[Complete androgen blockade versus monotherapy].

J E Altwein

doi:10.1007/s001200050163

Home/Archive/PubMed

PubMed · 9563124

[Complete androgen blockade versus monotherapy].

J E Altwein

View original source ↗Export metadata ↓

Abstract

In a comparative analysis of 29 studies, maximal androgen deprivation (MAD) was not found to be superior to partial androgen deprivation. Thus, MAD cannot be regarded as the new gold standard. Most trials focus on quality of life which--given the palliative aim of the treatment--deserves special attention. This aspect has not yet been evaluated, however, in the largest multicenter study, intergroup study 0105. In patients with advanced bone metastasis or severe pain, MAD treatment should be begun because of the flare phenomenon. The synergistic effects of LHRH agonists on the prostate are currently being investigated. Since no clear prognostic factors exist and reduction of serum-PSA levels under MAD does not delay progression, the patient must help to make the decision of whether or not MAD should be begun.

Explore related subjects

Androgen Antagonists Antineoplastic Agents, Hormonal Clinical Trials as Topic Combined Modality Therapy Humans Male Orchiectomy Palliative Care Prostatic Neoplasms Quality of Life Survival Rate English Abstract Journal Article Meta-Analysis

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

J E Altwein. 1998. [Complete androgen blockade versus monotherapy].. https://doi.org/10.1007/s001200050163

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Estrogen signaling and disruption of androgen metabolism in acquired androgen-independence during cadmium carcinogenesis in human prostate epithelial cells.

BACKGROUND: Lethal prostate cancers often become androgen-independent due to androgen receptor (AR) overexpression. The role of cadmium in prostate tumor progression was determined. METHODS: Control and cadmium-transformed prostate epithelial cells (CTPE) were compared for steroid-induced proliferation, steroid receptor expression, and androgen metabolism. RESULTS: CTPE cells showed rapid proliferation in complete medium and sustained proliferation in steroid-reduced medium. Androgens stimulated significantly less cell proliferation and AR-related genes expression in CTPE cells. 5alpha-Dihydrotestosterone increased PSA expression more effectively in control cells. Flutamide reduced 5alpha-dihydrotestosterone-stimulated growth less effectively in CTPE cells compared to control. CTPE cells showed decreased p27 expression. Estrogen receptors were overexpressed and estradiol markedly stimulated proliferation in CTPE cells. In CTPE cells 5alpha-aromatase was markedly increased, while 5alpha-reductase was decreased. CONCLUSIONS: Cadmium-induced malignant transformation stimulates androgen independence, unrelated to AR expression or activity. Increased estrogen receptor and 5alpha-aromatase expression suggest estrogen signaling may be critical to this process.

Androgen Antagonists↗

PubMed2007

Prosaposin upregulates AR and PSA expression and activity in prostate cancer cells (LNCaP).

BACKGROUND: Prosaposin overexpression and/or genomic amplification have been demonstrated in androgen-independent (AI) prostate cancer cell lines and tissues. Here, we explored the possibility for a functional relationship between prosaposin and androgen receptor (AR) in LNCaP cells. METHODS: The effect of prosaposin or its active molecular derivatives (e.g., saposin C) on expression and activity of androgen receptor (AR) and prostate-specific antigen (PSA) was examined by using immunoblotting, RT-PCR, transfection, and reporter gene assays, immunofluorescence staining, and inhibitors of signal transduction pathways. RESULTS: Prosaposin or saposin C, in an AI-manner, (a) increased AR mRNA and protein expression and nuclear AR content and its phosphorylation state; (b) increased PSA mRNA and protein expression; and (c) upregulated PSA- and an androgen-inducible probasin (PB)-reporter gene activity in LNCaP and AR-transfected PC-3 cells. Induction of PSA expression and reporter activity was substantially blocked or prevented with the antiandrogen bicalutamide, pertussis toxin, or inhibitors of MAPK- and PI3K/Akt-signaling pathways, indicating an androgen-agonistic effect for saposin C that involves AR and multiple signaling pathways. CONCLUSIONS: The results for the first time introduce prosaposin as an androgen-agonist in prostate cancer cells. This finding, together with the growth-promoting effect and overexpression of prosaposin, may support a growth advantage to AI prostate cancer cells.

Androgen Antagonists↗

PubMed2007

A role for neurotensin in bicalutamide resistant prostate cancer cells.

BACKGROUND: Anti-androgens are administered as a principal treatment for prostate cancer. Aggressive hormone refractory disease is characterized in some cases by the development of a neuroendocrine phenotype. However little attention has been paid to resistance pathways selected for by long-term treatment with non-steroidal anti-androgens. METHODS: Using a resistant sub-line, LNCaP-Bic, we performed a comparative gene expression profiling using cDNA microarrays and target validation by qRT-PCR. Targets were then explored using cell proliferation, cell cycle analysis and in vitro invasion assays using siRNA technology. RESULTS: Neurotensin/Neuromedin N (NTS) was upregulated in the LNCaP-Bic line at both the transcript and protein level. The resistant line was found to have an increased proliferation rate, more rapid cell cycle progression and increased invasiveness through Matrigel. Each phenotypic difference could be reduced using siRNA knockdown of NT. CONCLUSION: Increased expression of NT in bicalutamide resistant prostate cancer cells induces cell proliferation and invasion suggesting that this peptide may contribute to the development of bicalutamide resistant prostate cancer.

Androgen Antagonists↗