Research group - Mikael Björnstedt
The main focus of the research group involves translational and clinical studies on the use of redox-active selenium compounds as cancer chemotherapeutics.
Cancer is a devastating disease with more than 1.25 million deaths yearly within the EU. The prevalence is increasing over the years. Despite improvements in the treatment of some cancers, there are no or very limited options to treat a large group of patients, particularly those diagnosed with cancer of the visceral organs. The latter group are characterized by advanced stage of disease upon diagnosis and inherent resistance to conventional cancer chemotherapy.
The research group focuses on targeting the redox axis of cancer cells survival - a relatively new cancer chemotherapeutic strategy. Certain redox-active selenium compounds have unique properties to target the redox imbalance and other survival pathways in cancer cells, hence “multi-target” in nature. These compounds can also efficiently kill tumour cells that are highly resistant to conventional cancer chemotherapy.
The group has an excellent national and international network with complementing expertise in order to perform preclinical studies and clinical trials. We have established advanced organotypic slice culture models, applicable to a large group of tumours, for studying the pharmacokinetics and pharmacodynamics of candidate chemotherapeutics with possible applications in personalized medicine.
The main projects:
- Clinical trials exploring the pharmacokinetics, pharmacodynamics, safety and efficacy of selenium compounds in the treatment of cancer.
- Studying the modes and mechanisms of anti-tumour actions of natural and synthetic selenium compounds and development of new strategies to increase the efficacy these selenium compounds in pre-clinical studies.
- Mechanistic studies focusing on drug actions and how selenium compounds specifically kill tumour cells.
Research group leader Mikael Björnstedt
Cell and tissue culture
Biochemical methods (enzymology, functional assessment of transcription factors, assay development)
Transcriptomics and proteomics
Histology and Immunohistochemistry
Cancerfonden, Cancer- och Allergifonden, Jochnick Foundation, Radiumhemmets Forskningsfonder, The County Council of Stockholm
Quantification of low molecular weight selenium metabolites in human plasma after treatment with selenite in pharmacological doses by LC-ICP-MS.
Flouda K, Dersch JM, Gabel-Jensen C, Stürup S, Misra S, Björnstedt M, et al
Anal Bioanal Chem 2016 Mar;408(9):2293-301
Relatively high mortality risk in elderly Swedish subjects with low selenium status.
Alehagen U, Johansson P, Björnstedt M, Rosén A, Post C, Aaseth J
Eur J Clin Nutr 2016 Jan;70(1):91-6
Selenite in Cancer Therapy, In Diversity of Selenium Functions in Health and Disease
Sougat, M., Marita, W., Ola, B., and Mikael, B. (2015)
pp 109-136, CRC Press.
Redox-active selenium compounds--from toxicity and cell death to cancer treatment.
Misra S, Boylan M, Selvam A, Spallholz JE, Björnstedt M
Nutrients 2015 May;7(5):3536-56
Pharmacokinetics and Toxicity of Sodium Selenite in the Treatment of Patients with Carcinoma in a Phase I Clinical Trial: The SECAR Study.
Brodin O, Eksborg S, Wallenberg M, Asker-Hagelberg C, Larsen EH, Mohlkert D, et al
Nutrients 2015 Jun;7(6):4978-94
Selenium cytotoxicity in cancer.
Wallenberg M, Misra S, Björnstedt M
Basic Clin. Pharmacol. Toxicol. 2014 May;114(5):377-86
Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.
Alehagen U, Johansson P, Björnstedt M, Rosén A, Dahlström U
Int. J. Cardiol. 2013 Sep;167(5):1860-6
Methylselenol formed by spontaneous methylation of selenide is a superior selenium substrate to the thioredoxin and glutaredoxin systems.
Fernandes AP, Wallenberg M, Gandin V, Misra S, Tisato F, Marzano C, et al
PLoS ONE 2012 ;7(11):e50727
Extracellular thiol-assisted selenium uptake dependent on the x(c)- cystine transporter explains the cancer-specific cytotoxicity of selenite.
Olm E, Fernandes AP, Hebert C, Rundlöf AK, Larsen EH, Danielsson O, et al
Proc. Natl. Acad. Sci. U.S.A. 2009 Jul;106(27):11400-5