Is hypermethylation of SOX1 gene an independent prognostic marker in surgically resected non-small cell lung cancer?

Background: Promoter hypermethylation of tumor suppressor genes presents promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine the association between the promoter hypermethylation of multiple genes and 5-year survival rate in patients with Non-small cell lung cancer (NSCLC). Materials and Methods: Primary tumor samples (n = 65), corresponding nonmalignant lung tissues (n = 65), and circulating blood were obtained from NSCLC patients who underwent curative surgery. Promoter methylation status in seven genes (RASSF1A, CDH13, MGMT, ESR1, DAPK, SOX1, and HOXA9) was quantified by using bisulfite pyrosequencing. Five-year survival data were obtained by a clinician. Cox proportional hazards models were used to analyze the associations between gene methylation status and overall patient survival. Results: The 5-year survival of the patients with SOX1 aberrant tumor methylation was found to be statistically significantly shorter than for those patients without aberrant tumor methylation (P = 0.01). This effect was independent of TNM stage. No significant survival differences were associated with aberrant methylation in other genes tested in either of the two tissue types. Conclusion: Our study shows that SOX1 promoter hypermethylation in NSCLC tumors is significantly associated with inferior survival, showing promise as a useful prognostic biomarker in patients with NSCLC.

Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro.

Although promising for active immunization in cancer patients, dendritic cells (DCs) vaccines generated in vitro display high inter-individual variability in their immunogenicity, which mostly limits their therapeutic efficacy. Gut microbiota composition is a key emerging factor affecting individuals' immune responses, but it is unknown how it affects the variability of donors' precursor cells to differentiate into immunogenic DCs in vitro. By analyzing gut microbiota composition in 14 healthy donors, along with the phenotype and cytokines production by monocyte-derived DCs, we found significant correlations between immunogenic properties of DC and microbiota composition. Namely, donors who had higher α-diversity of gut microbiota and higher abundance of short-chain fatty acid (SCFAs) and SCFA-producing bacteria in feces, displayed lower expression of CD1a on immature (im)DC and higher expression of ILT-3, costimulatory molecules (CD86, CD40) proinflammatory cytokines (TNF-α, IL-6, IL-8) and IL-12p70/IL-10 ratio, all of which correlated with their lower maturation potential and immunogenicity upon stimulation with LPS/IFNγ, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower α-diversity and higher abundance of Bifidobacterium and Collinsella in feces displayed higher CD1a expression and higher potential to up-regulate CD86 and CD40, increase TNF-α, IL-6, IL-8 production, and IL-12p70/IL-10 ratio upon stimulation. These results emphasize the important role of gut microbiota on the capacity of donor precursor cells to differentiate into immunogenic DCs suitable for cancer therapy, which could be harnessed for improving the actual and future DC-based cancer therapies.

Beneficial Effect of Virgin Coconut Oil on Alloxan-Induced Diabetes and Microbiota Composition in Rats.

The gut microbiota is composed of a diverse population of obligate and facultative anaerobic microorganisms which are shown to influence host metabolism and immune homeostasis. This study investigated the effects of virgin coconut oil on the weekly fasting glycaemia, daily food and water intake and weekly body mass gain over 16 weeks, as well as the changes in composition of gut microbiota in both non-diabetic and alloxan-induced diabetic rats. Although the intake of virgin coconut oil did not decrease the diabetes-induced hyperglycemia, it affected the secondary parameters, such as food and water intake and average body mass gain. Furthermore, its potential to positively affect the fecal microbiome was proved, since it significantly increased the abundance of probiotic bacteria, such as Lactobacillus, Allobaculum and Bifidobacterium species.

HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in the Serbian population.

This study provides the first published detailed analysis of five loci polymorphisms as well as reports of two, three and five loci haplotype frequencies in the Serbian population in a sample of 1992 volunteer bone marrow donors recruited from different part of the country. Typing was performed by PCR SSO method combined with PCR SSP techniques to resolve ambiguities. In total, 16 HLA-A, 28 HLA-B, 14 HLA-C, 13 HLA-DRB1 and 5 HLA-DQB1 allelic groups were identified. The most frequent in allele groups are HLA-A(∗)02 (29.5%), HLA-A(∗)01 (14.2%), HLA-B(∗)35 (13.1%), HLA-B(∗)51 (12.8%), HLA-C(∗)07 (24.8%), HLA-DRB1(∗)11 (16.9%), HLA-DRB1(∗)13 (13.2%), HLA-DQB1(∗)03 (33.3%) and DQB1(∗)05 (33.0%). The most frequent three- and five-loci haplotypes were A(∗)01-B(∗)08-DRB1(∗)03 (5.9%) and A(∗)02-B(∗)18-DRB1(∗)11 (1.9%), A(∗)01-B(∗)08-C(∗)07-DRB1(∗)03-DQB1(∗)02 (6.6%) followed by A(∗)02-B(∗)18-C(∗)07-DRB1(∗)11-DQB1(∗)03 (2.5%), then A(∗)33-B(∗)14-C(∗)08-DRB1(∗)01-DQB1(∗)05 and A(∗)02-B(∗)35-C(∗)04-DRB1(∗)16-DQB1(∗)05 (2.2% both), respectively. The results of cluster analysis showed that the Serbian population is closely related to the populations living in central Balkan and neighboring European regions. The level of allelic diversity found in this study are relevant to facilitate searching for unrelated matched donor and provide a healthy control population from our region that should be useful in the future disease association study.

Diagnostic value of NT-proBNP in identifying impaired coronary flow reserve in asymptomatic moderate or severe aortic stenosis.

AIM: NT-proBNP has been shown to be a reliable biochemical marker for left ventricular wall stress. The relationship between NT-proBNP and coronary flow reserve (CFR) was evaluated in patients with significant asymptomatic aortic stenosis (AS). METHODS: A total of 74 patients with moderate or severe AS, mean age 66.68 ± 10.02 years (56.75% males), were enrolled in this prospective study. All patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis >50% in diameter). They had all undergone standard transthoracic Doppler-echo study and adenosine stress transthoracic-echo for CFR measurement and laboratory analysis for NT-proBNP measurement. RESULTS: The median NT-proBNP value was significantly increased (417.0 pg/ml; interquartile range [IQR]: 176.8-962.2 pg/ml). NT-proBNP was significantly higher in the group with CFR ≤2.5 (median: 549.0 pg/ml; IQR: 311.5-1131.0 pg/ml; as opposed to median: 291.5 pg/ml; IQR: 123.0-636.2 pg/ml; W = 452; p = 0.012). NT-proBNP showed significant negative correlation with CFR (ρ = -0.377, p = 0.001). There was also significant correlation between NT-proBNP and E/E´, S´ and aortic valve resistance. The NT-proBNP value of 334.00 pg/ml was determined as the best cut-off value for the diagnosis of CFR ≤2.5 (area under the curve: 0.67; 95%CI: 0.54-0.79; p < 0.01) and the sensitivity and specificity were 74 and 64%, respectively. CONCLUSION: Elevated NT-proBNP can indicate patients with impaired CFR in asymptomatic moderate or severe AS patients with preserved ejection fraction and nonobstructive coronary arteries.

Evaluation of quality of life after radical prostatectomy-experience in Serbia.

The aim of this study was to compare health related quality of life (QoL) of patients with prostate cancer, who had undergone radical prostatectomy (RP), with patients who were carefully monitored. This prospective study included 56 patients who had undergone the radical prostatectomy (RP) and 48 non-operated patients (watchful waiting, WW). All patients filled EPIC questionnaire at baseline, 1th, 3rd, 6th and 12th month. At baseline, mean scores were similar in both groups, but one month after the surgery in RP group, patients had statistically significant lower score of urinary incontinency, urinary function and sexual function compared with WW patients. These scores were significantly higher in the 3rd, 6th and 12th month in operated patients, but there was no improvement in the WW group. Radical prostatectomy does not significantly improve quality of life. Prostatectomized patients had worse scores on the QoL scale, with exception of the urinary disturbance dimension.