[Orgasm after curietherapy with permanent iodine-125 radioimplants for localized prostate cancer]. / Orgasme après curiethérapie de prostate par implants permanents d'iode 125 pour cancer localisé de la prostate.

OBJECTIVES: Orgasm is a domain of male sexuality that remains underreported in literature. Our aim was to realize the first detailed analysis of orgasm in patients treated by 125 I permanent prostate brachytherapy for localized prostate cancer. PATIENTS AND METHODS: In a series of 270 sexually active men treated by prostate brachytherapy (125I permanent implantation), 241 (89%), mean age of 65 (43-80), participated in a mailed survey about sexual function after a mean time of 36 months (9-70). Erectile and ejaculatory functions and orgasm were explored using a mailed questionnaire. Two questions focused on orgasm. The first was about quality of orgasm (fast/intense/late, difficult/weak/absent) and the second about the presence of painful orgasm and its frequency (always/sometimes/often). RESULTS: After prostate brachytherapy, 81.3% of sexually active men conserved ejaculation and 90% orgasm. There was a significant deterioration of the quality of orgasm (P=0.0001). More than 50% of the patients had an altered orgasm (weak, difficult, absent) after brachytherapy, vs 16% before implantation (P=0.001). Men with a diminished ejaculation volume often had a weak/difficult orgasm (P=0.007). Neoadjuvant hormonal therapy did not seem to impact the quality of orgasm or the frequency of painful ejaculation. Patients who had an IIEF-5 score higher than 12 had frequently intense orgasm (26.7% vs 2.7%; P<0.001) after brachytherapy. Sixty patients (30.3%) experienced often/sometimes painful ejaculation 12.9% (n=31) before implantation (P=0.0001). CONCLUSION: Most of the patients treated by prostate brachytherapy conserved orgasm after treatment. However, most of the patients described a deterioration of the quality of orgasm.

[Cardiovascular risks with prostate cancer hormonal treatment: rationale for a department of oncocardiology]. / Risques cardiovasculaires avec les hormonothérapies pour cancer de la prostate : rationnel pour une unité oncocardiologique.

Prostate cancer, the most frequent cancer in man, is an adenocarcinoma sensible to chemical castration in more than 80% of cases due to its hormonal dependency. Androgen deprivation is the treatment for advanced cancer and can be associated with radiotherapy locally or in locally advanced situations. Multidisciplinary therapeutic choice depends on patient age and co-morbidities and clinical stage. The impact of hormonal treatment confers varied side effects and cardiovascular effects are now better known. Responsible mechanisms of this cardiotoxicity are at the same time direct but also indirect by metabolic thermogenic effects. Analysis of these clinical or biological effects, their correlations to the used type of hormonal treatment and the possible precautions of prescription will be detailed in this analysis of the literature. The collaboration of the oncologist or the urologist with the cardiologist becomes necessary and the existence of a unit of oncocardiology could improve the evaluation of the risk-benefit balance and the tolerance of the treatment.

Activation of Flk-1/KDR mediates angiogenesis but not hypotension.

OBJECTIVE: The concept of therapeutic angiogenesis with vascular endothelial growth factor (VEGF) has been validated in peripheral arterial disease. Its use in myocardial ischemia may be delayed as the result of the description in a porcine model of peripheral vasodilation after intraluminal injections of VEGF resulting in a 50% fatality rate by hypotension. We carried out this study to test whether VEGF-induced hypotension (1) is species specific, (2) is mediated by the receptor mediating angiogenesis, (3) is prevented by inhibition of nitric oxide synthase. METHODS: In the rabbit corneal pocket assay we tested whether a previously published anti-idiotypic antibody (AIA) agonist of the VEGF receptor Flk-1/KDR could elicit angiogenesis. Various doses of recombinant VEGF or AIA were injected into anesthetized normotensive Wistar-Kyoto rats and the mean arterial blood pressure (MABP) was recorded. To test the implication of nitric oxide in VEGF-induced hypotension we treated the animals with a competitive inhibitor of nitric oxide synthase prior to the injection of VEGF. RESULTS: Both VEGF and AIA induce angiogenesis but only intravenous injections of VEGF induced a rapid, transient and dose-dependent decrease in MABP. The ED50 was 0.5 micrograms. The interval between two VEGF injections required to lead to a decrease of MABP was 40 minutes. Nitric oxide synthesis inhibitor prevented, in a reversible fashion, the effect of VEGF. CONCLUSION: VEGF-induced hypotension is not species specific. It is prevented by nitric oxide inhibition. VEGF-induced angiogenesis and hypotension are not mediated in vivo by the same VEGF receptor.

Vascular endothelial growth factor is an autocrine growth factor for hair dermal papilla cells.

The transition of the late anagen to the catagen phase is concomitant with the disappearance of perifollicular capillaries, and therefore cyclical hair growth might depend on the ability of the dermal papilla to synthesize and release soluble growth and differentiation factors toward pre-existing capillaries. We characterized an angiogenic growth factor in the conditioned medium of dermal papilla cells indistinguishable from vascular endothelial growth factor as judged by biochemical and immunologic criteria. In addition, these cells bind vascular endothelial, growth factor on two binding sites and proliferate or migrate in the presence of this growth factor. Moreover, neutralizing antibodies inhibit these biologic effects, confirming that vascular endothelial growth factor might contribute to hair growth either by acting directly on papilla cells or by stimulating the local vascularization.

[Predicting prostate cancer with dynamic endorectal coil MR and proton spectroscopic MR imaging]. / Détection du cancer de la prostate par IRM endorectale dynamique et spectroscopique-proton.

PURPOSE: Determine the feasibility of dynamic gadolinium enhanced MRI and spectroscopic imaging in routine clinical practice using standard equipment and its usefulness for patients with negative biopsies and high degree of suspicion of prostate cancer. PATIENTS AND METHODS: Fifty five patients underwent endorectal MRI using T2W spin echo (SE) imaging, dynamic gadolinium enhanced imaging and proton spectroscopic imaging before repeat US-guided transrectal biopsies. The statistical analysis consisted in the correlation of the results obtained with each of the two MRI techniques and the results of the biopsies in the corresponding prostate lobe. RESULTS: 32 patients were included in the analysis. Biopsies revealed cancer for 15 patients. The statistical analysis showed a lack of significant correlation between T2W-SE imaging and biopsy results. A correlation with statistical significance was found between dynamic gadolinium enhanced imaging and biopsies (p=0,0018) and between spectroscopic imaging results and biopsies in the corresponding lobe (p=0,0001). CONCLUSION: Endorectal MRI with a standard clinical equipment using dynamic gadolinium enhanced imaging and spectroscopic imaging may be used in clinical routine to improve detection and localization in prostate cancer compared to T2 weighted spin echo imaging.

Systemic activation of the vascular endothelial growth factor receptor KDR/flk-1 selectively triggers endothelial cells with an angiogenic phenotype.

The hypothesis that tumor growth is angiogenesis dependent has been documented by a considerable body of direct and indirect experimental data. A prerequisite for the development of novel anti-angiogenic agents is the design of drugs that would be active only on those endothelial cells with an angiogenic phenotype. We took advantage of the anti-idiotypic strategy to obtain circulating agonists specific for the vascular endothelial growth factor receptor KDR/flk-1 (J-IgG). They induced in the absence of VEGF cell proliferation in vitro and angiogenesis in the corneal pocket assay either through local or systemic delivery. Intraperitoneal injections of J-IgG in nude mice grafted with a prostatic adenocarcinoma led to tumor enlargement associated with an increase in both tumor vascularization and proliferation. In contrast KDR/flk-1 overstimulation had no detectable effect on normal tissues. These data underline that KDR/flk-1 is a functional marker of the angiogenic phenotype of endothelial cells.

Cell release of bioactive fibroblast growth factor 2 by exon 6-encoded sequence of vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor which is synthesized and secreted by many differentiated cells in response to various stimuli including hypoxia and growth factor exposure. Alternative splicing of vascular endothelial growth factor mRNA results in three distinct molecular forms: V189 and V165 or V121 which lack the exons 6 or 6 and 7, respectively. To clarify the functions of the 24-amino acid insertion, the biological activity of V165 was compared with that exerted by purified recombinant V189 and a synthetic peptide designed on the sequence encoded by exon 6 (Ex6P). V189 and Ex6P, but not V165, induced cell proliferation on corneal endothelial cells cultured in vitro. These effects were due to the release of fibroblast growth factor 2 (FGF2) stored in the extracellular matrix but not to direct interactions with FGF receptors since V189 was inefficient on heparan sulfate-deficient cells expressing constitutively FGF-R1. Moreover corneas incubated ex vivo with Ex6P solubilized 10-fold more FGF2 than a isocationic peptide containing a scrambled sequence. Ex6P elicited an angiogenic response in a corneal pocket assay which was totally inhibited by addition of anti-FGF2 IgG. Moreover the angiogenic response to V189, but not to V165, was inhibited by FGF2 immunoneutralization. These findings demonstrate that the presence of the exon 6-encoded sequence confers VEGF with the ability to exert its biological effects through FGF2 signaling pathways.

[Modulation of the tumoral progression by anti-idiotypic antibodies of angiogenesis factors]. / Modulation de la progression tumorale par des anticorps anti-idiotypiques de facteurs angiogéniques.

We took advantage of the anti-idiotypic strategy to design circulating probes mimicking the biological effects of VEGF (vascular endothelial growth factor) or FGF2 (fibroblast growth factor 2). The activation of the VEGF receptor KDR/flk-1 induced endothelial cell proliferation but not their migration, whereas that of the FGF receptor FGF-R1 gave opposite results. The long lasting delivery of KDR/flk-1 agonists, but not that of FGF-R1, in nude mice grafted with tumor fragments enhanced the tumor volume. Microscopic examination showed an increase in both the vascularization and the proliferation of cancer cells. In contrast, no difference in cell proliferation was observed within normal tissues.