Association between the c.*229C>T polymorphism of the topoisomerase IIb binding protein 1 (TopBP1) gene and breast cancer

Topoisomerase IIb binding protein 1 (TopBP1) is involved in cell survival, DNA replication, DNA damage repair and cell cycle checkpoint control. The biological function of TopBP1 and its close relation with BRCA1 prompted us to investigate whether alterations in the TopBP1 gene can influence the risk of breast cancer. The aim of this study was to examine the association between five polymorphisms (rs185903567, rs116645643, rs115160714, rs116195487, and rs112843513) located in the 30UTR region of the TopBP1 gene and breast cancer risk as well as allele-specific gene expression. Five hundred thirty-four breast cancer patients and 556 population controls were genotyped for these SNPs. Allele-specific Top- BP1 mRNA and protein expressions were determined by using real time PCR and western blotting methods, respectively. Only one SNP (rs115160714) showed an association with breast cancer. Compared to homozygous common allele carriers, heterozygous and homozygous for the T variant had significantly increased risk of breast cancer (adjusted odds ratio = 3.81, 95 % confidence interval: 1.63–8.34, p = 0.001). Mean TopBP1 mRNA and protein expression were higher in the individuals with the CT or TT genotype. There was a significant association between the rs115160714 and tumor grade and stage. Most carriers of minor allele had a high grade (G3) tumors classified as T2-T4N1M0. Our study raises a possibility that a genetic variation of TopBP1 may be implicated in the etiology of breast cancer

Planck pre-launch status: The optical system

Planck is a scientific satellite that represents the next milestone in space-based research related to the cosmic microwave background, and in many other astrophysical fields. Planck was launched on 14 May of 2009 and is now operational. The uncertainty in the optical response of its detectors is a key factor allowing Planck to achieve its scientific objectives. More than a decade of analysis and measurements have gone into achieving the required performances. In this paper, we describe the main aspects of the Planck optics that are relevant to science, and the estimated in-flight performance, based on the knowledge available at the time of launch. We also briefly describe the impact of the major systematic effects of optical origin, and the concept of in-flight optical calibration. Detailed discussions of related areas are provided in accompanying papers

Utilization of acute and long-term care in the last year of life: comparison with survivors in a population-based study

Background. It is well-known that the use of care services is most intensive in the last phase of life. However, so far only a few determinants of end-of-life care utilization are known. The aims of this study were to describe the utilization of acute and long-term care among older adults in their last year of life as compared to those not in their last year of life, and to examine which of a broad range of determinants can account for observed differences in care utilization. Methods. Data were used from the Longitudinal Aging Study Amsterdam (LASA). In a random, age and sex stratified population-based cohort of 3107 persons aged 55 ? 85 years at baseline and representative of the Netherlands, follow-up cycles took place at 3, 6 and 9 years. Those who died within one year directly after a cycle were defined as the "end-of-life group" (n = 262), and those who survived at least three years after a cycle were defined as the "survivors". Utilization of acute and long-term care services, including professional and informal care, were recorded at each cycle, as well as a broad range of health-related and psychosocial variables. Results. The end-of-life group used more care than the survivors. In the younger-old this difference was most pronounced for acute care, and in the older-old, for long-term care. Use of both acute and long-term home care in the last year of life was fully accounted for by health problems. Use of institutional care at the end of life was partly accounted for by health problems, but was not fully explained by the determinants included. Conclusion. This study shows that severity of health problems are decisive in the explanation of the increase in use of care services towards the end-of-life. This information is essential for an appropriate allocation of professional health care to the benefit of older persons themselves and their informal caregivers. © 2009 Pot et al; licensee BioMed Central Ltd

Relationship of urinary isoprostanes to prostate cancer occurence

To estimate the oxidative stress in patients with prostate cancer and in a control group, we used the biomarker of lipid peroxidation–isoprostanes (8-isoPGF2) and the level of selected antioxidants (glucose and uric acid [UA]). The level of urinary isoprostanes was determined in patients and controls using an immunoassay kit according to the manufacturer’s instruction. The levels of UA and glucose were also determined in serum by the use of UA Assay Kit and Glucose Assay Kit. We observed a statistically increased the level of isoprostanes in urine of patients with prostate cancer in compared with a control group. The concentration of tested antioxidants in blood from patients with prostate cancer was also higher than in healthy subjects. Moreover, our experiments indicate that the correlation between the increased amount of UA and the lipid peroxidation exists in prostate cancer patients (in all tested groups). Prostate cancer risk by urinary isoprostanes level was analyzed, and a positive association was found (relative risk for highest vs. lowest quartile of urinary isoprostanes = 1.6; 95 % confidence interval 1.2–2.4; p for trend = 0.03). We suggest that reactive oxygen species induce peroxidation of unsaturated fatty acid in patients with prostate cancer, and the level of isoprostanes may be used as a non-invasive marker for determination of oxidative stress. We also propose that UA may enhance the oxidative stress in patients with prostate cancer.This study was supported by the Grant 506/810(KBO) from University of Lodz, Polan

Planck pre-launch status : The Planck mission

Peer reviewe

Gene and protein expression of O-GlcNAc-cycling enzymes in human laryngeal cancer

Aberrant protein O-GlcNAcylation may contribute to the development and malignant behavior of many cancers. This modification is controlled by O-linked β-N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA). The aim of this study was to determine the expression of O-GlcNAc cycling enzymes mRNA/protein and to investigate their relationship with clinicopathological parameters in laryngeal cancer. The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. The level of OGT and OGA proteins was analyzed by Western blot. A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). An inverse association between OGT and MGEA5 transcripts was determined with regard to prognosis (p < 0.05). In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). No correlations with other parameters were noted, but the results showed a trend of more advanced tumors to be more frequently OGT and OGA positive. The results suggest that increased O-GlcNAcylation may have an effect on tumor aggressiveness and prognosis in laryngeal cancer.This work was supported, in part, by a grant from the National Science Council, Poland (N403 043 32/2326), by the statutory fund of the Department of Cytobiochemistry, University of Łódź, Poland (506/811