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Despite therapeutic advances, lung cancer remains one of the most common causes of cancer‐related deaths worldwide. The ZNF703 gene has been identified as the driver of the 8p11‐12 region and its amplification or overexpression has been associated with several types of cancers. It has also been shown that ZNF703 overexpression can activate the Akt/mTOR signaling pathway. The aim of our study was to investigate the role of the ZNF703 gene in association with Akt/mTOR activation in non‐small cell lung cancer (NSCLC). Expression levels in tumors and matched noncancerous tissue samples from 47 patients were analyzed by qRT‐PCR and the Akt phosphorylation levels were investigated by Western blotting. Our results show that ZNF703 is up‐regulated in 63.4% of NSCLC tumor samples. Althogh the correlation did not reach a statistically significant level Akt phosphorylation was increased in tumor tissues expressing high levels of ZNF703. The role of the ZNF703 gene has not been investigated in NSCLC. Our data show that ZNF703 may contribute to tumor development in NSCLC by activating the Akt/mTOR pathway.

The aim of this study was to investigate the relationships between the maternal levels of oxidized LDL (ox-LDL), lipid peroxidation marker malondialdehyde (MDA) and LOX-1 3'UTR188C/T and K167N single nucleotide polymorphisms in pregnant Turkish women with gestational diabetes mellitus (GDM).116 pregnant women with GDM and 120 healthy pregnant women from the same geographic region were included in the study. Polymerase chain reaction-based restriction analysis was used to identify 3'UTR188C/T and K167N polymorphisms of the LOX-1 gene. Plasma ox-LDL and MDA levels were determined by enzyme-linked immunosorbent assay and spectrophotometric method in all study subjects, respectively.Our results indicated that the distribution of the LOX-1 3'UTR188C/T and K167N genotypes and alleles did not differ significantly among subjects with or without GDM (p0.05). TT and NN genotype carriers are associated with some glucose metabolism parameters (p0.05). There were no significant differences among plasma ox-LDL and MDA levels with regard to LOX-1 3'UTR188C/T and K167N polymorphisms in GDM group and control subjects (p0.05). According to the combined genotype analysis of LOX-1 3'UTR 188 TT and K167N NN polymorphisms, plasma MDA and ox-LDL levels were significantly different between women with GDM and healthy subjects either with or without combined TT/NN genotype carriers (p0.001).According to our results, ox-LDL and MDA levels were increased in GDM pregnant women and healthy pregnant women either with or without combined TT/NN genotype carriers, for our Turkish sample, these genotype carriers appear to be related with increased oxidative stress in patients with GDM.

Radiotherapy (RT) may result in platelet activation and thrombosis development. To the best of our knowledge, the potential effect of volumetric-modulated arc therapy (VMAT), a novel radiotherapy technique, on platelet function and microRNA (miRNA/miR) expression has not been previously investigated. The present study aimed to determine the effect of VMAT on the alterations in platelet function parameters and miRNA expression levels. A total of 25 patients with prostate cancer and 25 healthy subjects were included in the present study. Blood samples were collected from the patient group on the day prior to RT (pre-RT), the day RT was completed (post-RT day 0), and 40 days following the end of therapy (post-RT day 40). Platelet count, mean platelet volume (MPV) value, platelet aggregation, plasma P-selectin, thrombospondin-1, platelet factor 4, plasma miR-223 and miR-126 expression levels were measured. A significant decrease in platelet count in the post-RT day 0 group was measured in comparison with the pre-RT and the post-RT day 40 groups. Pre-RT MPV values were higher than those of the post-RT day 0 and the post-RT day 40 groups. No significant differences were observed in the levels of platelet activation markers or miR-223 and miR-126 expression levels between the RT groups. Although RT may result in a reduction in platelet and MPV counts, the results of the present study indicate that platelet activation markers are not affected by VMAT. Therefore, it is possible that no platelet activation occurs during VMAT, owing to the conformal dose distributions, improved target volume coverage and the sparing of normal tissues from undesired radiation.

Background Graves Disease (GD) is an autoimmune disorder affected by an interaction of multiple genes such as Nuclear Factor-κB (NF-κB), Nuclear Factor-κB Inhibitor (NF-κBIA), Poly (ADP-ribose) polymerase-1 (PARP-1) and cytokines like Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) and mostly accompanied by an ocular disorder, Graves Ophthalmopathy (GO). We hypothesize that there is a relationship between GD, GO, polymorphisms of inflammatory related genes and their association with cytokines, which may play important roles in autoimmune and inflammatory processes. Subjects and methods To confirm our hypothesis, we studied the polymorphisms and cytokine levels of 120 patients with GD and GO using PCR-RFLP and ELISA methods, respectively. Results We found that patients with GG genotype and carriers of G allele of PARP-1 G1672A polymorphism are at risk in the group having GD (p = 0.0007) while having GA genotype may be protective against the disease. PARP-1 C410T polymorphism was found to be associated with GO by increasing the risk by 1.7 times (p = 0.004). Another risk factor for development of GO was the polymorphism of del/ins of NFkB1 gene (p = 0.032) that increases the risk by 39%. Levels of cytokines were also elevated in patients with GD, but no association was found between levels of cytokines and the development of GO as there was no change in levels of cytokines. Conclusions We suggest that, PARP-1 and NFkB1 gene polymorphisms may be risk factors for developing Graves Disease and Ophthalmopathy.

About 10% of patients with severe hemophilia exhibit a milder clinical phenotype with less frequent bleeds. Among many other factors, coinheritance of prothrombotic mutations have been proposed to act as modulators of clinical severity in severe hemophilia. We conducted a study to evaluate the impact of 3 prothrombotic mutations (factor V Leiden, factor II, and methylenetetrahydrofolate reductase mutations) on clinical phenotype of patients with severe hemophilia in our institution. For this purpose we compared the average annual factor concentrate consumption between carriers and noncarriers of prothrombotic mutations. A total of 38 hemophilia A and B patients with factor levels less than 1 were recruited between October 2006 and October 2007. Prothrombotic mutations were detected in venous blood using polymerase chain reaction amplification technique. Eighteen patients (47%) carried no prothrombotic mutations. The remaining 20 patients (53%) were found to be carriers of either 1 or 2 mutations. Median age in both carrier and the non-carrier groups was 27 years. None of the patients in either group gave a history of thromboembolic event. Median annual factor concentrate consumptions in carriers and noncarriers were 610 ± 530 units/kg and 770 ± 670 units/kg, respectively ( P = .203). Our results demonstrated no significant difference in annual factor concentrate consumption between carriers and noncarriers of prothrombotic mutations. Considering that average annual factor consumption is a surrogate indicator of clinical phenotype, we concluded that coinheritance of prothrombotic mutations was not associated with occurrence of different clinical phenotypes in severe hemophilia.

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is one of the most common medically intractable epilepsy syndromes and the pathogenesis of HS remains highly obscure. Recent studies demonstrated controversial results about the relationship between interleukin (IL) gene polymorphism and epilepsy in different ethnic groups. This correlation was investigated in Turkish patients with MTLE-HS. The allele distribution of IL-1alpha and IL-1beta in 47 patients of Turkish ancestry was determined and compared with 99 ethnically matched control subjects. Analysis of genotype frequencies between patients and controls showed no statistically significant difference (p0.05). Our data suggest that IL-1alpha and IL-1beta gene polymorphisms do not act as a strong susceptibility factor for MTLE-HS in individuals of Turkish ancestry.

To evaluate the hypothetical link between apolipoprotein E (APOE) polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and whether presence of APOE epsilon4 allele shortens the latent period between febrile seizures and epilepsy. A further interest is whether presence of APOE epsilon4 allele has an impact on severity of the disease. Forty-seven patients with MTLE-HS were compared with 62 controls. APOE polymorphisms were determined from lymphocytes by standard methods. Eight patients (17%) and 10 controls (16.1%) were demonstrated to have one APOE epsilon4 allele. There was not any statistically significant difference in APOE epsilon4 frequency between patients and controls (P > 0.05). There was not any difference statistically according to onset age of epilepsy and the presence of APOE epsilon4 allele within patient group. APOE epsilon4 polymorphisms did not influence the severity of epilepsy. APOE epsilon4 polymorphisms had no impact on outcome after surgery. Patients with bilateral memory deficits, bilateral hippocampal atrophy and with bilateral epileptiform interictal EEG transients, were independently compared with patients having unilateral features and there were not any statistically significant differences. This study has found no association between APOE epsilon4 polymorphisms and presentation of MTLE-HS in a group of Turkish patients.

Lung cancer is a result of uncontrolled cell growth in lung tissue and is the most common type of cancer leading to death in men and second after breast cancer in women. Even though smoking is the main reason of lung cancer, genetic and environmental factors play an important role in the onset and prognosis of the disease. The WW domain-containing oxidoreductase (WWOX) gene is a putative tumor suppressor gene located on chromosome 16q23.3-24.1 and is composed of 9 exons. Several studies have reported the role of WWOX gene in different types of carcinomas including lung, breast, ovarian, stomach and nasopharyngeal cancer. The 46kDa WWOX protein has two WW (tryptophan) domains which can recognize and bind the proline-rich region (PPXY) of other proteins. Its main function is to inhibit tumor cell growth. WWOX also plays an important role in wnt/beta-catenin signaling pathway. The lost-on-transformation 1 (LOT1/ZAC1/PLAGL1) gene is another putative tumor suppressor gene located on chromosome 6q24-25, a common site known for loss of heterozygosity in many tumors. Deletions of the 6q region are observed in different types of cancers including breast, prostate, small cell lung cancer and mesotheliomas. The LOT1 gene codes for a 55 kDa protein with seven C2H2 type zinc finger motifs located in amino terminal half of the protein. This zinc-finger nuclear transcription factor interacts with other proteins and transcription factors exerting antiproliferative effects in cancer cells. The aim of this study was to investigate the expression levels of the WWOX and LOT1 genes by RT-PCR in tumor tissue samples from 39 patients with non small cell lung cancer (NSCLC). We observed down-regulation of WWOX and LOT1 expression in 82.1% and 48.7% of the patients, respectively. Expression levels of both genes were down-regulated simultaneously in 18 (46.1%) of the patients. When we analyzed the association between gene expression and age, sex, smoking, histology and stage, we found that WWOX expression was decreased in 28 of 31 (90.3%) patients older than 50 years (p = 0.02). Lower expression levels of both genes supports the hypothesis that WWOX and LOT1 act as tumor suppressors in NSCLC and that both genes may have a common effect on tumor progression which warrants further studies to analyze a possible cooperation between the two proteins. Citation Format: Onur Baykara, Seda Ekizoglu Eratak, Kamil Kaynak, Hikmet Koseoglu, Nur Buyru. WWOX and LOT1 genes are down-regulated in non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4952. doi:10.1158/1538-7445.AM2015-4952

Buyru, Nur/0000-0002-6920-1455; Baykara, Onur/0000-0002-9754-8456; Uzan, Mustafa/0000-0001-7214-380X; Sanus, Galip Zihni/0000-0001-6539-7254 WOS: 000234773600003 PubMed: 16378839 Background: Interleukin (IL) I is a proinflammatory cytokine that has been identified as an important mediator of neurodegeneration induced by ischemia or traumatic brain injury. Accumulating evidence to date has suggested that the major cytokine contributing to neurodegeneration after head injury is IL-1 beta rather than IL-1 alpha; however, there is no sufficient data regarding IL-1 alpha in literature, and there may be an association between IL1A gene polymorphism and outcome after head injury. Methods: We performed a prospective clinical study and included a recruited series of 71 patients who had head injury and were admitted to our neurosurgical unit. Severity of initial injury was assessed by the Glasgow Coma Scale. Outcome at 6 months after injury was assessed by means of the Glasgow Outcome Score. Interleukin la genotypes were determined from blood samples by standard methods. Results: Of 40 patients with ILIA*2, 18 (45%) had an unfavorable outcome (dead, vegetative state, or severe disability) compared with 7 (22.5%) of 31 without ILIA*2 (P =.08). Conclusion: Our findings show that there is no genetic association between ILIA gene polymorphism and outcome after head injury. Further clinical studies should be designed to confirm and further evaluate these findings. (c) 2006 Elsevier Inc. All rights reserved.

Chronic obstructive pulmonary disease (COPD) is a disease which genetic and environmental factors play an important role in COPD development. VDBP (Vitamin D Binding Protein ) gene might be responsible for COPD development. The purpose of this study to investigate the possible effect of VDBP on progression of COPD. We studied VDBP genotypes in 75 COPD patients, 36 smoker healthy subjects and 19 non-smoker healthy subjects with PCR-RFLP method to analyze the association between VDBP and COPD. In our study, the most frequently seen genotype was 1S-2 with a frequency of 32% in COPD group; and 1F-1S genotype with a frequency of 33.3% in smoker healthy group. There was no significant difference between these genotypes. In our study groups, we did not find any 2-2 genotype in non-smoker healthy subject group while it has been found 4% and 8% in COPD and healthy smoker subject groups, respectively. Although we did not find any significant difference for protective effect of the 2 allele on the disease or susceptibility of 1F allele to COPD formation in COPD patients and smoker healthy subjects (p: 0.346, p: 0.249, respectively), the only significant difference was between the patient and the healthy non-smoker groups with 1S-1S genotype (p=0.032). Our results do not show any evidence that indicate a protective or susceptibility effect of VDBP 2 and 1F alleles in progression of COPD, respectively but results indicate that having the 1S-1S genotype may be associated with the etiology of COPD. [Med-Science 2013; 2(1.000): 403-13]

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide with poor differential diagnosis of the disease and with low response rates to standard chemotherapy. Individuals classified as Stage I by the present clinical-based scoring system may display survival characteristics ranging from 10 to 90 %. Identification of reliable biomarkers to detect NSCLC at early stages is therefore a subject of extensive research. Surface-enhanced laser-desorption-ionization time-of-flight mass spectrophotometry (SELDI-TOF-MS) combines chromatographic surfaces with solid-state TOF-MS for the high throughput analysis of proteins in diverse clinical samples such as serum, urine, cerebrospinal fluids and has overcome the limitations of earlier proteomic approaches. The method has been widely used for biomarker discovery. Therefore, in this study we used the SELDI-TOF protein Chip system to achieve a stratification based on the protein expression profile and to identify differentially expressed proteins in sera from 50 patients with NSCLC and 50 healthy controls. IMAC 30-Cu protein chips were used to fractionate the proteins according to their metal binding affinity. The arrays were analyzed using the Ciphergen Protein Chip Reader PB IIa. The spectra were normalized to the total ion current of the mass to charge between 3000 — 10 000 Da. Protein peak clustering and classification analysis were performed using the Express 3.0 Biomarker Pattern Analysis Software. Several proteins with masses ranging from 2000-20000 Da were differentially expressed between NSCLC patients and healthy controls. Among the peak clusters revealing differences we selected two specific clusters as prospective candidate biomarkers in sera of the patients. High expression of one peak and underexpression of the other with respect to the healthy control sera were evaluated in a blind test in terms of the ability to classify a separate group of patients and controls.