Objective To assess the level and morphological distribution of cyclooxygenase (COX)-1 and -2 in human prostates and to determine any association with the Gleason grade of prostate cancer. Materials and methods The study comprised 30 samples from patients with benign prostatic hyperplasia (BPH) and 82 with prostate cancer. Immunohistochemistry was used to assess the expression of COX-1 and -2, and 13 samples were also assessed using immunoblotting (six BPH and seven cancers). Results For both BPH and prostate cancer, COX-1 expression was primarily in the ®bromuscular stroma, with variable weak cytoplasmic expression in glandular/neoplastic epithelial cells. In contrast, COX-2 expression differed markedly between BPH and cancer. In BPH there was membranous expression of COX-2 in luminal glandular cells and no stromal expression. In cancer the stromal expression of COX-2 was unaltered, but expression by tumour cells was signi®cantly greater (P=0.008), with a change in the staining pattern from membranous to cytoplasmic (P<0.001). COX-2 expression was signi®cantly higher in poorly differentiated than in well differentiated tumours (P<0.001). These results were supported by immunoblotting, which showed similar levels of COX-1 in both BPH and cancer, but four times greater expression of COX-2 in cancer than in BPH. Conclusion This is the ®rst study to assess the coexpression of COX-1 and COX-2 proteins in benign and malignant human prostates, and showed the induction and signi®cantly greater expression of COX-2 in cancer, which was also associated with tumour grade. The regular use of nonsteroidal anti-in¯am-matory drugs is associated with a reduced incidence of cancers. The present results provide the basis for a potential role for COX-2 inhibitors in the prevention and treatment of prostate cancer.
Background There is no effective intravesical second-line therapy for non-muscle invasive bladder cancer (NMIBC) when bacillus Calmette-Guérin (BCG) fails. Objective To compare disease-free survival time (DFS) between radiofrequency-induced thermo-chemotherapy effect (RITE) and institutional standard second-line therapy (control) in NMIBC patients with recurrence following induction/ maintenance BCG. Design, settings, and participants Open-label, phase III randomised controlled trial accrued across 14 centres between May 2010 and July 2013 [HYMN (ClinicalTrials.gov: NCT01094964)].
MUC1 mucin is transcriptionally regulated by estrogen, progesterone, and glucocorticoids. Our objective was to determine whether androgen receptor (AR) activation regulates expression of MUC1. The following breast and prostatic cell lines were phenotyped and grouped according to AR and MUC1 protein expression: 1) AR+MUC1 + [DAR17+19 (AR transfectants of DU-145), ZR-75-1, MDA-MB-453, and T47D]; 2) AR-MUC1 + [DZeo1 (AR-vector control), DU-145, BT20, MDA-MB-231, and MCF7]; 3) AR+MUC1 - (LNCaP and LNCaP-r). Cell proliferation was determined using the MTT assay in the presence of synthetic androgen R1881, 0.1 microM to 1 microM. Cell surface MUC1 expression was determined by flow cytometry in the presence or absence of oestradiol, medroxy progesterone acetate or R1881, with and without 4 hydroxy-flutamide (4-OH), a nonsteroidal AR antagonist. The functional significance of MUC1 expression was investigated with a cell-cell aggregation assay. Only AR+MUC1 + cell lines showed a significant increase in MUC1 expression with AR activation (P (range) =.01 to .0001), reversed in the presence of 4-OHF. Cell proliferation was unaffected. Increased expression of MUC1 was associated with a significant (P (range) = .002 to .001) reduction in cell-cell adhesion. To our knowledge, this is the first description of androgen-dependent regulation of MUC1 mucin. This is also functionally associated with decreased cell-cell adhesion, a recognised feature of progressive malignancy. These findings have important implications for physiological and pathological processes.
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