History of LHRH agonist and combination therapy in prostate cancer

Labrie, Fernand; Bélanger, Alain; Cusan, Lionel; Labrie, Claude; Simard, Jacques; Luu‐The, Van; Diamond, P.; Gómez, J.A. Font; Candas, Bernard

doi:10.1677/erc.0.0030243

Cited by 52 publications

(28 citation statements)

References 22 publications

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“…Short-term administration of cyproterone acetate resulted in a substantial reduction of testicular androgen production. Cyproterone acetate is an antagonist of androgens acting at the receptor (reviewed in Labrie et al, 1996) and has also been shown to reduce serum testosterone concentrations both in rats and in men (Knuth et al, 1984;Gonzalvo et al, 1993), as well as in hyperandrogenic states in women (Grunwald et al, 1994;Grigoriou et al, 1996;Grisaru et al, 1996). The latter effect is due to the action of cyproterone acetate (particularly at high doses such as those used in our study) acting as a progestagen at the hypothalamus to inhibit the release of GnRH (Couzinet et al, 1986).…”

Section: Discussionmentioning

confidence: 49%

Apoptosis and expression of apoptotic regulators in the human testis following short- and long-term anti-androgen treatment

Woolveridge

Bryden²,

Taylor³

et al. 1998

Molecular Human Reproduction

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Apoptosis and its augmentation by androgen withdrawal is an important event in the testis. In other tissues apoptosis is regulated by genes belonging to the bcl-2 family. However, little is known about these pathways in the human testes. Human testes were obtained from patients with prostate cancer, undergoing orchidectomy for permanent androgen ablative treatment. The patients were either untreated or had previously received short-or long-term anti-androgen therapy by cyproterone acetate or GnRH agonist (goserelin). In comparison with untreated patients, testicular testosterone concentrations were reduced by 83% in patients treated with cyproterone acetate and by 99% in patients treated with goserelin. Apoptotic cells were identified in tissue sections by in-situ end labelling of fragmented DNA. The expression of Bcl-2, Bcl-xl, Bax, p53 and poly(ADP) ribose polymerase (PARP) was demonstrated in tissue extracts by Western blotting. Apoptotic germ cells were present in the spermatogenic epithelium of untreated patients and patients who received short-term anti-androgen treatment. There were few or no apoptotic cells in the seminiferous tubules following longterm anti-androgen treatment. Following short-term treatment, the concentrations of the apoptosis-related proteins examined did not change. However, in the long-term treated testes, Bcl-xl and PARP expression declined, Bax and p53 protein concentrations were unchanged, and Bcl-2 was up-regulated. In conclusion, apoptosis occurs in spermatogenic cells of the human testis and may contribute to the regulation of germ cell populations. The apoptosis-related gene products which have been described in other tissues are present in the human testis and are modulated by androgenic stimuli.

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Section: Discussionmentioning

confidence: 49%

Apoptosis and expression of apoptotic regulators in the human testis following short- and long-term anti-androgen treatment

Woolveridge

Bryden²,

Taylor³

et al. 1998

Molecular Human Reproduction

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show abstract

“…Today, prostate cancer can be diagnosed at the clinically localized stage in more than 95% of cases Despite the progress achieved in the treatment of advanced or metastatic prostate cancer using LHRH agonists [35,56] and especially with combined androgen blockade [36,37,39,40,[45][46][47][48], it is well recognized that the only possibility of a significant reduction in prostate cancer mortality is the treatment of localized disease [57]. It is reasonable to suggest that the observed decrease in deaths from prostate cancer is due to earlier diagnosis with serum PSA [58,59] and transrectal ultrasound of the prostate [60] coupled with improved treatment of localized disease by surgery, radiotherapy, brachytherapy, and endocrine therapy [57,[61][62][63][64].…”

Section: Combined Androgen Blockade In Advanced Diseasementioning

confidence: 99%

Major impact of hormonal therapy in localized prostate cancer—death can already be an exception

Labrie¹,

Cusan²,

Luu‐The³

et al. 2004

The Journal of Steroid Biochemistry and Molecular Biology

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“…In the prostate epithelium 3 -HSD expression was colocalized with 17 -HSD type V in normal conditions. 3 -HSD was found in human hyperplastic prostates suggesting the capacity of the human prostate for local androgen production, that increase the hypertrophic potential of the organ [80,81]. Hepatic 3 -HSD expression is presumed to be important in the metabolism and inactivation of steroids.…”

Section: -H S D I M M U N O H I S T O C H E M I S T R Y I S a L S O Umentioning

confidence: 99%

Hydrohysteroid Dehydrogenases – Biological Role and Clinical Importance – Review

Atanassova¹,

Koeva²

2012

Dehydrogenases

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History of LHRH agonist and combination therapy in prostate cancer

Abstract: An LHRH agonist was first administered to a prostate cancer patient 16

Cited by 52 publications

References 22 publications

Apoptosis and expression of apoptotic regulators in the human testis following short- and long-term anti-androgen treatment

Apoptosis and expression of apoptotic regulators in the human testis following short- and long-term anti-androgen treatment

Major impact of hormonal therapy in localized prostate cancer—death can already be an exception

Hydrohysteroid Dehydrogenases – Biological Role and Clinical Importance – Review

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