Search

The peroxisome proliferator-activated receptor gamma (PPARG) C161T polymorphism (rs3856806) may be a risk factor for in-stent restenosis (ISR) due to its known associations with type 2 diabetes (T2DM), obesity, and coronary artery disease (CAD). This study aims to investigate the relationship between PPARG-C161T polymorphism and the risk of ISR, considering clinical features.

Recent reports showing that neo-atherosclerosis formation in stented coronary artery is characterized by the accumulation of lipid-laden macrophages within the neointima has strengthened the possibility that elevated low-density lipoprotein (LDL)-cholesterol may be a risk factor for in-stent restenosis (ISR). Protein Convertase Subtilisin/Kexin-9 (PCSK9) protein plays an important role in cholesterol metabolism by degrading of LDL receptors. The gain-of-function E670G (rs505151) mutation of the PCSK9 gene is a well-known genetic risk factor for hypercholesterolemia. This study evaluated for the first time the association of the E670G variation with the serum lipids, PCSK9 levels and concomitant diseases on the ISR risk. The study included 109 ISR, and 82 Non-ISR patients, based on the results of coronary angiography. Genotypes were determined using the real-time PCR and serum PCSK9 levels were measured by ELISA technique. The rare G allele of PCSK9 E670G (p < 0.05), hyperlipidemia (HL) (p < 0.001), and type 2 diabetes (T2DM) (p < 0.01) were associated with increased risk for ISR. In hyperlipidemic conditions, the E670G-G allele was associated with hypercholesterolemia and a higher risk of ISR (p < 0.001), while the E670G-AA genotype has been associated with a high prevalence of T2DM and hypertension. In addition, diabetic ISRs had higher serum PCSK9 levels (p < 0.05) and the E670G-AA genotype was associated with increased levels of diabetes markers. Our results indicated that the unusual effects of both G allele and AA genotype of the PCSK9 E670G variation may be involved in the risk of ISR in association with concomitant metabolic diseases. This study evaluated the association of the Protein Convertase Subtilisin/Kexin-9 (PCSK9) E670G mutation with the serum lipids, PCSK9 levels and concomitant diseases on the in-stent restenosis (ISR) risk. The E670G-G allele, hyperlipidemia, and type 2 diabetes (T2DM) were found risk factors for ISR. In hyperlipidemic conditions, the E670G-G allele was associated with hypercholesterolemia and a higher risk of ISR, while the E670G-AA genotype has been associated with a high prevalence of T2DM and hypertension. Our results indicated that the unusual effects of both genotypes of the E670G that may be involved in the ISR risk in association with concomitant diseases. [ABSTRACT FROM AUTHOR]

Genetic variations of LGALS3 (Galectin-3) were found to be associated with treatment resistance, mortality, recurrence, high tumor volume and multiple tumor involvement in solid organ cancers. The modulators of extracellular matrix (ECM), which is a dynamic factor in the larynx tissue with high biomechanical and regenerating ability, can play an important role. We aimed to investigate the relationship between the genetic variants of LGALS3, one of these modulators, with Laryngeal Squamous Cell Carcinoma (LSCC).

Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) was the first immune checkpoint molecule to be used as a drug target and led the way in the field of immunooncology. CTLA-4 increases the activation threshold of T-cells and reduces immune responses to weak antigens, such as self and tumour antigens. In our study, 56 patients were diagnosed with NSCLC, and a control group of 98 healthy volunteers was included. CTLA-4 +49A/G gene polymorphism and serum CTLA-4 levels were assessed. However, we found that CTLA-4 +49A/G gene polymorphism was associated with lymphovascular invasion (LVI) (P=0.049). The ratio of the heterozygous AG variant was 42.9% in patients with LVI, while it was 14.3% without LVI. This could indicate that the CTLA-4 +49A/G heterozygote AG variant increases the risk of LVI. In addition, we detected with the CTLA-4 +49A/G heterozygote AG variant had the worst mean overall survival at 56 weeks in the NSCLC patient group (X±SE=56.00±11.52, 95%CI 33.41-78.58, P=0.048). Furthermore, the patient group had significantly higher CTLA-4 serum levels (X±SE=121.57±11.89 pg/mL) compared with the control group (X±SE=79.09±3.09 pg/mL)( P=0.02). Our study data serve as a guide for future studies to elucidate the pathogenesis of NSCLC and evaluate the therapeutic significance of CTLA-4. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Biochemistry / Turk Biyokimya Dergisi is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The aim of this study was to determine the role of polymorphic variants of apolipoprotein E ( APOE) and peroxisome proliferator-activated receptor delta ( PPARD) genes in the development of coronary heart disease (CHD), and the PPARD and APOE gene-gene interaction in a Turkish population. This study was carried out using a sample of 223 patients with CHD (103 with diabetes and 120 without diabetes) and 101 controls. PPARD +294T/C and APOE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism technique. The PPARD and APOE genotype distributions were the same between study groups ( p>0.05). In the nondiabetic CHD patients, the PPARD +294 C allele showed higher serum low-density lipoprotein cholesterol (LDL-C) level than the common +294 TT homozygote genotype (3.83±1.01 vs. 3.33±1.14, p=0.015). In addition, a significant association between APOE 4 and PPARD +294 C alleles was detected based on their effects on LDL-C in the nondiabetic CHD patients (+294 C/ APOE4: 4.43±0.88 vs. +294 TT/non APOE 4: 3.48±1.09, p=0.009). This association indicated the interaction of two genes on plasma LDL-C levels ascended in the order +294 T<+294 T- APOE 4<+294 C< APOE 4<+294 C- APOE 4. The PPARD +294 C allele was associated with higher incidence of left ventricular hypertrophy (LVH) in all male patients with body mass index >27. In addition, the CHD patients who were +294 C allele carriers had a 2.48-fold higher risk of LVH than subjects homozygous for the T allele. An increasing effect of the PPARD +294 C allele was shown on serum LDL-C levels in nondiabetic CHD patients. In addition, the results suggested that the +294 C allele might be associated with an increased LVH risk especially in male CHD patients. Furthermore, gene-gene interaction between the PPARD +294T/C and the APOE polymorphisms was observed regarding LDL-C concentrations. [ABSTRACT FROM AUTHOR]

[Display omitted] • The RAGE -374 AA genotype and A allele significantly increases the risk of CAE. • In controls without systemic disease, -374A allele was associated with low sRAGE levels. • In CAEs receiving antihypertensive and antidiabetic treatment, sRAGE levels were increased. • Antihypertensive treatment may contribute to the CAE prognosis by increasing sRAGE. • The -374A allele is also associated with younger patient age and higher platelet count in CAE. Although the implication of receptor of advanced glycation endproducts (RAGE) has been reported in coronary artery disease, its roles in coronary artery ectasia (CAE) have remained undetermined. Furthermore, the effect of RAGE polymorfisms were not well-defined in scope of soluble RAGE (sRAGE) levels. Thus, we aimed to investigate the influence of the functional polymorphisms of RAGE -374T > A (rs1800624) and G82S (rs2070600) in CAE development. This prospective observational study was conducted in 2 groups selected of 2452 patients who underwent elective coronary angiography (CAG) for evaluation after positive noninvasive heart tests. Group-I included 98 patients with non-obstructive coronary artery disease and CAE, and Group-II (control) included 100 patients with normal coronary arteries. SNPs were genotyped by real-time PCR using Taqman® genotyping assay. Serum sRAGE and soluble lectin-like oxidized receptor-1 (sOLR1) were assayed by ELISA and serum lipids were measured enzymatically. The frequencies of the RAGE -374A allele and -374AA genotype were significantly higher in CAE patients compared to controls (p < 0.001). sRAGE levels were not different between study groups, while sOLR1 levels were elevated in CAE (p = 0.004). In controls without systemic disease, -374A allele was associated with low sRAGE levels (p < 0.05), but this association was not significant in controls with HT. Similarly, sRAGE levels of CAE patients with both HT and T2DM were higher than those no systemic disease (p = 0.02). The -374A allele was also associated with younger patient age and higher platelet count in the CAE group in both total and subgroup analyses. In the correlation analyses, the -374A allele was also negatively correlated with age and positively correlated with Plt in all of these CAE groups. In the total CAE group, sRAGE levels also showed a positive correlation with age and a negative correlation with HDL-cholesterol levels. On the other hand, a negative correlation was observed between sRAGE and Plt in the total, hypertensive and no systemic disease control subgroups. Multivariate logistic regression analysis confirmed that the -374A allele (p < 0.001), hyperlipidemia (p < 0.05), and high sOLR1 level (p < 0.05) are risk factors for CAE. ROC curve analysis shows that RAGE -374A allele has AUC of 0.713 (sensitivity: 83.7 %, specificity: 59.0 %), which is higher than HLD (sensitivity: 59.2 %, specificity: 69.0 %), HT (sensitivity: 62.4 %, specificity: 61.1 %) and high sOLR1 level (≥0.67 ng/ml)) (sensitivity: 59.8 %, specificity: 58.5 %). Beside the demonstration of the relationship between -374A allele and increased risk of CAE for the first time, our results indicate that antihypertensive and antidiabetic treatment in CAE patients causes an increase in sRAGE levels. The lack of an association between the expected -374A allele and low sRAGE levels in total CAE group was attributed to the high proportion of hypertensive patients and hence to antihypertensive treatment. Moreover, the RAGE -374A allele is associated with younger age at CAE and higher Plt, suggesting that -374A may also be associated with platelet activation, which plays a role in the pathogenesis of CAE. However, our data need to be confirmed in a large study for definitive conclusions. [ABSTRACT FROM AUTHOR]

Background/aim: New compounds for cancer treatment are needed due to persistenly unsatisfactory management of cancer. [PdCl(terpy)](sac)·2H2O] (sac=saccharinate, and terpy=2,2':6',2"-terpyridine) is a compound synthesized for this purpose. We investigated its anti-proliferative and pro-apoptotic effects on Ehrlich Ascites Carcinoma (EAC) in vivo., Materials and Methods: 42 Balb-c female mice were subcutaneously (s.c.) injected with EAC cells (1st day) and then randomly divided into 5 groups: control (0.9% NaCl), complex (2 mg/kg), complex (3 mg/kg) cisplatin (4 mg/kg) and paclitaxel (12.5 mg/kg). On the 5th and 12th day animals were drug administrated. At 14th day, animals were sacrificed. Expression of cell death and/or cell cycle-related markers (Bcl-2, Bax, active caspase-3, p53, PCNA) and apoptosis were investigated immunohisto-chemically. Survival-related markers (Akt, GSK-3β, IGF-1R, IR, IRS-1, p70S6K, PRAS40) were evaluated by luminex analysis., Results: Expression of p53, PCNA, Bcl-2 was found decreased (p<0.001) and that of active caspase-3, Bax, and apoptotic cells was found increased (p<0.001) in all groups. The survival-related markers did not show any statistical difference in complex groups., Conclusion: The Pd(II)-complex seems to have a strong anticancer activity on EAC by inducing apoptosis via both suppression of proliferation and activation of apoptosis in vivo, similar to the effects of cisplatin and paclitaxel., (Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: Breast cancer is one of the most common and lethal types of cancer among women. We focused on the importance of the immune system in the etiology of breast cancer by investigating critical polymorphisms of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and cluster of differentiation 28 (CD28) gene, and circulating levels of these proteins., Materials and Methods: A total of 79 patients with breast cancer and 76 healthy controls were enrolled. Molecular assessment of CTLA4 (rs231775&rs5742909) and CD28 (rs3116496) variants were determined with polymerase chain reaction restriction fragment length polymorphism techniques. Circulating levels of soluble forms of CTLA4 and CD28 were analyzed by ELISA., Results: Although no significant association was found between study groups, CTLA4 +49AA genotypic frequency, and sCTLA4 and sCD28 levels were higher in patients. Some clinicopathological features were also related with CTLA4 and CD28 variants and blood levels., Conclusion: While CTLA4 +49AA genotype is increased in patients with breast cancer, the CTLA4 -318T allele may have a prognostic value. In addition, sCTLA4 and sCD28 can be used for diagnostic purposes in patients with breast cancer., (Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Colorectal cancer (CRC) is the third most frequent cancer worldwide. Research has revealed the contributions of the immune system and anti-inflammatory pathways in the development of cancer. The balance between cluster of differentiation 28 (CD28) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) signaling is important for the regulation of immune responses. The oxidant-antioxidant balance by sustaining redox control via several defense mechanisms is also an important factor for the progression of cancer. The aim of the present study was to determine the distribution of CTLA4/CD28 variants and oxidant-antioxidant status in patients with CRC., Materials and Methods: This study enrolled 80 patients with CRC and 115 healthy controls. We used a spectrophotometric assay to detect the levels of lipid peroxidation products malon dialdehyde (MDA) and lipid hydroperoxide (LHP), and measured the concentration of protein damage products, advanced oxidation protein products (AOPP) and protein carbonyl (PCO). Additionally, antioxidant levels were detected by measuring copper, zinc, superoxide dismutase (Zn-Cu SOD) and total thiol (T-SH) levels, and advanced glycation end-products (AGEs). The CTLA4 -318C>T, CTLA4 49A>G and CD28C>T genotypes were determined by using restriction enzymes., Results: AOPP and PCO levels were increased in patients with CRC as well as those of LHP, MDA and AGE, while the levels of antioxidants such as Cu-Zn SOD and T-SH were lower. Lower serum levels of CTLA4 and higher serum levels of CD28 were detected in patients and, an association of the CTLA4 -318C/T polymorphism was found in patients with CRC., Conclusion: Our oxidative stress was increased in patients with CRC, suggesting the contribution of this disturbed oxidative status to serum CTLA4 and CD28 levels, and to the pathogenesis of CRC., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

miRNA involvement has been observed in almost every type of cancer, including breast cancer. The etiology of abnormal expression of miRNAs in cancer is still not clearly understood. In order to obtain insight into miRNA de-regulation in breast cancer, we analyzed expression levels of five breast cancer-related miRNAs, miRNA21, miRNA155, miRNA19a, miRNA17-5p and let7a miRNA, in both malignant and neighboring non-tumoral paraffin-embedded tissues of 47 patients with invasive ductal breast cancer. The targeted miRNAs, and a reference snRNA, U6, were analyzed by real-time polymerase chain reaction. let7a Levels were significantly lower in patients with lymphatic invasion than in those without (p=0.047). miR21 was down-regulated in 93.3% of patients with necrosis [p=0.017 (Fisher's exact test (FE))], while at least one oncogenic miRNA was up-regulated in 87.3% of the patients with invasive ductal carcinoma [p=0.009 (FE)]. In addition, tumor-suppressor miRNA was down-regulated or unaltered in 65.8% of the patients with tumor grade 2 or 3 and in all with grade 1 [p=0.047 (FE)]. Based on this preliminary study, we suggest that these miRNAs, especially let7a and miRNA21, might be useful markers in follow-up of breast cancer and in prognosis., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: The present study investigated the effects of growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and GH-receptor (GHR)/exon-3 polymorphism on diabetes mellitus (DM) and coronary heart disease (CHD) patients., Patients and Methods: Ninety patients with CHD, 90 patients with DM and 96 controls were included in this study. The GH, IGF-1 and IGFBP-3 serum levels were measured with enzyme-linked immunosorbent assay. GHR/exon-3 variants were determined by multiplex-polymerase chain reaction., Results: The frequency of all alleles and genotypes in all study groups were distributed according to the Hardy-Weinberg equilibrium. In addition, any association between GHR/exon-3 variants and the presence of risk factors were detected. The blood levels of GH, IGF-1 and IGFBP-3 were not distributed according to GHR/exon-3 variants. However, in the DM group, higher levels of IGF-1 and lower levels of GH and IGFBP-3, and in CHD group lower levels of IGF-1, GH and IGFBP-3 were observed. The order of GH levels were DM

Background: In this study we aimed to determine the possible risks for the development of coronary artery disease (CAD) in diabetic (DM(+)) and non-diabetic (DM(-)) patients according to the -374T/A polymorphism of the receptor for advanced glycation end products (RAGE) gene which affects the function of RAGE itself., Materials and Methods: This study was carried out in 52 non-diabetic and 62 diabetic patients with CAD, and 55 CAD-free, healthy volunteers as controls. The A-T transversion polymorphism at position -374 in the promotor region of the RAGE gene was analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) techniques., Results: The -374T/A AA genotype frequency was statistically higher in the whole patient group when compared with the control group (p=0.034), and statistically higher in the DM(+) group when compared with the control group (p=0.003). Homozygosity for the -374A allele was found to be higher, but not statistically meaningful, in DM(-) patients (17.3%) when compared with the control group (13.2%). In this study, in contrast with other studies, we found possesion of the A allele to be an independent risk factor in CAD in patients with diabetes mellitus., Conclusion: Possesion of the -374A allele may contribute to the CAD in diabetic patients with triggering macrophages by increased levels of AGEs.