Thesis defence in the University of Oulu

Doctoral Candidate

Doctor of Medicine Esa Kari

Faculty and research unit

University of Oulu Graduate School, Faculty of Medicine, Medical Research Center Oulu

Field of study

Oncology

Date and time of the thesis defence

20.3.2020 12:00

Place of the thesis defence

Remote access: https://us04web.zoom.us/j/8576752044

Topic of the dissertation

Clinical Impact of Antioxidant Enzymes Prx6 and Trx and their Regulators Nrf1 and Nrf2 in Diffuse Large B-Cell Lymphoma

Opponent

Professor Anna-Liisa Levonen, University of Eastern Finland

Custos

Professor Taina Turpeenniemi-Hujanen, University of Oulu

Antioxidant enzymes and transcription factors have prognostic relevance in lymphoma

Oxygen radicals and antioxidant enzymes are connected with aggressive behavior and dismal prognosis in many cancers. In this project, we explored oxidative stress marker 8-OHdG, antioxidant enzymes Prx6 ja Trx-1 and their regulators Nrf1, Nrf2, Keap-1 ja Bach1 in diffuse large B-cell lymphoma (DLBCL), the most common lymphoma.

DLBCL is an aggressive malignancy with significantly improved prognosis since the introduction of rituximab in the late 90s. 30 – 40% of patients succumb to their disease and clinicians are unable to recognize these patients for intensive therapies. Based on clinical presentation, risk is evaluated with IPI score that correlates well with overall survival. However, cancers seem to differ with metabolism and oxygen consumption which is reflected as improved free radical defensive capabilities. These diseases would likely require different treatment modalities.

Main finding of this thesis was that antioxidant transcription factors are able to discern patients with poor prognosis among high IPI patients. Antioxidant enzymes predict risk for treatment related neutropenic infections, treatment response and overall survival.

Project included over two hundred patients whose cancer tissue samples and blood serum samples were examined. Results were also verified in cell culture model. Patients were from Oulu University Hospital, Kuopio University Hospital, North Karelia Central Hospital, and other central hospitals of Northern Finland.

According to the data of this thesis, antioxidant enzymes and transcription factors could be potentially used to evaluate prognosis, need for colony stimulating factors, and treatment selection. These results should be first inspected in larger prospective patient material.

Dissertation

Last updated: 20.3.2020