The biological basis for the use of an anti-androgen and a 5-α-reductase inhibitor in the treatment of recurrentprostate cancer: Case report and review

Wang, Long G.; Mencher, Simon K.; McCarron, James P.; Ferrari, Anna C.

doi:10.3892/or.11.6.1325

Cited by 6 publications

(5 citation statements)

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“…Bicalutamide treatment reduced the size of both LNCaP and C4-2B prostaspheres but did not inhibit prostasphere formation. The bicalutamide-treated spheres were associated with a significant decrease in both AR and PSA expression, consistent with the expected effects of bicalutamide treatment [64,68]. No inhibition of CD133 levels were observed, suggesting AR activity does not contribute to CD133 expression.…”

Section: Discussionsupporting

confidence: 64%

“…Interestingly, the expression of ABCG2 was significantly higher in C4-2B spheres, whereas AR was expressed by the majority but not all LNCaP and C4-2B prostasphere cells. We therefore determined whether AR activity contributed to cell proliferation and sphere self-npg renewal in both LNCaP and C4-2B cultures, utilizing the AR antagonist bicalutamide, which is widely used to treat patients with hormone naïve prostate cancer and is associated with a reduction in PSA levels [64]. Bicalutamide inhibits the activity and expression of AR in adherent LNCaP cultures [64,65], causing an AR-specific, progressive inhibition of cell growth and an associated reduction in the percentage of S-phase cells [66].…”

Section: Discussionmentioning

confidence: 99%

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WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

2009

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Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the selfrenewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

2009

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“…Nevertheless, testosterone did not alter the H19 expression. Consistently, testosterone is converted to DHT by 5-alpha-reductase in prostate (Schroder 1994, Wang et al 2004 and consequently, DHT is more active than testosterone during prostate growth (Van Coppennolle et al 2001).…”

Section: Discussionmentioning

confidence: 87%

Hormonal regulation of H19 gene expression in prostate epithelial cells

Berteaux

Lottin²,

Adriaenssens³

et al. 2004

Journal of Endocrinology

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The H19 gene is transcribed in an mRNA-like noncoding RNA. When tumors of various organs or cell types are considered, H19 oncogene or tumor-suppressor status remains controversial. To address the potential regulation of H19 gene expression by an androgen steroid hormone (DHT: dihydrotestosterone) or by a peptidic hormone (PRL: prolactin), we performed experiments in rats systemically treated with chemical mediators. This range of in vivo experiments demonstrated that chronic hyperprolactinemia upregulated the H19 expression in epithelial and stromal cells whereas DHT downregulated the gene. PRL and DHT appeared to be opposite mediators in the H19 RNA synthesis. We investigated these hormonal effects in three human prostate epithelial cell lines. In LNCaP cancer cells, the opposite effect of PRL and DHT was corroborated. However, in normal cells (PNT1A), H19 remained insensitive to the hormones in fetal calf serum (FCS) medium but became responsive in a serumstripped medium. In the DU-145 cancer cell line, tested for its androgen-independence and aggressiveness, the hormones had no effect on H19 expression whatever the culture conditions. Finally, we demonstrated that PRL upregulated the H19 expression in LNCaP cells by the JAK2-STAT5 transduction pathway. We conclude that H19 expression is regulated by both a peptidic and a male steroid hormone.

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“…This data could imply a fundamental role of 5AR in the expression of the androgen receptor18. However, evidence differs in some in vitro studies with prostate cancer cells exposed to finasteride, in which the expression of the androgen receptor is downregulated [36], although the physiopathology could differ with a different population or target. On the other hand, different polymorphisms of the exon 1 of the androgen receptor gene are implicated in its affinity to androgens.…”

Section: Discussionmentioning

confidence: 94%

Post-Finasteride Syndrome: About 2 Cases and Review of the Literature

Alej¹,

Garreton²,

Valzacchi³

et al. 2016

Andrology (Los Angel)

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Introduction: Finasteride is widely used in the treatment of benign prostatic hyperplasia and androgenetic alopecia. Persistent sexual adverse events in patients that withdraw the drug was poorly studied. Materials and methods: case report study of two clinical cases of post-finasteride syndrome. Case 1: 27 year old male who, after 7 months of finasteride 1mg/day intake for androgenetic alopecia, began with erectile dysfunction, low libido, hypospermia, muscular hipotrophy and penile shrinking, in a persistent and progressive way although withdrawal of the drug. He was also evaluated by a psychiatrist. Case 2: 23 year old male that after the intake of 1 pill of finasteride 1mg for androgenetic alopecia began with erectile dysfunction, low libido, hypospermia, less intense orgasms, asthenia, muscle pain and penile shrinking, in a persistent and progressive way although withdrawal of the drug. He is under psychiatric evaluation. Results: Case 1: Hormonal profiles were normal, with a dihydrotestosterone of 192 pg/ml and the penile ultrasound showed an hyperechogenicity at the distal portion of the right corpus cavernosum. The genetic determination of the CAG triplets of the androgen receptor gene showed a value of 24 repetitions. Treatment with Tadalafil and vacuum therapy was effective, although not complete, but he didn't benefit from the 3 month application of Andractim®, with a posterior benefit from the application of HCG 6000 UI/week associated with Anastrozole 2mg/week, with normal hormonal controls. Case 2: penile Doppler and hormonal profiles were normal. Treatment with Tadalafil was effective, although not complete. There was no adherence to other treatments. Conclusion: post-finasteride syndrome is a little known entity with an unknown physiopathology, and is currently under study. Awareness should be promoted about the existence of this syndrome in order to give the best assistance to these patients until we have a better comprehension of this entity.

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The biological basis for the use of an anti-androgen and a 5-α-reductase inhibitor in the treatment of recurrentprostate cancer: Case report and review

Cited by 6 publications

References 0 publications

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Hormonal regulation of H19 gene expression in prostate epithelial cells

Post-Finasteride Syndrome: About 2 Cases and Review of the Literature

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