Association between a Genetic Variant in the hsa-miR-146a Gene and Cancer Risk: An Updated Meta-Analysis.

BACKGROUND AND AIMS: A large number of studies have investigated the association between the potentially functional genetic variant rs2910164 located in the hsa-miR-146a gene and susceptibility to various types of cancer. Nevertheless, the results obtained in these studies are contradictory. Therefore, we conducted a meta-analysis of data from eligible reports comprising a total of 28,359 cases and 41,678 controls. METHODS: The literature included in this meta-analysis was selected from the PubMed database. Quantitative data synthesis was performed by using the OpenMeta-analyst software. RESULTS: The meta-analysis yielded no evidence of an association between rs2910164 and the overall cancer risk. Conversely, the C allele of this genetic variant was found to be associated with a decreased risk of developing bladder and cervical cancer in multiple genetic models. The same direction of association was found for the C allele and liver cancer, gastric cancer and oral squamous cell carcinoma risk. In contrast to these results, the same allelic variant of rs2910164 was found to confer an increased risk of developing lung cancer. The stratified meta-analysis based on ethnicity did not show significant differences in the association between rs2910164 and cancer risk in populations with different ethnic backgrounds. CONCLUSION: We conclude that rs2910164 may represent a valuable biomarker associated with the risk of developing specific types of cancer.

Genetic variants within endothelial nitric oxide synthase gene and prostate cancer: a meta-analysis.

Several variants within gene-encoding endothelial isoform of nitric oxide synthase have been reported to confer prostate cancer (PCa) susceptibility and/or progression. Nevertheless, studies referring to this issue have yielded inconsistent results. In order to elucidate the involvement of these variants in prostate carcinogenesis, we have conducted a meta-analysis of previously published case-control and relevant case-only studies. Eleven studies comprising in total 3,806 cases and 4,466 controls were included in the meta-analysis which yielded evidence of association of rs2070744 (ORCC = 1.43, 95% CI 1.04-1.97; p = 0.03) and intron 4a/b variant (ORab+aa = 1.47, 95% CI 1.00-2.14; p = 0.05) with PCa risk under recessive and dominant model, respectively. Furthermore, PCa patients carrying 4a/b a allele were found to have an increased risk of cancer progression to a less differentiated form, characterized by a high Gleason score (OR = 2.29, 95% CI 1.51-3.49; p < 0.01) and to higher TNM stage (OR = 2.55, 95% CI 1.71-3.81; p < 0.01). These results support the involvement of NOS3 variants in molecular pathogenesis of PCa.

Association between genetic variant in hsa-miR-146a gene and prostate cancer progression: evidence from Serbian population.

PURPOSE: Two previous studies of association between rs2910164 in miR-146a gene and prostate cancer (PCa) risk have provided opposing results. Furthermore, no evidence of association of this SNP with standard prognostic parameters of PCa progression was obtained in mentioned studies. The main aim of this study was to evaluate the possible association between PCa onset and progression to a more aggressive form, since it has not been assessed in a population of European descent. METHODS: In this study, 286 samples of peripheral blood were obtained from patients with PCa, while the control group comprised 199 volunteers derived from general population who gave samples of buccal swabs. For individuals diagnosed with PCa clinicopathological characteristics including serum prostate-specific antigen level at diagnosis, Gleason score (GS), and clinical stage were determined. Genotyping of rs2910164 was performed using Taqman(®) SNP Genotyping Assay. Analysis of SNP association was done using PLINK and SNPStats software. RESULTS: rs2910164 showed no association with PCa risk. Nevertheless, heterozygous genotype was found to be associated with higher GS, as well as with the presence of distant metastases. rs2910164 was also shown to be associated with cancer aggressiveness (p = 0.0067; ORGC = 2.22, 95 %CI 1.24-3.97; ORCC = 0.47, 95 %CI 0.13-1.68). CONCLUSIONS: Our results show no evidence of association between rs2910164 and PCa risk in Serbian population. Conversely, this variant was found to be associated with PCa aggressiveness.

Assessment of association between common variants at 17q12 and prostate cancer risk-evidence from Serbian population and meta--analysis.

This study aimed to evaluate possible association between genotypes and alleles of two 17q12 polymorphisms (rs3760511 and rs7501939) and prostate cancer (PCa) risk and progression. Two hundred seventy-one patients with PCa, 261 patients with benign prostatic hyperplasia (BPH), and 171 controls were included in the study. Single nucleotide polymorphisms (SNPs) were genotyped by using PCR followed by restriction fragment length (PCR-RFLP) analysis. We conducted meta-analysis of published studies regarding association of these SNPs with PCa risk. Evidence of positive association between the AC genotype of the SNP rs3760511 and BPH risk for the best-fitting overdominant model of association (BPH vs. controls comparison, p = 0.026; odds ratio [OR] = 1.58; 95% confidence interval [95%CI] 1.05-2.36) were obtained. The association between T allele of rs7501939 and PCa risk was determined in PCa versus controls comparison (p = 0.0032; OR = 0.66, 95%CI 0.50-0.87) with the best-fitting model of inheritance being log-additive. This variant was also found to be associated with the risk of BPH (p = 0.0023; OR = 0.65, 95%CI 0.49-0.86). We found no association between parameters of PCa progression and the analyzed SNPs. Meta-analysis showed strong association between these variants and PCa risk. Our study shows association between SNPs at locus 17q12 and the risk of prostatic diseases in Serbian population. At the same time, results of meta-analysis suggest the association of these SNPs with PCa risk.

Common variants at 8q24 are associated with prostate cancer risk in Serbian population.

Previous studies have shown correlation between single nucleotide polymorphisms (SNPs) at 8q24 and prostate cancer (PCa) risk. This study aimed to evaluate possible association between genotypes and alleles of 8q24 polymorphisms (rs1447295, rs4242382, rs6983267, rs7017300, and rs7837688) and PCa risk and progression. 150 patients with PCa, 150 patients with benign prostatic hyperplasia (BPH), and 100 healthy controls selected from the general population were recruited for this study. SNPs were genotyped by using PCR-RFLP analysis. There was a significant positive association between the A allele of the SNP rs4242382 and PCa risk [PCa vs. BPH comparison, P = 0.014 for the best-fitting dominant model; odds ratio (OR) =1.98; 95 % confidence interval (95%CI) 1.14-3.43]. We found evidence (P = 0.0064) of association between PCa risk and rs7017300 (heterozygote OR = 1.60; 95%CI 0.95-2.69) when comparing genotype distributions in PCa and BPH patients. The association between T allele rs7837688 and PCa risk was determined in PCa vs. BPH comparison with the best-fitting model of inheritance being log-additive (P = 0.0033; OR = 2.14, 95%CI 1.27-3.61). Odds ratio for carriers of rs6983267 TT genotype under recessive model of association with PCa was found to be 0.36 (PCa vs. control comparison, P = 0.0029; 95%CI 0.19-0.71). For rs1447295, deviation from Hardy-Weinberg equilibrium was observed in BPH patients and controls. We found no association between parameters of PCa progression and five 8q24 SNPs. Locus 8q24 harbors genetic variants associated with PCa risk in Serbian population.

Assessment of possible association between rs3787016 and prostate cancer risk in Serbian population.

Recent study, which included meta-analysis of two genome-wide association studies (GWAS), followed by a replication, identified the association between single nucleotide polymorphism (SNP) rs3787016 at 19p13 and prostate cancer (PCa) risk. Considering possible genetic differences between populations, we conducted the study in order to evaluate the association of this polymorphism with prostate cancer risk in Serbian population. 261 samples of peripheral blood were obtained from the patients with PCa and 257 samples from patients with benign prostatic hyperplasia (BPH). 106 volunteers who gave samples of bucal swabs comprised the control group. For individuals diagnosed with PCa clinicopathological characteristics including serum prostate-specific antigen (PSA) level at diagnosis, Gleason score (GS) and clinical stage were determined. Genotypization of rs3787016 was performed by using Taqman(®) SNP Genotyping Assay. The differences in alelle and genotype frequencies between analyzed groups of subjects were performed by using PLINK, SPSS 17.0 for Windows and SNPStats statistical software. No significant association of rs3787016 with PCa risk was determined comparing allele and genotype frequencies among group of patients diagnosed with PCa and the control group, as well as among groups of patients with PCa and BPH. Also, no evidence of association of rs3787016 with PCa risk was shown using tests for association under dominant and recessive genetic models. SNP rs3787016 showed no significant association with standard prognostic parameters regarding PCa progression, nor with the risk of disease progression assessed according to two different risk classification systems.

Value of first day angiography/angioplasty in evolving Non-ST segment elevation myocardial infarction: an open multicenter randomized trial. The VINO Study.

AIMS: Direct angioplasty is an effective treatment for ST-elevation myocardial infarction. The role of very early angioplasty in non-ST-elevation infarction is not known. Thus, a randomized study of first day angiography/angioplasty vs early conservative therapy of evolving myocardial infarction without persistent ST-elevation was conducted. METHODS: One hundred and thirty-one patients with confirmed acute myocardial infarction without ST-segment elevations were randomized within 24 h of last rest chest pain: 64 in the first day angiography/angioplasty group and 67 in the early conservative group (coronary angiography only after recurrent or stress induced myocardial ischaemia). RESULTS: All patients in the invasive group underwent coronary angiography on the day of admission (mean randomization-angiography time 6.2 h). First day angioplasty of the infarct related artery was performed in 47% of the patients and bypass surgery in 35%. In the conservative group, 55% underwent coronary angiography, 10% angioplasty and 30% bypass surgery within 6 months. The primary end-point (death/reinfarction) at 6 months occurred in 6.2% vs 22.3% (P<0.001). Six month mortality in the first day angiography/angioplasty group was 3.1% vs 13.4% in the conservative group (P<0.03). Non-fatal reinfarction occurred in 3.1% vs. 14.9% (P<0.02). CONCLUSIONS: First day coronary angiography followed by angioplasty whenever possible reduces mortality and reinfarction in evolving myocardial infarction without persistent ST-elevation, in comparison with an early conservative treatment strategy.

[In Time? Time interval between first symptoms to hospital admission of patients with acute coronary syndromes]. / VCAS? Casový interval od prvních symptomu do prijetí do nemocnice u nemocných s akutními koronárními syndromy.

OBJECTIVE: To assess the pre-hospital delay, i.e. the period which elapses between the onset of pain on the chest and admission to hospital in patients hospitalized on account of acute coronary syndrome. To analyze factors which influence this time interval and obtain thus data for a strategy leading to reduction of the pre-hospital delay. METHOD: Collection of data by means of a questionnaire focused on the time of onset of pain on the chest, time of contact with the health service, time of admission to hospital, type of transport of the patient to hospital, socioeconomic data, manifestations of ischaemic heart disease during the premorbid period and health care provided. Statistical evaluation by the non-paired Mann-Whitney test. RESULTS: Data were assembled from 126 patients admitted to hospital on account of acute coronary syndrome. The median of pre-hospital delay was 5 hours 40 mins., the median of the patient's hesitation 3 hours 44 mins., the median of the transport period was 59 mins. The pre-hospital delay is significantly reduced by transport by the rapid emergency service (p < 0.0001), dispensary care of a cardiologist (p < 0.02) and a previous hospitalization on account of acute myocardial infarction or unstable angina pectoris (p < 0.04). Pre-hospital delay is significantly prolonged in old age pensioners (p < 0.05). On the borderline of signficance is the reduction of pre-hospital delay in patients younger than 80 years (p < 0.06) and patients with higher than elementary education (p = 0.102). CONCLUSION: Prehospital delay in the investigated group is almost three times longer as compared with data from abroad. A most significant part in this delay is played by the long hesitation of patients and transport of the patient to the health institution by other means than the rapid emergency service. In order to provide effective treatment to a larger number of patients with acute coronary syndrome within the shortest time interval it is necessary to inform the population at large on the importance of sudden pain on the chest and the necessity of the quickest possible contact with the rapid emergency service on phone 155. Only then can we expect further improvements of the prognosis of these patients.

[Serum copper levels in patients with chronic heart failure associated with systolic left ventricular dysfunction and its relation to the severity of cardiac failure]. / Sérové koncentrace medi u pacientu s chronickým srdecním selháním a systolickou dysfunkcí levé komory srdecní, jejich vztah k závaznosti srdecní insuficience.

UNLABELLED: The authors examined the serum copper concentrations in a group of 40 patients with chronic heart failure and significant systolic left ventricular dysfunction with an ejection fraction of less than 35%. In 21 patients the examination was made on admission to hospital on account of deterioration of cardiac insufficiency (group A), in 19 patients with stable chronic cardiac failure the examination was made at the out-patient department (group B). Assessment of serum copper concentrations was made by the method of absorption spectrophotometry under standard conditions. Assessment of the ejection fraction of the left ventricle and dimensions of the cardiac compartments was made by two-dimensional echocardiography. The heart rate was assessed from the electrocardiogram at rest. RESULTS: The authors found statistically significantly higher copper concentrations in patients of group A (19.78 +/- 1.67 mumol/l) as compared with group B (14.80 +/- 1.54 mumol/l, p < 0.001). The correlation between copper concentrations, the left ventricular ejection fraction, dimensions of the cardiac compartments and heart rate are not significant. CONCLUSION: Serum copper concentrations in patients with chronic heart failure and significant systolic left ventricular dysfunction are related to the severity of the disease and are higher in patients admitted on account of cardiac insufficiency than in patients with stable cardiac failure.

[Serum copper levels in patients with acute and chronic types of ischemic heart disease and its relation to lipoprotein levels and extent of coronary atherosclerosis]. / Sérové koncentrace medi u pacientu s akutními a chronickými formami ischemické choroby srdecní, jejich vztah ke koncentracím lipoproteinu a k rozsahu koronární aterosklerózy.

The authors assessed serum copper and lipoprotein concentrations in a group of 67 patients hospitalized successively at the cardiological department. During hospitalization they were subjected to selective coronarography with assessment of the angiographic score. In 35 patients the angiographic examination was made during the chronic stage of IHD (group A), in 32 patients it was indicated on account of acute coronary syndrome (group B). The authors found that serum copper concentrations are significantly higher in patients with acute forms of IHD (group B, p < 0.001). Serum copper concentrations do not correlate significantly with lipoprotein concentrations nor with the extent of coronary atheroclerosis (angiographic score).

On the melanization of the rat's eye.

Electron-microscopic study of the size of the melanosomes, the mean percentage of melanosomal profile area (MPMA) of the cells, and the duration of melanogenesis in the pigmented layers of the rat's eye (inbred strain BDE/Han) revealed the following: 1) The melanosomes in the cells of the retina vary in size and shape in different locations of the eye. The MPMA of the cells also differs. Only in the two layers of the iris epithelium do the minor diameters of the melanosomes not differ significantly from each other, but the MPMA of the cells is different. The pigmented outer layer of the ciliary epithelium stands out on account of its especially large, round melanosomes. 2) The melanosomes of the uveal melanocytes are uniformly small but exhibit the largest MPMA. 3) Only in the pigment epithelium of the fundus does melanogenesis cease in the fifth week of life. As a result the MPMA decreases. In the other areas of the pigmented epithelium and the uvea tyrosinase activity and premelanosomes are present from the new-born to the adult animal. These signs indicate continued melanogenesis. 4) Compound melanosomes are present in all pigmented locations of the eye. Giant melanosomes occur regularly only in the outer layer of the retina.

On the morphology of the terminal microvasculature during endochondral ossification in rats.

The investigation was carried out on the proximal tibia metaphysis by means of India ink-injection, reconstruction, corrosion casting combined with scanning electron microscopy, and transmission electron microscopy of thin sections. The terminal vasculature during endochondral ossification proved to be a labyrinth of interconnected sinusoidal complexes with bulbous buds invading the chondrocyte cavities of the growth plate. This system of vessels was canalized throughout. A special feature was the existence of endothelial pockets. The formation of the terminal microvasculature as a labyrinthine cavity during endochondral ossification, together with the still incompletely developed bone could be a weak point for compression injuries.

[Revascularization of colonic anastomoses]. / Revaskularisation von Kolonanastomosen.

The revascularization of colonic anastomosis after colon segmental resection in rabbits in 9 different end-on-end and inverting suture techniques was examined macroscopically, microangiographically, micropreparatorily and histologically. Independently of the suture technique revascularization started 4 days after surgery. 8 days postoperatively the suture line is mainly bridged, 14 days postoperatively the vasal connection to the opposite side is completed. The new vessels mainly originate from the subserosal and submucosal tissue. The adhesions participate in the revascularization, too. It (the revascularization) directly correlates with the development of granulation tissue. This is evident from the excess reactive revascularization of abscesses and ulcers in the anastomoses. There always results a vascular scar in the angioarchitecture of the colonic wall. Start and extent of the revascularization cannot--in contrast to former literature--be looked at as a guarantee of quality for the healing of anastomoses.

On the formation and degradation of melanosomes in smooth muscle cells: electron microscopic investigation on the m. sphincter pupillae of the rat.

The electron microscopic investigation of the m. sphincter pupillae of adult black hooded rats showed the presence of melanosomes in the smooth muscle cells. In shape and size the melanosomes were like those of the iridial epithelium. In addition, premelanosomes and tyrosinase activity were observed as well as melanosomes with disintegrated content and acid phosphatase activity. The data suggest that the smooth muscle cells of the m. sphincter pupillae are capable of the formation and degradation of melanosomes.

Demonstration of carbohydrates in premelanosomes by ultrastructural cytochemistry.

The framework for melanin synthesis in the interior of the premelanosomes - the matrix - was subjected to ultrastructural cytochemical examination in cells of the retinal pigment epithelium of chick embryos, in melanocytes of rat skin, and in melanocytes and nevus cells of human skin. The positive results obtained using the silver methods of Thiéry and Rambourg indicated the presence of carbohydrates in the matrix of the premelanosomes.

Light and electron microscopic study on the osteoclastic phagocytosis of cells in the rat.

By means of micromorphological and cytochemical investigations of the tibia metaphyses of growing rats the phagocytosis of cells by multinucleated osteoclasts could be demonstrated. On the average 1.9% of osteoclasts exhibited included cells. With very few exceptions the phagocytosed cells belonged to the monocyte/macrophage lineage, as shown by evidence from the ultrastructure. After the animals were treated with parathyroid hormone the number of osteoclasts increased significantly, but not, however, the number of osteoclasts with a cell inclusion.

Experimental study on the haematogenous origin of multinucleate osteoclasts in the rat.

When the resorption zones of the distal femoral and proximal tibial epiphyseal plates of rats are examined with the electron microscope, numerous macrophages can be seen surrounding degenerated chondrocytes. Macrophages are also found in the neighbourhood of the invading sinusoids and in close proximity to multinucleate osteoclasts. Cell fusion, however, could not be observed. Repeated transfusions of female leukocytes to isohistogenic growing male rats caused an increase in the number of nuclei containing a Barr body in the osteoclasts of the males. The result suggests that leukocytes--of which only the monocytes come in question--are the source of multinucleate osteoclasts in endochondral ossification.

Evidence of membrane transformation during melanogenesis. Electron microscopic study on the retinal pigment epithelium of chick embryos.

Some characteristics of early premelanosomes (PM) suggest that primarily a continuous cisternal complex of the endoplasmic reticulum (ER) is transformed simultaneously to PM. These characteristics are: (i) the form and size, which are similar to ER cisternae; (ii) the localization in groups in the ER; )iii) the same stage of maturation within a group; (iv) the continuities between early PM, and (v) the lack of continuities between ER and PM. Comparative measurements reveal that the limiting membrane of PM, with a total thickness of 7.6 +/- 0.19 nm and a center-to-center distance of 5.2 +/- 0.06 nm, is significantly thicker than the ER membrane (6.3 +/- 0.15 nm and 4.3 +/- 0.04 nm, respectively) and the melanosome limiting membrane (6.5 +/- 0.22 nm and 4.4 +/- 0.05 nm, respectively). Therefore, during the formation of melanosomes, the limiting membrane must be transformed from a thin (ER) to a thick (PM) and again to a thin (melanosome)stage.

[Treatment of molluscum contagiosum]. / Bemerkungen zur Behandlung des Molluscum contagiosum

Puncture with a toothpick dipped in phenolum liquefactum is a suitable method for the treatment especially of small mollusca contagiosa in children. The danger of phenol intoxication through resorption during the treatment of multiple molluscs always must be borne in mind. Comparable studies in rats' nipples using the puncture technique showed that up to 0.7 mg phenol can be applied to one molluscum.