A Dursun

Gazi University, Ankara, Ankara, Turkey

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Publications (85)139.29 Total impact

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    ABSTRACT: Background/aims: The risk of gastric cancer is increased in patients with intestinal metaplasia. Cyclooxygenase-2 activity is crucial for gastric cancer cell survival and proliferation. We aimed to assess cyclooxygenase-2 expression in patients with intestinal metaplasia or chronic active gastritis and in patients with or without a family history of gastric cancer, i.e. a first-degree relative with gastric cancer. Materials and Methods: One hundred and six patients with histologically proven intestinal metaplasia, chronic active gastritis or normal gastric mucosa were included. Immunohistochemical staining was performed using the immunoperoxidase method. Results: Cyclooxygenase-2 expression was detected in 23.1% of normal gastric mucosa, 70.6% of chronic active gastritis, and 90.5% of intestinal metaplasia patients. Cyclooxygenase-2 expression was significantly higher in intestinal metaplasia than in chronic active gastritis (p=0.018). Cyclooxygenase-2 expression was significantly more severe in the intestinal metaplasia group when compared to the chronic active gastritis group (p=0.017). Severe cyclooxygenase-2 expression (>60% of cells) was more frequent in the intestinal metaplasia group. Cyclooxygenase-2 expression was higher in the Helicobacter pylori-positive group when compared to the Helicobacter pylori-negative group (80.3% vs 57.1%, respectively; p=0.012). Cyclooxygenase-2 expression did not significantly differ according to presence of a first-degree relative with gastric cancer. Conclusions: Patients with intestinal metaplasia demonstrated increased presence and severity of cyclooxygenase-2 expression. Our findings suggest that cyclooxygenase-2 plays an important role in the stepwise process that eventually leads to gastric cancer. There was no statistically significant difference between the patients with and without a first-degree relative with a history of gastric cancer in terms of cyclooxygenase-2 expression.
    The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 10/2012; 23(5):Isayfa-Ssafya. · 0.48 Impact Factor
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    ABSTRACT: The primary aim is to compare individuals with intestinal metaplasia (IM), chronic active gastritis (CAG), and normal gastric mucosa (NGM) in terms of apoptosis, proliferation, and Bcl-2 expression. The secondary aim is to determine whether these parameters are different between patients with and without gastric cancer in first-degree relatives. We enrolled 106 patients whose histopathological results were consistent with IM (n: 42), CAG (n: 51), or NGM (n: 13). Antral biopsies were immunohistochemically stained for Bcl-2 and Ki-67 expression. Apoptosis was detected using TUNEL assay. While no significant difference was determined between three groups with regard to apoptosis and Bcl-2 expression (p>0.05), Ki-67 expression was significantly higher in the IM group when compared with the CAG and NGM groups (29.90±22.87 vs. 18.18±16.22 vs. 18.54±20, respectively; p=0.012). Helicobacter pylori was determined to increase apoptosis (49.3% vs. 25.7%, p<0.05), nevertheless, it had no significant effect on proliferation and Bcl-2 expression. Bcl-2 and Ki-67 expression and apoptosis were not different among patients with and without a history of gastric cancer in first degree relatives. Although intestinal metaplasia cases demonstrate an increase in proliferation, no elevation is observed in apoptosis. This can be an important factor in the progression to gastric cancer.
    Pathology - Research and Practice 02/2012; 208(2):89-93. · 1.21 Impact Factor
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    ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) may develop secondary to infections, malignancies, immune deficiency syndromes, and rheumatologic and metabolic disorders. Associations between HLH and inborn errors of metabolism, including lysinuric protein intolerance, multiple sulfatase deficiency, galactosemia, Gaucher disease, Pearson syndrome, and galactosialidosis, have previously been reported in the literature. In this report the authors present 3 children with disorders of propionate metabolism--1 with methylmalonic acidemia and 2 with propionic acidemia--who developed secondary HLH during their metabolic attacks. All patients fulfilled the 5 HLH criteria of the Histiocyte Society. Familial HLH was ruled out by molecular analysis. Plasma exchange was performed for 2 of them. Unfortunately 1 died of multiorgan failure despite intensive therapy. This is the first report of such an association.
    Pediatric Hematology and Oncology 02/2012; 29(1):92-8. · 0.90 Impact Factor
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    ABSTRACT: Primary systemic carnitine deficiency (SCD) is an autosomal recessive disorder caused by defective cellular carnitine transport. Patients usually present with predominant metabolic or cardiac manifestations. SCD is caused by mutations in the organic cation/carnitine transporter OCTN2 (SLC22A5) gene. Mutation analysis of SLC22A5 gene was carried out in eight Turkish patients from six families. Six patients presented with signs and symptoms of heart failure, cardiomyopathy, and low plasma carnitine levels, five of them with concurrent anemia. A patient with dilated cardiomyopathy had also facial dysmorphia, microcephaly, and developmental delay. Tandem MS analyses in siblings of the patients revealed two more cases with low plasma carnitine levels. SCD diagnosis was confirmed in these two cases by mutation screening. These two cases were asymptomatic but echocardiography revealed left ventricular dilatation in one of them. Carnitine treatment was started before the systemic signs and symptoms developed in these patients. Mean value of serum carnitine levels of the patients was 2.63±1.92μmol/L at the time of diagnosis. After 1year of treatment, carnitine values increased to 16.62±5.11 (p<0.001) and all responded to carnitine supplementation clinically. Mutation screening of the OCTN2 gene study in the patients revealed two novel (p.G411V, p.G152R), and four previously identified mutations (p.R254X, p.R282X, p.R289X, p.T337Pfs12X). Early recognition and carnitine supplementation can be lifesaving in this inborn error of fatty acid oxidation.
    JIMD reports. 01/2012; 3:17-23.
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    ABSTRACT: Acrodermatitis enteropathica (AE) is a rare autosomal recessive disorder of zinc deficiency due to an abnormal intestinal zinc transporter. It is characterized by the triad of acral dermatitis, alopecia, and diarrhoea. Once AE is correctly diagnosed, patients are treated with orally administered zinc sulphate. In some patients, relapses occur during adolescence, despite the regular treatment. Here, we discuss the clinical and molecular features of a 13-year-old adolescent girl with acrodermatitis enteropathica who was resistant to high-dose zinc sulphate therapy. We successfully treated the patient with zinc gluconate and vitamin C, and we detected a novel homozygous c.541_551dup (p.Leu186fsX38) mutation in the exon 3 of her SLC39A4 gene.
    JIMD reports. 01/2012; 2:25-8.
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    ABSTRACT: This study was designed to determine the level of survivin expression and its clinical significance as a prognostic factor in gastrointestinal stromal sarcoma (GIST). Twenty patients (12 males and 8 females) ranging in age from 25 to 72, with a median age of 53 were evaluated. Failure of TKI treatment was higher in the survivin-positive group (p=0.06). The rate of metastasis was significantly higher in the survivin positive group vs. the negative group (80% vs. 30%, p=0.18). The median overall survival (OS) time was 114 (range 29-199)months, and the median disease-free survival (DFS) time was 88 (range 40-135) months. The median progression-free survival (PFS) time was 40 (range 24-55) months. Further, a comparison of patients with survivin positive versus negative tumors, revealed no significant difference for OS, DFS, and PFS (p=0.45, p=0.19, p=0.55, respectively), number of mitoses in 50 HPF (p=0.14), and tumor size (p=0.94). In conclusion, survivin was highly expressed in GISTs, although we found no correlation between survivin expression and PFS, DFS and OS, survivin may be a predictive marker in GISTs for disease progression. We believe that additional studies are warranted to determine the clinical significance of survivin expression as a prognostic or predictive marker in patients with GIST.
    International immunopharmacology 12/2011; 11(12):2227-31. · 2.21 Impact Factor
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    ABSTRACT: Tyrosinemia type I (OMIM 276700) is a rare, autosomal recessive disorder caused by a deficiency in the fumarylacetoacetate hydrolase (FAH) enzyme. This study examined the spectrum of FAH gene mutation in 32 patients with tyrosinemia type I. In addition, clinical and biochemical findings were evaluated to establish a genotype-phenotype relationship in the patients. Mutation screening was performed using a 50K custom-designed resequencing microarray chip (TR_06_01r520489, Affymetrix) and sequencing analysis. Of the 12 different mutations found, 6 are categorized as novel. Three of the mutations-IVS6-1G>A, D233V, and IVS3-3C>G-are the most common in Turkish patients, comprising 25%, 17.1%, and 12.5% of mutant alleles, respectively.Clinical evaluations suggest that the spectrum of symptoms observed in the patients with very early and early disease were of the more nonspecific form, whereas the patients with late-presenting disease had more of the distinctive form over the course of the disease. This study adds support to the notion that the D233V mutation is specific to the Turkish population.
    JIMD reports. 01/2011; 1:17-21.
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    ABSTRACT: To determine the association between Helicobacter pylori (H. pylori) and globus sensation (GS) in the patients with cervical inlet patch. Sixty-eight patients with esophageal inlet patches were identified from 6760 consecutive patients undergoing upper gastrointestinal endoscopy prospectively. In these 68 patients with cervical inlet patches, symptoms of globus sensation (lump in the throat), hoarseness, sore throat, frequent clearing of the throat, cough, dysphagia, odynophagia of at least 3 mo duration was questioned prior to endoscopy. Cervical heterotopic gastric mucosa (CHGM) was found in 68 of 6760 patients. The endoscopic prevalence of CHGM was determined to be 1%. H. pylori was identified in 16 (23.5%) of 68 patients with inlet patch. Fifty-three patients were classified as CHGM II. This group included 48 patients with globus sensation, 4 patients with chronic cough and 1 patient with hoarseness. All the patients who were H. pylori (+) in cervical inlet patches had globus sensation. Often patients with CHGM have a long history of troublesome throat symptoms. We speculate that disturbances in globus sensation are like non-ulcer dyspepsia.
    World Journal of Gastroenterology 01/2010; 16(1):42-7. · 2.55 Impact Factor
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    ABSTRACT: The pyruvate dehydrogenase (PDH) complex is a mitochondrial multienzyme that catalyses the irreversible oxidative decarboxylation of pyruvate to acetyl-CoA. We report four novel PDHA1 mutations in patients with pyruvate dehydrogenase deficiency. Analysis of PDH activity showed decreased activity in fibroblasts from all four patients, around 16-52% of mean control, similar to what has been found in previous studies. Two of the mutations were missense mutations: c.616G>A (p.Glu206Lys) and c.457A>G (p.Met153Val), one was a 3 bp in-frame deletion: c.429_431delAGG (p.Gly143del), and one was a 65 bp duplication: c.900-6_958dup65. cDNA analysis of the 65 bp duplication showed a small amount of normal transcript in addition to the transcript corresponding to the duplication. The small amount of normal transcript likely explains the survival of the patient, who was a boy. The duplication and one of the missense mutations were associated with decreased amounts of E(1)alpha And E(1)beta protein on western blot analysis, whereas the other two mutations were associated with normal amounts. This study adds four novel mutations to the around 90 reported mutations in PDHA1 (HGMD PDHA1 mutation database). The phenotypes of patients with PDH deficiency have been divided into three groups: a neonatal form with severe lactic acidosis, a form observed only in males and characterized by episodes of ataxia with relapses associated with hyperlactataemia, and an infantile form with hypotonia, lethargy, onset of seizures or dystonia, psychomotor retardation, in some cases Leigh-like lesions and mild to moderate hyperlactataemia. The four patients reported here all belong to the latter group, which is the largest.
    Journal of Inherited Metabolic Disease 06/2009; · 4.07 Impact Factor
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    ABSTRACT: Lymphangiogenesis and angiogenesis are critical processes for tumor growth, invasion, and metastasis, and are crucial for therapeutic strategies. The aim of the present study was to evaluate the clinical significance of lymphangiogenesis and its regulation in gastric carcinomas. The lymphatic vessel density (LVD) in 65 gastric carcinoma cases was investigated by immunohistochemistry using D2-40 antibody, and evaluated with prognostic parameters. The intratumoral microvessel density (MVD), using CD31 antibody, was assessed and correlated with LVD. D2-40 identified peritumoral lymphatics in all cases, and lymphatic vessel density (LVD) ranged from 3 to 19 (median, 5; mean ± SD, 7.69 ± 4.67). The peritumoral LVD significantly correlated with large tumor size (P=0.0001), lymph node metastasis (P=0.004), visceral organ metastasis (P=0.0001), and TNM stage (P=0.001). Survival was also significantly lower in patients with high LVD tumors than in patients with low LVD tumors (P=0.04). Among various clinicopathologic characteristics, CD31 expression was associated only with lymph node metastasis (P=0.001). However, there was no significant correlation between CD31 and D2-40. Our study showed that lymphangiogenesis plays an important role in the progression of gastric carcinoma. Therefore, D2-40, as an indicator for tumor lymphangiogenesis, may serve as a prognostic marker in gastric carcinoma.
    Journal of Surgical Research 06/2009; 164(1):110-5. · 2.02 Impact Factor
  • European Journal of Paediatric Neurology - EUR J PAEDIATR NEUROL. 01/2009; 13.
  • European Journal of Paediatric Neurology - EUR J PAEDIATR NEUROL. 01/2009; 13.
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    ABSTRACT: Cyclooxygenase-2 (COX-2) is upregulated in gastric carcinoma, and its increased levels were found to have a prognostic significance in some studies. Both angiogenesis and Helicobacter pylori infection have been reported to be associated with COX-2 expression of gastric cancer in recent studies. In this study, COX-2 expression and its association with CD31 staining, H.-pylori infection, and well-known clinicopathological factors were investigated in 65 gastric cancer patients. COX-2 and CD31 expression assessment was done by immunohistochemical methods. Whartin Starry stain was performed for H.-pylori infection. Of 65 patients, 32 (49%) revealed intense COX-2 immunostaining. Among various clinicopathologic characteristics, COX-2 expression was inversely correlated with tumor size, TNM stage, and lymph node status. Thirty-two (49%) patients revealed intense CD31 immunostaining. Among various clinicopathologic characteristics, CD31 expression was associated only with lymph node metastasis. COX-2 expression was not correlated with CD31 staining and H.-pylori infection. Both COX-2 and CD31 staining had no prognostic significance. In conclusion, we found that COX-2 expression was significantly higher in earlier stages of gastric cancer. It can be suggested that COX-2 expression may be important in the initial development of gastric cancer but not in progression of the disease. Other factors which may be associated with COX-2 in gastric cancer, including angiogenesis and H.-pylori infection, should be investigated in further studies.
    Pathology - Research and Practice 09/2008; 204(8):527-36. · 1.21 Impact Factor
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    ABSTRACT: ObjectiveThe carbon-14 (14C) urea breath test (UBT) is a reliable and noninvasive technique for the diagnosis of Helicobacter pylori (HP) infection. The diagnostic performance of a new practical and low dose 14C UBT system (Heliprobe, Stockholm, Sweden) was compared with those of other diagnostic tests, namely, rapid urease test (RUT), histopathology, and DNA detection using polymerase chain reaction (PCR). MethodsEighty-nine patients (mean age = 45 ± 13, 30 men) with dyspeptic complaints who underwent an endoscopic procedure were studied. Biopsy specimens acquired during the procedure were subjected to RUT, histopathological examination using hematoxylin and eosin (HP-HE) and PCR. All patients underwent UBT using the Heliprobe system on a different day. The gold standard for HP positivity was defined as any two of the three tests being positive, excluding UBT, and the sensitivity and specificity of any single test alone were determined using this gold standard. Whenever only one test was positive, it was considered to be a false-positive one. ResultsWith the gold standard used in this study, 59 (66%) patients were diagnosed HP positive. The Heliprobe method detected HP infection with 96.6% sensitivity and 100% specificity and had the best diagnostic performance when compared with all the other methods. The sensitivity and specificity of the other methods for the detection of HP positivity were 89.8% and 100% for RUT, 93.2% and 63.3% for PCR, and 93.2% and 76.6% for HP-HE, respectively. Areas under the receiver-operating characteristic were 0.977 for UBT, 0.947 for RUT, 0.84 for HP-HE, and 0.775 for PCR. ConclusionsUsing a combination of invasive diagnostic tests as the gold standard, Heliprobe UBT was found to be highly sensitive and specific for the diagnosis of HP infection in patients with dyspeptic complaints.
    Annals of Nuclear Medicine 08/2008; 22(7):611-616. · 1.41 Impact Factor
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    ABSTRACT: Using the 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) (2004 WHO), 1999 WHO/ISUP, and 1973 WHO classifications, we examined Ki67, BCL-2, TP53, and MDM-2 expressions in invasive and noninvasive urothelial neoplasias of the bladder of 72 patients, and compared the results regarding tumor category and grade with clinical outcome to determine the clinicopathological relevance of these classifications. Ki67 and TP53 expressions were correlated with tumor grades of the 1973 WHO classification, and they also distinguished "papillary urothelial neoplasm with low malignant potential" from other WHO/ISUP grades (p < 0.05). No difference was observed for Ki67 and TP53 expressions between the other WHO/ISUP grades (p > 0.05). Neither tumor grade nor tumor category correlated with MDM-2 or BCL-2 expressions (p > 0.05). WHO/ISUP classifications are obviously not superior to the 1973 WHO classification for grading urothelial neoplasia of the bladder. However, if the "papillary urothelial neoplasm with low malignant potential" is distinguished from grade 1 tumors of the 1973 WHO classification, more precise prognostic information may be obtained.
    Pathology - Research and Practice 07/2008; 204(10):707-17. · 1.21 Impact Factor
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    ABSTRACT: The aim of this study was to compare the level of maternal knowledge and the blood phenylalanine (Phe) control in phenylketonuria (PKU; OMIM 261600). The study was conducted on 144 children (81 boys, 63 girls) with PKU, aged between 1 and 15 years, at Hacettepe University Ihsan Dogramaci Children's Hospital, Metabolism and Nutrition Unit. All subjects were treated with a low-Phe diet using a Phe-exchange system. A 20-question multiple-choice questionnaire was applied to the mothers to determine their knowledge about PKU and its dietary treatment. Questions in the test consisted of the knowledge about the disease (6 questions), general dietary knowledge (14 questions) and knowledge about specific exchange within the dietary questions (6 questions). The median blood Phe concentration for the previous 3-year period was used as an indicator of metabolic control. Eighty-seven children had a median blood Phe concentration above the MRC Working Party Guidelines. There was a negative correlation between maternal knowledge about exchange and median blood Phe concentration in the child (p<0.05). Maternal knowledge about a standard 15 mg Phe exchange system is correlated with dietary compliance as measured by blood Phe concentrations in our subjects. We would like to implement an easier method of measuring Phe exchanges to improve dietary knowledge in the mothers.
    Journal of Inherited Metabolic Disease 06/2008; 31 Suppl 2:S213-7. · 4.07 Impact Factor
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    ABSTRACT: The matrix-metalloproteinases (MMPs) are thought to be critically involved in tumor invasion and metastasis. This retrospective study was aimed both to examine the gelatinase expression status in patients with rectal cancer and to investigate their prognostic value on survival. Sixty patients who underwent postoperative adjuvant chemoradiotherapy for Stage II and III rectal carcinoma were included. Expressions of MMP-2, MMP-9, and tissue inhibitors of MMP (TIMP-1 and TIMP-2) were analyzed by immunohistochemistry in paraffin-embedded primary rectal cancers and graded for the intensity and the percentage of cells stained. The relation between the expression of the markers studied and clinicopathologic features were evaluated for the primary study endpoint. The data were also analyzed using a multivariate Cox proportional hazards model for prognosis as a secondary endpoint. Positive MMP-9 expression was observed in 70% of the tumors. The ratio of tumors with positive MMP-9 expression was increased according to N stage (P = 0.005), AJCC stage (P = 0.005), and tumor differentiation (P = 0.017). Overall survival was reduced in poorly differentiated tumors and tumors with positive MMP-9 expression (P = 0.002). Disease-free survival was lower in patients with positive MMP-9 expression (P = 0.007). Multivariate analysis indicated that positive MMP-9 expression was an independent predictor of reduced overall survival (P = 0.0103) and reduced disease-free survival (P = 0.0360). The other markers studied were associated with neither any clinicopathologic feature nor any survival parameter. MMP-9 expression was observed in the tumors of patients with Stage II and III rectal carcinoma in comparable values and was characterized by poor overall survival and disease-free survival.
    American journal of clinical oncology 03/2008; 31(1):55-63. · 2.21 Impact Factor
  • Colorectal Disease 02/2008; 10(7):735-6. · 2.08 Impact Factor
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    ABSTRACT: Lamotrigine is an antiepileptic drug that inhibits presynaptic voltage-gated sodium channels and reduces the presynaptic release of glutamate in pathological states. Neuroprotective effects of this drug have already been demonstrated in cerebral ischemia models. The aim of the present study was to determine the effects of presynaptic glutamate release inhibition on experimental spinal cord injury (SCI). A total of 66 adult Wistar rats were randomly allocated into 6 groups. Group I was the control group used to obtain normal blood samples and spinal cord specimens. Spinal cord injury was introduced by using the extradural clip compression technique, but no medication was given to Group II (trauma group) rats. Group III was treated with vehicle, and the same amount of dimethyl sulfoxide used in treatment groups was administered to these rats. A dose of 50 mg/kg lamotrigine was administered intraperitoneally to Group IV (pretreatment), Group V (peritreatment), and Group VI (posttreatment) rats 30 minutes before, during, and 30 minutes after SCI, respectively. Oxidative stress parameters and transmission electron microscopic findings were examined. Blockade of presynaptic release of glutamate by lamotrigine treatment yielded protective effects on the spinal cord ultrastructure even when administered after the SCI, but it prevented oxidative stress only when it was administered before or during the SCI. Currently, no available agent has been identified, that can block all the glutamate receptors at the same time. To prevent excitotoxicity in SCI, inhibiting glutamate release from the presynaptic buttons instead of blocking the postsynaptic glutamate receptors seems to be a more rational approach. Further research, such as neurobehavioral assessment, is warranted to demonstrate the probable neuroprotective effects of presynaptic glutamate release inhibition in SCI.
    Neurosurgical FOCUS 02/2008; 25(5):E6. · 2.49 Impact Factor
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    ABSTRACT: The aim of this article was to investigate the efficacy of ultrasonography-guided core needle biopsy and prognostic factor analysis of breast cancer to plan overall treatment strategy. A consecutive series of nonpalpable and palpable breast cancers constituted our study group (n= 201 lesions; mean size, 20.4 mm) Mean number of core samples was 3.4. Malignant lesions diagnosed with core biopsy underwent therapeutic surgical excision. Core biopsy and surgical excisions were compared for histologic type, grade, estrogen receptors (ERs), progesterone receptors (PgRs), and c-erbB2 levels. Cutoff values for ER, PgR, and c-erbB2 affecting the management strategy were selected as 10%, 10%, and 50%, respectively. Eighty-five lesions (42.3%) were malignant in core biopsy (mean size, 18.4 mm). Among these, 11 were inoperable and 13 were surgically excised at other institutions. In 61 lesions, core and surgical excision specimens were evaluated in the same institution (mean tumor size, 18.6 mm; range 6-60 mm). Concordance between the 2 biopsy methods was 85.2% (52 of 61) for histologic type of tumor, 68.8% (33 of 48) for tumor grade, 90% (27 of 30) for ER, 86.7% (26 of 30) for PgR, and 79.3% (23 of 29) for c-erbB2 levels. Appropriate site selection for sampling was indicated to be of paramount importance, especially in determining reliable ER, PgR, and c-erbB2 levels. Core needle biopsy of breast cancer is equally effective compared with surgical biopsy and can be used in overall treatment planning. However, appropriate site selection for sampling should be guaranteed using ultrasonographic guidance.
    Clinical Breast Cancer 11/2007; 7(10):791-5. · 2.42 Impact Factor

Publication Stats

533 Citations
139.29 Total Impact Points

Institutions

  • 1996–2012
    • Gazi University
      • • Faculty of Medicine
      • • Department of Pathology
      • • Department of Radiation Oncology
      • • Department of Pediatric Surgery
      Ankara, Ankara, Turkey
  • 2000–2011
    • Hacettepe University
      • • Department of Pediatrics
      • • Faculty of Medicine
      Ankara, Ankara, Turkey
  • 2006
    • Mersin University
      • Department of Obstetrics and Gynaecology
      Zephyrium, Mersin, Turkey