DPYD, TYMS and MTHFR Genes Polymorphism Frequencies in a Series of Turkish Colorectal Cancer Patients.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadFluoropyrimidine-based chemotherapy is extensively used for the treatment of solid cancers, including colorectal cancer. However, fluoropyrimidine-driven toxicities are a major problem in the management of the disease. The grade and type of the toxicities depend on demographic factors, but substantial inter-individual variation in fluoropyrimidine-related toxicity is partly explained by genetic factors. The aim of this study was to investigate the effect ofDokuz Eylul University Research Foundatio

Vitamin D Intake, Serum 25-Hydroxyvitamin-D (25(OH)D) Levels, and Cancer Risk: A Comprehensive Meta-Meta-Analysis Including Meta-Analyses of Randomized Controlled Trials and Observational Epidemiological Studies

It is a well-established fact that inadequate Vitamin D (Vit-D) levels have negative effects on the development and progression of malignant diseases, particularly cancer. The purpose of this paper was to elucidate the effects of Vit-D intake and serum 25-hydroxyvitamin-D (25(OH)D) levels on cancer incidence and mortality, the current evidence in this field, and the biases of this evidence, using the meta-meta-analysis method. Meta-analyses focusing on Vit-D intake, serum 25(OH)D levels, and cancer risk/mortality were identified. A structured computer literature search was undertaken in PubMed/Medline, Web of Science (WoS), and Scopus electronic databases using predetermined keyword combinations. Primary and secondary meta-meta-analyses were carried out, combining odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) for outcomes reported in selected meta-analyses. A total of 35 eligible meta-analyses (59 reports yielded from these studies) assessing the association between Vit-D and cancer incidence and/or mortality were included in this study. In the pooled analysis, higher Vit-D intake and serum 25(OH)D levels were associated with lower cancer risk (OR = 0.93, 95% confidence interval (CI): 0.90–0.96, p p p p p = 0.320). In subgroup analysis, Vit-D consumption was associated with a significant decrease in colorectal and lung cancer incidence (OR = 0.89, 95% CI: 0.83–0.96, p = 0.002; OR = 0.88, 95% CI: 0.83–0.94, p < 0.001, respectively). Taken together, both Vit-D intake and higher 25(OH)D levels may provide remarkable benefits in terms of cancer incidence and mortality; however, careful evaluation according to cancer types is critically important and recommended

The Role of Cyanidin-3-O-glucoside in Modulating Oxaliplatin Resistance by Reversing Mesenchymal Phenotype in Colorectal Cancer.

Background: Epithelial-mesenchymal transition (EMT) plays an important role in the biological and biochemical processes of cells, and it is a critical process in the malignant transformation, and mobility of cancer. Additionally, EMT is one of the main mechanisms contributing to chemoresistance. Resistance to oxaliplatin (OXA) poses a momentous challenge in the chemotherapy of advanced colorectal cancer (CRC) patients, highlighting the need to reverse drug resistance and improve patient survival. In this study, we explored the response of cyanidin-3-O-glucoside (C3G), the most abundant anthocyanin in plants, on the mechanisms of drug resistance in cancer, with the purpose of overcoming acquired OXA resistance in CRC cell lines. Methods: We generated an acquired OXA-resistant cell line, named HCT-116-ROx, by gradually exposing parental HCT-116 cells to increasing concentrations of OXA. To characterize the resistance, we performed cytotoxicity assays and shape factor analyses. The apoptotic rate of both resistant and parental cells was determined using Hoechst 33342/Propidium Iodide (PI) fluorescence staining. Migration capacity was evaluated using a wound-healing assay. The mesenchymal phenotype was assessed through qRT-PCR and immunofluorescence staining, employing E-cadherin, N-cadherin, and Vimentin markers. Results: Resistance characterization announced decreased OXA sensitivity in resistant cells compared to parental cells. Moreover, the resistant cells exhibited a spindle cell morphology, indicative of the mesenchymal phenotype. Combined treatment of C3G and OXA resulted in an augmented apoptotic rate in the resistant cells. The migration capacity of resistant cells was higher than parental cells, while treatment with C3G decreased the migration rate of HCT-116-ROx cells. Analysis of EMT markers showed that HCT-116-ROx cells exhibited loss of the epithelial phenotype (E-cadherin) and gain of the mesenchymal phenotype (N-cadherin and Vimentin) compared to HCT-116 cells. However, treatment of resistant cells with C3G reversed the mesenchymal phenotype. Conclusion: The morphological observations of cells acquiring oxaliplatin resistance indicated the loss of the epithelial phenotype and the acquisition of the mesenchymal phenotype. These findings suggest that EMT may contribute to acquired OXA resistance in CRC. Furthermore, C3G decreased the mobility of resistant cells, and reversed the EMT process, indicating its potential to overcome acquired OXA resistance

Evaluation of children's dental anxiety levels at a kindergarten and at a dental clinic

WOS: 000404458100004PubMed ID: 27556551This study evaluated the dental anxiety levels of preschool children at a kindergarten and at a dental clinic. The anxiety levels of ninety 4-6-year-old (4.99 +/- 0.81) preschool children were evaluated according to pulse rates, the facial image scale (FIS), the Venham picture test (VPT), and the Frankl behavior rating scale. The children's mothers were asked to complete the state-trait anxiety inventory (STAI) forms 1 and 2 (STAI 2 and STAI 2). The sample t-test, Mann-Whitney U test, and Pearson's correlation test were used. A statistically significant difference was observed between the children's pulse rates when measured at the dental clinic and those when measured at the kindergarten (p < 0.001). Although the results were not statistically significant, more negative facial expressions were observed in the children at the dental clinic than in those at the kindergarten when assessed using FIS and VPT (p = 0.090 and p = 0.108, respectively). There was a statistically significant correlation between the transient anxiety levels (STAI 1) of mothers and the VPT scores of their children evaluated at the dental clinic (r = 0.506, p < 0.001). The continuous anxiety level of the mothers of males was found to be significantly higher (p = 0.033) than that of the mothers of females (STAI 2). Although the children had been informed about dentistry and were introduced to a dentist at the kindergarten, their anxiety levels seemingly increased as they arrived at the dental clinic. The significant increase observed in the children's pulse rates was a physical indicator that their anxiety levels had increased. It can be concluded that the children felt more anxious at the dental clinic that at the kindergarten

Effect of repeated low-dose organophosphorothionate pesticide exposure on digoxin pharmacokinetics in rats; a possible interaction involving P-glycoprotein

Aside from acute occupational exposure, an important part of the population may be chronically exposed to the trace amounts of organophosphorothionate pesticides (OPTs) via residues in nutrients and drinking water. P-glycoprotein (P-gp) is a transmembrane protein responsible for the efflux of numerous drugs. OPTs were shown to inhibit P-gp function in vitro and increase its expression in vivo. Digoxin is a probe drug for the investigation of P-gp. To evaluate the effect of repeated low-dose OPT exposure on P-gp, commercial formulations of diluted OPT or tap water were administered to female Wistar rats for 8 consecutive days. On the ninth day each group was further divided into two groups and digoxin was administered either intraduodenally ( ID) or intravenously (IV). Blood sampling and bile and urine collection were taken during 6 h at various intervals. The peak concentration in serum (C-max) of digoxin was found to be decreased and the mean absorption time (MAT) was significantly increased in the digoxin OPT group. The mean residence time was significantly elevated in the digoxin(ID) OPT group. The biliary excretion% digoxin was significantly increased in the digoxin OPT group, while the renal excretion% digoxin rose only in the digoxinID OPT group. No significant differences in time to reach C-max (t(max)), area under the plasma concentration-time curve (AUC)(0-360), area under the moment curve (AUMC) 0-360, and bioavailability (F) were detected. In our study, repeated low-dose OPT exposure reduced the absorption and increased the excretion% digoxin, which may be related to enhanced P-gp expression. However, alterations of digoxin pharmacokinetic parameters did not change the systemic availability of digoxin

Association of ischemia-modified albumin with oxidative stress status and insulin resistance in obese patients

Objectives: Obesity is associated with oxidative stress due to the overproduction of free radicals in some accompanying states, such as hyperglycemia, elevated lipid levels and chronic inflammation. Free radical accumulation may modify the structure of human serum albumin, generating ischemia-modified albumin (IMA), and increased serum levels of IMA have been linked to obesity-related diseases and oxidative damage. The association of IMA levels with oxidative stress and insulin resistance (IR) has not been evaluated in the context of obesity. The aim of this study is to determine IMA levels in the context of obesity and their relationship with oxidative status and insulin resistance. Methods: Sixty-one adult obese cases with body mass index (BMI) ≥ 30 were evaluated, with 30 healthy adults with 18.5 ≤ BMI ≤ 24.9 included in the control group. IMA, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), total cholesterol, triglycerides, HDL and LDL-cholesterols were determined. Results: IMA, TAS, TOS, OSI, total cholesterol and LDL-cholesterol levels were not different between the control and obese groups (P-value >0.05), while triglyceride levels were determined to be higher and HDL-cholesterol levels were determined to be lower in the obese group (P-value 0.05), but the fasting blood glucose level was determined to be higher in the obese/IR(+) group than in the control group. Conclusions: We concluded that obesity and insulin resistance had no effect on IMA levels in the obese group, who showed no impairment in their oxidative balanc

Association of ischemia-modified albumin with oxidative stress status and insulin resistance in obese patients

Objectives: Obesity is associated with oxidative stress due to the overproduction of free radicals in some accompanying states, such as hyperglycemia, elevated lipid levels and chronic inflammation. Free radical accumulation may modify the structure of human serum albumin, generating ischemia-modified albumin (IMA), and increased serum levels of IMA have been linked to obesity-related diseases and oxidative damage. The association of IMA levels with oxidative stress and insulin resistance (IR) has not been evaluated in the context of obesity. The aim of this study is to determine IMA levels in the context of obesity and their relationship with oxidative status and insulin resistance. Methods: Sixty-one adult obese cases with body mass index (BMI) ≥ 30 were evaluated, with 30 healthy adults with 18.5 ≤ BMI ≤ 24.9 included in the control group. IMA, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), total cholesterol, triglycerides, HDL and LDL-cholesterols were determined. Results: IMA, TAS, TOS, OSI, total cholesterol and LDL-cholesterol levels were not different between the control and obese groups (P-value >0.05), while triglyceride levels were determined to be higher and HDL-cholesterol levels were determined to be lower in the obese group (P-value <0.05). When IMA, TAS, TOS, OSI levels were compared between the control/IR(-), obese/IR(+) and obese/IR(-) groups, no statistically significant differences were detected (P-value >0.05), but the fasting blood glucose level was determined to be higher in the obese/IR(+) group than in the control group. Conclusions: We concluded that obesity and insulin resistance had no effect on IMA levels in the obese group, who showed no impairment in their oxidative balanc

In silico identification of novel biomarkers for key players in transition from normal colon tissue to adenomatous polyps.

Adenomatous polyps of the colon are the most common neoplastic polyps. Although most of adenomatous polyps do not show malign transformation, majority of colorectal carcinomas originate from neoplastic polyps. Therefore, understanding of this transformation process would help in both preventive therapies and evaluation of malignancy risks. This study uncovers alterations in gene expressions as potential biomarkers that are revealed by integration of several network-based approaches. In silico analysis performed on a unified microarray cohort, which is covering 150 normal colon and adenomatous polyp samples. Significant gene modules were obtained by a weighted gene co-expression network analysis. Gene modules with similar profiles were mapped to a colon tissue specific functional interaction network. Several clustering algorithms run on the colon-specific network and the most significant sub-modules between the clusters were identified. The biomarkers were selected by filtering differentially expressed genes which also involve in significant biological processes and pathways. Biomarkers were also validated on two independent datasets based on their differential gene expressions. To the best of our knowledge, such a cascaded network analysis pipeline was implemented for the first time on a large collection of normal colon and polyp samples. We identified significant increases in TLR4 and MSX1 expressions as well as decrease in chemokine profiles with mostly pro-tumoral activities. These biomarkers might appear as both preventive targets and biomarkers for risk evaluation. As a result, this research proposes novel molecular markers that might be alternative to endoscopic approaches for diagnosis of adenomatous polyps

The factors that have an impact on the development of brain metastasis in the patients with breast cancer

Background: To evaluate the factors that have an impact on the development of brain metastasis in patients with breast cancer. Materials and Methods: Among the patients who were followed-up and treated for breast cancer between January 2000 and January 2010, the ones with brain metastasis were included to the analysis. Metastatic breast cancer patients without brain metastasis, which had similar duration of follow-up and median age were included as the control group. Both group were compared for prognostic and predictive factors in terms of relationship between with or without brain metastasis and survival. Results: There were a total of 63 female patients with metastatic breast cancer who had brain metastasis and the researchers enrolled the same number of female patients as the control group. In the univariate analysis, as a significant finding, it was found that, the patients with breast cancer who had brain metastasis had vascular invasion positivity, human epidermal growth factor receptor-2 (HER-2) positivity, a rare detection of invasive lobular carcinoma component in the tumor, estrogen receptor negativity, and no bone and liver metastasis and they did not receive chemotherapy due to several reasons after the detection of metastasis in any organ. In the multivariate analysis, HER-2 positivity, no bone and liver metastasis and not receiving chemotherapy due to several reasons after the detection of metastasis in any organ were detected as significant findings. Conclusions: As the prognostic and predictive factors showing the development of brain metastasis in breast cancer patients may be identified, follow-up also including the brain is important in order to take preventive measures

A 5 years follow-up for ischemic cardiac outcomes in patients with carotid artery calcification on panoramic radiographs confirmed by doppler ultrasonography in Turkish population

WOS: 000528252700007PubMed: 32058807Objective: To evaluate the diagnostic accuracy of digital panoramic radiograph (DPR) for detection of carotid artery calcification (CAC) confirmed by Doppler Ultrasonography (DUSG) and to clarify the relationship between between CAC identified by DPR and cardiovascular events through a 5 year follow-up period. Methods: of 3600 consecutive patients examined, 158 patients presented with CAC as detected by DPR. the final study group was composed of 96 patients who had CAC confirmed by DUSG or CT angiogram. the control group was composed of 62 patients who has normal DUSG. the end point of the study was the occurrence of any cardiovascular event. Results: 72 (75%) of the 96 patients with CAC confirmed by DUSG (16 patients had significant stenosis) had bilateral and 24 (25%) had unilateral CAS as detected by DUSG. There was a low agreement between the examination results with a kappa value of 0.488 (p < 0.005) for calcification. Study data revealed that smoking, chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM) and diastolic hypertension were significantly more common in patients with CAC than the control group (p < 0.05). During the follow-up period, 13 subjects had myocardial infarction and 1 subject died; in the control group, 1 patient died after MI and 1 patient died of a non-cardiac event. Conclusion: Patients with CAC detectable by DPR concomitant with COPD, DM, smoking or diastolic hypertension are more likely to suffer from vascular events. Therefore, patients with detectable carotid plaque in DPR require referral to a cardiovascular surgery clinic for further investigations