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Klinisk institutt 1

Midtveisevaluering- Lea Landolt

Midtveisevaluering for ph.d.-graden ved Universitetet i Bergen for kandidat Lea Landolt

Hovedinnhold

Lea Landolt er tilknyttet Klinisk institutt 1. Veiledere er Hans Peter Marti, James Bradley Lorens og Bjørn Egil Vikse

PhD project

"Epithelial-to-mesenchymal transition in renal cell cancer and renal fibrosis"

By Lea Landolt


Abstract

Epithelial-to-mesenchymal transition (EMT) is an established driver of both malignancy as well as tumor progression and partial EMT also of solid organ fibrosis.

After having established the method to sequence mRNA from archival formalin-fixed and paraffin embedded (FFPE) kidney biopsies, we have characterized markers associated with EMT in both clear cell renal cancer tissues and in kidney fibrosis tissues. We then have analysed mRNA sequencing data of renal cancer tissues in the light of EMT and seen that augmented EMT is a prominent feature and correlates with worse patient survival.

To study EMT in kidney fibrosis, we have blocked Axl receptor tyrosine kinase by BGB324 in a murine kidney fibrosis model (unilateral ureteral obstruction, UUO) over two weeks. First results demonstrated a reduced EMT and fibrosis development in the BGB324 treated group of mice as compared to vehicle and other control groups. In conclusion, inhibition of Axl and EMT represent promising targets to treat clear cell kidney cancer and kidney fibrosis.