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1.  Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress 
British Journal of Cancer  2013;109(4):983-993.
We have previously identified peroxiredoxin-3 (PRDX-3) as a cell-surface protein that is androgen regulated in the LNCaP prostate cancer (PCa) cell line. PRDX-3 is a member of the peroxiredoxin family that are responsible for neutralising reactive oxygen species.
Experimental design:
PRDX-3 expression was examined in tissue from 32 patients using immunohistochemistry. Subcellular distribution was determined using confocal microscopy. PRDX-3 expression was determined in antiandrogen-resistant cell lines by western blotting and quantitative RT–PCR. The pathways of PRDX-3 overexpression and knockdown on apoptosis and response to oxidative stress were investigated using protein arrays.
PRDX-3 is upregulated in a number of endocrine-regulated tumours; in particular in PCa and prostatic intraepithelial neoplasia. Although the majority of PRDX-3 is localised to the mitochondria, we have confirmed that PRDX-3 at the cell membrane is androgen regulated. In antiandrogen-resistant LNCaP cell lines, PRDX-3 is upregulated at the protein but not RNA level. Resistant cells also possess an upregulation of the tricarboxylic acid (TCA) pathway and resistance to H2O2-induced apoptosis through a failure to activate pro-apoptotic pathways. Knockdown of PRDX-3 restored H2O2 sensitivity.
Our results suggest that PRDX-3 has an essential role in regulating oxidation-induced apoptosis in antiandrogen-resistant cells. PRDX-3 may have potential as a therapeutic target in castrate-independent PCa.
PMCID: PMC3749568  PMID: 23880827
prostate cancer; anti-androgen; oxidation
2.  Pathogenesis of prostate cancer and hormone refractory prostate cancer 
Prostate cancer is the second most common malignancy in males and the leading cause of cancer death. Prostate cancer is initially androgen dependent and relies upon the androgen receptor (AR) to mediate the effects of androgens. The AR is also the target for therapy using antiandrogens and LHRH analogues. However, all cancers eventually become androgen independent, often referred to as hormone refractory prostate cancer. The processes involved in this transformation are yet to be fully understood but research in this area has discovered numerous potential mechanisms including AR amplification, over-expression or mutation and alterations in the AR signaling pathway. This review of the recent literature examines the current knowledge and developments in the understanding of the molecular biology of prostate cancer and hormone refractory prostate cancer, summarizing the well characterized pathways involved as well as introducing new concepts that may offer future solutions to this difficult problem.
PMCID: PMC2721494  PMID: 19675761
Prostate cancer; refractory androgen receptor
3.  Use of routinely collected data on trihalomethane in drinking water for epidemiological purposes 
OBJECTIVES—To explore the use of routinely collected trihalomethane (THM) measurements for epidemiological studies. Recently there has been interest in the relation between byproducts of disinfection of public drinking water and certain adverse reproductive outcomes, including stillbirth, congenital malformations, and low birth weight.
METHOD—Five years of THM readings (1992-6), collected for compliance with statutory limits, were analysed. One water company in the north west of England, divided into 288 water zones, provided 15 984 observations for statistical analysis. On average each zone was sampled 11.1 times a year. Five year, annual, monthly, and seasonal variation in THMs were examined as well as the variability within and between zones.
RESULTS—Between 1992 and 1996 the total THM (TTHM) annual zone means were less than half the statutory concentration, at approximately 46 µg/l. Differences in annual water zone means were within 7%. Over the study period, the maximum water zone mean fell from 142.2 to 88.1 µg/l. Mean annual concentrations for individual THMs (µg/l) were 36.6, 8.0, and 2.8 for chloroform, bromodichloromethane (BDCM), and dibromochloromethane (DBCM) respectively. Bromoform data were not analysed, because a high proportion of the data were below the detection limit. The correlation between chloroform and TTHM was 0.98, between BDCM and TTHM 0.62, and between DBCM and TTHM −0.09. Between zone variation was larger than within zone variation for chloroform and BDCM, but not for DBCM. There was only little seasonal variation (<3%). Monthly variation was found although there were no consistent trends within years.
CONCLUSION—In an area where the TTHM concentrations were less than half the statutory limit (48 µg/l) chloroform formed a high proportion of TTHM. The results of the correlation analysis suggest that TTHM concentrations provided a good indication of chloroform concentrations, a reasonable indication of BDCM concentrations, but no indication of DBCM. Zone means were similar over the years, but the maximum concentrations reduced considerably, which suggests that successful improvements in treatment have been made to reduce high TTHM concentrations in the area. For chloroform and BDCM, the main THMs, the component between water zones was greater than variation within water zones and explained most of the overall exposure variation. Variation between months and seasons was low and showed no clear trends within years. The results indicate that routinely collected data can be used to obtain exposure estimates for epidemiological studies at a small area level.

Keywords: chlorination byproducts; exposure; birth outcomes; routine data; trihalomethanes
PMCID: PMC1740158  PMID: 11404449
4.  Disturbed nights and 3-4 month old infants: the effects of feeding and thermal environment. 
Archives of Disease in Childhood  1990;65(5):499-501.
Parents completed a prospective diary of a night's sleep for 87, 3-4 month old infants at home whose body temperatures were continuously recorded. We found that about half of the babies disturbed their parents in the night. Breast fed babies were more likely to wake parents in the middle of the night. The babies who disturbed their parents in the middle of the night were significantly more heavily wrapped in significantly warmer rooms. We suggest that discomfort from efforts at active thermoregulation in warm environments may lead some babies to disturb their parents at 'unsocial hours'.
PMCID: PMC1792160  PMID: 2357087

Results 1-4 (4)