sildenafil-citrate and Carcinoma

Recent studies have revealed in normal thyroid tissue the presence of the transcript of several phosphodiesterases (PDEs), enzymes responsible for the hydrolysis of cyclic nucleotides. In this work, we analyzed the expression of PDE5 in a series of human papillary thyroid carcinomas (PTCs) presenting or not BRAF V600E mutation and classified according to ATA risk criteria. Furthermore, we tested the effects of two PDE5 inhibitors (sildenafil, tadalafil) against human thyroid cancer cells. PDE5 gene and protein expression were analyzed in two different cohorts of PTCs by real-time PCR using a TaqMan micro-fluid card system and Western blot. MTT and migration assay were used to evaluate the effects of PDE5 inhibitors on proliferation and migration of TPC-1, BCPAP, and 8505C cells. In a first series of 36 PTCs, we found higher expression levels of PDE5A in tumors versus non-tumor (normal) tissues. PTCs with BRAF mutation showed higher levels of mRNA compared with those without mutation. No significant differences were detected between subgroups with low and intermediate ATA risk. Upregulation of PDE5 was also detected in tumor tissue proteins. Similar results were obtained analyzing the second cohort of 50 PTCs. Moreover, all tumor tissues with high PDE5 levels showed reduction of Thyroglobulin, TSH receptor, Thyroperoxidase, and NIS transcripts. In thyroid cancer cells in vitro, sildenafil and tadalafil determined a reduction of proliferation and cellular migration. Our findings demonstrate for the first time an overexpression of PDE5 in PTCs, and the ability of PDE5 inhibitors to block the proliferation of thyroid cancer cells in culture, therefore, suggesting that specific inhibition of PDE5 may be proposed for the treatment of these tumors.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Papillary; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cyclic Nucleotide Phosphodiesterases, Type 5; Female; Humans; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Proto-Oncogene Proteins B-raf; Sildenafil Citrate; Tadalafil; Thyroid Cancer, Papillary; Thyroid Neoplasms; Young Adult

To assess sexual dysfunction in sexually active men after radical cystectomy (RC) and to determine whether sildenafil citrate can improve erectile dysfunction after surgery.. The baseline and follow-up data from 49 sexually active male patients (mean age 57.8 +/- 9.1 years) undergoing RC (1995 to 2002) were obtained. Of the 49 patients, 16 (33%) had undergone nerve-sparing RC; 38 (78%) had undergone orthotopic diversion; 8 (16%) had undergone ileal conduit diversion; and 3 (6%) had undergone cutaneous continent diversion. The data were assessed using the abridged 5-item International Index of Erectile Function questionnaire, referred to as the Sexual Health Inventory for Men (SHIM).. At a mean follow-up of 47.6 +/- 22.7 months, the total mean SHIM score decreased from 22.08 +/- 3.96 to 4.33 +/- 5.72 after RC (P <0.05). Of the 49 patients, 42 (86%) did not have erections sufficient for vaginal penetration. Of these 42 patients, 22 (52%) tried sildenafil citrate. Of these 22 patients, only 2 (9%) responded positively, with a total mean SHIM score of 23.50 +/- 2.12. Although the mean SHIM score after orthotopic substitution (5.24 +/- 6.21) was statistically significant compared with that after ileal conduit (1.13 +/- 0.33) and cutaneous continent (1.33 +/- 0.58) diversions, this was not clinically significant.. Male erectile dysfunction after RC is a prevalent problem. In our series, only 9 (14%) of 49 sexually active men were potent after surgery. Of these 9 potent patients, 8 (89%) had undergone nerve-sparing RC. Of concern, only 52% of the patients with erectile dysfunction sought treatment after RC.

Topics: Aged; Carcinoma; Comorbidity; Coronary Disease; Cystectomy; Diabetes Mellitus; Drug Evaluation; Drug Resistance; Erectile Dysfunction; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Patient Acceptance of Health Care; Patient Satisfaction; Peripheral Nerve Injuries; Piperazines; Purines; Quality of Life; Sildenafil Citrate; Spouses; Sulfones; Surveys and Questionnaires; Urinary Bladder Neoplasms; Urinary Diversion