Ufuk Berber

CYP1A1 (Ile462Val), CYP1B1 (Ala119Ser and Val432Leu), GSTM1 (null), and GSTT1 (null) polymorphisms and bladder cancer risk in a Turkish population.

We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.

miR-205 and miR-200c: Predictive Micro RNAs for Lymph Node Metastasis in Triple Negative Breast Cancer

Purpose We examined expression profiles of 16 micro RNAs (miRNAs) in triple negative breast cancers to identify their potential as biomarkers for lymph node metastasis. Methods The expression profiles of miR-9, miR-21, miR-30a, miR-30d, miR-31, miR-34a, miR-34c, miR-100, miR-122, miR-125b, miR-146a, miR-146b, miR-155, miR-181a, miR-200c, and miR-205 were examined by using real-time quantitative reverse transcription polymerase chain reaction in tumor samples and corresponding benign breast tissues. Their associations with histopathological features and prognostic parameters were assessed. Results When compared with the expression in benign breast tissues, seven of the miRNAs (miR-31, miR-205, miR-34a, miR-146a, miR-125b, miR-34c, and miR-181a) were downregulated more than 1.5-fold in tumor tissues, whereas, only miR-21 was found to be upregulated more than 1.5-fold in tumor tissues. Although miR-200c levels were decreased only 1.12-fold in tumor tissues, the reduced expressions of miR-200c and miR-205 were significantly associated with lymph node metastasis (p=0.021 and p=0.016, respectively). Conclusion Our results demonstrate that miR-205 and miR-200c expression levels may be useful in predicting lymph node metastasis in triple negative breast cancer patients.

Is combination of neutrophil to lymphocyte ratio and platelet lymphocyte ratio a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma

Dear editor We read with interest the recent article entitled “Combination of neutrophil to lymphocyte ratio and platelet lymphocyte ratio is a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma” by Feng et al.1 In their study, authors aimed to investigate the usefulness of a novel inflammation-based prognostic system, using the combination of neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), for predicting survival in patients with esophageal squamous cell carcinoma (ESCC). Finally, they concluded that combination of NLR and PLR is a useful predictor of postoperative survival in patients with ESCC and combination of these parameters is superior to NLR or PLR as a predictive factor in patients with ESCC. We would like to thank the authors for their contribution. PLR has been recently suggested to be a marker of thrombotic and inflammatory condition, mainly in patients with malignancies.2,3 NLR is a readily available and inexpensive laboratory marker which is used to assess systemic inflammation. In literature, it was shown that diabetes mellitus, thyroid functional abnormalities, essential hypertension, valvular heart diseases, acute coronary syndromes, renal and/or hepatic failure, metabolic syndrome, and many inflammatory diseases may potentially affect the NLR.4–7 Thus, it would be more relevant if Feng et al had mentioned these NLR-affecting factors while evaluating the predictive role of NLR in postoperative survival of patients with ESCC. Besides, medication may alter NLR and/or PLR, so it would have been useful if the patients were described in greater detail in terms of antibiotic, anti-diabetic, anti-hypertensive drug use and/or other medications. In addition, it would also have been better if the authors indicated the elapsed time between taking the blood samples and measuring NLR and PLR, since waiting period prior to analysis may affect these parameters. We believe that the findings of Feng et al1 will lead to further studies concerning the predictive role of NLR and PLR for postoperative survival of patients with ESCC. But, it should be clearly kept in mind that NLR or PLR itself alone without other variables may not secure true information about postoperative survival of patients with ESCC. Finally we concluded that these parameters should be evaluated with other variables as mentioned above.

Peptic ulcer and intestinal metaplasia associated with Helicobacter pylori colonization in gastric heterotopia of the tongue.

To the Editor, Gastric heterotopia (GH) can occur throughout the digestive tract; however, involvement of the tongue is rare, and fewer than 40 cases have been reported up to date. In the head and neck region, it is frequently seen in infants or young adults, with a male predominance (1). Clinical presentation varies, depending on the involved site, as well as the extent of the lesion. An interesting issue of GH is the colonization of Helicobacter pylori (H. pylori) and its association with complications. Here, we report the first case of peptic ulcer and intestinal metaplasia associated with colonization of H. pylori in GH of the tongue. A 21-year-old man was referred to the ear, nose, and throat (ENT) department for a slowly growing mass on his tongue that lasted for 4 years and became ulcerated in the last 3 months. Physical examination revealed an ulcerated polypoid mass of 0.9 cm in the biggest diameter at the anterior part of the tongue. Examination of the oropharynx and nasopharynx did not reveal any other finding. The patient was a nonsmoker, and his family history was unremarkable for orofacial abnormalities. An excisional biopsy was performed for diagnostic and therapeutic purposes. Histologic evaluation revealed the presence of gastric tissue that extended into the striated muscle layer of the tongue (Figure 1). There were scattered intestinal metaplasia foci containing Goblet cells. Toluidine bluestained sections suggested the presence of H. pylori in the lumina of the glandular epithelium. Colonization of H. pylori was demonstrated by immunohistochemical method using polyclonal H. pylori antibody (Cell Marque, Rocklin, CA, USA) and confirmed by polymerase chain reaction-based methods. H. pylori colonization in GH is mostly limited to esophageal and intestinal lesions (2,3). It is consistently not present in gallbladder (4) and was not reported in the oral cavity before. Although proton pump inhibitors were advised for the treatment of ulcerated lesions, our case suggested that proton pump inhibitors alone may not be sufficient for treatment of GH in the oral cavity. Moreover, besides the predisposing role of H. pylori for gastric cancer, its association with oral cancer has also been indicated (5). Therefore, surgical removal may likely be the preferred treatment choice for GH of the oral cavity.

Effectiveness of interleukin-1 receptor antagonist (Anakinra) on cerulein-induced experimental acute pancreatitis in rats

Abstract Aim. Acute pancreatitis (AP) is defined as an inflammatory disease of the pancreas. The purpose of this study was to examine the effectiveness of Anakinra on cerulein-induced experimental pancreatitis rat model by using the results of biochemical and histopathological findings. Materials and methods. Cerulein was administered to induce AP in rats. Group 1 was the sham group. Subcutancerulein was injected to the rats in group 2 for experimental pancreatitis group. In groups 3 and 4, 100 and 50 mg/kg intraperitoneal Anakinra were injected after the induction of experimental pancreatitis by subcutaneous cerulein in rats, respectively. Lastly, in group 5, rats were injected with intraperitoneal saline and subcutan cerulean for placebo group. The following parameters were evaluated: histopathological score of pancreatitis, apoptotic index, amylase, lipase, TNF-α levels, IL-1β and the leukocyte count. Results. When the results of serum amylase, lipase, TNF-α and IL-1β levels, the leukocyte count, histopathologic scores and apoptotic indices of control group compared to the results of other groups, the differences exhibited statistical significance (all p < 0.05). On the other hand, when the results of fourth group compared with the results of third group, the data demonstrated statistical insignificance (p > 0.05). However, no any significant differences were found between the results of fourth and fifth groups (p > 0.05). Conclusion. In the light of these results, cerulein is an appropriate agent for experimental AP rat model and Anakinra has a favorable therapeutic effect on acute experimental pancreatitis model. Moreover, Anakinra significantly decreases cerulein-related pancreatic tissue injury and pancreatic apoptosis.

microRNA Expression Profile in Patients with Stage II Colorectal Cancer: A Turkish Referral Center Study

BACKGROUND There are increasing data about microRNAs (miRNA) in the literature, providing abundant evidence that they play important roles in pathogenesis and development of colorectal cancer. In this study, we aimed to investigate the miRNA expression profiles in surgically resected specimens of patients with recurrent and non-recurrent colorectal cancer. MATERIALS AND METHODS The study population included 40 patients with stage II colorectal cancer (20 patients with recurrent tumors, and 20 sex and age matched patients without recurrence), who underwent curative colectomy between 2004 and 2011 without adjuvant therapy. Expression of 16 miRNAs (miRNA-9, 21, 30d, 31, 106a, 127, 133a, 133b, 135b, 143, 145, 155, 182, 200a, 200c, 362) was verified by quantitative real-time polymerase chain reaction (qRT-PCR) in all resected colon cancer tissue samples and in corresponding normal colonic tissues. Data analyses were carried out using SPSS 15 software. Values were statistically significantly changed in 40 cancer tissues when compared to the corresponding 40 normal colonic tissues (p<0.001). MiR-30d, miR-133a, miR-143, miR-145 and miR-362 expression was statistically significantly downregulated in 40 resected colorectal cancer tissue samples (p<0.001). When we compared subgroups, miRNA expression profiles of 20 recurrent cancer tissues were similar to all 40 cancer tissues. However in 20 non-recurrent cancer tissues, miR-133a expression was not significantly downregulated, moreover miR-133b expression was significantly upregulated (p<0.05). CONCLUSIONS Our study revealed dysregulation of expression of ten miRNAs in Turkish colon cancer patients. These miRNAs may be used as potential biomarkers for early detection, screening and surveillance of colorectal cancer, with functional effects on tumor cell behavior.

Trimetazidine significantly reduces cerulein-induced pancreatic apoptosis

OBJECTIVE Acute pancreatitis continues to be associated with significant rates of mortality and morbidity, and therapeutic options are still very limited. We aimed to investigate the efficacy of trimetazidine on cerulein-induced pancreatic apoptosis and histopathological and biochemistrical consequences of acute pancreatitis. METHODS Thirty-two Wistar albino rats were randomized into four groups (group 1: control group; group 2: acute pancreatitis group; group 3: acute pancreatitis and trimetazidine treatment group; group 4: placebo group). Acute edematous pancreatitis was induced by subcutaneous cerulein injection (20 μg/kg) four times at one-hour intervals. Trimetazidine was prepared in suspension form. In group 3, after gas anesthesia, trimetazidine was administrated to rats via a catheter. Serum interleukin (IL)-1β, tumor necrosis factor (TNF)-α, amylase, lipase and leukocyte levels, pancreatic apoptotic status and pancreatic Schoenberg scores were determined for all groups. Results are given as the mean ± SD. A value of P<0.05 was accepted as statistically significant. SPSS for Windows v15.0 was used for statistical analyses. RESULTS In the acute pancreatitis group IL-1β, amylase, lipase and leukocyte levels were elevated and pancreatic histopathological evaluation revealed a diagnosis of acute pancreatitis IL-1β amylase and lipase levels and pancreatic inflammation were decreased significantly in the trimetazidine group (P<0.01). White blood cell counts and TNF-α concentrations for the trimetazidine group and the acute pancreatitis group were not significantly different. Trimetazidine significantly reduced apoptosis in pancreatic tissues and Schoenberg scores were also significantly reduced (P<0.05). CONCLUSION In this study, we showed that trimetazidine treatment significantly decreases the levels of IL-1β, amylase and lipase reduces pancreatic apoptosis and ameliorates the histopathological findings of cerulein-induced acute pancreatitis. Trimetazidine could be a new therapeutic option in the early treatment of acute pancreatitis.

Expression of P-cadherin (cadherin-3) and E-selectin in the villous trophoblast of first trimester human placenta.

OBJECTIVE Although trophoblastic invasion has a critical role in human placental development, very little is known about them. The aim of the present study was to localise the expression of P-cadherin (cadherin-3) and E-selectin in first trimester placenta. MATERIAL AND METHODS This study was conducted on 140 patients who had applied to Gülhane Military Medical Academy, Haydarpaşa Education Hospital, Department of Obstetrics and Gynaecology between 2005 and 2006. The patients were divided into three groups: ectopic pregnancy group (Group 1), spontaneous abortion group (group 2) and curettage group (group 3 and/or control group). Patients with a history of systemic diseases (such as thrombophilia), a disease or anatomical diagnosis that may cause recurrent abortion or an aetiological factor for ectopic pregnancy were excluded from the study. Paraffin blocks were stained with E-selectin and P-cadherin in accordance with the procedure. Demographic characteristics of patients (patient age, gravida, parity, number of previous abortions, and last menstrual period) and staining intensities were compared using Analysis of Variance (ANOVA) among groups. RESULTS According to the average scale score of P-cadherin staining of cells, the three groups were statistically different from each other (p=0.0001). This difference stems from statistically significantly lower scores in the spontaneous abortion group than in both the ectopic pregnancy group (p<0.001) and the control group (p<0.001). E-selectin immunostaining showed no positive staining in the groups. CONCLUSION In placental trophoblasts, decreased P-cadherin immunoreactivity plays a role in the aetiopathogenesis of spontaneous abortion.

Is the Combination of Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratios a Useful Predictor of Treatment Response and Prognosis in Patients with Non-Small Cell Lung Cancer?

We read with interest the recent article entitled ‘Are neutrophil/lymphocyte and platelet/lymphocyte rates in patients with non small cell lung cancer associated with treatment response and prognosis?’ by Unal et al. (2013). In their study, the authors aimed to research effects of the pretreatment neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) on survival and chemoradiotherapy response in non-small-cell lung cancer patients (NSCLC). At the end of the study, they concluded that pretreatment NLR and PLR assessment may secure valuable prognostic results in patients with NSCLC. We would like to thank the authors for their contribution. PLR has been recently proposed to be a predictor of thrombotic and inflammatory conditions, principally in patients with many kind of malignancies (Smith et al., 2008; Wang et al., 2013). NLR is an inexpensive and easily available laboratory marker which is used to estimate systemic inflammatory status. To date, it has been shown that thyroid functional abnormalities, diabetes mellitus, essential hypertension, renal failure, metabolic syndrome, valvular heart diseases, many inflammatory diseases may potentially affect the NLR (Stotz et al., 2013; Zheng et al., 2013; Tanoglu et al., 2014, Tanoglu and Karagoz 2014). Thus, it would have been better if Unal et al. (2013) had mentioned these NLR-affecting factors while evaluating the pretreatment neutrophil to lymphocyte ratio on survival and chemoradiotherapy response in patients with non-small-cell lung cancer. Moreover, any kind of medication may easily change NLR and/or PLR, so it would have been more useful if the NSCLC patients were described in a detailed manner regarding antidiabetic drug, antihypertensive drug, antibiotic, steroid use and/or other medications. Besides, it would also have been more useful if the authors indicated the elapsed time between obtaining the blood samples and measuring NLR and PLR, since any time delay prior to analysis may affect these two parameters (Tanoglu et al., 2014, Tanoglu and Karagoz, 2014). We believe that the paper of Unal et al. (2013) will lead to further studies concerning effects of the pretreatment NLR and PLR on survival and chemoradiotherapy response in non-small-cell lung cancer patients. However, it should be clearly kept in mind that NLR or PLR itself alone without other variables may not provide accurate and

Differential diagnosis of cervical lymphadenitis mimicking malignancy due to tularemia: Our experiences

BACKGROUND Tularemia is a disease caused by a Gram-negative coccobacillus Francisella tularensis. This bacterium may cause different types of clinical pictures owing to acquisition route and entrance site, such as ulceroglandular, oropharyngeal, glandular, pneumonic, typhoid and ocular forms. Oropharyngeal tularemia (OPT) is the most common form of tularemia in some regions. OPT may cause tonsillopharyngitis followed by cervical lymphadenopathies (LAPs). Without treatment LAP may persist for several months and may mimic other diseases causing cervical LAPs. MATERIALS AND METHODS A total of six cases of OPT, five male and one female, between 21 and 31 years old, diagnosed serologically and clinically recorded in GATA Haydarpasa Training Hospital were included in this study. Detailed story including the region they lived for last 6 months, their occupation, family and neighborhood story with similar complaints were obtained. Patient data were also obtained from manually written patients files and electronical patient file system. Formalin fixed paraffin embedded tissue blocks of all biopsy material were submitted for polymerase chain reaction (PCR) study for F. tularensis. RESULTS A total of six cases with head and neck mass following a story of tonsillopharyngitis admitted to different clinics including infectious diseases, ear-nose-throat and internal medicine in our tertiary care hospital. Physical examination revealed immobile, hard, conglomerated unilateral cervical lymphadenopathy in all cases. Histopathological examination revealed granulomatous inflammation in four cases. Acute suppurative inflammatory changes were also seen in two cases. Large necrotic areas mimicking casseifying necrosis were seen in two cases. PCR amplification of F. tularensis genom from isolated deoxyribonucleic acids was successful in five cases. CONCLUSION Tularemia should be kept in mind in patients with tonsillopharyngitis not responding to penicillins and beta lactam antibiotics. Furthermore, persisting LAPs mimicking tumor with or without the story of previously experienced sore throat or tonsillopharyngitis in past few days or weeks should be evaluated for glandular or OPT. At this point, easily applicable serological tests such as tularemia micro-agglutination tests will confirm the diagnosis of OPT. However, if lymph node were already sampled to exclude especially malignancy or T cell lymphoma, tularemia PCR test may be used to make a certain diagnosis.