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Projects / Programmes source: ARIS

VPLIV METABOLITOV ARZENOVEGA TRIOKSIDA NA ZDRAVLJENJE AKUTNE PROMIELOCITNE LEVKEMIJE IN MULTIPLEGA MIELOMA (Slovene)

Research activity

Code Science Field Subfield
3.04.00  Medical sciences  Oncology   
Evaluation (rules)
source: COBISS
Researchers (11)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  07012  PhD Peter Černelč  Microbiology and immunology  Researcher  2008 - 2011  480 
2.  10582  PhD Ingrid Falnoga  Neurobiology  Researcher  2008 - 2011  344 
3.  03310  PhD Zvonka Jeran  Control and care of the environment  Researcher  2008 - 2011  266 
4.  30137  Hermina Kavčič  Microbiology and immunology  Technical associate  2009 - 2011 
5.  12684  PhD Helena Podgornik  Microbiology and immunology  Researcher  2008 - 2011  350 
6.  23126  PhD Irena Preložnik Zupan  Oncology  Researcher  2008 - 2011  418 
7.  29594  PhD Katarina Reberšek  Microbiology and immunology  Junior researcher  2008 - 2011  41 
8.  01873  PhD Vekoslava Stibilj  Chemistry  Researcher  2008 - 2011  687 
9.  01411  PhD Zdenka Šlejkovec  Chemistry  Head  2008 - 2011  240 
10.  09864  PhD Magda Tušek Žnidarič  Biology  Researcher  2008 - 2011  414 
11.  23817  PhD Samo Zver  Microbiology and immunology  Researcher  2008 - 2011  375 
Organisations (3)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0105  National Institute of Biology  Ljubljana  5055784  13,239 
2.  0106  Jožef Stefan Institute  Ljubljana  5051606000  90,600 
3.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,334 
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
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