Browsing by Subject "human"

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Open Access
Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells
(Nature Publishing Group, 2015) Küçük, C.; Jiang, B.; Hu X.; Zhang W.; Chan J.K.C.; Xiao W.; Lack, N.; Alkan, C.; Williams J.C.; Avery, K.N.; Kavak P.; Scuto, A.; Sen, E.; Gaulard P.; Staudt L.; Iqbal J.; Zhang W.; Cornish, A.; Gong Q.; Yang Q.; Sun H.; D'Amore F.; Leppä, S.; Liu W.; Fu, K.; De Leval L.; McKeithan, T.; Chan W.C.
Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy. © 2015 Macmillan Publishers Limited. All rights reserved.
Unknown
Anti-cancer and anti-hepatitis C virus NS5B polymerase activity of etodolac 1,2,4-triazoles
(Taylor and Francis Ltd, 2015) Çikla-Süzgün P.; Kaushik-Basu, N.; Basu, A.; Arora P.; Talele, T.T.; Durmaz I.; Çetin-Atalay, R.; Küçükgüzel, S.G.
Arachidonic acid is an unsaturated fatty acid liberated from phospholipids of cell membranes. NSAIDs are known as targets of cyclooxygenase enzyme (COX-1, COX-2 and COX-3) in arachidonic acid metabolism. This mechanism of COX-2 in carcinogenesis causes cancer. In addition, COX-2 plays a role in the early stages of hepatocarcinogenesis. Hepatitis C virus (HCV) infection is cause of liver cirrhosis and hepatocellular carcinoma (HCC). The aim of our study was to improve effective agents against HCV. A novel series of new etodolac 1,2,4-triazoles derivatives (4a-h) have been synthesized and investigated for their activity against HCV NS5B polymerase. Compound 4a was found to be the most active with IC50 value of 14.8 M. In accordance with these results, compound 4a was screened for anti-cancer activity on liver cancer cell lines (Huh7, Mahlavu, HepG2, FOCUS). Compound 4a showed anti-cancer activity against Huh7 human hepatoma cell line with IC50 value of 4.29 M. Therefore, compound 4a could be considered as a new anti-cancer and anti-HCV lead compound. © 2015 Informa UK Ltd.
Open Access
Application of the Ugi reaction with multiple amino acid-derived components: Synthesis and conformational evaluation of piperazine-based minimalist peptidomimetics
(Royal Society of Chemistry, 2015) Stucchi, M.; Cairati, S.; Cetin-Atalay, R.; Christodoulou, M.S.; Grazioso G.; Pescitelli G.; Silvani, A.; Yildirim, D.C.; Lesma G.
The concurrent employment of α-amino acid-derived chiral components such as aldehydes and α-isocyanoacetates, in a sequential Ugi reaction/cyclization two-step strategy, opens the door to the synthesis of three structurally distinct piperazine-based scaffolds, characterized by the presence of l-Ala and/or l-Phe-derived side chains and bearing appropriate functionalities to be easily applied in peptide chemistry. By means of computational studies, these scaffolds have been demonstrated to act as minimalist peptidomimetics, able to mimic a well defined range of peptide secondary structures and therefore potentially useful for the synthesis of small-molecule PPI modulators. Preliminary biological evaluation of two different resistant hepatocellular carcinoma cellular lines, for which differentiation versus resistance ability seem to be strongly correlated with well defined types of PPIs, has revealed a promising antiproliferative activity for selected compounds. © The Royal Society of Chemistry 2015.
Open Access
Assessment of diagnostic enzyme-linked immunosorbent assay kit and serological markers in human brucellosis
(2008) Cakan G.; Bezirci F.B.; Kacka, A.; Cesur, S.; Aksaray, S.; Tezeren, D.; Saka, D.; Ahmed, K.
This study was performed to evaluate commercial brucella immunoglobulin G and M-enzymelinked immunosorbent assay (IgG and IgM ELISA) kits for the diagnosis of human brucellosis and to suggest a candidate prognostic marker for human brucellosis. We determined the serum levels of brucella IgG, IgM, C-reactive protein (CRP), soluble CD14 (sCD 14), and neopterin in patients with brucellosis and compared them with those of normal healthy persons, patients with tuberculosis, and patients with other diseases. It was found that the sensitivity of ELISA to diagnose brucellosis was high when both IgG and IgM ELISA were used together. This study showed that serum CRP, sCD14, or neopterin levels were significantly high during the course of human brucellosis. The above markers, alone or in combination, might have the potential to evaluate treatment outcomes in human brucellosis. The markers that can predict the variability of agglutination titer was also determined. It was found that the titer value alone does not fully represent disease status.
Open Access
Asymmetric dimethylarginine concentrations are elevated in women with gestational diabetes
(2010) Akturk, M.; Altinova, A.; Mert I.; Dincel, A.; Sargin, A.; Buyukkagnici, U.; Arslan, M.; Danisman, N.
As shown in the previous studies, asymmetric dimethylarginine (ADMA) is related to endothelial dysfunction, whereas high-sensitive C-reactive protein (hCRP) is the marker of inflammation. In our study, we investigated ADMA, hCRP, and homocysteine concentrations in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) during late pregnancy. Fifty-four women with GDM and 69 women with NGT between 32 and 39 weeks of gestation were included in this study. ADMA, hCRP, homocysteine, lipid parameters, glycated hemoglobin (HbA1c) levels, insulin, and homeostasis model assessment for insulin resistance (HOMA-IR) were measured. The plasma ADMA concentrations were significantly higher in GDM patients than in NGT subjects (P = 0.03) and the hCRP levels were also significantly increased in GDM group when compared with those in the NGT group (P = 0.008). However, plasma homocysteine levels did not differ between the groups (P = 0.4), while HOMA-IR, insulin, and triglyceride levels were higher in the GDM group than in the NGT group (P = 0.001, 0.002, and 0.02, respectively). The ADMA concentrations in the third trimester were positively correlated with the glucose levels the 50-g glucose challenge test (GCT) during 24-28 weeks in the whole group (r = 0.21, P = 0.02). Our results demonstrate that ADMA and hCRP are elevated in women with GDM during late pregnancy. Further studies are needed to clarify the significance and the underlying mechanisms of the elevated ADMA and hCRP levels in women with GDM. © 2010 Springer Science+Business Media, LLC.
Unknown
Audiovisual associations alter the perception of low-level visual motion
(Frontiers Research Foundation, 2015) Kafaligonul H.; Oluk, C.
Motion perception is a pervasive nature of vision and is affected by both immediate pattern of sensory inputs and prior experiences acquired through associations. Recently, several studies reported that an association can be established quickly between directions of visual motion and static sounds of distinct frequencies. After the association is formed, sounds are able to change the perceived direction of visual motion. To determine whether such rapidly acquired audiovisual associations and their subsequent influences on visual motion perception are dependent on the involvement of higherorder attentive tracking mechanisms, we designed psychophysical experiments using regular and reverse-phi random dot motions isolating low-level pre-attentive motion processing. Our results show that an association between the directions of low-level visual motion and static sounds can be formed and this audiovisual association alters the subsequent perception of low-level visual motion. These findings support the view that audiovisual associations are not restricted to high-level attention based motion system and early-level visual motion processing has some potential role. © 2015 Kafaligonul and Oluk.
Open Access
Benzothiazole derivatives as human DNA topoisomerase IIα inhibitors
(2013) Kaplan-Ozen, C.; Tekiner-Gulbas, B.; Foto, E.; Yildiz I.; Diril, N.; Aki, E.; Yalcin I.
Benzothiazole derivatives resembling the structure of DNA purine bases were tested to determine their topoisomerase inhibition activities. Based on DNA topoisomerase I and II relaxation assay results, all 12 derivatives acted as human topoisomerase IIα inhibitors, whereas only two compounds inhibited Calf thymus topoisomerase I. 3-amino-2-(2-bromobenzyl)-1,3-benzothiazol-3-ium 4-methylbenzensulfonate (BM3) was observed to be the most effective human topoisomerase IIα inhibitor with the lowest IC50 value of 39 nM. The mechanistic studies suggested that BM3 was neither a DNA intercalator nor a topoisomerase poison, it was only a DNA minor groove-binding agent. BM3 initially bound to the DNA topoisomerase IIα enzyme, then to DNA. As a result, the tested benzothiazole derivatives were obtained as strong topoisomerase IIα inhibitors. The benzothiazole tosylated salt form BM3 was found as the most effective topoisomerase IIα inhibitor. BM3's mechanisms of action might be its direct interaction with the enzyme. BM3's minor groove-binding property might also contribute to this action. Hence, BM3 could be a good candidate as a new anticancer agent. © 2013 Springer Science+Business Media New York.
Unknown
Beyond the 'East-West' dichotomy: Global variation in cultural models of selfhood
(American Psychological Association Inc., 2016) Vignoles, V. L.; Owe, E.; Becker, M.; Smith, P. B.; Easterbrook, M. J.; Brown, R.; González, R.; Didier, N.; Carrasco, D.; Cadena, M. P.; Lay, S.; Schwartz, S. J.; Rosiers, S. E. D.; Villamar, J. A.; Gavreliuc, A.; Zinkeng, M.; Kreuzbauer, R.; Baguma, P.; Martin, M.; Tatarko, A.; Herman, G.; de Sauvage, I.; Courtois, M.; Gardarsdóttir, R. B.; Harb, C.; Gallo, I. S.; Gil, P. P.; Clemares, R. L.; Campara, G.; Nizharadze, G.; Macapagal, M. E. J.; Jalal, B.; Bourguignon, D.; Zhang, J.; Lv, S.; Chybicka, A.; Yuki, M.; Zhang X.; Espinosa, A.; Valk, A.; Abuhamdeh, S.; Amponsah, B.; Özgen E.; Guner, E. Ü.; Yamakoglu, N.; Chobthamkit, P.; Pyszczynski, T.; Kesebir, P.; Trujillo, E. V.; Balanta, P.; Ayala, B. C.; Koller, S. H.; Jaafar, J. L.; Gausel, N.; Fischer, R.; Milfont, T. L.; Kusdil, E.; Çağlar, S.; Aldhafri, S.; Ferreira, M. C.; Mekonnen, K. H.; Wang, Q.; Fülöp, M.; Torres, A.; Camino, L.; Lemos, F. C. S.; Fritsche, I.; Möller, B.; Regalia, C.; Manzi, C.; Brambilla, M.; Bond, M. H.
Markus and Kitayama's (1991) theory of independent and interdependent self-construals had a major influence on social, personality, and developmental psychology by highlighting the role of culture in psychological processes. However, research has relied excessively on contrasts between North American and East Asian samples, and commonly used self-report measures of independence and interdependence frequently fail to show predicted cultural differences. We revisited the conceptualization and measurement of independent and interdependent self-construals in 2 large-scale multinational surveys, using improved methods for cross-cultural research. We developed (Study 1: N = 2924 students in 16 nations) and validated across cultures (Study 2: N = 7279 adults from 55 cultural groups in 33 nations) a new 7-dimensional model of self-reported ways of being independent or interdependent. Patterns of global variation support some of Markus and Kitayama's predictions, but a simple contrast between independence and interdependence does not adequately capture the diverse models of selfhood that prevail in different world regions. Cultural groups emphasize different ways of being both independent and interdependent, depending on individualism-collectivism, national socioeconomic development, and religious heritage. Our 7-dimensional model will allow future researchers to test more accurately the implications of cultural models of selfhood for psychological processes in diverse ecocultural contexts. © 2016 American Psychological Association.
Open Access
The bonobo genome compared with the chimpanzee and human genomes
(2012) Prüfer, K.; Munch, K.; Hellmann I.; Akagi, K.; Miller J.R.; Walenz, B.; Koren, S.; Sutton G.; Kodira, C.; Winer, R.; Knight J.R.; Mullikin J.C.; Meader, S.J.; Ponting, C.P.; Lunter G.; Higashino, S.; Hobolth, A.; Dutheil J.; Karakoç, E.; Alkan, C.; Sajjadian, S.; Catacchio, C.R.; Ventura, M.; Marques-Bonet, T.; Eichler, E.E.; André, C.; Atencia, R.; Mugisha L.; Junhold J.; Patterson, N.; Siebauer, M.; Good J.M.; Fischer, A.; Ptak, S.E.; Lachmann, M.; Symer, D.E.; Mailund, T.; Schierup, M.H.; Andrés, A.M.; Kelso J.; Pääbo, S.
Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other. © 2012 Macmillan Publishers Limited. All rights reserved.
Open Access
Cd81 Interacts with the T Cell Receptor to Suppress Signaling
(2012) Cevik, S.I.; Keskin, N.; Belkaya, S.; Ozlu, M.I.; Deniz, E.; Tazebay, U.H.; Erman, B.
CD81 (TAPA-1) is a ubiquitously expressed tetraspanin protein identified as a component of the B lymphocyte receptor (BCR) and as a receptor for the Hepatitis C Virus. In an effort to identify trans-membrane proteins that interact with the T-cell antigen receptor (TCR), we performed a membrane yeast two hybrid screen and identified CD81 as an interactor of the CD3delta subunit of the TCR. We found that in the absence of CD81, in thymocytes from knockout mice, TCR engagement resulted in stronger signals. These results were recapitulated in T cell lines that express low levels of CD81 through shRNA mediated silencing. Increased signaling did not result from alterations in the levels of TCR on the surface of T lymphocytes. Although CD81 is not essential for normal T lymphocyte development, it plays an important role in regulating TCR and possibly pre-TCR signal transduction by controlling the strength of signaling. CD81 dependent alterations in thymocyte signaling are evident in increased CD5 expression on CD81 deficient double positive (DP) thymocytes. We conclude that CD81 interacts with the T cell receptor to suppress signaling. © 2012 Cevik et al.
Open Access
Cognitive individualism and the child as scientist program
(2011) Wringe, B.
In this paper, I examine the charge that Gopnik and Meltzoff's 'Child as Scientist' program, outlined and defended in their 1997 book Words, Thoughts and Theories is vitiated by a form of 'cognitive individualism' about science. Although this charge has often been leveled at Gopnik and Meltzoff's work, it has rarely been developed in any detail.I suggest that we should distinguish between two forms of cognitive individualism which I refer to as 'ontic' and 'epistemic' cognitive individualism (OCI and ECI respectively). I then argue - contra Ronald Giere - that Gopnik and Meltzoff's commitment to OCI is relatively unproblematic, since it is an easily detachable part of their view. By contrast, and despite their explicit discussion of the issue, their commitment to ECI is much more problematic.
Open Access
Coiled-Coil Domain Containing Protein 124 Is a Novel Centrosome and Midbody Protein That Interacts with the Ras-Guanine Nucleotide Exchange Factor 1B and Is Involved in Cytokinesis
(2013) Telkoparan P.; Erkek, S.; Yaman, E.; Alotaibi H.; Bayik, D.; Tazebay, U.H.
Cytokinetic abscission is the cellular process leading to physical separation of two postmitotic sister cells by severing the intercellular bridge. The most noticeable structural component of the intercellular bridge is a transient organelle termed as midbody, localized at a central region marking the site of abscission. Despite its major role in completion of cytokinesis, our understanding of spatiotemporal regulation of midbody assembly is limited. Here, we report the first characterization of coiled-coil domain-containing protein-124 (Ccdc124), a eukaryotic protein conserved from fungi-to-man, which we identified as a novel centrosomal and midbody protein. Knockdown of Ccdc124 in human HeLa cells leads to accumulation of enlarged and multinucleated cells; however, centrosome maturation was not affected. We found that Ccdc124 interacts with the Ras-guanine nucleotide exchange factor 1B (RasGEF1B), establishing a functional link between cytokinesis and activation of localized Rap2 signaling at the midbody. Our data indicate that Ccdc124 is a novel factor operating both for proper progression of late cytokinetic stages in eukaryotes, and for establishment of Rap2 signaling dependent cellular functions proximal to the abscission site. © 2013 Telkoparan et al.
Open Access
Common telomerase reverse transcriptase promoter mutations in hepatocellular carcinomas from different geographical locations
(WJG Press, 2015) Cevik, D.; Yildiz G.; Ozturk, M.
AIM: To determine the mutation status of human telomerase reverse transcriptase gene (TERT ) promoter region in hepatocellular carcinoma (HCC) from different geographical regions. METHODS: We analyzed the genomic DNA sequences of 59 HCC samples comprising 15 cell lines and 44 primary tumors, collected from patients living in Asia, Europe and Africa. We amplified a 474 bp DNA fragment of the promoter region of TERT gene including the 1295228 and 1295250 sequence of chromosome 5 by using PCR. Amplicons were then sequenced by Sanger technique and the sequence data were analyzed with by using DNADynamo software in comparison with wild type TERT gene sequence as a reference. RESULTS: The TERT mutations were found highly frequent in HCC. Eight of the fifteen tested cell lines displayed C228T mutation, and one had C250T mutation with a mutation frequency up to 60%. All of the mutations were heterozygous and mutually exclusive. Ten out of forty-four tumors displayed C228T mutation, and additional five tumors had C250T mutation providing evidence for mutation frequency of 34% in primary tumors. Considering the geographic origins of HCC tumors tested, TERT promoter mutation frequencies were higher in African (53%), when compared to non-African (24%) tumors (P = 0.056). There was also a weak inverse correlation between TERT promoter mutations and murine double minute 2 single nucleotide polymorphism 309 TG polymorphism (P = 0.058). Mutation frequency was nearly two times higher in established HCC cell lines (60%) compared to the primary tumors (34%). CONCLUSION: TERT promoter is one of most frequent mutational targets in liver cancer, and hepatocellular carcinogenesis is highly associated with the loss of telomere-dependent cellular senescence control. © The Author(s) 2015.
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
Cost-effectiveness of adjuvant FOLFOX and 5FU/LV chemotherapy for patients with stage II colon cancer
(2013) Ayvaci, M.U.S.; Shi J.; Alagoz O.; Lubner, S.J.
Purpose. We evaluated the cost-effectiveness of adjuvant chemotherapy using 5-fluorouracil, leucovorin (5FU/LV), and oxaliplatin (FOLFOX) compared with 5FU/LV alone and 5FU/LV compared with observation alone for patients who had resected stage II colon cancer. Methods. We developed 2 Markov models to represent the adjuvant chemotherapy and follow-up periods and a single Markov model to represent the observation group. We used calibration to estimate the transition probabilities among different toxicity levels. The base case considered 60-year-old patients who had undergone an uncomplicated hemicolectomy for stage II colon cancer and were medically fit to receive 6 months of adjuvant chemotherapy. We measured health outcomes in quality-adjusted life-years (QALYs) and estimated costs using 2007 US dollars. Results. In the base case, adjuvant chemotherapy of the FOLFOX regimen had an incremental cost-effectiveness ratio (ICER) of $54,359/QALY compared with the 5FU/LV regimen, and the 5FU/LV regimen had an ICER of $14,584/QALY compared with the observation group from the third-party payer perspective. The ICER values were most sensitive to 5-year relapse probability, cost of adjuvant chemotherapy, and the discount rate for the FOLFOX arm, whereas the ICER value of 5FU/LV was most sensitive to the 5-year relapse probability, 5-year survival probability, and the relapse cost. The probabilistic sensitivity analysis indicates that the ICER of 5FU/LV is less than $50,000/QALY with a probability of 99.62%, and the ICER of FOLFOX as compared with 5FU/LV is less than $50,000/QALY and $100,000/QALY with a probability of 44.48% and 97.24%, respectively. Conclusion. Although adjuvant chemotherapy with 5FU/LV is cost-effective at all ages for patients who have undergone an uncomplicated hemicolectomy for stage II colon cancer, FOLFOX is not likely to be cost-effective as compared with 5FU/LV.
Open Access
Cytotoxic activities of some benzothiazole-piperazine derivatives
(Taylor and Francis Ltd, 2015) Gurdal, E.E.; Durmaz I.; Cetin-Atalay, R.; Yarim, M.
Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Based on the GI50 values of the compounds, most of the benzothiazole-piperazine derivatives are active against HUH-7, MCF-7 and HCT-116 cancer cell lines. Compound 1d is highly cytotoxic against all tested cancer cell lines. Further investigation of compound 1d by Hoechst Staining and Fluorescence-Activated Cell Sorting Analysis (FACS) revealed that this compound causes apoptosis by cell cycle arrest at subG1 phase. © 2014 Informa UK Ltd. All rights reserved.
Open Access
Differences in the accumulation and distribution profile of heavy metals and metalloid between male and female crayfish (Astacus leptodactylus)
(2013) Tunca, E.; Ucuncu, E.; Ozkan, A.D.; Ulger, Z.E.; Cansizoǧlu, A.E.; Tekinay, T.
Concentrations of selected heavy metals and a metalloid were measured by ICP-MS in crayfish (Astacus leptodactylus) collected from Lake Hirfanli, Turkey. Aluminum (Al), chromium (52Cr, 53Cr), copper ( 63Cu, 65Cu), manganese (Mn), nickel (Ni) and arsenic (As) were measured in the exoskeleton, gills, hepatopancreas and abdominal muscle tissues of 60 crayfish of both genders. With the exception of Al, differences were determined between male and female cohorts for the accumulation trends of the above-mentioned elements in the four tissues. It was also noted that the accumulation rates of Ni and As were significantly lower in gill tissue of females compared to males and no significant difference was observed for Cu isotopes in female crayfish. Cluster Analysis (CA) recovered similar results for both genders, with links between accumulations of Ni and As being notable. Accumulation models were described separately for male and female crayfish using regression analysis, and are presented for models where R2 > 0.85. © 2013 Springer Science+Business Media New York.
Open Access
Differential p21 expression after ionizing and UVC radiation in EBV-transformed lymphoblastoid cells
(2000) Moyret-Lalle, C.; Lalle P.; Pedeux, R.; Guillot, C.; Martel, S.; Magaud J.-P.; Puisieux, A.; Ozturk, M.
Responses to DNA-damaging agents appear to be coordinated by p53 through transcriptional activation of critical target genes. Among them, p21WAF1 encodes a protein preventing cells from entering S phase. It is not clear whether p53-mediated response varies depending on the type of DNA damage. Here, we have decided to compare the p53-mediated response of EBV-transformed lymphoblasts to ionizing radiation and UVC irradiation. We have shown that these cells respond to ionizing radiation by a cell cycle arrest as expected. Surprisingly they failed to do so after UVC treatment. Accordingly there was no significant induction of p21 protein in UVC exposed cells despite p53 accumulation. Using isogenic EBV-transformed lymphoblastoid cells expressing E6 protein of HPV18, we have demonstrated that there was no evidence of p53-dependent cell cycle arrest after UVC irradiation. These observations suggest that the p53-mediated response to UVC, in contrast to ionizing radiation, was compromised in EBV-transformed cells and might be cell type-dependent.
Open Access
Effect of patient sex on white matter alterations in unilateral medial temporal lobe epilepsy with hippocampal sclerosis assessed by diffusion tensor imaging
(2013) Oguz, K.K.; Tezer I.; Sanverdi, E.; Has, A.C.; Bilginer, B.; Dolgun, A.; Saygi, S.
BACKGROUND AND PURPOSE: Studies shows ictal behavior and symptoms are affected by patient sex in temporal lobe epilepsy. The purpose of our study was to determine whether alterations in the WM as assessed by DTI display different patterns in male and female patients with unilateral HS. MATERIALS AND METHODS: Patients with unilateral HS were categorized as women with right HS ( n=12), men with right HS ( n=10), women with left HS ( n=12), and men with left HS ( n=10). DTI of the brain along 64 noncollinear directions was obtained from 44 patients and 37 sex-matched control participants. We used TBSS to analyze whole-brain WM. Regions with significant changes of FA and MD, and their mean FA, MD, total number of significant voxels, and asymmetry indices were determined for each group. RESULTS: All groups showed bilateral and extensive reductions of FA and elevated MD in the WM, more prominent ipsilateral to the affected hippocampus. The total number of voxels with decreased FA in patients compared with that of control participants was higher in women with right HS (24,727 vs 5,459) and in men with left HS (27,332 vs 14,013) than in their counterparts. Changes in MD associated with right HS were more extensive in both men and women (right vs left HS, women: 16,926 vs 5,458; men: 5,389 vs 4,764) than in those with left HS. In patients with right HS, the ipsilateral cingulum, uncinate fasciculus, internal and external capsules, and right acoustic radiation were involved extensively in women. CONCLUSIONS: Women and men showed different patterns in extent of WM alterations associated with HS.