The Prostate. Supplement最新文献

Background: The search for novel agents for the treatment of the lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) is dependent on an increased understanding of the pathophysiology of the disease. Unfortunately, in vitro and animal models have been of limited value.

Methods: This article describes a novel model system in which the interactions of the stromal and epithelial components of the prostate gland can be determined.

Results: The coculture system provides a simple model of the cellular interactions occurring in the adult human prostate.

Conclusions: This coculture system could potentially be used to determine the precise molecular site of action of agents such as terazosin on prostatic apoptosis.

Endocrine treatment of prostate cancer can be performed under several different regimes. They all have side effects which in different ways influence quality of life and the patient's general health. This paper is a survey of the most important early side effects of the different modes of endocrine treatment, their etiology, and possible ways to avoid or treat them.

Background: Recent studies suggest that aberrant regulation of apoptosis, including acquired apoptosis resistance, contributes to perturbations in cell growth that, in part, underlie the development of benign prostatic hyperplasia (BPH) and prostate cancer. Importantly, apoptosis resistance can enhance the malignant properties of prostate cancer cells, contributing to their widespread metastatic activities. Since apoptosis resistance likely contributes to benign and malignant prostate disease, the promotion of apoptosis represents a reasonable therapeutic objective.

Methods: This brief review focuses on the role of apoptosis in prostatic disease and discusses potential intervention points for novel therapeutics.

Conclusions: Novel therapies for prostatic disease, including gene therapy and biological therapy that involve apoptosis as a mechanism of action, are being developed and tested. Ultimately, the identification of proapoptotic and antiapoptotic genes and the pathways through which they operate will serve to provide more rational approaches for further development of more efficacious therapeutic strategies for benign and malignant prostatic disease.

Frailty is characterized by generalized weakness, impaired mobility and balance, and poor endurance. Loss of muscle strength is an important factor in the process of frailty, and is the limiting factor for an individual's chances of living an independent life until death. In men, several hormonal systems show a decline in activity during aging. Serum bioavailable testosterone (T) and estradiol (E2), dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), and growth hormone (GH) and insulin-like growth factor (IGF)-I concentrations all decrease during aging in men. Physical changes during aging have been considered physiologic, but there is evidence that some of these changes are related to this decline in hormonal activity. In a cross-sectional study performed among 403 independently living elderly men, positive independent associations were observed between serum bioavailable T and muscle strength and bone mineral density (BMD). Serum T was negatively associated with fat mass. Serum luteinizing hormone (LH) increased with age and was inversely associated with T. Independent of T, LH was negatively related with muscle strength and positively with the number of problems in activities of daily living. Further, a positive relation was present between serum E2 and BMD. A positive association between DHEAS and BMD was dependent on T and E2 concentrations. Finally, in the same study, men with the highest E2 concentrations were significantly more satisfied with life, measured with a questionnaire developed by Herschbach and Huber, compared to men with the lowest E2 concentrations. In conclusion, these findings are in agreement with other studies, which suggest that the maintenance of a good physical functional ability and quality of life is related to serum T, E2, and DHEA(S) concentrations.

In the last decade of the 20th century, there was a distinct reappraisal of male sexual dysfunction and its pharmaco-medical treatment. Although representative studies of sexual (dys)function in the aging male (i.e., between 60-90 years of age) are still lacking, one might assume with certainty that many men and their partners could benefit from sexological counseling and treatment. At the same time, it is obvious that many older men with erectile dysfunction do not seek or want treatment for various reasons. Nevertheless, it is obligatory that modern physicians include sexual matters in dealing with their aging patients, as an essential part of their quality of life. The doctor of today should approach the old(er) male patient with sexual dysfunction (regardless of comorbidity) in an identical manner as young(er) patients, i.e., with proper sexological history-taking, proper physical examination, and/or sexological diagnostic screening, and discussing the various available treatments. Needless to say, that they should not "create" sexual problems when patients are satisfied with their current way of life. However, with the increasing number of efficacious treatments, doctors will satisfy many of their older patients with sexual difficulties who seek treatment.

Androgen ablation has been the standard treatment of symptomatic patients with metastatic prostate cancer for more than 50 years. Within the last 15 years, the introduction of prostate-specific antigen (PSA) has induced a stage migration toward less extensive disease and a dramatic decrease in the proportion of men presenting with N+/M+ disease. Historical studies, conducted during the pre-PSA era, are therefore of limited interest in counseling modern patients. The routine use of radical therapies such as radical prostatectomy and radiotherapy has considerably expanded the problem of timing of endocrine treatment in range and complexity. Advanced disease is now diagnosed in patients with limited involvement of extraprostatic sites and even in patients presenting an isolated elevation of PSA after radical treatment. In the absence of clear guidelines, data from past literature and ongoing modern studies were compiled in the present review in an attempt to generate practical considerations.

Background: alpha1-adrenoceptor (alpha1-AR) antagonists, used to relieve the lower tract urinary symptoms (LUTS) in benign prostate hyperplasia (BPH) patients, are thought to act in inhibiting the contraction of stromal smooth muscle. An attempt was made using new technology to visualize and quantify the effect of alpha1-AR antagonists in a cell culture model of prostatic smooth muscle cells (SMC).

Methods: Prostatic smooth muscle cells cultured from human prostate tissue were treated with alpha1-AR agonists and antagonists. The effects on cell growth, cell contraction, differentiation status, and apoptosis were determined by means of an MTT cell viability assay, time-lapse video microscopy, RT-PCR analysis, and FACS analysis of annexin V/propidium iodide-stained cells, respectively.

Results: Prostatic smooth muscle cells derived from prostate tissue expressed SMC-specific markers. They showed spontaneous contractions, and phenylephrine increased the percentage of contracting cells by 3-fold. alpha1-AR antagonists inhibited spontaneous as well as phenylephrine-induced contractions. Long-term treatment with doxazosin induced differentiation tended towards a contractile phenotype, as indicated by an increase of the ratio of smooth muscle heavy chain myosin subtypes SM2/SM1. There was, however, no effect on cell growth. High concentrations of antagonist (100 microM) induced apoptosis in about 80% of the treated SMC. This effect was not cell-type-specific and was also seen in skin fibroblasts and immortalized prostate epithelial cells.

Conclusion: In an easy-to-handle cell culture model of prostatic smooth muscle cells, the effects of alpha1-AR antagonists on cell contraction, growth, and differentiation can be investigated. The results indicate that in addition to inhibition of cell contraction, alpha1-AR antagonists have the potential to induce apoptosis.