Association of miR-1266 with Recurrence/Metastasis Potential in Estrogen Receptor Positive Breast Cancer Patients

Sevinc, Elif Demirdogen,Egeli, Unal,Cecener, Gulsah,Tezcan, Gulcin,Tunca, Berrin,Gokgoz, Sehsuvar,Tasdelen, Ismet,Tolunay, Sahsine,Evrensel, Turkkan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.1

The Homeobox B13 (HOXB13):Interleukin 17 Receptor B (IL17BR) index of estrogen receptor (ER)-positive breast cancer (ER (+) BC) patients may be a potential biomarker of recurrence/ metastasis. However, effects of microRNA (miRNA) binding to the 3' untranslated region (3' UTR) of HOXB13 and IL17BR and its function on recurrence/metastasis in ER (+) BC remains elusive. The aims of this study were to determine the expression of miRNAs that bind to 3' UTR of HOXB13 and IL17BR in ER (+) BC patients and asess the effects of these miRNAs on recurrence/metastasis. The expression profiles of HOXB13 and IL17BR were evaluated using RT-PCR in tumors and normal tissue samples from 40 ER (+) BC patients. The expression level of 4 miRNAs, which were predicted to bind the 3' UTR of HOXB13 and IL17BR using TargetScan, microRNA.org and miRDB online databases, were further evaluated with RT-PCR. Our findings demonstrated that high miR-1266 levels might be significant prognostic factor for recurrence/metastasis occurrence (3.05 fold p=0.004) and tamoxifen response (3.90 fold; p=0.2514) in ER (+) BC cases. Although we suggest that modulation of miR-1266 expression may be an important mechanism underlying the chemoresistance of ER (+) BC, advanced studies and validation are required.

Validation of Three Breast Cancer Nomograms and a New Formula for Predicting Non-sentinel Lymph Node Status

Derici, Serhan,Sevinc, Ali,Harmancioglu, Omer,Saydam, Serdar,Kocdor, Mehmet,Aksoy, Suleyman,Egeli, Tufan,Canda, Tulay,Ellidokuz, Hulya,Derici, Solen Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Background: The aim of the study was to evaluate the available breast nomograms (MSKCC, Stanford, Tenon) to predict non-sentinel lymph node metastasis (NSLNM) and to determine variables for NSLNM in SLN positive breast cancer patients in our population. Materials and Methods: We retrospectively reviewed 170 patients who underwent completion axillary lymph node dissection between Jul 2008 and Aug 2010 in our hospital. We validated three nomograms (MSKCC, Stanford, Tenon). The likelihood of having positive NSLNM based on various factors was evaluated by use of univariate analysis. Stepwise multivariate analysis was applied to estimate a predictive model for NSLNM. Four factors were found to contribute significantly to the logistic regression model, allowing design of a new formula to predict non-sentinel lymph node metastasis. The AUCs of the ROCs were used to describe the performance of the diagnostic value of MSKCC, Stanford, Tenon nomograms and our new nomogram. Results: After stepwise multiple logistic regression analysis, multifocality, proportion of positive SLN to total SLN, LVI, SLN extracapsular extention were found to be statistically significant. AUC results were MSKCC: 0.713/Tenon: 0.671/Stanford: 0.534/DEU: 0.814. Conclusions: The MSKCC nomogram proved to be a good discriminator of NSLN metastasis in SLN positive BC patients for our population. Stanford and Tenon nomograms were not as predictive of NSLN metastasis. Our newly created formula was the best prediction tool for discriminate of NSLN metastasis in SLN positive BC patients for our population. We recommend that nomograms be validated before use in specific populations, and more than one validated nomogram may be used together while consulting patients.

Effects of EGFR, CK19, CK20 and Survinin Gene Expression on Radiotherapy Results in Patients with Locally Advanced Head and Neck Cancer

Kekilli, Kezban Esra,Abakay, Candan Demioz,Tezcan, Gulcin,Tunca, Berrin,Egeli, Unal,Saraydaroglu, Ozlem,Esbah, Onur,Ekinci, Ahmet Siyar,Arslan, Sonay,Uslu, Nuri,Ozkan, Lutfi Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.7

Purpose: To investigate the effects of epidermal growth factor receptor (EGFR), cytokeratin 19 (CK19), cytokeratin 20 (CK20) and survinin gene expression on local control (LC) and overall survival (OS) in patients with locally advanced head and neck cancer (LAHNC) who were administered radiotherapy (RT). Materials and Methods: Twenty-six patients who were admitted to Uludag University Medical Faculty Department of Radiation Oncology with a diagnosis of LAHNC (GIII-GIV) were included in this study. Gene expression was evaluated in tumor tissues and peripheral blood. RNA isolation was performed on paraffinized tumor tissues and peripheral blood samples obtained before RT (BR). The densities of the obtained RNAs were analyzed at 260/280 nm. cDNA samples obtained from total RNA,EGFR, CK19, CK20 and survinin gene expression levels were assessed via the Sybr Green method and data were analyzed with the ${\Delta}{\Delta}Ct$ method. The same process was repeated for peripheral blood samples taken after RT (AR). Results: The female/male ratio was 3:23 and the mean age was 56.5 years (38-75years). After radiotherapy, CK19 and CK20 levels in the peripheral blood were found to be correlated according to Pearson correlation analysis(p=0.049). This result indicates a possibility of remaining positive for CK19 and CK20 in the peripheral blood even after RT in patients with CK19, CK20, and EGFR positive tumors before RT. There was a statistically significant correlation between survinin levels measured BR and AR (p=0.028). Conclusions: In this study, we found that patients with any EGFR, CK19, CK20 or survinin positivity in their peripheral blood obtain less benefit from radiotherapy. A wider patient population and advanced protein analyses are necessary in order to increase the reliability of our findings.

Evaluation of Genetic Variations in miRNA-Binding Sites of BRCA1 and BRCA2 Genes as Risk Factors for the Development of Early-Onset and/or Familial Breast Cancer

Erturk, Elif,Cecener, Gulsah,Polatkan, Volkan,Gokgoz, Sehsuvar,Egeli, Unal,Tunca, Berrin,Tezcan, Gulcin,Demirdogen, Elif,Ak, Secil,Tasdelen, Ismet Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

Although genetic markers identifying women at an increased risk of developing breast cancer exist, the majority of inherited risk factors remain elusive. Mutations in the BRCA1/BRCA2 gene confer a substantial increase in breast cancer risk, yet routine clinical genetic screening is limited to the coding regions and intronexon boundaries, precluding the identification of mutations in noncoding and untranslated regions. Because 3' untranslated region (3'UTR) polymorphisms disrupting microRNA (miRNA) binding can be functional and can act as genetic markers of cancer risk, we aimed to determine genetic variation in the 3'UTR of BRCA1/BRCA2 in familial and early-onset breast cancer patients with and without mutations in the coding regions of BRCA1/BRCA2 and to identify specific 3'UTR variants that may be risk factors for cancer development. The 3'UTRs of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis and DNA sequencing in 100 patients from 46 BRCA1/2 families, 54 non-BRCA1/2 families, and 47 geographically matched controls. Two polymorphisms were identified. SNPs $c.^*1287C$ >T (rs12516) (BRCA1) and $c.^*105A$ >C (rs15869) (BRCA2) were identified in 27% and 24% of patients, respectively. These 2 variants were also identified in controls with no family history of cancer (23.4% and 23.4%, respectively). In comparison to variations in the 3'UTR region of the BRCA1/2 genes and the BRCA1/2 mutational status in patients, there was a statistically significant relationship between the BRCA1 gene polymorphism $c.^*1287C$ >T (rs12516) and BRCA1 mutations (p=0.035) by Fisher's Exact Test. SNP $c.^*1287C$ >T (rs12516) of the BRCA1 gene may have potential use as a genetic marker of an increased risk of developing breast cancer and likely represents a non-coding sequence variation in BRCA1 that impacts BRCA1 function and leads to increased early-onset and/or familial breast cancer risk in the Turkish population.

Molecular Markers for Patients with Thymic Malignancies: not Feasible at Present?

Avci, Nilufer,Cecener, Gulsah,Deligonul, Adem,Erturk, Elif,Tunca, Berrin,Egeli, Unal,Tezcan, Gulcin,Akyildiz, Elif Ulker,Bayram, Ahmet Sami,Gebitekin, Cengiz,Kurt, Ender,Evrensel, Turkkan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

Background: Thymomas and thymic carcinomas are rare malignancies and devising clinically effective molecular targeted therapies is a major clinical challenge. The aim of the study was to analyze BLC2 and vascular endothelial growth factor receptor (VEGFR) expression and KRAS and EGFR mutational status and to correlate them with the clinical characteristics of patients with thymomas and thymic carcinomas. Materials and Methods: A total of 62 patients (mean age: $50.4{\pm}13.2$ years) with thymomas and thymic carcinomas were enrolled. The expression of BLC2 and VEGFR in tumor cells and normal tissues was evaluated by RT-PCR. The mutational status of the KRAS and EGFR genes was investigated by PCR with sequence specific primers. Results: The BLC2 and VEGFR expression levels did not differ significantly between tumor and normal tissues. Moreover, there were no clearly pathogenic mutations in KRAS or EGFR genes in any tumor. None of the molecular markers were significantly related to clinical outcomes. Conclusions: Changes in levels of expression of BLC2 and VEGFR do not appear to be involved in thymic tumorigenesis. Moreover, our data suggest that KRAS and EGFR mutations do not play a major role in the pathogenesis of thymomas and thymic carcinomas.

Circulating miR-195 as a Therapeutic Biomarker in Turkish Breast Cancer Patients

Cecener, Gulsah,Ak, Secil,Eskiler, Gamze Guney,Demirdogen, Elif,Erturk, Elif,Gokgoz, Sehsuvar,Polatkan, Volkan,Egeli, Unal,Tunca, Berrin,Tezcan, Gulcin,Topal, Ugur,Tolunay, Sahsine,Tasdelen, Ismet Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.9

Background: Dysregulation of miRNA expression may be used as a biomarker for specific tumours because it may contribute to development of cancer. Circulating miRNA profiles have been highlighted for their potential as predictive markers in heterogeneous diseases such as breast cancer. In the literature, there is evidence that miR-195 levels are differentially expressed pre- and post-operative periods in breast cancer patients. At the same time, miRNA expression levels may vary because of ethnic origins. This study aimed to determine expression levels and potential roles of miR-195 in Turkish breast cancer patients. Materials and Methods: The expression patterns of miR-195 were initially examined in breast cancer tissues (luminal A and B type) (n=96). Subsequently, blood samples were prospectively collected from preoperative and postoperative Turkish breast cancer patients and disease free controls. Total RNA was isolated, and the expression level of miR-195 was quantified by real-time PCR. Results: We found that miR-195 level was altered in Turkish breast cancer patients, with down-regulation evident in breast cancer tissues compared to normal adjacent specimens. Furthermore, circulating levels of miR-195 was significantly decreased in post-operative blood samples compared with pre-operative levels (p=0.01 and <0.05). However, miR-195 was significantly increased in pre-operative blood samples of the luminal B type (p=0.04 and <0.05). Conclusions: This study represents the first report of a miR-195 expression profile in Turkish breast cancer patients. Our data suggests that miR-195 levels might be a clinically useful biomarker in the earliest stage of Turkish breast cancer patients.

COMPLEX VALUED DISLOCATED METRIC SPACES

Ege, Ozgur,Karaca, Ismet The Kangwon-Kyungki Mathematical Society 2018 한국수학논문집 Vol.26 No.4

In this paper, we introduce complex valued dislocated metric spaces. We prove Banach contraction principle, Kannan and Chatterjea type fixed point theorems in this new space. Moreover, we give some applications of the results to differential equations and iterated functions.

Premature Ejaculation and Erectile Dysfunction Prevalence and Attitudes in the Asia‐Pacific Region-A Comment

SEREFOGLU, EGE C.,DIREK, NESE,HELLSTROM, WAYNE J.G. Elsevier 2012 JOURNAL OF SEXUAL MEDICINE Vol.9 No.5

Microcalcified Hepatic Metastases Incidentally Detected on F-18 NaF PET/CT in a Patient with Prostate Cancer

Gul Ege Aktas,Ali Sarıkaya,Nuray Can,Selin Soyluoglu Demir 대한핵의학회 2017 핵의학 분자영상 Vol.51 No.4

F-18 NaF PET/CT evaluation has gained importance in recent years. Achievements from F-18 NaF PET/CT are: higher sensitivity of positron imaging, higher target background ratio with higher tracer accumulation in bone hydroxyapatite and higher specificity through CT correlation. These properties have also given directions to new research fields based on imaging microcalcifications, very recently. A limited number of cases have reported the F-18 NaF uptake in macrocalcified soft tissue metastases. Although the presence of microcalcification was not proved; accumulation of F-18 NaF in the metastatic brain lesion with no visible calcification on the CT, in a patient with ductal breast carcinoma has also been reported. Herein we present a patient with microcalcified hepatic metastasis of prostate cancer incidentally detected on F-18 NaF PET/CT which was confirmed with histochemical staining.

Analysis of C-Reactive Protein and Biochemical Parameters in Pericardial Fluid

Turan Ege,Melih Hulusi US,Mustafa Cikirikcioglu,Cavidan Arar,Enver Duran 연세대학교의과대학 2006 Yonsei medical journal Vol.47 No.3

This study was designed to examine the relationship between pericardial fluid and plasma CRP levels, and to alterations in other biochemical parameters in patients undergoing Coronary Artery Bypass Grafting (CABG). The study group consisted of 96 Coronary Artery Disease (CAD) patients who were referred to our clinic for a CABG procedure and from whom sufficient amount of pericardial fluid could be collected. The patients were classified into 3 groups: Stable Angina Pectoris (SAP) (n=27), Unstable Angina Pectoris (USAP) (n=36), and Post-Myocardial Infarction (PMI) (n=33). Levels of CRP, glucose, albumin, total protein, Creatine Kinase (CK), Creatine Kinase-MB (CK- MB), and Lactate Dehydrogenase (LDH) were determined in pericardial fluid samples and in simultaneously collected blood samples from radial artery. The pericardial CRP and LDH levels in the PMI group were higher than in the SAP (p=0.015 and p=0.000, respectively) and USAP (p=0.011, p=0.047) groups. Serum CRP levels in USAP (p=0.014) and PMI (p= 0.000) groups were higher than those in the SAP group. Pericardial albumin levels in the PMI group were higher than in the USAP group (p=0.038). In all groups, the pericardial fluid/serum protein ratio was > 0.5, the LDL ratio was >0.6, and pericardial fluid LDH concentrations were >300mg/dl. CRP level of pericardial fluid was significantly higher in the PMI group than in other groups. However, pericardial fluid LDH levels were higher than blood LDH levels in this group and were also higher than pericardial fluid LDH levels of other groups.