UMLS:C0376358 - FACTA Search

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Query: UMLS:C0376358 (prostate cancer)
59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Finasteride, an orally active type II 5 alpha-reductase (5 alpha R) inhibitor, blocks conversion of testosterone (T) to dihydrotestosterone (DHT). The utility of finasteride in effectively managing benign prostatic hyperplasia has been documented. Use of the drug results in reduced prostate volume and serum levels. Patients receiving finasteride should be monitored with periodic digital-rectal examination (DRE) and serum PSA measurement. Patients with a sustained increase in serum PSA or an abnormal DRE require additional evaluation. There is no evidence that use of finasteride has an adverse effect on prostate cancer detection, if the drug's effect on serum PSA is recognized and accounted for.
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PMID:Evaluation of men on finasteride. 886 75

The literature contains many accounts of studies in which tumour growth has been accelerated by administration of a particular mitogen and the response then inhibited by co-administration of the corresponding antagonist. Much effort has been focused on the development of cytokine or growth factor antagonists. Like most other cancer therapies, biological therapies will undoubtedly have undesirable toxicities because the proteins they target may not be unique to malignant cells. We reviewed the clinical and therapeutic potential of growth factor agonists and antagonists in some non urologic and urologic diseases. In a recent report we demonstrated that both androgen and antiandrogen treatments enhance the proliferation rate of the hormone-dependent prostate cancer cell line LNCaP, expressing a mutated androgen receptor. Simultaneous treatment with 1 nM R1881 and 100 nM OH-Flutamide, completely counteracted the androgen-induced increase of Epidermal Growth Factor (EGF) levels. Moreover we found that Testosterone, DHT and EGF are mainly concentrated in the periurethral zone in human BPH and long term treatment with Finasteride and with Flutamide modify the distribution and concentration of these factors. Some authors analyzed whether and addition of aurin tricarboxylic acid (ATA) can reduce the growth rate of basic FGF-dependent cells in a manner similar to suramin.
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PMID:Peptide growth factors: clinical and therapeutic strategies. 922 27

Prostate cancer is a disease associated with androgens. It has been hypothesized that reducing the conversion of testosterone (T) to dihydrotestosterone (DHT) in the prostate by the use of the drug finasteride, a 5alpha-reductase inhibitor, will reduce the incidence of prostate cancer. We investigated the chemopreventive potential of finasteride by evaluating its effect on the prostate gland of men with elevated serum prostate-specific antigen (PSA). Fifty-two men with elevated PSA and prostate sextant biopsies negative for cancer were randomized to receive finasteride 5 mg day(-1) (27 patients) or no medication (25 patients) for 12 months and were rebiopsied at 12 months. The biopsies were evaluated for the presence of cancer, the proportion of glandular and hyperplastic tissue, and the presence of high-grade prostatic intraepithelial neoplasia (PIN). Epithelial proliferation was assessed in the prestudy and 12-month biopsies by immunohistochemistry using antibody to proliferating cell nuclear antigen (PCNA). Serum blood samples were drawn at baseline and after 1, 3, 6 and 12 months of study. In the control group, serum levels of PSA and T were unchanged throughout the 12 months. In the finasteride group, PSA decreased 48% (P < 0.001), DHT decreased 67% (P < 0.001) and T increased 21% (P < 0.001). Histological evaluation of prestudy and 12-month biopsy specimens revealed that the finasteride group had a 30% reduction in the percentage of hyperplastic epithelial tissue (P = 0.002), although this decrease was not statistically significantly different between the finasteride and control groups (P = 0.11). In patients with PIN on prestudy biopsy, no change occurred in the PIN lesions with finasteride treatment. Finasteride also had no effect on the proliferation index of prostatic epithelial cells. Of the 27 patients treated with finasteride, eight (30%) had adenocarcinoma of the prostate detected on the 12-month biopsy, compared with one (4%) of the control patients (P = 0.025). In the treatment group, six cancers occurred in the eight patients with PIN on the prestudy biopsy; in the observation group no cancers were detected in the five patients with PIN on the prestudy biopsy (P = 0.021). Two cancers occurred in the 19 men in the treatment group with no evidence of PIN on the prestudy biopsy, compared with one cancer in the 20 men in the observation group with no evidence of PIN on the prestudy biopsy (P = 0.60). This study, using a novel model for evaluating short-term efficacy of chemopreventive or therapeutic agents in men at high risk of prostate cancer, provides little evidence that finasteride is an effective chemopreventive agent for prostate cancer in men with elevated PSA.
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PMID:The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels. 1048 32

Finasteride is commonly used for the treatment of benign prostatic hyperplasia and has been suggested to prevent prostate cancer development. To gain insight to the molecular effects of finasteride on prostate cancer development, we studied six prostate cancers diagnosed during finasteride treatment for benign prostatic hyperplasia. Comparative genomic hybridization detected genetic alterations in four tumors (1-5 changes/tumor). Xq gains and 6q losses were the most common alterations. The recurrent Xq gains motivated us to study the involvement of the androgen receptor (AR) gene. One tumor with Xq gain had a 3-fold amplification of the AR gene, suggesting that tumor development in finasteride-treated patients may require increased AR copy number and expression, as has previously been shown for prostate cancers recurring during hormonal therapy. Furthermore, in another tumor, an Arg726Leu mutation of the AR gene was found. This mutation was also present in the germ-line DNA of the patient. Arg726Leu mutation has previously been reported to affect the transactivational properties of the AR. In summary, prostate cancers developing during finasteride therapy may have distinct biological properties, such as a low number of chromosomal alterations and frequent involvement of the AR gene. Further studies are needed to explore the role of germ-line AR mutations in these patients.
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PMID:Androgen receptor gene alterations and chromosomal gains and losses in prostate carcinomas appearing during finasteride treatment for benign prostatic hyperplasia. 1058 74

A phenomenon of the prostate gland, which is also shared by hair follicles, is that it is little influenced by testosterone (T) for androgenic stimulation, but instead by its metabolite 5alpha-dihydrotestosterone (DHT). By blocking the conversion of T to DHT, the circulating level of DHT is reduced by 80%, the size of the prostate gland is reduced by about 20% and the level of prostate-specific antigen (PSA) by about 50%. Treatment of patients with obstructive benign prostatic hypertrophy (BPH) with the drug Finasteride leads to a moderately improved urinary flow, symptomatic improvement and halts the natural progress of the disease. Since DHT potentiates the effect of testosterone on erectile function, the side-effects are impotence in 3% of patients, decreased ejaculatory volume, and gynaecomastia in 0.4% of patients. The drug could be regarded as a safe way to treat moderately symptomatic BPH. The efficacy of the drug is long-lasting (more than 7 years). It has also been tried in prostate cancer, but is less effective. It reduces PSA levels by 50% and, in combination therapy, therefore, PSA levels remain low for longer when Finasteride is added. An important finding is the efficacy of Finasteride treatment in haematuria from BPH. The drug interacts with vascular endothelium growth factor and efficiently prevents new bleeding. It could be regarded as a first-line therapy for this type of haematuria. Finasteride can also be used to stop male baldness. It seems particularly effective in men aged 20-40 years; 85% of patients stopped losing hair when given Finasteride. When the treatment was stopped hair loss continued, thus therapy may have to be "lifelong".
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PMID:Finasteride in the treatment of benign prostatic hypertrophy: an update. New indications for finasteride therapy. 1063 64

This article summarizes discussions of the importance of androgens and androgen antagonists in the genesis of prostate cancer. These discussions occurred at a recent symposium on prostate cancer chemoprevention sponsored by the National Cancer Institute. Considerable information exists indicating the importance of androgens in the development of prostate cancer. Trials in breast cancer indicate that estrogen antagonists prevent breast cancer-suggesting, by analogy, that the blockade of androgen action might prevent the emergence of prostate cancer. The 5alpha-reductase inhibitors block the intracellular metabolism of testosterone and inhibit the growth of the prostate. Limited data suggest that 5alpha-reductase inhibitors reduces prostate-specific antigen in men with localized and advanced, primary or recurrent prostate cancer. An ongoing national trial of 18,000 men over 50 years of age has completed accrual and will evaluate whether a standard dose of finasteride will prevent the development of prostate cancer. The toxicity profile of finasteride (Proscar, Merck & Co., West Point, PA), the only approved 5alpha-reductase inhibitor, is favorable leading to its evaluation as a potential chemopreventive agent for prostate cancer. Anti-androgens such as bicalutamide (Casodex, AstraZeneca, Wilmington, DE) are active in the treatment of prostate cancer and comparable, in some trials, to testicular androgen suppression. These data suggest that antiandrogens may be active in the prevention of prostate cancer; however, the toxicity of antiandrogens (gynecomastia, gastrointestinal toxicity) poses concerns for application in prevention studies. Opportunities for study of factors predictive or associated with the development of prostate cancer and new agents that may interrupt this process offer numerous leads that may reduce the incidence of prostate cancer.
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PMID:Androgen antagonists: Potential role in prostate cancer prevention. 1129 97

Prostate cancer is the most diagnosed invasive malignancy in males. Androgens and oestrogens have been implicated in the pathogenesis of prostate cancer. We report herein that the pure anti-oestrogen ICI 182,780 (ICI) reduces Ki-67 labelling index and IGF-I receptor levels in rat prostate. Increase of IGF-I mRNA and IGF-binding protein 3 (IGFBP-3) accumulation occur without any effect on prostate weight. Finasteride significantly decreases prostate weight and inhibits IGF-I gene expression. IGFBP-3 mRNA, Akt and phospho-Akt are not affected by finasteride. Co-administration of ICI plus finasteride reduces prostate weight by approximately 50% and causes acinar dilation with decreased luminal epithelial cell thickness. The acinar epithelial cells became atrophic and inactive with minimal cytoplasm. We also demonstrate a synergistic effect of ICI and finasteride on induction of IGFBP-3 accumulation and inhibition of Akt phosphorylation. Because the IGF and IGFBP-3 system plays an important role in prostate epithelial cell proliferation, apoptosis and tumour progression, the inhibitory effects of finasteride and ICI on IGF system may contribute to their anti-proliferative activity. These observations support a potential use of ICI in conjunction with finasteride in the prevention and/or treatment of prostate cancer.
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PMID:Co-administration of finasteride and the pure anti-oestrogen ICI 182,780 act synergistically in modulating the IGF system in rat prostate. 1157 95

Bleeding of prostatic origin is usually caused by the friable hypervascularity of the prostate, the vessels of which are easily disrupted by physical activity. The condition is often ignored after the patient has been fully investigated and more serious causes for bleeding excluded and treatment is often withheld unless the bleeding becomes excessive. We analysed the clinical effect of finasteride in the treatment of this condition. We retrospectively reviewed 42 patients diagnosed as having haematuria secondary to bleeding from a benign prostate. Eighteen patients were simply reassured and given no treatment. Twenty-four patients with prostatic bleeding were treated using finasteride. All case notes were reviewed and the patients were contacted by telephone. Of 18 patients who had prostatic bleeding but did not receive treatment the mean age was 70 y and the mean follow-up was 10 months; two had died, nine had no further bleeding, two had a single episode of bleeding requiring no treatment, six had several bleeding episodes of whom one started finasteride, one refused treatment, and three required TURP. In the group treated with finasteride the mean follow up was 9 months, the mean age of the patients was 75 y. Twenty patients had no further bleeding, one patient experienced minor intermittent bleed and required no further treatment. Two patients died of non-urological causes, one patient stopped the treatment because of impotence and one patient had mild gynecomastia. Haematuria secondary to prostatic bleeding can be significant if not treated. Finasteride appears to be effective in suppressing haematuria caused by benign prostatic hyperplasia and should be considered in treating this problem.
Prostate Cancer Prostatic Dis 1998 Mar
PMID:Haematuria associated with BPH-Natural history and a new treatment option. 1249 9

The purpose of this paper is to examine effects of finasteride 5 mg across different age groups in an ethnically diverse population of men with symptomatic benign prostatic hyperplasia (BPH) seen in community urology and primary care practices. Data were combined from two previous placebo-controlled randomised trials of finasteride that evaluated changes in urinary symptoms, blinded global assessments of urologic status, adverse experiences, and effects on dihydrotestosterone (DHT) and prostate-specific antigen (PSA) in over 4500 men. Finasteride showed a favourable efficacy and tolerability profile in this large ethnically diverse population and was similarly effective in middle-aged and older men with BPH and prostate gland enlargement.
Prostate Cancer Prostatic Dis 1997 Sep
PMID:Combined analysis of two multicenter studies of finasteride 5 mg in the treatment of symptomatic benign prostatic hyperplasia. 1249 30

Finasteride is widely used for the treatment of benign prostatic hyperplasia (BPH). Its therapeutic efficacy is believed to be mediated through selective inhibition of prostatic 5alpha-reductase (type II). This prospective, controlled, randomized study examines various relationships between changes in tissue 5alpha-reductase isozyme activity, epithelial proliferative index and morphology in men with BPH treated with finasteride for 6 months, and correlates these with clinical response. Thirty-one patients presenting with symptomatic bladder outflow obstruction were prospectively randomized to receive either finasteride or placebo (2:1) for 24 weeks. Of these, 27 men aged 55-80 y (median 69 y) completed the study, including 18 patients on treatment. Symptom score determination, uroflow and prostate volume were assessed at baseline and end of study. Prostatic tissue was obtained by ultrasound-guided needle biopsy at baseline and by transurethral resection (TURP) at end of study for biochemical and morphometric analysis. Epithelial proliferation was examined quantitatively in the resected tissue using MIB-1 antibody to Ki-67 and counting the percentage of positively staining cells. Type II 5alpha-reductase activity was strongly inhibited by finasteride in resected BPH tissue, with over 100-fold decrease in V(max) (P=0.001), whereas the type I isozyme was inhibited 5-fold (P=0.005). Selective inhibition of type II 5alpha-reductase was demonstrated in all treated patients. No significant difference in epithelial proliferation was observed between the finasteride and placebo groups. Epithelial proliferation was, however, greater in prostatic tissue with histological manifestation of inflammation (2.02% vs 0.89%, P=0.001). Positive correlation between the total epithelial volume and the ratio of transition zone volume/total prostate volume was observed in the placebo group (r=0.834), whereas there was no such correlation in men taking finasteride (r=-0.300), consistent with a reduction in epithelial content in the treatment group. Improvement in uroflow and reduction in prostatic volume in patients treated with finasteride did not reach statistical significance. This study shows that finasteride causes inhibition of 5alpha-reductase activity in human BPH tissue with selectivity for the type II isozyme. In spite of this, no significant effects in epithelial proliferation or tissue morphology were demonstrated. The presence of inflammation was, however, associated with significantly greater proliferative activity. The power of this study was limited by the small number of recruited patients, and a larger study would be required for further investigation of morphological changes induced by finasteride in BPH tissue and their biochemical basis.
Prostate Cancer Prostatic Dis 1999 Dec
PMID:A prospective randomized trial evaluating tissue effects of finasteride therapy in benign prostatic hyperplasia. 1249 74

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