Brachytherapy for penile cancer: Efficacy and impact on sexual function

AbstractPurposePenis brachytherapy (PB) remains an alternative in the cancer treatment. The objective of this study was to assess the oncologic outcomes, sexual function, and the sexual behavior of men treated by PB for a cancer of the penis.Methods and MaterialsBetween 1992 and 2009, 47 patients with a cancer of the penis were treated by PB (192Ir), in the Toulouse, Montpellier, and Barcelona cancer centers. The investigation into their sexuality was obtained by means of questionnaire. A total of 21 French patients were approached, of whom 19 (mean age=73.2 years) agreed to answer the questionnaire (participation rate=90.5%).ResultsOncologic data: The specific survival and the disease-free survival at 5 years was 87.6% (95% confidence interval, 72.4–94.7%) and 84% (95% confidence interval, 57.6–94.7%), respectively. The rate of preservation of the penis was 66% (n=31). Sexual data: Among the 17 patients sexually active before brachytherapy, 10 patients remained sexually active after treatment (58.8%). Of the 18 patients who had erections before PB, 17 still had them after treatment (94.4%). Age was the main predictive factor.ConclusionThe PB seems to have a moderated impact on the sexual functions and the sexual behavior of the patients

Sphingosine Kinase-1 Is Central to Androgen-Regulated Prostate Cancer Growth and Survival

BACKGROUND: Sphingosine kinase-1 (SphK1) is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent prostate cancer cell growth and survival. METHODOLOGY/PRINCIPAL FINDINGS: Short-term androgen removal induced a rapid and transient SphK1 inhibition associated with a reduced cell growth in vitro and in vivo, an event that was not observed in the hormono-insensitive PC-3 cells. Supporting the critical role of SphK1 inhibition in the rapid effect of androgen depletion, its overexpression could impair the cell growth decrease. Similarly, the addition of dihydrotestosterone (DHT) to androgen-deprived LNCaP cells re-established cell proliferation, through an androgen receptor/PI3K/Akt dependent stimulation of SphK1, and inhibition of SphK1 could markedly impede the effects of DHT. Conversely, long-term removal of androgen support in LNCaP and C4-2B cells resulted in a progressive increase in SphK1 expression and activity throughout the progression to androgen-independence state, which was characterized by the acquisition of a neuroendocrine (NE)-like cell phenotype. Importantly, inhibition of the PI3K/Akt pathway--by negatively impacting SphK1 activity--could prevent NE differentiation in both cell models, an event that could be mimicked by SphK1 inhibitors. Fascinatingly, the reversability of the NE phenotype by exposure to normal medium was linked with a pronounced inhibition of SphK1 activity. CONCLUSIONS/SIGNIFICANCE: We report the first evidence that androgen deprivation induces a differential effect on SphK1 activity in hormone-sensitive prostate cancer cell models. These results also suggest that SphK1 activation upon chronic androgen deprivation may serve as a compensatory mechanism allowing prostate cancer cells to survive in androgen-depleted environment, giving support to its inhibition as a potential therapeutic strategy to delay/prevent the transition to androgen-independent prostate cancer

Field template-based design and biological evaluation of new sphingosine kinase 1 inhibitors

Purpose: Sphingosine kinase 1 (SK1) is a protooncogenic enzyme expressed in many human tumours and is associated with chemoresistance and poor prognosis. It is a potent therapy target and its inhibition chemosensitises solid tumours. Despite recent advances in SK1 inhibitors synthesis and validation, their clinical safety and chemosensitising options are not well described. In this study, we have designed, synthesised and tested a new specific SK1 inhibitor with a low toxicity profile. Methods: Field template molecular modelling was used for compound design. Lead compounds were tested in cell and mouse cancer models. Results: Field template analysis of three known SK1 inhibitors, SKI-178, 12aa and SK1-I, was performed and compound screening identified six potential new SK1 inhibitors. SK1 activity assays in both cell-free and in vitro settings showed that two compounds were effective SK1 inhibitors. Compound SK-F has potently decreased cancer cell viability in vitro and sensitised mouse breast tumours to docetaxel (DTX) in vivo, without significant whole-body toxicity. Conclusion: Through field template screening, we have identified a new SK1 inhibitor, SK-F, which demonstrated antitumour activity in vitro and in vivo without overt toxicity when combined with DTX

Dysfonction érectile par lésion du nerf pudendal après traitement chirurgical des fractures diaphysaires fémorales, étude clinique, anatomique et biomécanique

Les fractures du membre inférieur sont fréquentes touchant une population jeune. Le traitement de référence des fractures fémorales est l'enclouage centro-médullaire sur table orthopédique munie d'un billot pubien. De rares cas de troubles sexuels post-opératoires sont rapportés dans la littérature. De manière inattendue, notre étude conduite par auto-questionnaire chez 168 patients (taux de réponse : 60,1%) présentant une fracture fémorale ou tibiale (groupe contrôle) montre 41% de dysfonction érectile après fracture fémorale et 17,1% après fracture tibiale. Les doses de curare utilisées chez les patients souffrant de dysfonction érectile après fracture fémorale sont moindres que celles de ceux sans dysfonction érectile (p<0.003).Après étude anatomique sur cadavre frais les conséquences sur le nerf pudendal de la traction sur billot pubien ont été modélisées sur squelette synthétique.Le nerf pudendal est comprimé ou étiré en plusieurs endroits et de manière bilatérale. Les pressions mesurées sont réduites en augmentant le diamètre du billot. Au total, curarisation optimale et large billot sont essentiels pour prévenir la dysfonction érectile post-chirurgicaleTOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Impact des traitements sur la qualité de vie sexuelle des hommes transplantés rénaux

TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocSudocFranceF

Conseil pharmaceutique et sexualité féminine

Les dysfonctions sexuelles féminines sont souvent sous évaluées :on estime que 40% des femmes souffrirait de ce type de pathologies . Les dysfonctions sexuelles incluent dans leur définition les désordres du désir ;de l'excitation ,de l'orgasme et les douleurs sexuelles responsables d'un désarroi personnel . Les étiologies de ces troubles sont psychologiques mais aussi physiologiques . Une étude menée auprès de 93 femmes grâce à un auto questionnaire multidimensionnel ;le BISF-W ;montre que la ménopause ,le tabac ,les pathologies ostéoarticulaires sont autant de facteurs qui influent de manière négative sur la sexualité de la femme. Les solutions thérapeutiques actuelles sont pour la plupart en cours d'évaluation . La demande de conseil pour ce type de pathologie est rare en officine . Toutefois elle existe et les pharmaciens peuvent proposer des solutions à leur clientes.TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocSudocFranceF

Le principe de risque appliqué au diagnostic du cancer localisé de la prostate

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF