Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two open-label, multicenter studies were conducted to evaluate the efficacy and safety of a long-acting depot formulation of leuprolide acetate (22.5 mg) administered intramuscularly every 12 weeks to patients with stage D2 prostate cancer. Clinical evaluations were performed every 12 weeks, and serum testosterone levels were monitored biweekly or weekly for 24 weeks. Onset of castrate levels (< or = 50 ng/dL) of testosterone was achieved within 30 days of the initial depot injection in 87 (95%) of the 92 assessable patients enrolled in the two studies. Mean testosterone levels remained well within the castrate range throughout each dosing interval. Two patients experienced a transient escape (testosterone levels > 50 ng/dL on two consecutive determinations). Delay of an injection of up to 2 weeks did not have an effect on testosterone suppression: in 16 patients in whom the depot injection was delayed by 3 to 14 days, testosterone values remained within the castrate range. A favorable objective tumor response (no progression) to treatment occurred in 85% of the patients. Prostate-specific antigen and prostatic acid phosphatase decreased by 50% or more in 96% and 84% of patients, respectively, with elevated pretreatment values and at least one treatment value. Assessment of local disease status and overall performance status showed improvement or stability in most patients. The most common adverse events were hot flashes (59%), pain (27%), and testicular atrophy (21%). The 22.5-mg depot formulation of leuprolide, which acts in a manner similar to the monthly 7.5-mg depot formulation, was shown to be effective and safe in treating patients with advanced prostate cancer.
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PMID:Leuprolide acetate 22.5 mg 12-week depot formulation in the treatment of patients with advanced prostate cancer. 887 93

The X-linked androgen receptor (AR) gene contains two polymorphic trinucleotide repeat segments that code for polyglutamine and polyglycine tracts in the N-terminal trans-activation domain of the AR protein. Changes in the lengths of these polymorphic repeat segments have been associated with increased risk of prostate cancer, an androgen-dependent tumor. Expansion of the polyglutamine tract causes a rare neuromuscular disease, spinal bulbar muscular atrophy, that is associated with low virilization, reduced sperm production, testicular atrophy, and infertility. As spermatogenesis is exquisitely androgen dependent, it is plausible that changes in these two repeat segments could have a role in some cases of male infertility associated with impaired spermatogenesis. To test this hypothesis, we examined the lengths of the polyglutamine and polyglycine repeats in 153 patients with defective sperm production and compared them to 72 normal controls of proven fertility. There was no significant association between the polyglycine tract and infertility. However, patients with 28 or more glutamines (Gln) in their AR had more than 4-fold (95% confidence interval, 4.9-3.2) increased risk of impaired spermatogenesis, and the more severe the spermatogenic defect, the higher the proportion of patients with a longer Gln repeat. Concordantly, the risk of defective spermatogenesis was halved when the polyglutamine tract was short (< or = 23 Gln). Whole cell transfection experiments using AR constructs harboring 15, 20, and 31 Gln repeats and a luciferase reporter gene with an androgen response element promoter confirmed an inverse relationship between Gln number and trans-regulatory activity. Immunoblot analyses indicated that the reduced androgenicity of the AR was unlikely to be due to a change in AR protein content. The data indicate a direct relation between length of the AR polyglutamine tract and the risk of defective spermatogenesis that is attributable to the decreased functional competence of AR with longer glutamine tracts.
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PMID:Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. 936 May 40

In the last decade, testosterone replacement therapy (TRT) has been increasingly prescribed to treat a controversial condition known as 'late-onset hypogonadism (LOH)'. This syndrome is diagnosed in men who, for no discernible reason other than older age, obesity or ill health have serum testosterone concentrations below the normal range for healthy young men and report one or more of the following symptoms: muscle weakness or wasting, mood, behaviour and cognition-related symptoms and sexual function or libido impairment. However, recent evidence has demonstrated that testosterone drugs do not substantially ameliorate these symptoms and, more worryingly, that their long-term use may be associated with severe adverse effects (i.e. increased risk of prostate cancer, stroke and myocardial infarction, worsening of benign prostatic hyperplasia symptoms and testicular atrophy). Nonetheless, testosterone drugs have exhibited extraordinary commercial success and their pharmaceutical sales are steadily rising. Behind this apparently unjustifiable trend there are deliberate, well designed direct and indirect pharmaceutical marketing initiatives that exploit the conviction rooted in contemporary society that testosterone can reverse the effects of ageing and ensure social accomplishment. Commercial mechanisms have laid the foundation for disease mongering of LOH and also have resulted a considerable expansion of the indications for treatment. This promotion model deserves particular attention since it is applicable to any drug with a purportedly favourable risk-benefit ratio not supported by evidence.
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PMID:'Forever Young'-Testosterone replacement therapy: a blockbuster drug despite flabby evidence and broken promises. 2833 14