3-D conformal HDR brachytherapy as monotherapy using intraoperative real-time planning is a feasible and highly conformal treatment for localized prostate cancer associated with minimal acute toxicity. Longer follow-up is needed to evaluate late toxicity and biochemical control.
The prerequisite of an IAD treatment is the testosterone recovery during off-treatment periods. In this study, in patients with PSA relapse after radical prostatectomy, a real achievement of intermittent castration with normalisation of testosterone levels during off-treatment periods could be confirmed.
Intermittent androgen deprivation (IAD) is one approach to hormonal therapy for prostate cancer that has been developed with the aim of minimizing the negative effects of therapy while maximizing the clinical benefits and the patient’s quality of life (QoL). It can be used in any clinical situation where continuous AD (CAD) treatment could be applied. IAD is a cyclic therapy consisting of on‐treatment periods followed by observation periods, known as off‐treatment periods or intervals (OTIs), and the response to therapy, or occurrence of disease progression, is monitored by measuring the patient’s prostate‐specific antigen (PSA) levels. The on‐treatment period is generally fixed, normally lasting for 6–9 months or in some protocols until a PSA nadir of <4 ng/mL is reached. By contrast, the OTI is variable and treatment is re‐instituted depending on the patient’s PSA level; however, the exact trigger point is chosen empirically. The potential advantages of IAD over CAD therapy are an improved QoL, a prolonged period of androgen dependence, a reduced incidence of the side‐effects normally associated with AD therapy, and a decrease in the cost of care. Results from phase II clinical studies of IAD have shown that it has good acceptance and feasibility. QoL improves during the OTIs, there is reduced toxicity, and a positive affect on bone density compared with CAD therapy. In these studies IAD appeared to have no negative effects on time to progression or survival. Further investigations of IAD are ongoing in randomized, controlled, phase III trials in the USA, Canada and Europe. Most of these studies are not yet mature and final results are awaited; however, interim analyses from some studies suggest IAD and CAD therapy are equally effective in terms of progression‐free survival.
The effect of cyproterone acetate (CA) on experimentally induced benign prostatic hyperplasia (BPH) in the castrated dog was investigated. BPH was induced by 6 months' treatment with 3\g=a\-androstanediol (3\g=a\-diol) alone and in combination with 17\g=b\-oestradiol(Oe2). RNA, DNA and zinc content of the glands were determined in addition to histological examination and measurement of the prostates. Two different types of prostatic enlargement were observed. First, 3\g=a\-diolinduced typical diffuse canine hyperplasia with replacement of functional activity. DNA, RNA and the zinc content of total glands were increased compared with intact controls.
Human renal proximal and distal (thick ascending limb and early distal convoluted tubule) epithelial cells have been isolated according to their specific antigen expression. The cells were well characterized by flow cytometry, enzyme cytochemistry and electron microscopy and cultured for up to 3 months. Cultured tubular cells coexpressed cytokeratin and vimentin as intermediate filament proteins. While primary isolated cells, proximal as well as distal, revealed the phenotypic characteristics of their nephron origin, cultured distal cells showed the tendency to dedifferentiate/transdifferentiate. Distal cells lost their characteristic expression of Tamm-Horsfall glycoprotein and started de novo expression of the proximal marker proteins aminopeptidase M, γ-glutamyl transferase and dipeptidyl peptidase IV. The expression of these antigens by distal cells could be shown by flow-cytometric analysis and fluorescence microscopy. Enzyme activity assays revealed the activity of aminopeptidase M, γ-glutamyl transferase and dipeptidyl peptidase IV, but not of the proximal marker enzyme alkaline phosphatase. This antigenic shift could not be prevented in different culture media, and the original phenotype could not be restored. Cultured cells displayed characteristic hormonal stimulation patterns indicative of their proximal and distal origins, as shown by activation of adenylate cyclase by different peptide hormones. These results indicate that distal tubular cells possibly transdifferentiate to a more proximal phenotype in view of loss of the distal marker enzyme Tamm-Horsfall protein and de novo expression of proximal marker enzymes like dipeptidyl peptidase IV and aminopeptidase M.
PSA-N 100 or more is a new, independent molecular staging criterion for localized PC that identifies high-risk group patients with clinically relevant occult micrometastases in N0-PLN, who may benefit from additional therapy to prevent BCR.
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