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    Promoter length polymorphism in UGT1A1 and the risk of sporadic colorectal cancer
    (Elsevier BV, 2012-04)
    Hiljadnikova Bajro, Marija
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    Josifovski, Toni
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    Panovski, Milco
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    Kapedanovska Nestorovska, Aleksandra
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    The association of C3435T single-nucleotide polymorphism, Pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy.
    (Dove Medical Press, 2012)
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    The ABCB1 gene encodes the P-glycoprotein (Pgp) protein, which is thought to transport various antiepileptic drugs. The single nucleotide polymorphism (SNP) (C3435T) in exon 26 of this gene correlates with the altered expression levels of P-glycoprotein, range of drug response and clinical conditions. In order to investigate the influence of this polymorphism on the susceptibility to and efficacy of carbamazepine therapy, we evaluated the allelic frequency and genotype distribution of this variant in 162 epilepsy patients from the Republic of Macedonia. Statistically significant differences were detected neither in the allelic frequency and genotype distribution between carbamazepine-resistant and carbamazepine-responsive epilepsy patients nor between the subgroups of carbamazepine (CBZ)-responsive patients treated with different CBZ doses. However, the T-allele was enriched in CBZ-responsive patients who required higher maintenance CBZ doses, This observation was substantiated by the findings that the median total plasma levels were the lowest in patients with CC (20 μmol/L) followed by CT (23 μmol/L) and TT (29 μmol/L) genotypes. Patients with a CC genotype also had a higher likelihood of response compared to patients with CT or TT genotypes over a wide range (400-1000 mg/day) of initial doses of CBZ. The T allele showed a reduced expression of ~5% compared to the C allele in peripheral blood mononuclear cells in heterozygotes for the variant. This difference might be translated into ~10% difference in homozygotes for the variant, which would explain the trend towards a dose-dependent efficacy of the CBZ treatment in patients with different genotypes. A larger prospective study is warranted to clarify the clinical utility of a genotypespecific individualized CBZ therapy.
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    Preliminary results of introducing the method multiparameter flow cytometry in patients with acute leukemia in Republic of Macedonia
    (ID Design 2012/DOOEL Skopje, 2008-12-05)
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    Hadzi-Pecova, Liljana
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    Abstract Background. In this paper we present the initial results of introducing the method of multiparameter flow cytometry (MPF) in patients with acute leukemia in the Republic of Macedonia. Aim. The aim of our study is to improve the diagnosis and management of acute leukemia, to establish the correct lineage assignment of the blast cells and to select effective treatment strategy for each single acute leukemia patient. Material and methods. A total of 44 adult (>15 years) patients (from initially 45 tested) with acute leukemia who were consecutively admitted at the Clinic of Hematology-Skopje from January through June 2008, were enrolled in this study. The MPF was introduced for the first time in the Republic of Macedonia and was performed at the Institute for Immunobiology and Human Genetics, Faculty of Medicine-Skopje. Results. Our results showed that morphology and cytochemistry established lineage in 39 of patients, but not in 5 cases that presented as acute leukemia, of which 4 were assigned as myeloid and in one nonhematopoietic malignancy was indicated. Furthermore immunophenotyping change the lineage assigned based on morphology and cytochemistry in one case from lymphoid to myeloid. Results from our study showed that routine immunophenotyping improved the diagnosis in 6 (13.3%) cases. The exact lineage assignment of the blasts cells guides to implementation of specific molecular analyses in some subtypes of acute leukemia and their further definition, which is essential for more appropriate single patient therapeutic decisions. Conclusion. Our data support routine implementation of MPF in the diagnostic evaluation of acute leukemia.