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.

Promoting Effects of Sanguinarine on Apoptotic Gene Expression in Human Neuroblastoma Cells

Cecen, Emre,Altun, Zekiye,Ercetin, Pinar,Aktas, Safiye,Olgun, Nur Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Neuroblastoma is the most common extracranial solid tumor in children. Approximately half of the affected patients are diagnosed with high-risk poor prognosis disease, and novel therapies are needed. Sanguinarine is a benzophenanthridine alkaloid which has anti-microbial, anti-oxidant and anti-inflammatory properties. The aim of this study is whether sanguinarine has in vitro apoptotic effects and which apoptotic genes might be affected in the human neuroblastoma cell lines SH-SY5Y (N-myc negative), Kelly (N-myc positive, ALK positive), and SK-N-BE(2). Cell viability was analysed with WST-1 and apoptotic cell death rates were determined using TUNEL. After RNA isolation and cDNA conversion, expression of 84 custom array genes of apoptosis was determined. Sanguinarine caused cell death in a dose dependent manner in all neuroblastoma cell lines except SK-N-BE(2) with rates of 18% in SH-SY5Y and 21% in Kelly human neuroblastoma cells. Cisplatin caused similar apoptotic cell death rates of 16% in SH-SY5Y and 23% in Kelly cells and sanguinarine-cisplatin combinations caused the same rates (18% and 20%). Sanguinarine treatment did not affect apoptototic gene expression but decreased levels of anti-apoptotic genes NOL3 and BCL2L2 in SH-SY5Y cells. Caspase and TNF related gene expression was affected by the sanguinarine-cisplatin combination in SH-SY5Y cells. The expression of regulation of apoptotic genes were increased with sanguinarine treatment in Kelly cells. From these results, we conclude that sanguinarine is a candidate agent against neuroblastoma.

Ultrasonographic and macroscopic comparison of the thickness of the capsule, corium, and soft tissues in bovine claws: an in vitro study

Goksen Cecen,Hakan Salci,Deniz Seyrek Intas,Nureddin Celimli,Gulsum Ulke Caliskan 대한수의학회 2015 Journal of Veterinary Science Vol.16 No.1

This study aimed to compare thickness of the capsule, corium, and soft tissues measured ultrasonographically and macroscopically in selectedregions of bovine claws. A hundred and twenty claws (n = 120) of 15 healthy Holstein bovines were obtained. After cleaning the claws,ultrasonographic measurement of the capsule, corium, and soft tissues was performed while submerging the claws in a water bath. Macroscopicmeasurements were taken after cutting of the claws axially. These values were compared statistically. According to the macroscopicmeasurements, the mean thickness ± standard deviation (SD) of the capsule for dorsal wall and sole was 6.2 ± 0.1 and 9.5 ± 0.4 mm, respectively. The thickness of the corium and soft tissues for dorsal wall and sole was 4.5 ± 0.1 and 5.3 ± 0.1 mm, respectively. Ultrasonographically, themean thickness ± SD of the capsule for dorsal wall and sole was 4.7 ± 0.1 and 7.8 ± 0.3 mm, respectively. The thickness of the corium andsoft tissues for dorsal wall and sole was 4.3 ± 0.1 and 5.9 ± 0.2 mm, respectively. Findings demonstrated that ultrasonography can be reliablyto measure of the thickness of the hoof capsule, corium, and soft tissue in bovine claw.

A Path Stretching Model for Effective Terminal Airspace Management

Ramazan Kursat Cecen 한국항공우주학회 2022 International Journal of Aeronautical and Space Sc Vol.23 No.5

This study presents a mathematical model to optimize the total fuel consumption per aircraft for the aircraft landing problem (ALP) using the path stretching (PS) method. The PS model applies vector maneuver (VM), speed reduction (SR), and flight path angle (FPA) change methods for aircraft operation. In addition, two different mixed-integer linear programming models utilizing the point merge system (PMS) are presented to compare the PS model as PMS is a widely used method in ALP. The first PMS model uses the VM to handle arrival traffic and solve aircraft conflicts. The second one implements the VM and the SR techniques. Furthermore, an exact solution algorithm is selected to obtain the optimal solution. The PS model aims to increase the number of continuous descent operations by eliminating the level flights. Two different linear regression equations are generated to calculate the fuel consumption and flight time values in descent operations considering realistic aircraft parameters, FPA, and average airspeed. The results demonstrate that the PS model can reduce the total fuel consumption per aircraft by 8.94% and 3.45% compared to the PMS models.

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.

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.

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.