Çağdaş Aktan

MicroRNA-520a-5p displays a therapeutic effect upon chronic myelogenous leukemia cells by targeting STAT3 and enhances the anticarcinogenic role of capsaicin.

Aberrant expression profiles of microRNAs (miRNAs) have been previously demonstrated for having essential roles in a wide range of cancer types including leukemia. Antiproliferative or proapoptotic effects of capsaicin have been reported in several cancers. We aimed to study miRNAs involved in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway in chronic myeloid leukemia cell model and the effects of the capsaicin treatment on cell proliferation and miRNA regulation. miR-520a-5p expression was extremely downregulated in capsaicin-treated cells. Repressing the level of miR-520a-5p by transient transfection with specific miRNA inhibitor oligonucleotides resulted in induced inhibition of proliferation in leukemic cells. According to bioinformatics analysis, STAT3 messenger RNA was predicted as a putative miR-520a-5p target; which was confirmed by quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) and Western blot analysis. Cell proliferation inhibition was enhanced upon knockdown of STAT3 by RNA interference applications, but when miR-520a-5p inhibitor was additionally transfected onto STAT3 silenced cells, cell viability was dramatically decreased in leukemia cells. Finally, we observed the effects of capsaicin following miR-520a-5p inhibitor transfection upon cell proliferation, apoptosis, and STAT3 expression levels. We determined that, downregulation of miR-520a-5p affected the proliferation inhibition enhanced by capsaicin and reduced STAT3 mRNA and protein expression levels and increased apoptotic cell number. In summary, miR-520a-5p displays a therapeutic effect by targeting STAT3 and impacting the anticancer effects of capsaicin; whereas capsaicin, potentially through the miR-520a-5p/STAT3 interaction, induces apoptosis and inhibits K562 leukemic cell proliferation with need of further investigation.

Bortezomib induces apoptosis by interacting with JAK/STAT pathway in K562 leukemic cells

In the current study, we aimed to identify the cytotoxic and apoptotic effects of bortezomib (BOR) on human K562 chronic myelogenous leukemia cells and to evaluate the potential roles of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway members STAT3, STAT5, and JAK2 on BOR-induced cell death of leukemic cells. Cell viability was assessed via trypan blue dye exclusion test, and cytotoxicity of the BOR-treated cells was conducted by 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) assay. The relative messenger RNA (mRNA) expression levels of STAT3, STAT5A, STAT5B, and JAK2 were analyzed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). On the other hand, their protein expression levels were detected by western blot method. The obtained results indicated that BOR treatment reduced cell viability and induced leukemic cell apoptosis in a dose- and time-dependent manner as compared to untreated control cells. While mRNA expression levels of STAT5A, STAT5B, and STAT3 were significantly reduced following BOR treatment when compared to untreated controls, it had no effect upon JAK2 mRNA expression. As for protein levels, STAT expressions were downregulated after BOR treatment especially at 72nd and 96th hours. Our results pointed out that BOR treatment had a significant potential of being an anticancer agent for chronic myelogenous leukemia therapy, and this effect could be due to the expressional downregulations of JAK/STAT pathway members.

Two cases with hypereosinophilic syndrome shown with real-time PCR and responding well to imatinib treatment

The aim of this work was to report two cases of hypereosinophilic syndrome (HES). FIP1L1-PDGFRA fusion was assessed with two protocols at RNA level. The fusion transcript was found positive at the RNA level with both PCR methods in two cases. In this study, the efficiency of imatinib treatment and a dramatic response in two HES cases with multisystemic involvement showing the characteristics of a chronic myeloproliferative disease were presented. Both cases showed complete responses confirming that imatinib mesylate treatment could be successful even in patients with advanced HES having myeloproliferative disease.

TET2, ASXL1, IDH1, and IDH2 Single Nucleotide Polymorphisms in Turkish Patients with Chronic Myeloproliferative Neoplasms

We aimed to determine the genotype distribution, allele frequency, and prognostic impact of IDH1/2, TET2, and ASXL1 single nucleotide polymorphisms (SNPs) in myeloproliferative neoplasms (MPNs). TET2 (rs763480), ASXL1 (rs2208131), and IDH1 (rs11554137) variant homozygous genotype frequencies were found at rates of 1.5%, 9.2%, and 2.3%, respectively. No IDH2 SNP was identified. IDH1 and TET2 frequencies were 5% in essential thrombocythemia (ET) and 1.7% in ET and 5% in primary myelofibrosis (PMF), respectively. ASXL1 frequencies were 8.3%-10% in MPN subgroups. The TET2 mutant allele T and ASXL1 mutant allele G had the highest frequencies with 0.272 in the PMF and 0.322 in the polycythemia vera (PV) group, respectively. There was no impact of the SNPs on prognosis. IDH1 frequency in MPNs was found similar to the literature. ASXL1 frequencies were similar between ET, PV, and PMF patients. The ASXL1 and TET2 allele frequencies of the Turkish population are similar to those of the European population. The role of SNPs in MPNs might be further evaluated in larger multicenter studies.

Do preoperative serum vascular endothelial growth factor and migration-inhibitory factor predict the nature of the adnexal masses? A prospective-controlled trial.

The aim of this study was to identify the role of preoperative serum vascular endothelial growth factor (VEGF) and migration inhibitor factor (MIF) in differentiation of benign and malignant adnexal masses, as well as the relationship between prognostic factors and VEGF and MIF in ovarian cancer patients. This prospective study included 41 patients who were admitted between November 2010 and March 2012. In the malignant group, there were 21 patients, and remaining 20 had benign adnexal masses. Age, CA125 levels, grade, stage, presence of ascites and the degree of cytoreduction performed were noted. There was no significant difference between two groups in preoperative serum VEGF and MIF levels (p = 0.118 and p = 0.297, respectively). CA125 levels were significantly higher in the malignant group (p < 0.0001). There was no significant difference for VEGF and MIF between the groups evaluated for tumour grade, stage, presence of ascites and degree of cytoreduction performed in the malignant group. Preoperative serum, VEGF and MIF levels are not suitable for the differentiation of malignant and benign adnexal masses, and they do not correlate with the prognostic factors of ovarian cancer in this cohort of patients.

PP-091 INVESTIGATING THE POTENTIAL EFFECTS OF SUNITINIB IN K-562 CHRONIC MYELOGENOUS LEUKEMIA CELL LINE AND ASSESSMENT OF GENE PROFILING

Introduction: The bone marrow in addition to being the origin of primary hematological malignancies is also commonly involved by metastatic solid tumors. The malignancies of prostate, breast, lungs, kidney, thyroid and gastric in adults are the primary tumors, which frequently involve bone marrow. Leukoerythroblastosis (LEB) and unexplained cytopenias are strong indicators of the necessity of bone marrow examination. Case report: A 45-year-old woman was referred from family physicians to our clinic because of cytopenia. Organomegaly and palpable lymphadenopathy was not detected at physical examination. The peripheral blood cell count parameters included anemia, leukocytosis, thrombocytopenia and

The effect of brain derived neurotrophic factor Val66Met polymorphism upon alcohol dependence tendency in Turkish alcohol dependents

Objective: The neurotrophine “brain derived neurotrophic factor” (BDNF) which is expressed in the brain is responsible for neuronal survive and functioning also plays a role in pathophysiology of alcohol dependence that show multifactorial and polygenic heredity. In the current study, we aimed to identify whether the functional Val66Met [G196A; (rs6265)] polymorphism in BDNF gene has effect upon tendency to alcoholism in Turkish male and female alcohol dependent cases. Methods: Genotype distribution and allele frequency of BDNF Val66Met polymorphism was identified via PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) method in 110 alcoholic cases (10 female, 100 male) and 376 healthy subjects (148 female, 228 male) constituting our study and control groups, statistical analyses were revealed by chi-square and ANOVA tests. Results: The distribution of the mutant AA genotype was 3.6% to 1.6% and frequency of the A allele was 16.0% to 15.0% in the study group when compared to control group. Our results didn’t show any significant differences in genotype distribution and allele frequencies of polymorphism neither between the study and control groups nor between female case and female controls and male alcoholics and male controls. The power of the study for genotype analysis was set at 80.2%. Conclusion: These results indicate that the polymorphic A allele of BDNF gene is not related with alcoholism in Turkish subjects. But since AA genotyped male subjects’ starting ages of alcohol usage and pathological drinking were detected to be earlier among other genotypes, this gave rise to a conclusion that BDNF polymorphism might be important in the alcoholism phenotype.