Androgen receptor (AR) signaling in stromal cells is important in prostate cancer, yet the mechanisms underpinning stromal AR contribution to disease development and progression remain unclear. Using patient-matched benign and malignant prostate samples, we show a significant association between low AR levels in cancer associated stroma and increased prostate cancer-related death at one, three and five years post-diganosis, and in tissue recombination models with primary prostate cancer cells that low stromal AR decreases castration-induced apoptosis. AR-regulation was found to be different in primary human fibroblasts isolated from adjacent to cancerous and non-cancerous prostate epithelia, and to represent altered activation of myofibroblast pathways involved in cell cycle, adhesion, migration, and the extracellular matrix (ECM). Without AR signaling, the fibroblast-derived ECM loses the capacity to promote attachment of both myofibroblasts and cancer cells, is less able to prevent cell-matrix disruption, and is less likely to impede cancer cell invasion. AR signaling in prostate cancer stroma appears therefore to alter patient outcome by maintaining an ECM microenvironment inhibitory to cancer cell invasion. This paper provides comprehensive insight into AR signaling in the non-epithelial prostate microenvironment, and a resource from which the prognostic and therapeutic implications of stromal AR levels can be further explored.
While there has been widespread recent interest in men's health issues, and prostate cancer in particular, there have been few studies to determine which issues are important from the viewpoint of men themselves. This study was undertaken to identify genitourinary issues of concern to older men. A series of 19 focus groups involved 137 men and 14 women from a broad demographic background. Men expressed consistent concern about urinary symptoms, prostate cancer and sexual function. They revealed misunderstanding and a desire for more information about all issues. Urinary symptoms had a high impact on quality of life that could be made worse by environmental constraints such as working conditions and availability of toilets. Prostate cancer was a concern in all groups, even those at low risk, and men believed that screening for prostate cancer should be offered. Men believed sexuality was not recognised as an issue of concern to older people. Potential barriers to health action included stoicism, not talking about health issues and poor relationships with doctors. The study suggests a substantial need for community and professional education and for health promotion focused on preventable morbidity.
Effervescent lozenges containing 10 mg of zinc acetate were evaluated as a treatment of upper respiratory tract infections in a double-blind randomized trial by using a placebo which was indistinguishable to most observers in taste and appearance from the active material. Of the 70 treatment courses used by 55 individuals in 34 families, 63 (33 zinc and 30 placebo) were considered evaluable, in that the volunteer used the medication at least four times daily for at least 3 days, the average utilization being 5.4 days at an average dose of six lozenges daily. Six users of zinc reported nausea (versus no placebo users), and eight reported an unpleasant taste or aftertaste (versus one placebo user). No benefit was observed among the users of zinc acetate. The mean duration of symptoms in users of the zinc was 12.1 days, compared with 7.7 days in those who used the placebo. Nor was any beneficial effect of zinc evident among the four zinc-treated versus the two placebo-treated individuals from whom rhinovirus was grown.
Objective To investigate the prevalence of erectile dysfunction (ED) in the South Australian community, and the influence of demographic and other risk factors. Design Survey by mailed questionnaire (based on the University of California, Los Angeles prostate cancer index) of a subset (men who agreed to participate) of a probability sample of the South Australian community who completed a multiuser interview survey. Participants and setting Men over the age of 40 in South Australia. Main outcome measures Sexual desire, orgasm, ability to have an erection, adequacy (firmness) of erections for intercourse, frequency of erections when wanted, frequency of intercourse, nocturnal or morning erections, and history of prostate surgery; total sexual function score based on these. Results 612 men (86.7%) agreed to answer the sexual function survey; 427 (69.8%) returned questionnaires. ED was strongly correlated with age in all seven domains of sexual function. Erections inadequate for intercourse affected 3% of 40–49‐year‐olds, increasing to 64% of 70–79‐year‐olds. The frequency of intercourse considered normal for age by men 50–69 years was 1–6 times weekly; the disparity between this and reported frequency increased in men over 60 years, as did the difference between sexual desire and potency. A history of vigorous exercise was protective across all ages. High triglyceride levels, blood pressure medication and non‐cancer surgery for prostate disease were independent predictors of poor sexual function at older ages. High cholesterol level was an independent predictor of impotence. Conclusions We found similar or higher levels of ED than in comparable overseas studies. Disparity between potency and desire was greatest, and hence the age group in whom demand for treatment may be highest, in those 60 years and older. Cardiovascular risk factors were predictors of ED in these older men, suggesting that prevention may benefit sexual function. Non‐cancer prostate surgery may be a greater contributor to ED than previously realised.
ObjectiveTo determine the prevalence of troublesome lower urinary tract symptoms (LUTS) In men and women In the community. DesignInterview‐based prevalence survey. SettingMetropolitan and rural communities In South Australia, September, 1995. SubjectsProbability sample of 1204 men and 1686 women (aged over 18 years) weighted to reflect the age and sex distribution of the South Australian population. Data collectedPresence of storage (Irritative) and voiding (obstructive) symptoms, based on the International Prostate Symptom Score questionnaire; satisfaction with urinary condition (quality‐of‐llfe measure); and visits to a doctor for urinary symptoms In the preceding 12 months. ResultsThe prevalence of one or more troublesome LUTS was 26% (318/1204) for men and 39% (662/1686) for women (all ages) and 48% (314/649) for men and women over 65. The most common troublesome symptoms In men and women were nocturia and frequency. Symptoms were significantly age‐related In men, but less so In women, In whom symptom prevalence exceeded 30% for all age groups. Ten per cent of men (123/1204) and 15% of women (249/1686) had visited a doctor for a urinary problem In the previous 12 months. Nine per cent of men (104/1204) and 16% of women (274/1686) were substantially dissatisfied with their urinary condition. Symptom prevalence and dissatisfaction with urinary condition were significantly associated with visiting the doctor (P< 0.0001), but only 28% (88/318) of men and 27% (179/662) of women with troublesome LUTS saw a doctor, and 63% (65/104) of men and 59% (162/274) of women dissatisfied with their urinary condition did not seek medical help. ConclusionsAlthough the prevalence of troublesome LUTS In the community Is high, the number of people whose quality of life Is substantially affected Is much lower. The Impact of these symptoms upon quality of life Is a major reason for patients to see a doctor, yet many who are “bothered” by the symptoms do not do so.
OBJECTIVE To assess clinicians’ knowledge and attitudes to prostate cancer peer‐support groups, essential in improving support services for men with prostate cancer, as patients’ perceptions of their clinicians’ attitudes to such groups predict patients’ positive and negative perceptions of their experiences at such groups. SUBJECTS AND METHODS In all, 36 clinicians (75% response) across Australia, of whom 27 were urologists and nine were radiation oncologists, were interviewed in‐depth using a key‐informant approach. Nine clinicians were from regional Australia, with the remaining 27 from major metropolitan settings. Subsequently, 30 clinicians (69% response) completed surveys to confirm identified themes. RESULTS Peer support was rated positively by most clinicians and most report a fair to good knowledge of such groups. However, less than a quarter regularly refer their patients to these groups. While clinicians can describe positive aspects of peer support, many are concerned that biased viewpoints and misinformation within these groups might potentially contribute to patients’ decisional uncertainty and regret. CONCLUSIONS Further research is needed to establish for whom these support groups are most helpful. Concerns about misleading information that might be proffered in support groups is a barrier to clinician referral to these groups. Dialogue between prostate cancer interest groups and clinicians to resolve concerns presents as a key strategy to improve support for men with prostate cancer.
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