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The Nuffield Department of Surgical Sciences is the academic department of surgery at the University of Oxford, and hosts a multidisciplinary team of senior clinical academic surgeons, senior scientists, junior clinicians and scientists in training.
Expression of S100 proteins in normal human tissues and common cancers using tissue microarrays: S100A6, S100A8, S100A9 and S100A11 are all overexpressed in common cancers.
AIMS: To survey the expression of members of the S100 family of calcium-binding proteins in normal human tissues and common cancers using tissue microarrays. S100A6, S100A8, S100A9 and S100A11 have all been suggested to have potential roles in carcinogenesis and tumour progression but their expression has not been described in a wide range of human tissues and tumours. METHODS AND RESULTS: A custom-made tissue array, containing 291 tissue cores representing 28 tissue types and 21 tumour types, was used to produce sections that were immunostained for S100A2, S100A6, S100A8, S100A9, S100A11, calbindin 1, calbindin 2, S100B and parvalbumin. S100A6, S100A8 and S100A9 were expressed in 32%, 12% and 28% of breast cancers, respectively. There was a translocation of S100A11 expression from exclusively nuclear in normal tissues to cytoplasmic and nuclear in all common cancers. CONCLUSIONS: S100A6, S100A8, S100A9 and S100A11 are all expressed in common cancers, especially breast cancer. In addition, S100A11 undergoes a nucleocytoplasmic translocation which may have a direct influence on the proliferation of the cancer cells.
Recent trends in the use of radical prostatectomy in England: the epidemiology of diffusion.
OBJECTIVE: To describe recent trends in the use of radical prostatectomy (RP) in England, as there is currently no consensus on the most effective treatment for localized prostate cancer, although RP is the treatment of choice among urological surgeons for men aged < 70 years. METHODS: Routine data were assessed to establish the number of RPs performed in England in 1991-99. Age-standardized operation rates were compared by region and socio-economic group, and the geographical spread of use mapped. RESULTS: The number of RPs performed annually increased nearly 20-fold between 1991 and 1999. Rates of surgery were greatest in the London National Health Service (NHS) regions and lowest in the Trent region. Outside London, the risk of surgery in a NHS hospital was significantly greater for men living in the least deprived areas; in London this trend was reversed. CONCLUSION: Rapid increases in the use of RP showed marked regional variations, most likely related to access to prostate-specific antigen testing and the location of surgeons able to carry out radical surgery. By 1999, a third of procedures were still being undertaken in 'low-volume' hospitals, with implications for the quality of care and outcomes. Crucially, these developments occurred in the absence of robust information about the effectiveness of RP. Recent funding of a randomized trial of treatment options in this area is welcome, but wider questions remain about the timing of the evaluation of surgical technologies.
The survival effect of prolactin on PC3 prostate cancer cells.
OBJECTIVES: Recent studies suggest a paracrine/autocrine loop involving prolactin (PRL) within the human prostate. The aims of this study were to determine the effects of PRL on the growth and survival of prostate cancer cells and the intracellular signalling mechanisms underlying such effects. METHODS: The effect of PRL on proliferation of LNCaP, PC3 and DU145 was assessed by Coulter counting. The effect of PRL on TRAIL-, staurosporine- and flavopiridol-induced apoptosis was assessed by Timelapse microscopy and Annexin V binding. The status of the PRL receptor (PRL-R) and Akt/PKB (protein kinase B) activity were assessed by Western blotting. RESULTS: All three cell lines expressed both the short and long forms of the PRL receptor. Although, no significant effect of PRL on the proliferation of these cells was found, PRL partially inhibited TRAIL-induced apoptosis in PC3 cells. PRL also enhanced the phosphorylation of Akt/PKB in these cells. CONCLUSIONS: PRL had no significant effect on the proliferation of PC3, DU145 and LNCaP, but inhibited TRAIL-induced apoptosis in PC3 cells, possibly via enhanced Akt/PKB phosphorylation in PC3 cells. Further investigations are underway to determine the survival effect of PRL on the other two prostate cancer cell line.
Associations of adiponectin and leptin with stage and grade of PSA-detected prostate cancer: the ProtecT study.
PURPOSE: Obesity has been associated with an increased risk of advanced and fatal prostate cancer; adipokines may mediate this association. We examined associations of the adipokines leptin and adiponectin with the stage and grade of PSA-detected prostate cancer. METHODS: We conducted a nested case-control study comparing 311 men with mainly locally advanced (≥T3, N1, or M1 cases) vs. 413 men with localized (T ≤2 & NX-0 & M0 controls) PSA-detected prostate cancer, recruited 2001-2009 from 9 UK regions to the ProtecT study. Associations of body mass index and adipokine levels with prostate cancer stage were determined by conditional logistic regression and with grade (Gleason score ≥7 vs. ≤6) by unconditional logistic regression. RESULTS: Adiponectin was inversely associated with prostate cancer stage in overweight and obese men (OR 0.62; 95 % CI 0.42-0.90; p = 0.01), but not in normal weight men (OR 1.48; 0.77-2.82; p = 0.24) (p for interaction 0.007), or all men (OR 0.86; 0.66-1.11; p = 0.24). There was no compelling evidence of associations between leptin or leptin to adiponectin ratio and prostate cancer stage. No strong associations of adiponectin, leptin, or leptin:adiponectin ratio with grade were seen. CONCLUSIONS: This study provides some evidence that adiponectin levels may be associated with prostate cancer stage, dependent on the degree of adiposity of the man. Our results are consistent with adiponectin countering the adverse effects of obesity on prostate cancer progression.