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The role of telomerase in human cancer develpment and an evaluation of its potencial as a therapeutic target

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In the TACIT-project telomere and telomerase associated factors are investigated in order to find new parameters of significance for the diagnostic work out of human tumors. One aim is to better understand the regulation of telomerase activity in tumors, since a large number of factors are potentially involved in this regulation which seems to vary from cell type to cell type. Besides clinical tumors (breast cancer, colorectal cancer, renal cell carcinoma, malignant lymphoma, brain tumors) we study cell lines using various approaches to characterize the cells for the expression of established or suggested telomerase regulators. We also try to identify new factors of importance for telomere maintenance, including 2-d protein analysis. Hopefully this project will identify new parameters of diagnostic significance for specific tumor types.
There are indications from studies of various human tumors that the telomere length of tumor cells can carry prognostic information. We have focused on lymphoid malignancies and especially chronic lymphocytic leukemia (CLL) for which new diagnostic and prognostic subgroups have been defined the last years, mainly based on Ig gene mutation analysis. In our studies we have shown that the telomere length constitutes a strong prognostic factor and in fact can identify a previously unrecognised group of patients with a favorable outcome. Similar data regarding prognosis and telomere biology are presently collected from various tumor types. This project is of importance mainly from a diagnostic view and it is expected that specific features of the telomere biology, and especially telomere length, will be a tumor parameter to analyse in future routine diagnostic work. In order to make this possible simple and reliable diagnostic methods are needed, and one aim with this project is the development of such techniques. The results will be available to the scientific community via future publications. Presently, there are no commercial applications of the project.

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