Growing evidence supports the pivotal role played by periprostatic adipose tissue (PPAT) in prostate cancer (PCa) microenvironment. We investigated whether PPAT can affect response to Docetaxel (DCTX) and the mechanisms associated. Conditioned medium was collected from the in vitro differentiated adipocytes isolated from PPAT which was isolated from PCa patients, during radical prostatectomy. Drug efficacy was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide citotoxicity assay. Culture with CM of human PPAT (AdipoCM) promotes DCTX resistance in two different human prostate cancer cell lines (DU145 and PC3) and upregulated the expression of BCL-xL, BCL-2, and TUBB2B. AG1024, a well-known IGF-1 receptor inhibitor, counteracts the decreased response to DCTX observed in presence of AdipoCM and decreased TUBB2B expression, suggesting that a paracrine secretion of IGF-1 by PPAT affect DCTX response of PCa cell. Collectively, our study showed that factors secreted by PPAT elicits DCTX resistance through antiapoptotic proteins and TUBB2B upregulation in androgen independent PCa cell lines. These findings reveal the potential of novel therapeutic strategies targeting adipocyte-released factors and IGF-1 axis to overcome DCTX resistance in patients with PCa.
Abstract Implantation of inflatable penile prosthesis should be considered as a definitive treatment of erectile dysfunction. However, the sole procedure might not allow for optimal dimensional and functional outcomes. The aim of this study was to systematically review the literature and present the findings on the optimal choice of perioperative methods, surgical techniques, and pharmacotherapy to improve penile length, curvature, and erectile function. Fifteen studies and 697 men were included. Nine studies focused on intraoperative techniques only, while 6 described intra- and postoperative methods. Regarding the outcomes, curvature of the penis was reported in 12 studies, penile length in 5 studies, penile girth in 2 studies, and the International Index of Erectile Function-5 (IIEF-5) score in 7 studies. According to this systematic review, extreme angulation can be reduced using plaque/corporal incisions and grafting with collagen fleece, as well as “scratch” technique with postoperative vacuum therapy. Also, among patients with preoperative curvature of approximately 30°–40°, penile plication, corporoplasty, tunica expansion procedure, manual, and at-home modeling can provide good results. In addition, corporal incisions plus grafting, as well as postoperative vacuum therapy might be the most beneficial in terms of length improvement. Importantly, penile implant in combination with the sealing, daily, and early prosthesis activation proved to improve length. Moreover, postoperative vacuum therapy has also been shown to greatly increase penile circumference. Finally, penile implant in combination with the sealing, corporal incisions plus grafting, “scratch” technique, vacuum therapy, and phosphodiesterase-5 inhibitor are all associated with major improvements in sexual function.
To assess the value of bone scintigraphy and 18F-fluorocholine PET/computed tomography (CT) in predicting outcome in patients with prostate cancer and bone metastases treated with 223radium.Retrospective analysis of 48 patients that underwent 223radium therapy. End points were pain relief and overall survival.After therapy, pain relief was observed in 27 patients. Patients without pain relief had more bone lesions at PET/CT than at bone scintigraphy (pretherapy imaging mismatch). In 39 patients who completed treatment protocol, post-therapy alkaline phosphatase and pretherapy imaging mismatch were independent predictors of poor overall survival.Patients with more lesions at 18F-fluorocholine PET/CT than at bone scintigraphy had a poor prognosis. The combined imaging approach could be useful to predict outcome after 223radium therapy.
Among risk factors (apart from smoking) likely involved in bladder cancer (BCa), metabolic syndrome (MS), obesity and type 2 diabetes mellitus (T2DM) have been explored with contrasting results. In spite of these studies, there is little data on the association between nonalcoholic fatty liver disease (NAFLD), its main driver, i.e., insulin resistance (IR), and BCa. Implanting a cross-sectional retrospective study we tried to investigate both NAFLD and IR prevalence in a hospital based population of BCa patients. We studied laboratory data from 204 patients with histologically confirmed non metastatic BCa and 50 subjects with no BCa, but with bladder diseases (no Ca BD). We evaluated the presence of NAFLD by the triglycerides/glucose Index (TyG Index), using a cut-off of 0.59 and by the Aspartate Aminotransferase/Alanine Aminotransferase AST/ALT ratio. IR was assessed by the same TyG Index (cut-off 4.68) and the triglycerides/High-Density Lipoprotein HDL ratio (cut-off 2.197). The diagnosis of impaired fasting glucose (IFG), condition of prediabetes, as well as that of T2DM was assessed according to canonical guidelines. The TyG Index predicted NAFLD presence in both groups (p = 0.000), but the BCa group showed a major percentage of NAFLD cases with respect to no Ca BD group (59% versus 40%). A greater proportion of IR (47%) in BCa group than in no Ca BD one (37%) was evidenced by the TyG Index with its median value significantly different (p = 0.0092). This high rate of IR in the BCa group was confirmed by the triglycerides/HDL ratio (p = 0.02). Prediabetes and T2DM were more prevalent in the BCa group than no Ca BD group (p = 0.024). In this study a consistent NAFLD presence was found in BCa patients. This is an important comorbidity factor that deserves further consideration in prospective studies. The higher prevalence of NAFLD, IR, prediabetes and T2DM in the BCa group evidences the need that these disorders should be reckoned as adjunct factors that could impact on this cancerous disease.
We aimed to compare the efficacy of tamsulosin 0.4 mg once a day alone and the combination therapy involving tamsulosin 0.4 mg once a day plus the complementary and alternative medicine consisting of vitamins (C and D), herbal products (Cucurbita maxima, Capsicum annum, Polygonum capsicatum) and amino acid L-Glutamine bid in patients with lower urinary tract symptoms related to benign prostatic hyperplasia (LUTS/BPH).We performed a retrospective matched paired comparison. The clinical records of LUTS/BPH patients who underwent medical therapy with tamsulosin 0.4 mg/day plus the complementary and alternative medicine consisting of vitamins (C and D), herbal products (Cucurbita maxima, Capsicum annum, Polygonum capsicatum) and amino acid L-Glutamine bid between January 2019 to September 2019 were reviewed (Group 1). These patients were compared in a 1:1 fashion with LUTS/BPH patients who underwent therapy with tamsulosin 0.4 mg/day alone (Group 2). Total, storage, voiding and Quality of Life (QoL) international prostate symptom (IPSS) score, as well as overactive bladder (OAB)-v8 score and treatment- related adverse events recorded at 40 days follow-up in both groups were compared.At 40 days follow-up mean total, storage, voiding and QoL IPSS sub-scores as well as OAB-v8 score significantly improved in both groups. Intergroup comparison showed statistically significant lower mean total IPSS score (11.6 vs 12.4, p = 0.04) mean storage IPSS sub-score (6.5 vs 7.5, p = 0.01), and mean OAB v8 score (16.7 vs 18.8, p = 0.03) in patients in the Group 1.The combination of tamsulosin 0.4 mg/die plus the complementary and alternative medicine consisting of vitamins (C and D), herbal products (Cucurbita maxima, Capsicum annum, Polygonum capsicatum) and amino acid LGlutamine bid provides statistically significant advantages in terms of storage LUTS improvements in patients with LUTS/BPH compared to tamsulosin 0.4 mg/day alone. These findings are preliminary and further prospective studies on a greater number of patients are needed to confirm it.
