: 2006-09-01Bibliographically approved
In thesis
1. Molecular Screening for Target Discovery in Cancer
Open this publication in new window or tab >>Molecular Screening for Target Discovery in Cancer
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cancer is one of the major causes of death in the western world. Resistance to anti-cancer drugs and diagnostic difficulties are major obstacles to successful treatment. This thesis describes studies based on microarray expression analysis and high-throughput compound screening for identification of resistance mechanisms, drug targets and diagnostic markers.

In paper I-IV, we applied global expression analysis and measurements of drug response in a human tumor cell line panel to identify drug targets and resistance mechanisms. In paper I, we identified gene transcript levels that correlate with drug resistance and sensitivity. Both well known and new potential markers and mechanisms were identified. In paper II, we showed that STAT1 activity is associated with cross-resistance to both doxorubicin and radiation in vitro and that fludarabine can counteract STAT1 activity and reduce resistance. In Paper III-IV, cell lines were exposed to a compound library consisting of more than thousand different substances in a high-throughput screening effort. These studies revealed that cell line models of squamous cell carcinoma (Paper III) and drug resistant myeloma (Paper IV) are sensitive to phosphodiesterase inhibitors and glucocorticoids respectively. The target molecules for these drugs were over-expressed at the mRNA level and constitute likely explanations for the observed drug potency. In paper V, we identified mRNA markers for the distinction between two types of thyroid tumors, thyroid follicular adenomas and thyroid follicular carcinomas, by means of microarray expression analysis. Our results indicated that distinction between the two tumor types is possible with a small number of markers.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 42 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 162
Genetics, Cancer, Drug resistance, Microarray, High-throughput screening, Genetik
urn:nbn:se:uu:diva-7086 (URN)91-554-6620-6 (ISBN)
Public defence
2006-09-21, Rudbecksalen, C11, Rudbecklaboratoriet, Uppsala, 13:15 (English)
Available from: 2006-09-01 Created: 2006-09-01 Last updated: 2009-05-12Bibliographically approved

Open Access in DiVA

No full text

By organisation
Department of Genetics and Pathology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 163 hits
ReferencesLink to record
Permanent link

Direct link