Browsing by Subject "aged"

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Open Access
Comparison of original EuroSCORE, EuroSCORE II and STS risk models in a Turkish cardiac surgical cohort
(2013) Kunt, A.G.; Kurtcephe, M.; Hidiroglu, M.; Cetin L.; Kucuker, A.; Bakuy V.; Ruchan Akar, A.; Sener, E.
OBJECTIVESThe aim of this study was to compare additive and logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE), EuroSCORE II and the Society of Thoracic Surgeons (STS) models in calculating mortality risk in a Turkish cardiac surgical population.METHODSThe current patient population consisted of 428 patients who underwent isolated coronary artery bypass grafting (CABG) between 2004 and 2012, extracted from the TurkoSCORE database. Observed and predicted mortalities were compared for the additive/logistic EuroSCORE, EuroSCORE II and STS risk calculator. The area under the receiver operating characteristics curve (AUC) values were calculated for these models to compare predictive power.RESULTSThe mean patient age was 74.5 ± 3.9 years at the time of surgery, and 35.0% were female. For the entire cohort, actual hospital mortality was 7.9% (n = 34; 95% confidence interval [CI] 5.4-10.5). However, the additive EuroSCORE-predicted mortality was 6.4% (P = 0.23 vs observed; 95% CI 6.2-6.6), logistic EuroSCORE-predicted mortality was 7.9% (P = 0.98 vs observed; 95% CI 7.3-8.6), EuroSCORE II- predicted mortality was 1.7% (P = 0.00 vs observed; 95% CI 1.6-1.8) and STS predicted mortality was 5.8% (P = 0.10 vs observed; 95% CI 5.4-6.2). The mean predictive performance of the analysed models for the entire cohort was fair, with 0.7 (95% CI 0.60-0.79). AUC values for additive EuroSCORE, logistic EuroSCORE, EuroSCORE II and STS risk calculator were 0.70 (95% CI 0.60-0.79), 0.70 (95% CI 0.59-0.80), 0.72 (95% CI 0.62-0.81) and 0.62 (95% CI 0.51-0.73), respectively.CONCLUSIONSEuroSCORE II significantly underestimated mortality risk for Turkish cardiac patients, whereas additive and logistic EuroSCORE and STS risk calculators were well calibrated. © 2013 The Author 2013.
Open Access
A comprehensive methodology for determining the most informative mammographic features
(2013) Wu, Y.; Alagoz O.; Ayvaci, M.U.S.; Munoz Del Rio, A.; Vanness, D.J.; Woods, R.; Burnside, E.S.
This study aims to determine the most informative mammographic features for breast cancer diagnosis using mutual information (MI) analysis. Our Health Insurance Portability and Accountability Act-approved database consists of 44,397 consecutive structured mammography reports for 20,375 patients collected from 2005 to 2008. The reports include demographic risk factors (age, family and personal history of breast cancer, and use of hormone therapy) and mammographic features from the Breast Imaging Reporting and Data System lexicon. We calculated MI using Shannon's entropy measure for each feature with respect to the outcome (benign/malignant using a cancer registry match as reference standard). In order to evaluate the validity of the MI rankings of features, we trained and tested naïve Bayes classifiers on the feature with tenfold cross-validation, and measured the predictive ability using area under the ROC curve (AUC). We used a bootstrapping approach to assess the distributional properties of our estimates, and the DeLong method to compare AUC. Based on MI, we found that mass margins and mass shape were the most informative features for breast cancer diagnosis. Calcification morphology, mass density, and calcification distribution provided predictive information for distinguishing benign and malignant breast findings. Breast composition, associated findings, and special cases provided little information in this task. We also found that the rankings of mammographic features with MI and AUC were generally consistent. MI analysis provides a framework to determine the value of different mammographic features in the pursuit of optimal (i.e., accurate and efficient) breast cancer diagnosis. © 2013 Society for Imaging Informatics in Medicine.
Open Access
Expression of CK-19 and CEA mRNA in peripheral blood of gastric cancer patients
(2010) Kutun, S.; Celik, A.; Cem Kockar, M.; Erkorkmaz, U.; Eroǧlu, A.; Cetin, A.; Erkosar, B.; Yakicier, C.
Aim: To investigate the clinical and pathological relevance of detection of circulating tumor cells (CTC) in the peripheral blood of gastric carcinoma patients before operation. Patients and Methods: Fifty patients with gastric adenocarcinoma were analysed prospectively. Patients were divided into two groups according to the extent of the tumor. Group I (unresectable) consisted of 22, and group II (resectable) consisted of 28 patients. Peripheral blood samples were collected pre-operatively from all 50 patients as well as from ten healthy controls and analyzed for carcinoembryonic antigen (CEA) and cytokeratin-19 (CK-19) messenger ribonucleic acids (mRNAs). Tumor localisation, stage, presence of signet cell formation, nodal metastases, serousal and lymphovascular invasion were recorded for all patients. Results: Expression of CK-19 was detected in 24 (48%), and CEA in 10 (20%) cases. Nine patients (40%) in group I and 15 (53.6%) in group II were positive for CK-19 expression. CEA expression was more frequent among group I patients (6 vs. 4 cases). There was no significant difference between the groups in the expression of CK-19 and CEA mRNA, tumor localisation, presence of signet formation, and presence and extent of nodal metastases. Patients with major vascular invasion (MVI) expressed significantly higher levels of CTC mRNA compared to those without MVI (p = 0.023 for CEA, and p = 0.009 for CK-19). The median 1 and 2-year survival was 9.5 and 10.5 months for group I, and 20 and 28.5 months for group II, respectively (p = 0.001). The mean survival was 6.7 months for patients with MVI, and 30.2 months for those without MVI (p = 0.0001). Conclusions: High levels of CTCs were observed in patients with MVI invasion, rather than other causes of unresectability. It can be suggested that expression of both CEA and CK-19 in the peripheral blood of gastric cancer patients are strong predictors of MVI and significantly worse survival rates. Copyright © Experimental Oncology, 2010.
Open Access
Identification of endogenous reference genes for qRT-PCR analysis in normal matched breast tumor tissues
(Cognizant Communication Corporation, 2009) Gur-Dedeoglu, B.; Konu, O.; Bozkurt, B.; Ergul, G.; Seckin, S.; Yulug, I. G.
Quantitative gene expression measurements from tumor tissue are frequently compared with matched normal and/or adjacent tumor tissue expression for diagnostic marker gene selection as well as assessment of the degree of transcriptional deregulation in cancer. Selection of an appropriate reference gene (RG) or an RG panel, which varies depending on cancer type, molecular subtypes, and the normal tissues used for interindividual calibration, is crucial for the accurate quantification of gene expression. Several RG panels have been suggested in breast cancer for making comparisons among tumor subtypes, cell lines, and benign/malignant tumors. In this study, expression patterns of 15 widely used endogenous RGs (ACTB, TBP, GAPDH, SDHA, HPRT, HMBS, B2M, PPIA, GUSB, YWHAZ2, PGK1, RPLP0, PUM1, MRPL19, and RPL41), and three candidate genes that were selected through analysis of two independent microarray datasets (IL22RA1, TTC22, ZNF224) were determined in 23 primary breast tumors and their matched normal tissues using qRTPCR. Additionally, 18S rRNA, ACTB, and SDHA were tested using randomly primed cDNAs from 13 breast tumor pairs to assess the rRNA/mRNA ratio. The tumors exhibited significantly lower rRNA/mRNA ratio when compared to their normals, on average. The expression of the studied RGs in breast tumors did not exhibit differences in terms of grade, ER, or PR status. The stability of RGs was examined based on two different statistical models, namely GeNorm and NormFinder. Among the 18 tested endogenous reference genes, ACTB and SDHA were identified as the most suitable reference genes for the normalization of qRTPCR data in the analysis of normal matched tumor breast tissue pairs by both programs. In addition, the expression of the gelsolin (GSN) gene, a well-known downregulated target in breast tumors, was analyzed using the two most suitable genes and different RG combinations to validate their effectiveness as a normalization factor (NF). The GSN expression of the tumors used in this study was significantly lower than that of normals showing the effectivity of using ACTB and SDHA as suitable RGs in this set of tumor–normal tissue panel. The combinational use of the best performing two RGs (ACTB and SDHA) as a normalization factor can be recommended to minimize sample variability and to increase the accuracy and resolution of gene expression normalization in tumor–normal paired breast cancer qRT-PCR studies.
Open Access
Lack of association between the MDM2-SNP309 polymorphism and breast cancer risk
(Delinasios GJ & CO, 2006) Petenkaya, A.; Bozkurt, B.; Akilli-Ozturk, O.; Kaya, H. S.; Gur-Dedeoglu, B.; Yulug, I. G.
Background: A T-to-G polymorphism (SNP309) at the promoter region of MDM2 has been recently reported to extend the Sp1 binding site that positively regulates the MDM2 transcription level and consequently, its expression level. MDM2 is the negative regulator of p53 tumor suppressor protein and elevated levels of MDM2 hamper the stress response driven by the p53 pathway. Whether MDM2-SNP309 was associated with breast cancer as a predisposing factor was investigated. Patients and Methods: A case-control study of 223 females diagnosed with breast cancer and 149 female controls sampled from the Turkish population was carried out and the T/G MDM2-SNP309 genotype of participants was determined. Results: There was no significant association of the G/G or G/T genotypes with breast cancer risk (odds ratio (OR) 1.14, 95% confidence interval (CI) 0.59-2.22, and OR 1.20, 95% CI 0.67-2.12, respectively). Stratification of the data for onset age or for menopausal status at the time of diagnosis also revealed no association for either group.
Open Access
Mutations in the very low-density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humans
(National Academy of Sciences, 2008) Ozcelik, T.; Akarsu, N.; Uz, E.; Caglayan, S.; Gulsuner, S.; Onat, O. E.; Tan, M.; Tan, U.
Quadrupedal gait in humans, also known as Unertan syndrome, is a rare phenotype associated with dysarthric speech, mental retardation, and varying degrees of cerebrocerebellar hypoplasia. Four large consanguineous kindreds from Turkey manifest this phenotype. In two families (A and D), shared homozygosity among affected relatives mapped the trait to a 1.3-Mb region of chromosome 9p24. This genomic region includes the VLDLR gene, which encodes the very low-density lipoprotein receptor, a component of the reelin signaling pathway involved in neuroblast migration in the cerebral cortex and cerebellum. Sequence analysis of VLDLR revealed nonsense mutation R257X in family A and single-nucleotide deletion c2339delT in family D. Both these mutations are predicted to lead to truncated proteins lacking transmembrane and signaling domains. In two other families (B and C), the phenotype is not linked to chromosome 9p. Our data indicate that mutations in VLDLR impair cerebrocerebellar function, conferring in these families a dramatic influence on gait, and that hereditary disorders associated with quadrupedal gait in humans are genetically heterogeneous.
Open Access
SIP1 is downregulated in hepatocellular carcinoma by promoter hypermethylation
(2011) Acun, T.; Oztas, E.; Yagci, T.; Yakicier, M.C.
Background: Smad interacting protein-1 is a transcription factor that is implicated in transforming growth factor-β/bone morphogenetic protein signaling and a repressor of E-cadherin and human telomerase reverse transcriptase. It is also involved in epithelial-mesenchymal transition and tumorigenesis. However, genetic and epigenetic alterations of SIP1 have not been fully elucidated in cancers. In this study, we investigated mutations and promoter hypermethylation of the SIP1 gene in human hepatocellular carcinomas.Methods: SIP1 expression was analyzed in HCC cell lines and primary tumors in comparison to normal and non-tumor liver tissues by using semi-quantitative RT-PCR, quantitative real-time RT-PCR and immunohistochemistry. Mutation and deletion screening of the SIP1 gene were performed by direct sequencing in HCC-derived cells. Restoration of SIP1 expression was sought by treating HCC cell lines with the DNA methyl transferase inhibitor, 5-AzaC, and the histone deacetylase inhibitor, TSA. SIP1 promoter methylation was analyzed by the combined bisulfite restriction analysis assay in in silico-predicted putative promoter and CpG island regions.Results: We found that the expression of SIP1 was completely lost or reduced in five of 14 (36%) HCC cell lines and 17 of 23 (74%) primary HCC tumors. Immunohistochemical analysis confirmed that SIP1 mRNA downregulation was associated with decreased expression of the SIP1 protein in HCC tissues (82.8%). No somatic mutation was observed in SIP1 exons in any of the 14 HCC cell lines. Combined treatment with DNA methyl transferase and histone deacetylase inhibitors synergistically restored SIP1 expression in SIP1-negative cell lines. Analysis of three putative gene regulatory regions revealed tumor-specific methylation in more than half of the HCC cases.Conclusions: Epigenetic mechanisms contribute significantly to the downregulation of SIP1 expression in HCC. This finding adds a new level of complexity to the role of SIP1 in hepatocarcinogenesis. © 2011 Acun et al; licensee BioMed Central Ltd.