S100A6 (Calcyclin) is a prostate basal cell marker absent in prostate cancer and its precursors

S100A6 (Calcyclin) is a calcium-binding protein that has been implicated in a variety of biological functions as well as tumorigenesis. The aim of our study was to investigate the involvement of S100A6 during prostate cancer development and progression. Using immunohistochemistry, the expression of S100A6 was examined in benign (n ¼ 66), premalignant (n ¼ 10), malignant (n ¼ 66) and metastatic prostate (n ¼ 5) tissues arranged in a tissue-microarray or whole sections as well as in prostate cancer cell lines. The S100A6 immunostaining pattern in tissues was compared with that of cytokeratin 5 (a basal cell marker) and 18 (a benign luminal cell marker). In all cases of benign epithelium, intense S100A6 expression was seen in the basal cell layer with absent staining in luminal cells. In all cases of prostatic adenocarcinoma (matched), metastatic lesions and 3/10 high-grade prostatic intraepithelial neoplasia lesions, an absence of S100A6 was seen. Western blotting and RT–PCR analysis of cell lines showed S100A6 expression to be absent in LNCaP, LNCaP-LN3 and LNCaP-Pro5 but present in Du145, PC3, PC-3M and PC-3M-LN4. LNCaP cells treated with 5- Azacytidine, caused re-expression of S100A6 mRNA. Sequencing of bisulphite modified DNA showed CpG methylation within the S100A6 promoter region and exon 1 of LNCaP, LNCaP-LN3 and LNCaP-Pro5 cell lines but not in Du145 cells. Our data suggest that loss of S100A6 protein expression is common in prostate cancer development and may occur at an early stage. The mechanism of loss of expression may involve hypermethylation of CpG sites. The finding of intense S100A6 expression in the basal cells of benign glands but loss of expression in cancer could be useful as a novel diagnostic marker for prostate cancer

Computing Power and Sample Size for Case-Control Association Studies with Copy Number Polymorphism: Application of Mixture-Based Likelihood Ratio Test

Recent studies suggest that copy number polymorphisms (CNPs) may play an important role in disease susceptibility and onset. Currently, the detection of CNPs mainly depends on microarray technology. For case-control studies, conventionally, subjects are assigned to a specific CNP category based on the continuous quantitative measure produced by microarray experiments, and cases and controls are then compared using a chi-square test of independence. The purpose of this work is to specify the likelihood ratio test statistic (LRTS) for case-control sampling design based on the underlying continuous quantitative measurement, and to assess its power and relative efficiency (as compared to the chi-square test of independence on CNP counts). The sample size and power formulas of both methods are given. For the latter, the CNPs are classified using the Bayesian classification rule. The LRTS is more powerful than this chi-square test for the alternatives considered, especially alternatives in which the at-risk CNP categories have low frequencies. An example of the application of the LRTS is given for a comparison of CNP distributions in individuals of Caucasian or Taiwanese ethnicity, where the LRTS appears to be more powerful than the chi-square test, possibly due to misclassification of the most common CNP category into a less common category

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Using routine data to monitor inequalities in an acute trust: a retrospective study

<p><b>Abstract</b></p> <p><b>Background</b></p> <p>Reducing inequalities is one of the priorities of the National Health Service. However, there is no standard system for monitoring inequalities in the care provided by acute trusts. We explore the feasibility of monitoring inequalities within an acute trust using routine data.</p> <p><b>Methods</b></p> <p>A retrospective study of hospital episode statistics from one acute trust in London over three years (2007 to 2010). Waiting times, length of stay and readmission rates were described for seven common surgical procedures. Inequalities by age, sex, ethnicity and social deprivation were examined using multiple logistic regression, adjusting for the other socio-demographic variables and comorbidities. Sample size calculations were computed to estimate how many years of data would be ideal for this analysis.</p> <p><b>Results</b></p> <p>This study found that even in a large acute trust, there was not enough power to detect differences between subgroups. There was little evidence of inequalities for the outcome and process measures examined, statistically significant differences by age, sex, ethnicity or deprivation were only found in 11 out of 80 analyses. Bariatric surgery patients who were black African or Caribbean were more likely than white patients to experience a prolonged wait (longer than 64 days, aOR = 2.47, 95% CI: 1.36-4.49). Following a coronary angioplasty, patients from more deprived areas were more likely to have had a prolonged length of stay (aOR = 1.66, 95% CI: 1.25-2.20).</p> <p><b>Conclusions</b></p> <p>This study found difficulties in using routine data to identify inequalities on a trust level. Little evidence of inequalities in waiting time, length of stay or readmission rates by sex, ethnicity or social deprivation were identified although some differences were identified which warrant further investigation. Even with three years of data from a large trust there was little power to detect inequalities by procedure. Data will therefore need to be pooled from multiple trusts to detect inequalities.</p