Projects / Programmes
VPLIV METABOLITOV ARZENOVEGA TRIOKSIDA NA ZDRAVLJENJE AKUTNE PROMIELOCITNE LEVKEMIJE IN MULTIPLEGA MIELOMA (Slovene)
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
Researchers (11)
Organisations (3)
Significance for science
Mechanisms of As2O3 action against malignant cells are with the exception of acute promielocyte leukaemia still little known. Very few data exist in scientific literature on arsenic speciation in organism and in urine of patients treated with As2O3. The arsenic speciation itself is currently meeting several problems, among them presence/absence of trivalent arsenic metabolites and conversion of AsIII/V in pathologic conditions. In the first year of our study we analysed urine samples of patients, treated with arsenic, which were kept in liquid nitrogen till analysis. Trivalent arsenic metabolites (MAIII and DMAIII) were (almost) completely absent so we can be placed on a side of groups, who think that high concentrations of trivalent arsenic metabolites are artefact of unsuitable storage conditions and/or unsuitable analytical protocol. With cell experiments we questioned the therapeutic use of vitamin C together with arsenic due to high conversion of AsIII/V (prooxidative effect of vitamin C). Noticed supression of MTs during exposure to low conc. of As points to importance of study MTs dinamics. The influence of genetic and chromosomal rearangement of malignant clone on arsenic biotransformation is also relatively uncovered research field. In the project the experts from Karl-Franzens University in Graz (Austria) were included as a reference laboratory.
The influence of genetic and chromosomal anomalies in malignant clone to arsenic biotransformation is still largely unknown. Experiments on cell cultures from chemical point of view (arsenic biotransformation) and from the view of response of the organism (kinetics of biotransformation, apoptosis, metalothionein induction, selenoprotein P) in the connection with chromosomal abnormalities offer an insight into that still unknown field of research.
Significance for the country
Proposed research is a mutual project of University Medical Centre Ljubljana and Jožef Stefan Institute, which is connecting biochemical research on cells obtained from cancer patients with extensive study of analytical chemistry. We hope that arsenic with appropriate application, intensively studied via arsenic methabolite excretion,will become an efficient drug also for other malignancies. We also hope that important results gained in the duration of a project like
- (i)questionable addition of C vitamine and
- (ii) danger of selenium loss during arsenic treatment
will be taken into account at modification of treatment protocols. Since arsenic trioxide is a simple drug, which can be easily prepared in University Clinical Centre pharmacy in Ljubljana, is cheap comparing to cytostatics, project can also have some economic importance.
Prognostic significance of some newer chromosomal aberrations at multiple myeloma (MM) is confirmed in a literature. Our study found these aberrations at Slovene patients as well. More than 50% of Slovene MM patients were examined on their presence. New chromosomal aberrations were found at 69% of patients examined, of which 1p deletion at 10% of patients, 1q amplification at 40% of patients, 6q deletion at 10% of patients and 15q amplification at 47% of patients. Coappearance of 1q amplification with some routinely detwermined changes was noticed as well. On the base of results obtained up to now haematological consilium recommended routine determination of all these aberrations with a series of DNA-kits as a starting diagnostics at MM patients.
A method for estimation of apoptosis of multiple myeloma cells was adapted/developed allowing integrated data manipulation on cytogenetic aberrations and apoptosis extent estimation caused by ATO. Since these are technically very demanding procedures, where the ammount of sample available is often a limiting factor, the data analysis will only start after the end of the project.
Two PhD students work on a project, so that next to research work educational aspect is important. Due to interdisciplinary composition of the project team (medicine, pharmacy, chemistry) there is also a transfer of knowledge between different research fields.
Most important scientific results
Annual report
2008,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
