Tadalafil and Steroid Hormones Interactions in Adipose, Bone and Prostate Tissues: Focus on Translational Perspectives.

Tadalafil is a selective phosphodiesterase type-5 (PDE5) inhibitor that is approved for the treatment of men with erectile dysfunction (ED) and/or benign prostate hyperplasia (BPH) -associated symptoms. Besides its classical actions on PDE5 within the genitourinary tract, where the specific enzyme expression is maximal, it may exert different systemic effects. This is mainly due to the pleiotropic distribution of PDE5 enzyme throughout the human (and animal) body, where it can exert protective effects in different clinical conditions. Recently, it has been demonstrated that tadalafil may display novel actions on androgen receptor (AR) expression and activity and cytochrome P19a1 (Cyp19a1) and estrogen receptor ß (ERß) expression in different in vitro systems, such as adipose, bone and prostate cancer cells, where it can act as a selective modulator of steroid hormone production. This may determine novel potential mechanism(s) of control in pathophysiologic pathways. In this review, we summarize basic research and translational results applicable to the use of tadalafil in the treatment of obesity, bone loss and prostate cancer.

Oleuropein Counteracts Both the Proliferation and Migration of Intra- and Extragonadal Seminoma Cells.

Recent and growing literature has reported that oleuropein (OLE), the main polyphenol in olive leaf extract, inhibits tumor cell proliferation and reduces the invasiveness properties of cancer cells; therefore, OLE may play a significant role in the development of new drugs for cancer treatment. These antineoplastic properties have been reported in many experimental cancer models, but the effect of OLE on seminoma cells is yet to be evaluated. In the present study, we demonstrate, for the first time, that OLE reduces cell viability in both intra- and extragonadal TCAM-2 and SEM-1 seminoma cells, respectively, in a dose-dependent manner. As shown by Western-blot analysis, OLE exposure reduced cyclin-D1 expression and upregulated p21Cip/WAF1, concomitantly affecting the upstream pathway of NF-κB, leading to the reduction of its nuclear content, thereby suggesting that OLE could modulate cell-cycle regulators by inhibiting NF-κB. Moreover, Annexin V staining revealed that OLE induced apoptosis in cancer cells and upregulated the pro-apoptotic factor BAX. Through wound-healing scratch and transmigration assays, we also demonstrated that OLE significantly reduced the migration and motility of TCAM-2 and SEM-1 cells, and downregulated the expression of TGFß-1, which is known to be the main pro-fibrotic factor involved in the acquisition of the migratory and invasive properties of cancer cells. Collectively, our results indicate that OLE reduces seminoma cell proliferation, promotes apoptosis, and counteracts cell migration and motility. Further studies are needed to explore the molecular mechanisms underlying these observed effects.

The penile duplex ultrasound: How and when to perform it?

BACKGROUND: Because it is a superficial structure, the penis is ideally suited to ultrasound imaging. A number of disease processes, including Peyronie's disease, penile fractures and tumors, are clearly visualized with ultrasound. Baseline and dynamic assessment of cavernosal arterial changes after pharmaco-stimulation with alprostadil allows standardized diagnosis of arterial and venogenic causes of erectile dysfunction (ED). OBJECTIVE: To illustrate how to correctly perform flaccid and dynamic penile duplex ultrasound (D-PDU) and in which patients to recommend it. MATERIALS/METHODS: An extensive search of the literature was carried out on Pubmed with the insertion of the following Medical Subjects Headings (MeSH) terms and keywords "penile color Doppler ultrasound" "peak systolic velocity" "end-diastolic velocity", "acceleration time", "resistance index". EVIDENCE: In our experience, arterial erectile dysfunction is identified after standardized intracavernous injection (ICI) of alprostadil (10 mcg) when values of peak systolic velocity (PSV) are <35 cm/s and, in the most severe forms, for values <25 cm/s. Arterial insufficiency can also be identified by increased acceleration time (AT) values (>110 ms) and/or by a lack of visualization of helicine arteries at power Doppler mode along with incomplete achievement of penile rigidity. The veno-occlusive incompetence is determined when end-diastolic velocity (EDV) values are >4.5-5 cm/s or in the case of resistance index (RI) values <0.75. The assessment of additional surrogate markers of endothelial dysfunction, that is, intima-media thickness, mean platelet volume (MPV), endothelial progenitor cells (EPC), endothelial cell specific molecule-1(endocan) are also useful in assessing the patient's cardiovascular risk but are still considered investigational in the interpretation of D-PDU results. CONCLUSION: D-PDU scan after ICI with vasoactive drugs is a safe procedure and represents the gold standard for the diagnostics of penile pathologies and should be performed in men with ED not responding to oral conventional therapies and/or in those requiring accurate stratification of cardiovascular risk.

Overexpression of p75NTR in Human Seminoma: A New Biomarker?

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr = 40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in seminoma tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker for seminoma and staging in TGCTs.