Disputas – cand.med Lotte Olsen

Avhandlingen er tilgjengelig her!
The doctoral thesis is available here!

På grunn av koronautbruddet er auditoriet stengt for publikum. Disputasen vil i stedet bli strømmet. Opptak av disputasen vil være tilgjengelig i en uke.
The auditorium will be closed to the public because of the corona outbreak. The defense will be streamed. A recording of the disputation will be available for one week.

Prøveforelesning starter kl. 10.15
Tittel:  "Chemoresistance of cancer stem cells: mechanisms and therapeutic treatments"
Prøveforelesningen strømmes her!
The trail lecture will be streamed here!

Disputasen starter kl. 12.15
Disputasen strømmes her!
The defense will be streamed here!

De som ønsker å opponere ex auditorio kan sende e-post til leder av disputasen (ruth.paulssen@uit.no).
Opponents ex auditorio should sign up to leader of defense by e-mail (ruth.paulssen@uit.no).

Populærvitenskapelig sammendrag av avhandlingen/Summary:
The childhood cancer, neuroblastoma, is the most common cancer in infants. The last decades, therapy improvement has led to an increase in overall survival for the children afflicted by this cancer. Unfortunately, among the ones that have the most harmful stage of this disease only about 50% survive. We still have to find treatments that are more effective, in order to battle this cancer; both to save lives and to prevent short- and long-term adverse effects that come from intensive treatment. This thesis will show how specific alterations done to neuroblastoma cells can reduce the cancer cells’ growth and eventually kill them.

First, we studied microRNAs, small RNA molecules that can regulate other RNAs. We demonstrated that a microRNA called miR-323a-3p reduced the number of healthy, living cells when it stopped cells from dividing (cell cycle arrest) and caused programmed cell death (apoptosis). We also showed that a second microRNA, called miR-193b-3p, made neuroblastoma cells more susceptible to be killed by a drug called ABT-737. When we combined treatment with miR-193b-3p and ABT-737 in a specific type of neuroblastoma cells, it killed the cells more successfully than treatment with either alone.

Secondly, we tested two drugs, called CX-5461 and quarfloxin, and demonstrated that they could effectively kill neuroblastoma cells with several copies of the MYCN gene (MYCN amplification). This abnormality is often found in neuroblastoma, and gives the patient a worse prognosis. Both CX-5461 and quarfloxin reduced the levels of the MYCN protein, damaged the DNA within the cancer cells and led cells into programmed cell death. We also showed that the drugs reduced growth of cancer tumors in mice.

Collectively, this thesis presents possible new ways of treating neuroblastoma cancer in children, either by using microRNAs alone or in combination with other drugs, or by using the drugs CX-5461 or quarfloxin.

Veiledere/ Supervisors:
Hovedveileder/Main supervisor:
Professor II Christer Einvik, Institutt for klinisk medisin, Det helsevitenskapelige fakultet, UiT Norges arktiske universitetet
Biveileder/supervisor:
Professor Trond Flægstad, Institutt for klinisk medisin, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet

Bedømmelseskomité/Defensecomitee:
Professor Emeritus Raymond Stallings, Irland – 1. opponent
Professor Louis Chesler, England – 2. opponent
Førsteamanuensis Eva Sjøttem, Institutt for medisinsk biologi, UiT Norges arktiske universitet – leder av komitè

Disputasleder/ Leader of defense:
Professor Ruth Paulssen, Institutt for klinisk medisin, Det helsevitenskapelige fakultet, UiT Norges arktiske universitet