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1.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33771918

RESUMO

Knockout of ERß in the mouse leads to nuclear expression of epidermal growth factor receptor (EGFR) in the prostate. To examine whether ERß plays a similar role in the human prostate, we used four cohorts of men: 1) a Swedish cohort of normal prostates and PCa (prostate cancer) of different Gleason grades; 2) men with benign prostatic hyperplasia (BPH) treated with the 5α-reductase inhibitor, finasteride, and finasteride together with the ERß agonists, soy isoflavones; 3) men with PCa above Gleason grade 4 (GG4), treated with ADT (androgen deprivation therapy) and abiraterone (AA), the blocker of androgen synthesis for different durations; and 4) men with GG4 PCa on ADT or ADT with the AR (androgen receptor) blocker, enzalutamide, for 4 mo to 6 mo. In men with BPH, finasteride treatment induced EGFR nuclear expression, but, when finasteride was combined with isoflavones, EGFR remained on the cell membrane. In GG4 patients, blocking of AR for 4 mo to 6 mo resulted in loss of ERß and PTEN expression and increase in patients with nuclear EGFR from 10 to 40%. In the men with GG4 PCa, blocking of adrenal synthesis of testosterone for 2 mo to 7 mo had the beneficial effect of increasing ERß expression, but, on treatment longer than 8 mo, ERß was lost and EGFR moved to the nucleus. Since nuclear EGFR is a predictor of poor outcome in PCa, addition of ERß agonists together with abiraterone should be considered as a treatment that might sustain expression of ERß and offer some benefit to patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Receptor beta de Estrogênio/agonistas , Hiperplasia Prostática/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Androstenos/farmacologia , Androstenos/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Biópsia , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Estudos de Coortes , Receptores ErbB/metabolismo , Receptor beta de Estrogênio/metabolismo , Finasterida/farmacologia , Finasterida/uso terapêutico , Humanos , Masculino , Camundongos , Camundongos Knockout , Gradação de Tumores , Nitrilas/farmacologia , Nitrilas/uso terapêutico , PTEN Fosfo-Hidrolase/metabolismo , Feniltioidantoína/farmacologia , Feniltioidantoína/uso terapêutico , Fitoestrógenos/farmacologia , Fitoestrógenos/uso terapêutico , Próstata/citologia , Próstata/efeitos dos fármacos , Próstata/patologia , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo
2.
Urology ; 109: 184-189, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28712889

RESUMO

OBJECTIVE: To investigate the efficacy and safety of the Adjustable Transobturator Male System (ATOMS) in men with stress urinary incontinence after transurethral resection of the prostate (TURP). MATERIALS AND METHODS: From a large international prospectively administrated ATOMS register, we identified 49 patients with an ATOMS device as a result of persistent stress urinary incontinence after TURP. For evaluation, the men were divided into standard transurethral resection of the prostate (sTURP) and palliative transurethral resection of the prostate (pTURP) in radiated patients. Baseline and follow-up measurements included continence parameters, urodynamics, quality-of-life surveys (Patient Global Impression-Improvement and International Consultation on Incontinence Questionnaire-Short Form), and pain ratings. The dry rate (0-1 security pad/<10 mL urine loss), the success rate (overall improvement), removals, complications, and treatment failures were recorded. A P value of <.05 was considered statistically significant. RESULTS: After a median of 34 and 22 months' follow-up and 2-3 adjustments, the sTURP and pTURP cohorts had 58% and 50% dry rates and 90% and 87% success rates. Hence, no improvement was seen in 10% and 13%. The removal rate was higher in pTURP (50% vs 10%, P = .0171) and infection was the most common side effect (50%) observed. Neither intraoperative nor Clavien-Dindo 4 and 5 adverse events were recorded. In sTURP and pTURP, the median daily pad count and the pad test improved significantly (all P <.001), and quality-of-life parameters shifted to a high satisfaction level (P <.001 and P = .001). Urodynamics remained unchanged and postoperative pain was not an issue. CONCLUSION: The ATOMS device shows promising treatment outcomes in patients after TURP and a similar efficacy as in postprostatectomy incontinence. There is no difference in continence outcome between sTURP and pTURP; however, a higher removal rate was found after pTURP, which may be important for patient counseling.


Assuntos
Complicações Pós-Operatórias/cirurgia , Slings Suburetrais , Ressecção Transuretral da Próstata , Incontinência Urinária por Estresse/cirurgia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Humanos , Masculino , Estudos Retrospectivos , Slings Suburetrais/efeitos adversos , Resultado do Tratamento
3.
Urol Int ; 76(4): 327-31, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16679834

RESUMO

INTRODUCTION: A number of studies suggest that the low incidence of prostate cancer as well as benign prostatic enlargement in Asia depends on the extended consumption of phyto-oestrogens in these parts of the world. In most Asian men, phyto-oestrogen levels are multiple higher compared to Austrian (European) men. The aim of our study was to evaluate, according to the East-West decline, whether there were significant differences within the Austrian population. We compared prostate phyto-oestrogen tissue levels of men living in three different geographical regions of Austria. We further compared men living in rural and urban environments. MATERIAL AND METHODS: Prostatic tissue samples of 103 men undergoing surgery for benign prostatic hyperplasia or prostate cancer were collected and frozen at -40 degrees C. In tissue samples, enterolactone (representative for lignans) and genistein levels (representative for isoflavones) were determined in duplicate by monoclonal antibody-based immunoassays. We subsequently compared tissue levels of men living in rural and urban environments and different geographical regions of Austria. RESULTS: Prostatic enterolactone tissue levels were similar in men living in an urban (median 19.1 ng/g dry weight, range 1.5-76.4) or rural environment (median 15.7 range 0.6-140.6) p = 0.99. The respective values for genistein were 20.5 ng/g dry weight (range 4.6-47.4) and 9.3 (range 0.1-156.7) p = 0.77. Furthermore, enterolactone (p = 0.1) and genistein (p = 0.65) levels were similar in three different geographic regions in Austria. CONCLUSION: No significant differences regarding genistein and enterolactone were found between our study populations. However, we found a wide variation between individual patients.


Assuntos
Isoflavonas/análise , Fitoestrógenos/análise , Próstata/química , Áustria , Humanos , Masculino , População Rural , População Urbana
5.
Urology ; 64(4): 707-11, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15491706

RESUMO

OBJECTIVES: To compare phytoestrogen tissue levels in men with small-volume benign prostatic hyperplasia (BPH), large-volume BPH, and prostate cancer (PCa). METHODS: Prostatic tissue samples of men consuming a Western diet who underwent surgery for BPH (n = 63) or PCa (n = 31) were collected and frozen at -40 degrees C. In the tissue samples, the enterolactone and genistein levels were determined in duplicate by monoclonal antibody-based immunoassays. We subsequently compared the tissue levels in patients with BPH and PCa and studied the impact of enterolactone and genistein on prostate volume. RESULTS: The enterolactone tissue levels were comparable in patients with BPH and PCa and revealed no correlation to prostate volume. The genistein tissue levels tended to be lower in patients with PCa (median 8.4 ng/g dry weight) compared with the entire BPH group (11.0 ng/g dry weight; P = 0.072). In addition, the genistein tissue levels were significantly greater in men with small-volume BPH (median 20.9 ng/g dry weight) compared with those with large-volume BPH (8.8 ng/g dry weight; P = 0.023). CONCLUSIONS: Our data suggest an involvement of genistein in the pathogenesis of BPH and, possibly, of PCa. The impact of enterolactone is currently unknown.


Assuntos
4-Butirolactona/análogos & derivados , 4-Butirolactona/análise , Adenocarcinoma/química , Genisteína/análise , Lignanas/análise , Fitoestrógenos/análise , Próstata/química , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/química , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Dieta , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Próstata/patologia , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia
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