Elmas Kasap

The potential role of the NEK6, AURKA, AURKB, and PAK1 genes in adenomatous colorectal polyps and colorectal adenocarcinoma

Colorectal adenomatous polyp (CRAP) is a major risk factor for the development of sporadic colorectal cancer (CRC). Histone modifications are one of the epigenetic mechanisms that may have key roles in the carcinogenesis of CRC. The objective of the present study is to investigate the alternations in the defined histone modification gene expression profiles in patients with CRAP and CRC. Histone modification enzyme key gene expressions of the CRC, CRAP, and control groups were evaluated and compared using the reverse transcription PCR (RT-PCR) array method. Gene expression analysis was performed in the CRAP group after dividing the patients into subgroups according to the polyp diameter, pathological results, and morphological parameters which are risk factors for developing CRC in patients with CRAP. PAK1, NEK6, AURKA, AURKB, HDAC1, and HDAC7 were significantly more overexpressed in CRC subjects compared to the controls (p < 0.05). PAK1, NEK6, AURKA, AURKB, and HDAC1 were significantly more overexpressed in the CRAP group compared to the controls (p < 0.005). There were no significant differences between the CRAP and CRC groups with regards to PAK1, NEK6, AURKA, or AURKB gene overexpression. PAK1, NEK6, AURKA, and AURKB were significantly in correlation with the polyp diameter as they were more overexpressed in polyps with larger diameters. In conclusion, overexpressions of NEK6, AURKA, AURKB, and PAK1 genes can be used as predictive markers to decide the colonoscopic surveillance intervals after the polypectomy procedure especially in polyps with larger diameters.

Never in mitosis gene A-related kinase 6 and aurora kinase A: New gene biomarkers in the conversion from ulcerative colitis to colorectal cancer

Ulcerative colitis (UC) is an important risk factor for colorectal cancer (CRC). Histone modifications are one of the epigenetic mechanisms that may have key roles in the carcinogenesis of CRC. At present, there are no studies comparing histone modification patterns of UC and CRC in the literature. Therefore the aim of the present study was to investigate whether genes, particularly those involved in histone modification, have value in patient monitoring with regards to CRC development in UC. Key gene expressions of the histone modification enzyme were assessed and compared in CRC, UC and control groups using the RT-PCR array technique. Patients were divided into subgroups based on the extent and duration of the disease and inflammatory burden, which are considered risk factors for CRC development in UC patients. In UC and CRC groups, a significantly higher overexpression of the NEK6 and AURKA genes compared to the control group was identified. In addition, there was a significantly higher overexpression of HDAC1 and PAK1 genes in the UC group, and of HDAC1, HDAC7, PAK1 and AURKB genes in the CRC group. NEK6, AURKA, HDAC1 and PAK1 were significantly overexpressed in patients with a longer UC duration. Overexpression of AURKA and NEK6 genes was significantly more pronounced in UC patients with more extensive colon involvement. HDAC1, HDAC7, PAK1, NEK6, AURKA and AURKB are important diagnostic and prognostic markers involved in the carcinogenesis of CRC. HDAC1, PAK1, NEK6 and AURKA may be considered as diagnostic markers to be used in CRC screening for UC patients.

Angiotensin-Converting Enzyme Genotype and Acute Pancreatitis in Turkey

Angiotensin-Converting Enzyme Genotype and Acute Pancreatitis in Turkey The renin-angiotensin system (RAS) has been implicated in the pathogenesis of acute and chronic pancreatitis. Angiotensin-converting enzyme (ACE) is the key enzyme which activates RAS. The ACE intron 16 insertion/ deletion (I/D) polymorphism is associated with ACE activity and is considered to be a risk factor for several inflammatory processes. We investigated this polymorphism in 68 patients with acute pancreatitis (AP) and 157 healthy Turkish control subjects. Patients were evaluated with ultrasonography, abdominal tomography and laboratory markers and grouped by status for diabetes mellitus (DM), hypertension (HT), and both these diseases and by etiology. Genotyping of the I/D polymorphism was performed by polymerase chain reaction (PCR). The DD genotype was more prevalent in healthy controls, however, genotype II was significantly more frequent in AP patients (p <0.05). In severe AP patients, the genotype II frequency was significantly higher than in controls (p <0.05). Acute pancreatitis patients with both DM and HT had lower frequencies of genotype DD and of the D allele, and higher frequencies of genotype II and of the I allele than patients with either DM or HT (p <0.05).

Potential role of chromatin remodeling factor genes in atrophic gastritis/gastric cancer risk

BACKGROUND/AIMS Atrophic gastritis (AG), intestinal metaplasia (IM), and Helicobacter pylori (HP) are the risk factors for the development of gastric cancer (GC). Chromatin remodeling is one of the epigenetic mechanisms involved in the carcinogenesis of GC. The purpose of this study was to investigate the expression profiles of defined chromatin remodeling genes in gastric mucosal samples and their values as gastric carcinogenesis biomarkers. MATERIALS AND METHODS In total, 95 patients were included in the study. Patients were divided into 3 groups as: GC group (n=34), AG group (n=36), and control group (n=25). AG group was further divided into subgroups based on the presence of HP and IM in gastric mucosa. Chromatin remodeling gene expressions were analyzed using real-time PCR (RT-PCR) array in all groups. Data were evaluated using the RT-qPCR primer assay data analysis software. RESULTS EED, CBX3, and MTA1 were more overexpressed, whereas ARID1A, ING5, and CBX7 were more underexpressed in the AG and GC groups compared with the controls. No significant differences were observed between the AG and GC groups concerning the expression of these 6 genes, although the fold change levels of these genes in the GC group were well above than in the AG group. EED, CBX3, and MTA1 were significantly more overexpressed in HP- and IM-positive AG subgroup compared with the HP- or IM-negative AG subgroup. CONCLUSION In conclusion, our results provide an evidence of epigenetic alterations in AG. Expressions of EED, CBX3, MTA1, ARID1A, ING5, and CBX7 may be considered as promising markers to be used in GC screening for patients with AG.

Expression profiles of histone modification genes in gastric cancer progression

Gastric cancer (GC) development can be attributed to several risk factors including atrophic gastritis (AG), intestinal metaplasia (IM), and the presence of Helicobacter pylori (HP). Also, histone modification is an epigenetic mechanism that plays a pivotal role in GC carcinogenesis. In this preliminary study, we aimed to describe the expression profiles of histone modification in the AG, IM, and GC patient groups. A total of 80 patients with AG (n = 27), IM (n = 25), and GC (n = 28) with an additional 20 control subjects were included in the study. Expression profiles of three histone phosphorylation genes (PAK1, NEK6, and AURKA) and five histone deacetylation genes (HDACs 1, 2, 3, 5, and 7) were examined based on the results of Real Time qPCR method. It was observed that AURKA and HDAC2 genes were significantly overexpressed in all groups compared to the control (P < 0.05). In GC patients, overexpression of HDAC2 gene was detected in the absence of metastasis, and overexpression of AURKA, HDAC2, and NEK6 genes was detected in the presence of metastasis. When cancer involvements were compared, significant overexpression of the HDAC2 gene was noted in overall and corpus involvements (P < 0.05). In addition, overexpression of AURKA, NEK6, HDAC1, and HDAC2 genes and underexpression of HDAC5 gene were detected in the antrum involvement (P < 0.05). In conclusion, decreased expression of HDAC5 in GC is reported for the first time in this study, while supporting the existing literature in AURKA, NEK6, HDAC1, and HDAC2 up regulations during GC development.

Treatment of inflammatory bowel disease by leukocytapheresis

Studies about leukocytapheresis have emerged with the need of search for alternatives to conventional treatment in inflammatory bowel diseases (IBD). Leukocytapheresis is a novel non-pharmacologic approach for active ulcerative colitis (UC) and Crohns disease (CD), in which leukocytes are mechanically removed from the circulatory system. Patients with active IBD treated with leukocytapheresis using a Cellsorba E column between 2012 and 2015, were enrolled in Turkey. In our experience, the results of leukocytapheresis therapy in 6 patients with CD and 20 patients with active UC were overviewed. Leukocytapheresis (10 sessions for remission induction therapy, 6 sessions for maintenance therapy) was applied to the patients with their concomitant medications. Intensive leukocytapheresis (≥4 leukocytapheresis sessions within the first 2 weeks) was used in 30% patients with active severe UC. The overall clinical remission rate in patients with UC was 80%, and the mucosal healing rate was 65%. Patients were followed for an average of 24 months. It was observed that clinical remission has continued in 65% of patients with UC. Mild relapse was observed in 3 patients with UC during follow up period. In 5 patients with CD significant clinical remission was achieved except only one patient. Surgical needs were disappeared in 3 patients with obstructive type Crohns disease. Adverse events were seen in only 4.3% of 416 sessions. Any concomitant medications did not increase the incidence of adverse events. Our results indicate that leukocytapheresis is efficacious in improving remission rates with excellent tolerability and safety in patients with IBD.

Otoimmün karaciğer hastalıklarında Helicobacter pylori ve üst gastrointestinal endoskopi bulgularının sıklığı

Giris ve Amac: Helicobacter pylori bircok gastrik hastaligin nedenidir. Otoimmun karaciger hastaliklarina diger hastaliklar ile iliskisiz olan cesitli ust gastrointestinal sistem mukozal bulgulari eslik edebilir. Calismamizdaki amacimiz retrospektif olarak otoimmun karaciger hastaliklarinda ust gastrointestinal endoskopi bulgularini taramak ve Helicobacter pylori ile iliskisini arastirmaktir. Gerec ve Yontem: Bu calismaya 99 otoimmun karaciger hastasi ve 110 kontrol grubu hastasi dahil edilmistir. Her hastanin antrumdan ve gastrik yuzeyden alinan endoskopik biyopsileri incelenmis ve Helicobacter pylori varligi degerlendirilmistir. Hastalar daha oncesinde asit supresyon, antibiyotik ya da steroid disi inflamatuvar baskilayici ajan tedavisi almis ise ve veya cesitli nedenler ile gastrik biyopsi alinmamis ise calismaya dahil edilmedi.Bulgular: Helicobacter pylori otoimmun hepatit hastalarinda %60, primer biliyer siroz hastalarinda %57 ve kontrol grubunda %63 saptandi. Uc grup arasinda belirgin bir farklilik yoktu. Patolojik endoskopik bulgular otoimmun hepatit hastalarinda %45, primer biliyer siroz hastalarinda %52 ve kontrol grubunda %43 saptandi. Sonuc: Helicobacter pylori otoimmun hastalar ile kontrol grubu arasinda benzer bulundu. Endoskopik antral gastrit otoimmun hepatit hastalarinda yuksek saptansa da otoimmun karaciger hastalarinda dispeptik gruba gore belirgin bir endoskopik bulgu farkliligi saptanmadi.

Alteration in Methylation Pattern of Retinoblastoma 1 Gene Promotor Region in Intestinal Metaplasia with or without Helicobacter pylori and Gastric Cancer Patients

BACKGROUND Helicobacter pylori, intestinal metaplasia (IM), and gene methylation play important roles in gastric carcinogenesis. However, the association among H. pylori infection, IM, gastric cancer (GC), and gene methylation is not fully understood. Cell cycle control involving retinoblastoma 1 (RB1) gene is one of the main regulatory pathways reported to be altered in gastric carcinogenesis. OBJECTIVES The purpose of this research is to assess the methylation status of RB1 gene in GC and IM with or without H. pylori infection, and to discuss the possible role of H. pylori-induced RB1 gene methylation in the mechanism of gastric carcinogenesis. MATERIAL AND METHODS The methylation profile of RB1 gene was analyzed by sodium bisulfite modification and methylation-specific PCR in GC (n = 24), IM patients with H. pylori positive (n = 20) and negative (n = 20), and control subjects (n = 20). RESULTS According to methylation levels in RB1 gene; the high correlation values were detected between H. pylori positive-IM group and GC group, and between H. pylori positive-IM and H. pylori negative-IM groups (p < 0.05). No correlations between H. pylori negative-IM and GC groups and between GC and control groups were detected in methylation status of RB1 gene. CONCLUSIONS High methylation levels in RB1 gene in H. pylori positive individuals may suggest an elevated risk of gastric cancer occurrence.

Schizophrenia and gastroesophageal reflux symptoms.

Background: Psychological factors and psychiatric disorders play a role in a variety of gastrointestinal illnesses, including esophageal diseases. Aim: The aim of the present study was to evaluate the frequency of gastroesophageal reflux disease symptoms in patients with schizophrenia in Turkey. Patients and Methods: Ninety-eight patients with schizophrenia and one hundred control individuals were enrolled in the study, which was undertaken at the Manisa State Hospital for Mental Health and Neurological Disorders and Celal Bayar University Gastroenterology Department. Case and control subjects alike underwent 30–45 min oral interviews conducted by a designated study coordinator (E.K.). The coordinator gathered information about demographic characteristics, social habits, and a large variety of symptoms suggestive of reflux disease or other gastrointestinal conditions. Results: In terms of reflux symptoms, cough was the only significant association in schizophrenic patients than controls. Heartburn and regurgitation were more frequent in schizophrenic patients who smoked than in controls who were smokers. However, the prevalence of reflux symptoms in cigarette smokers versus nonsmoker patients with schizophrenia was similar. Heartburn and/or regurgitation occurred more frequently in patients with schizophrenic than controls with alcohol use. Conclusions: Psychiatric disorders might indirectly affect esophageal physiology through increased consumption of alcohol and nicotine.

Dispeptik olgularda ultrasonografinin yeri

Giris ve Amac: Dispepsi, yuksek siklikta gorulmesi nedeniyle toplumlarin onemli bir saglik sorunudur. Gastroskopi ve ust batin ultrasonografisi dispeptik hastalarda en sik kullanilan tetkiklerdir. Calismamizin amaci, dispepsi tanisi olan hastalarda ust batin ultrasonografi bulgularinin retrospektif olarak degerlendirilmesi ve ultrasonografinin dispeptik olgulardaki yerinin arastirilmasidir. Gerec ve Yontem: Celal Bayar Universitesi Tip Fakultesi Gastroenteroloji Polikliniginde dispepsi tanisi alan ve batin ultrasonografisi yapilmis olan 180 olgu ve 176 kontrol grubu calismaya dahil edildi. Bulgular: Dispepsi tanili hastalarin %23’unde, kontrol grubunun ise %51’inde batin ultrasonografisi normal olarak saptandi. Normal ultrasonografi bulgularinin kontrol grubunda dispeptik olgulara gore istatistiksel anlamli oldugu saptandi (p < 0.00004). Dispepsi tanili hastalarin %36’sinda, kontrol gurubunun ise %13’unde batin ultrasonografisinde safra kesesi tasi oldugu saptandi. Safra kesesi tasi gorulme sikliginin dispeptik olgularda, kontrol gurubuna gore istatistiksel anlamli oldugu goruldu (p < 0.0001). Sonuc: Ultrasonografi, dispeptik olgularda mutlaka tanida kullanilmasi gereken laboratuvar tetkiklerinden biri olmalidir.