Browsing by Author "Kurt, CC"

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    Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells
    Kutbay, NO; Avci, CB; Yurekli, BS; Kurt, CC; Shademan, B; Gunduz, C; Erdogan, M
    Anaplastic cancer constitutes 1% of thyroid cancers, and it is one of the most aggressive cancers. Treatment options are external radiation therapy and/or chemotherapy. The success rate with these treatment modalities is not satisfactory. We aimed to evaluate the effects of metformin (MET) and pioglitazone (PIO) combination on apoptosis and AMP-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway in human anaplastic thyroid cancer cells. In this study, we evaluated the effects of MET and PIO individually and the combination of the two drugs on the cellular lines SW1736 and C643 ATC. Genes contained in the mTOR signaling pathway were examined using human mTOR Signalization RT(2)Profiler PCR Array. In C643 and SW1736 cell lines, IC(50)doses of MET and PIO were found out as 17.69 mM, 11.64 mM, 27.12 mu M, and 23.17 mu M. Also, the combination of MET and PIO was determined as an additive according to isobologram analyses. We have found the downregulation of the expression levels of oncogenic genes:AKT3, CHUK, CDC42, EIF4E, HIF1A, IKBKB, ILK, MTOR, PIK3CA, PIK3CG, PLD1, PRKCA, andRICTORgenes, in the MET and PIO combination-treated cells. In addition, expression levels of tumor suppressorgenes, DDIT4, DDIT4L, EIF4EBP1, EIF4EBP2, FKBP1A, FKBP8, GSK3B, MYO1C, PTEN, ULK1, andULK2, were found to have increased significantly. The MET + PIO combination was first applied to thyroid cancer cells, and significant reductions in the level of oncogenic genes were detected. The decreases, particularly, inAKT3, DEPTOR, EIF4E, ILK, MTOR, PIK3C, andPRKCAexpressions indicate that progression can be prevented in thyroid cancer cells and these genes could be selected as therapeutic targets.
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    Distribution and Phylogenetic Analysis of Subtypes and Alleles of Blastocystis sp. in the Stool Samples Collected from Patients with Gastrointestinal Complaints in Izmir, Turkey
    Aykur, M; Kurt, CC; Erdogan, DD; Avci, CB; Vardar, R; Aydemir, S; Girginkardesler, N; Gunduz, C; Dagci, H
    PurposeBlastocystis sp. is one of the most prevalent intestinal protozoa found in humans and many other animals. The present study aimed to examine the distribution and genetic diversity of Blastocystis sp. in stool samples from patients with gastrointestinal complaints in Izmir, Turkey.MethodsAll stool samples of 439 patients with gastrointestinal complaints were examined by native-Lugol and trichrome staining. To investigate the presence of Blastocystis sp. in stool samples, DNA was isolated, and PCR was performed with the barcode region in the SSU rRNA gene. PCR positive samples were sequenced to identify subtypes and alleles of Blastocystis sp.ResultsThe prevalence of Blastocystis sp. was found to be 16.6% (73/439) in patients with gastrointestinal complaints in Izmir, Turkey. Three different Blastocystis sp. subtypes were identified. ST3 (28/55; 51.0%) was the most common subtype followed by ST2 (19/55; 34.5%) and ST1 (8/55; 14.5%). Itching and diarrhea were the most prominent clinical symptoms in Blastocystis sp. positive patients. When clinical symptoms and subtypes were compared, diarrhea was found in 62.5%, 47.4%, and 46.4% of patients with ST1, ST2, and ST3 subtypes, respectively. In addition, itching was found in 37.5%, 32.1%, and 21.1% of patients with ST1, ST3, and ST2, respectively. Six distinct alleles were identified by allele analysis of Blastocystis 18S rRNA gene: allele 4 for ST1, alleles 9, 11, and 12 for ST2, and alleles 34 and 36 for ST3. In this study, Blastocystis sp. was detected in 16 of 21 districts, including the central and rural districts of Izmir. Although ST1 was detected in central districts, it was not found in rural districts.ConclusionThis study provides comprehensive data on the prevalence and molecular epidemiology of the genetic diversity at the level of subtypes and alleles of Blastocystis sp. in different districts of Izmir province in Turkey. To the best of our knowledge, this is the first study which evaluates the distribution of subtypes and alleles of Blastocystis sp. according to PCR and SSU rRNA gene sequencing in patients with gastrointestinal complaints in different districts of Izmir province in Turkey.
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    Investigation of Dientamoeba fragilis Prevalence and Evaluation of Sociodemographic and Clinical Features in Patients with Gastrointestinal Symptoms
    Aykur, M; Kurt, CC; Erdogan, DD; Avci, CB; Vardar, R; Aydemir, S; Girginkardesler, N; Gündüz, C; Dagci, H
    BackgroundDientamoeba fragilis is a protozoan parasite of the human gastrointestinal tract and still controversial in association with gastrointestinal symptoms.PurposeWe present cross-sectional study of the prevalence of D. fragilis, and sociodemographic and clinical features in the patients with gastrointestinal symptoms.MethodsA total of 490 fecal specimens were collected from outpatients with gastrointestinal symptoms in the Department of Parasitology, Faculty of Medicine, Ege University and Celal Bayar University, Turkey. Fecal specimens were examined with microscopy and inoculated in Robinson medium. D. fragilis-positive samples were examined for the presence of other intestinal parasites using enzyme immunoassay. Real-time PCR analysis was performed on all samples.ResultsOf the 490 stool specimens examined by real-time PCR, 59 patients were positive for D. fragilis infection with prevalence rate of 12.04%. Forty-four of positive patients (74.5%) were found to be infected with only D. fragilis, while 23.7% were co-infected with Blastocystis and 1.7% were co-infected with Rotavirus. No statistically significant difference was found in all the examined patients in terms of D. fragilis positivity for all sociodemographic parameters. Loose stool consistency was associated with the presence of D. fragilis, with 18.3% (P=0.001). When the clinical symptoms of all the patients participating in this study were examined, diarrhea was statistically more significant in patients with the presence of D. fragilis (16.3%; P=0.001). The rate of diarrhea in D. fragilis-positive patients (84.09%; P=0.0005) was higher than that of D. fragilis-negative patients and it was statistically significant.ConclusionThis study is important for assessing the prevalence of D. fragilis and its association with other factors in symptomatic patients in a large sample group in Turkey, as well as investigating the relationship of identified symptoms with the D. fragilis pathogenicity. It is suggested that D. fragilis in this case is not a commensal parasite but a pathogenic parasite and that the most common clinical symptom is diarrhea.
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    Origanum Sipyleum Methanol Extract in Combination with Ponatinib Shows Synergistic anti-Leukemic Activities on Chronic Myeloid Leukemia Cells
    Kayabasi, C; Susluer, SY; Okcanoglu, TB; Yelken, BO; Mutlu, Z; Bagca, BG; Kurt, CC; Saydam, G; Durmuskahya, C; Kayalar, H; Ozbilgin, A; Avci, CB; Gunduz, C
    Origanum sipyleum is used in folk medicine due to its anti-inflammatory, antimicrobial, and antioxidant properties. Ponatinib, an effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML), has severe side effects. Thus, we aimed to determine a novel herbal combination therapy that might not only increase the anti-leukemic efficacy but also reduce the dose of ponatinib in targeting CML cells. Origanum sipyleum was extracted with methanol (OSM), and secondary metabolites were determined by phytochemical screening tests. The cytotoxic effects of OSM on K562 cells were measured by WST-1 assay. Median-effect equation was used to analyze the combination of ponatinib and OSM (p-OSM). Apoptosis, proliferation, and cell-cycle were investigated by flow-cytometry. Cell-cycle-related gene expressions were evaluated by qRT-PCR. OSM that contains terpenoids, flavonoids, tannins, and anthracenes exhibited cytotoxic effects on K562 cells. The median-effect of p-OSM was found as synergistic; OSM reduced the ponatinib dose similar to 5-fold. p-OSM elevated the apoptotic and anti-proliferative activity of ponatinib. Consistently, p-OSM blocked cell-cycle progression in G(0)/G(1), S phases accompanied by regulations in TGFB2, ATR, PP2A, p18, CCND1, CCND2, and CCNA1 expressions. OSM enhanced the anti-leukemic activity of ponatinib synergistically via inducing apoptosis, suppressing proliferation, and cell-cycle. As a result, OSM might offer a potential strategy for treating patients with CML.