Ege University
Medical Biology
, which is a polyphenol in green tea, induces apoptosis in different types of cancer cells. The purpose of this study was to determine the cytotoxic and apoptotic effects of ponatinib and EGCG combination in K562 CML cell line. This study... more
, which is a polyphenol in green tea, induces apoptosis in different types of cancer cells. The purpose of this study was to determine the cytotoxic and apoptotic effects of ponatinib and EGCG combination in K562 CML cell line. This study also aimed to detect alterations of the expression levels of cell cycle-regulation related genes after ponatinib and EGCG combination in K562 CML cell line.
- by Duygu Aygunes Jafari and +2
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Aim of the study: Genistein, an isoflavonoid, plays roles in the inhibition of protein tyrosine kinase phosphorylation, induction of apoptosis, and cell differentiation in breast cancer. This study aims to induce cellular stress by... more
Aim of the study: Genistein, an isoflavonoid, plays roles in the inhibition of protein tyrosine kinase phosphorylation, induction of apoptosis, and cell differentiation in breast cancer. This study aims to induce cellular stress by exposing genistein to determine alterations of miRNA expression profiles in MCF-7 cells. Material and methods: XTT assay and trypan blue dye exclusion assays were performed to examine the cytotoxic effects of genistein treatment. Expressions of miRNAs were quantified using Real-Time Online RT-PCR. Results: The IC 50 dose of genistein was 175 μM in MCF-7 cell, line and the cytotoxic effect of genistein was detected after 48 hours. miR-23b was found to be up-regulated 56.69 fold following the treatment of genistein. It was found that miR-23b was upregulated for MCF-7 breast cancer cells after genistein treatment. Conclusions: Up-regulated ex-expression of miR-23b might be a putative biomarker for use in the therapy of breast cancer patients. miR-23b up-regulation might be important in terms of response to genistein.
- by Duygu Aygunes Jafari and +2
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Caffeic acid phenethyl ester (CAPE) is one of the most effective components of propolis which is collected by honey bees. The aim of this study was to investigate the cytotoxic and apoptotic effects of CAPE in the CCRF-CEM cell line and... more
Caffeic acid phenethyl ester (CAPE) is one of the most effective components of propolis which is collected by honey bees. The aim of this study was to investigate the cytotoxic and apoptotic effects of CAPE in the CCRF-CEM cell line and to clarify the role of serine/threonine protein phosphatase 2A (PP2A) and human telomerase reverse transcriptase (hTERT) activity as an underlining mechanism of CAPE-induced apoptosis. Trypan blue dye exclusion test and XTT methods were used to evaluate the cytotoxicity and ELISA based oligonucleotide detection, which can be seen during apoptosis, was used to determine apoptosis. Acridine orange/ethidium bromide dye technique was also used to evaluate apoptosis. The cytotoxic effect of CAPE was detected in a dose and time dependent manner with the IC 50 of 1 mM. ELISA and acridine orange/ethidium bromide methods have shown remarkable apoptosis at 48th hour in CAPE treated cells. To investigate the role of PP2A in CAPE-induced apoptosis of CCRF-CEM cells, we performed combination studies with CAPE and, Calyculin A and Okadaic acid, which are very well known inhibitors of PP2A, in IC 20 of inhibitors and IC 50 of CAPE. Combination studies revealed synergistic effect of both drugs by concomitant use. Western blot analyses of PP2A catalytic and regulatory subunits showed down-regulation of expression of PP2A catalytic subunit in CAPE treated cells at 48th hour. Since, PP2A is important in hTERT (telomerase catalytic subunit) activation and deactivation, we also performed hTERT activity in CAPE treated cells simultaneously. Treating cells with IC 50 of CAPE for 96 h with the intervals of 24 h showed marked reduction of hTERT activity. The reduction of hTERT activity in CAPE treated CCRF-CEM cells was more prominent in the initial 48 h. The variation of hTERTactivity in CAPE treated CCRF-CEM cells may be the reason for the protein phosphatase interaction that occurred after treatment with CAPE.
- by Cumhur Gunduz and +2
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- Hematology, Enzyme Inhibitors, Apoptosis, Telomerase
The aim of this study is to evaluate (1) the human telomerase-specific reverse transcriptase (hTERT) mRNA expression in childhood acute leukemia, (2) the association between the hTERT mRNA expression with the patients' characteristics and... more
The aim of this study is to evaluate (1) the human telomerase-specific reverse transcriptase (hTERT) mRNA expression in childhood acute leukemia, (2) the association between the hTERT mRNA expression with the patients' characteristics and the known prognostic factors and (3) the correlation of the patients' survival with the initial hTERT mRNA value at diagnosis. A total of 40 newly diagnosed patients consist of children [31 cases with acute lymphoblastic leukemia (ALL) and 9 cases with acute myeloblastic leukemia (AML)] were prospectively included into the study. The online real-time reversetranscriptase PCR was used for the quantification of hTERT in bone marrow (BM). All cases were re-evaluated for their survival after 2 years. The highest hTERT mRNA value was observed in Pre B-cell ALL patients followed by B-cell ALL, T-cell ALL and AML. The hTERT mRNA relative ratio difference between the ALL and AML groups was significant. No significant association was found when hTERT mRNA expression was evaluated in relation with the hematological parameters (except hemoglobin level), blast percentages and the risk groups. No significant difference was determined between the rate of complete remission and relapse of cases with the hTERT mRNA values in all malignancy groups. Patients who had higher initial hTERT mRNA values showed significantly longer disease-free survival (DFS) and overall survival (OS) in ALL (P = 0.000 and 0.01, respectively). Although DFS and OS was longer in AML patients with lower initial hTERT mRNA, the difference was not significant. In conclusion, the hTERT mRNA expression values were not significantly associated with the known prognostic factors in children both with ALL and AML. hTERT mRNA value is a significant factor for childhood ALL at diagnosis in relation to the estimated survival.
- by Serap Aksoylar and +3
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- Hematology, Adolescent, Telomerase, Acute Myeloid Leukemia
Background Poor glycaemic control, hypertension and duration of diabetes are risk factors for the development of diabetic nephropathy, but there may be genetic factors. Recently, a common C to T mutation at nucleotide position 677 of the... more
Background Poor glycaemic control, hypertension and duration of diabetes are risk factors for the development of diabetic nephropathy, but there may be genetic factors. Recently, a common C to T mutation at nucleotide position 677 of the MTHFR gene (MTHFR677C>T) has been reported to be correlated with hyperhomocysteinemia and the severity of coronary artery disease as macroangiopathy. We aim to investigate Turkish type 2 diabetic patients with/without diabetic nephropathy and healthy group and examine the contribution of the MTHFR gene polymorphism to the development of diabetic nephropathy.
- by Buket Kosova and +2
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- Diabetes, Turkey, DNA, Polymerase Chain Reaction
Purpose CAPE (caffeic acid phenethyl ester) is one of the most valuable and investigated component of propolis which is composed by honeybees. In the current study, we aimed at examining apoptotic effects of CAPE on CCRF-CEM leukemic... more
Purpose CAPE (caffeic acid phenethyl ester) is one of the most valuable and investigated component of propolis which is composed by honeybees. In the current study, we aimed at examining apoptotic effects of CAPE on CCRF-CEM leukemic cells and at determining the roles of mitochondrial membrane potential (MMP) in cell death. Methods Trypan blue and XTT methods were used to evaluate the cytotoxicity. Apoptosis was examined by ELISA-based oligonucleotide and acridine orange/ethidium bromide dye techniques. Loss of mitochondrial membrane potential was evaluated using JC-1 dye by flow cytometric analysis and under fluorescent microscope. Results We detected the time-and dose-dependent increases in cytotoxic effect of CAPE on CCRF-CEM cells. ELISA and acridine orange/ethidium bromide results showed that apoptotic cell population increased significantly in CCRF-CEM cells exposed to increasing concentrations of CAPE. On the other hand, there was significant loss of MMP determined in response to CAPE in CCRF-CEM cells.
- by Cumhur Gunduz and +4
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- Cancer, Flow Cytometry, Cancer stem cells, Molecular Genetics
Objective: Recent studies have suggested an association between a deletion variant of the angiotensin-converting enzyme (ACE) gene and diabetic nephropathy. However, this finding has not been confirmed by all investigators. Furthermore,... more
Objective: Recent studies have suggested an association between a deletion variant of the angiotensin-converting enzyme (ACE) gene and diabetic nephropathy. However, this finding has not been confirmed by all investigators. Furthermore, an M235T variant of the angiotensinogen (AGT) gene has been associated with hypertension, an important risk factor for the development and progression of diabetic nephropathy. Research Design and Methods: We investigated the relationship of the ACE insertion/deletion (I/D) and AGT M235T gene polymorphisms in Turkish patients with type 2 diabetes mellitus (DM) with and without diabetic nephropathy. A total of 102 individuals were screened for the presence of the ACE I/D and AGT M235T polymorphism: 46 individuals who had type 2 DM with diabetic nephropathy and, as controls, 56 individuals who had type 2 DM without diabetic nephropathy. Gene polymorphisms were determined by the specific melting temperature (T m ) values of the resulting amplicons after real-time online polymerase chain reaction and melting curve analysis. Results: The frequencies of the ACE DD, ID, and II genotypes were 34.8%, 37.0%, and 28.3%, respectively, among type 2 diabetic patients with nephropathy, and 33.9%, 42.9%, 23.2%, respectively ( P=.788), in the control subjects without diabetic nephropathy. On the other hand, the frequencies of the AGT MM, MT, and TT genotypes among the same groups were 26.1%, 52.2%, 21.7% and 26.8%, 57.1%, 16.1%, respectively ( P=.758). Conclusions: There were no differences in the frequencies of the AGT M235T and ACE I/D genotypes between Turkish patients with type 2 DM with and without nephropathy. D
Propolis is a resinous substance which is used by bees to repair and maintain their hives. It has more than 180 compounds including flavonoids, phenolic acids and its esters which have anti-inflammatory, antibacterial, antiviral,... more
Propolis is a resinous substance which is used by bees to repair and maintain their hives. It has more than 180 compounds including flavonoids, phenolic acids and its esters which have anti-inflammatory, antibacterial, antiviral, immunomodulatory, antioxidant and antiproliferative effects. Propolis is shown to inhibit cell division and protein synthesis. However the exact mechanism underlying antitumor effect is not clearly described. On the other hand progressive telomere shortening to a critical level results with senescence of normal cells by inducing apoptosis and telomerase prevents erosion of telomeres. In this study we aimed to evaluate hTERT ratios in propolis-treated T-cell acute lymphoblastic leukemia (CCFR-CEM) cell line. Cell counts and cell viability of propolis-treated and propolis-free T-cell acute lymphoblastic leukemia (CCFR-CEM) cell line were assessed by trypan blue dye exclusion test and MTT assay. The LightCycler instrument was used (online real-time PCR) for the quantification of hTERT in CCFR-CEM cell line. The hTERT ratio significantly decreased 60 and 93% after 24 and 72 h respectively compared to the initial value of the cells incubated with propolis. It had almost no cytotoxic effect and caused 30, 30, 22 and 12% decrease in cell counts after 24, 48, 72 and 96 h respectively which is statistically significant.
- by Cumhur Gunduz and +2
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- Leukemia, Protein synthesis, Cell Division, Telomerase
A baby born to an epileptic mother had dysmorphological features associated with 47,XXX karyotype. The mother had been treated with valproic acid (1800 mg per day) and lamotrigine (100 mg per day) throughout pregnancy. Dysmorphological... more
A baby born to an epileptic mother had dysmorphological features associated with 47,XXX karyotype. The mother had been treated with valproic acid (1800 mg per day) and lamotrigine (100 mg per day) throughout pregnancy. Dysmorphological features detected in baby were intrauterine growth retardation, hypertelorism, flattened nasal bridge, low set malformed auriculas, micrognathia, very small an bow-shaped mouth with thin upper lip, cleft palate, arachnodactyly, camptodactyly, secundum atrial septal defect, bilateral hammer toes and decreased creases on the soles. At 6 months old she showed motor retardation. The molecular analysis of parents revealed that extra X chromosome was inherited from the mother. In this case whether the dysmorphological features and 47,XXX karyotype were caused by lamotrigine and valproic acid treatment during pregnancy or coincidence is in question.
Concerns about the health effects of radiofrequency (RF) waves have been raised because of the gradual increase in usage of cell phones, and there are scientific questions and debates about the safety of those instruments in daily life.... more
Concerns about the health effects of radiofrequency (RF) waves have been raised because of the gradual increase in usage of cell phones, and there are scientific questions and debates about the safety of those instruments in daily life. The aim of this study is to evaluate the genotoxic effects of RF waves in an experimental brain cell culture model. Brain cell cultures of the mice were exposed to 10.715 GHz with specific absorbtion rate (SAR) 0.725 W/kG signals for 6 h in 3 days at 25°C to check for the changes in the micronucleus (MNi) assay and in the expression of 11 proapoptotic and antiapoptotic genes. It was found that MNi rate increased 11-fold and STAT3 expression decreased 7-fold in the cell cultures which were exposed to RF. Cell phones which spread RF may damage DNA and change gene expression in brain cells.
Cell Society and Springer Japan. This eoffprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your... more
Cell Society and Springer Japan. This eoffprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".
- by Aysel Yurtsever and +2
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- Dendritic Cells, Methylation, Glioblastoma, Prognosis
Background : Celiac disease, also known as gluten-sensitive enteropathy, is a chronic inflammation disease of the small intestinal mucosa. Detection of Ig-A antigliadin antibodies (AGA) and antiendomysial antibodies (EMA) in serum is... more
Background : Celiac disease, also known as gluten-sensitive enteropathy, is a chronic inflammation disease of the small intestinal mucosa. Detection of Ig-A antigliadin antibodies (AGA) and antiendomysial antibodies (EMA) in serum is important in the diagnosis and screening for celiac disease. Antiendomysial antibodies have greater sensitivity compared to antigliadin antibodies. It has been reported that the prevalence of celiac disease is higher in children with Down syndrome than the other autoimmune conditions. The aim of the present study was to investigate the incidence of celiac disease in children with Down syndrome, to assess the availability of Ig-A AGA and EMA for serologic screening, and to highlight the importance of follow-up for children with Down syndrome. Methods : Forty-seven children with Down syndrome without known celiac disease were tested for total blood count, thyroid function tests, immunoglobulin values, Ig-A AGA and EMA. Duodenal biopsy was performed on eight patients who showed at least one serologically positive marker. Results : The ages of the children with Down syndrome ranged from 2 to 18 years (30 boys/17 girls). The mean age was 6.55 ± 3.88. Total blood count and immunoglobulin values were normal. Eleven of the 47 patients (23.40%) were found to be serologically positive, 10 (21.28%) having antigliadin antibody concentrations above normal; and six (12.77%) being positive for antiendomysial antibody. In five patients (10.64%), both Ig-A AGA and EMA concentrations were high and positive. Duodenal biopsies of three of eight cases (37.50%) revealed villous atrophy, lymphocyte infiltration and crypt hyperplasia. Three cases with abnormal biopsy results (100%) were below the 10th percentile for weight and height. Hypothyroidism was detected in one of 11 cases where at least one serologic marker was positive. Conclusion : Children with Down syndrome should be carefully examined in their follow up, and celiac disease should be considered in cases with growth retardation. Ig-A antigliadin antibodies and EMA are noninvasive, cheap and readily available serologic screening tests for celiac disease, and the positivity of both markers gives the most reliable result.
Objective: Follicular lymphoma (FL) is one of the most common lymphomas, and is characterized by t(14;18) (q32;q21) in more than 80% of patients. The aim of this study was to determine the rate of t(14;18) positivity based on the... more
Objective: Follicular lymphoma (FL) is one of the most common lymphomas, and is characterized by t(14;18) (q32;q21) in more than 80% of patients. The aim of this study was to determine the rate of t(14;18) positivity based on the detection of mbr or mcr in paraffin-embedded tissue samples.
- by Cumhur Gunduz and +2
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Propolis is a resinous substance which is used by bees to repair and maintain their hives. It has more than 180 compounds including flavonoids, phenolic acids and its esters which have anti-inflammatory, antibacterial, antiviral,... more
Propolis is a resinous substance which is used by bees to repair and maintain their hives. It has more than 180 compounds including flavonoids, phenolic acids and its esters which have anti-inflammatory, antibacterial, antiviral, immunomodulatory, antioxidant and antiproliferative effects. Propolis is shown to inhibit cell division and protein synthesis. However the exact mechanism underlying antitumor effect is not clearly described. On the other hand progressive telomere shortening to a critical level results with senescence of normal cells by inducing apoptosis and telomerase prevents erosion of telomeres. In this study we aimed to evaluate hTERT ratios in propolis-treated T-cell acute lymphoblastic leukemia (CCFR-CEM) cell line. Cell counts and cell viability of propolis-treated and propolis-free T-cell acute lymphoblastic leukemia (CCFR-CEM) cell line were assessed by trypan blue dye exclusion test and MTT assay. The LightCycler instrument was used (online real-time PCR) for th...
- by Cumhur Gunduz and +1
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- Leukemia, Protein synthesis, Cell Division, Telomerase