These goals can be reached by increased knowledge of the factors which affect the metabolism of cytostatics, as well as of mechanisms of action and mechanisms underlying side effects. Moreover, there is a need for the introduction of new drugs and treatment strategies which improve the balance between treatment efficacy and side effects. Basic experiments cannot be carried out in human test subjects due to ethical reasons; therefore, we test our hypotheses in cell cultures and animal models before moving on to clinical trials.
Stem cell transplantation (SCT)
Stem cell transplantation (SCT) is a curative treatment for a number of cancers and hematological disorders. Pre-transplant conditioning (cytostatics or irradiation) prepares the patient’s immune system to accept stem cells from a donor. This treatment should also have a direct effect on cancer cells. Pre-transplant conditioning can lead to side effects in the liver, urinary tract, mucous membranes etc. Graft-versus-host disease (GVHD) is one of the most serious complications of SCT, and it causes suffering, deteriorates quality of life and may results in the death of the patient. Cardiovascular disease appears a long time after SCT, as do secondary malignancies. On the other hand, the graft-versus-leukemia effect is crucial in preventing relapse. The mechanisms behind these side effects have not been completely elucidated. Knowledge of the mechanisms constitutes the first step toward new and more effective treatment strategies. We also want to develop new treatment strategies based on dose individualization, i.e. tailoring of dosage to each individual patient in order to achieve the maximum effect with minimal side effects.
Our projects are divided into the following categories:
- We have developed a transplantation model which enables us to study the mechanisms of the side effects (GVHD and arterial damage) and contributing factors in order to improve prophylactic treatment. Moreover, in the last few years we have developed reproducible models of hematological malignancies in order to facilitate understanding of the mechanisms behind the graft-versus-leukemia (GVL) effect.
- We are investigating the effect of genetic variations in individual patients on the metabolism of cytostatics and thereby on the outcome of SCT. The goal of these studies is to develop reliable methods for dose individualization based on the patient’s individual genome.
- We are investigating whether new cytostatics that block cell division and metastasis of cancer cells could prevent relapse after SCT. We are studying a number of cytostatics on a cellular and molecular level.
- We have recently entered into a joint project with the Royal technical high school (KTH) in which we build a number of different carriers (nano particles) which can be loaded with cytostatics. The advantage of these particles is that they can be delivered to a specific part of the body by tailoring particle construction. The goal of this project is to find target-seeking anti-cancer medication, enabling protection of the rest of the body.
Selected publications
Thermostable luciferase from Luciola cruciate for imaging of carbon nanotubes and carbon nanotubes carrying doxorubicin using in vivo imaging system.
El-Sayed R, Eita M, Barrefelt A, Ye F, Jain H, Fares M, et al
Nano Lett. 2013 Apr;13(4):1393-8
Early-phase GVHD gene expression profile in target versus non-target tissues: kidney, a possible target?
Sadeghi B, Al-Chaqmaqchi H, Al-Hashmi S, Brodin D, Hassan Z, Abedi-Valugerdi M, et al
Bone Marrow Transplant. 2013 Feb;48(2):284-93
Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study.
Güngör T, Teira P, Slatter M, Stussi G, Stepensky P, Moshous D, et al
Lancet 2014 Feb;383(9915):436-48
Biodegradable polymeric vesicles containing magnetic nanoparticles, quantum dots and anticancer drugs for drug delivery and imaging.
Ye F, Barrefelt A, Asem H, Abedi-Valugerdi M, El-Serafi I, Saghafian M, et al
Biomaterials 2014 Apr;35(12):3885-94
Cytochrome P450 2J2, a new key enzyme in cyclophosphamide bioactivation and a potential biomarker for hematological malignancies.
El-Serafi I, Fares M, Abedi-Valugerdi M, Afsharian P, Moshfegh A, Terelius Y, et al
Pharmacogenomics J. 2015 Oct;15(5):405-13