Ploutarchos Anezinis

Activation of membrane androgen receptors potentiates the antiproliferative effects of paclitaxel on human prostate cancer cells

Genomic signaling mechanisms require a relatively long time to get into action and represent the main way through which steroid hormones affect target cells. In addition, steroids may rapidly activate cellular functions by non-genomic signaling mechanisms involving membrane sites. Understanding in depth the molecular mechanisms of the non-genomic action represents an important frontier for developing new and more selective pharmacologic tools for endocrine therapies. In the present study, we report that membrane-impermeable testosterone-bovine serum albumin (BSA) acts synergistically with paclitaxel in modifying actin and tubulin cytoskeleton dynamics in LNCaP (androgen sensitive) and DU-145 (androgen insensitive) human prostate cancer cell lines. In addition, coincubation of either cell line with testosterone-BSA and paclitaxel induced inhibition of cell proliferation and apoptosis. Finally, in vivo experiments in LNCaP and DU-145 tumor xenografts in nude mice showed that both agents decrease tumor mass, whereas testosterone-BSA enhances the effect of paclitaxel. Our findings suggest that chronic activation of membrane androgen receptors in vitro and in vivo facilitates and sustains for a longer time the antitumoral action of cytoskeletal acting agents. [Mol Cancer Ther 2006;5(5):1342–51]

Membrane androgen binding sites are preferentially expressed in human prostate carcinoma cells

BackgroundProstate cancer is one of the most frequent malignancies in males. Nevertheless, to this moment, there is no specific routine diagnostic marker to be used in clinical practice. Recently, the identification of a membrane testosterone binding site involved in the remodeling of actin cytoskeleton structures and PSA secretion, on LNCaP human prostate cancer cells has been reported. We have investigated whether this membrane testosterone binding component could be of value for the identification of prostate cancer.MethodsUsing a non-internalizable testosterone-BSA-FITC analog, proven to bind on membrane sites only in LNCaP cells, we have investigated the expression of membrane testosterone binding sites in a series of prostate carcinomas (n = 14), morphologically normal epithelia, taken from areas of the surgical specimens far from the location of the carcinomas (n = 8) and benign prostate hyperplasia epithelia (n = 10). Isolated epithelial cells were studied by flow cytometry, and touching preparations, after 10-min incubation. In addition, routine histological slides were assayed by confocal laser microscopy.ResultsWe show that membrane testosterone binding sites are preferentially expressed in prostate carcinoma cells, while BPH and non-malignant epithelial cells show a low or absent binding.ConclusionsOur results indicate that membrane testosterone receptors might be of use for the rapid routine identification of prostate cancer, representing a new diagnostic marker of the disease.

Membrane testosterone binding sites in prostate carcinoma as a potential new marker and therapeutic target: Study in paraffin tissue sections

BackgroundSteroid action is mediated, in addition to classical intracellular receptors, by recently identified membrane sites, that generate rapid non-genomic effects. We have recently identified a membrane androgen receptor site on prostate carcinoma cells, mediating testosterone rapid effects on the cytoskeleton and secretion within minutes.MethodsThe aim of this study was to investigate whether membrane androgen receptors are differentially expressed in prostate carcinomas, and their relationship to the tumor grade. We examined the expression of membrane androgen receptors in archival material of 109 prostate carcinomas and 103 benign prostate hyperplasias, using fluorescein-labeled BSA-coupled testosterone.ResultsWe report that membrane androgen receptors are preferentially expressed in prostate carcinomas, and they correlate to their grade using the Gleasons microscopic grading score system.ConclusionWe conclude that membrane androgen receptors may represent an index of tumor aggressiveness and possibly specific targets for new therapeutic regimens.

Intraureteral metallic endoprosthesis in the treatment of ureteral strictures

OBJECTIVE We report our experience on intraureteral metallic stents placement for the treatment of malignant and benign ureteral strictures. METHODS Eight patients (six men and two women) with inoperable malignant or benign ureteral strictures, underwent insertion of metallic stents through percutaneous tracts. Six lesions (three malignant, three benign) involved ureterointestinal anastomoses after cystectomy for bladder cancer and ureteroileal urinary diversion or bladder substitution, and two malignant lesions involved the midureter. Self-expandable stents were used in seven cases and a balloon-expandable stent in the remaining one case. One stent was sufficient in seven ureters, and in one ureter, two overlapping stents were placed. RESULTS Metallic stents were inserted without technical difficulties in all obstructed ureters and patency was achieved in all patients. Ultrasonography revealed resolution of pre-existing hydronephrosis. The duration of follow-up was 6-17 months (mean, 9 months). One ureter was occluded 8 months after stent placement because of ingrowth of tumor and granulation tissue. The other ureters showed no signs of obstruction during follow-up. No major complications directly attributable to the metallic stent occurred. CONCLUSIONS Our results suggest that insertion of a metallic stent in the ureter is feasible and safe for the treatment of benign or malignant ureteral strictures. However, more work needs to be done to establish the use of these stents for the treatment of ureteral obstruction.

Suprapubic versus transrectal ultrasonography in assessing the volume of the prostate and the transition zone in patients with benign prostatic hyperplasia

Abstract. The reliability of suprapubic ultrasonography (SU) in assessing the size of the prostate was examined in 95 patients with benign prostatic hyperplasia (BPH). Volumetric measurements of the prostate and the transition zone of the prostate (TZP) performed by SU were compared with corresponding measurements obtained by transrectal ultrasonography (TU). A very strong correlation was found between suprapubically and transrectally performed measurements for both the total prostate gland (r= 0.948, p < 0.001) and the TZP volume (r= 0.953, p < 0.001). According to the results of this study, SU appears to be as reliable as TU in assessing the size of the prostate and the TZP and may be used effectively in the evaluation of patients with BPH, as it is less cumbersome, better tolerated, and a widely available examination technique.

Cystine stones : The efficacy of percutaneous and shock wave lithotripsy

Cystinuria is a rare cause of renal calculi, whose management presents a complex problem mainly due to the hardness and high recurrence rate of cystine stones. During the period 1987-1991, 28 established cases of cystine calculi were treated by extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolithotripsy (PCNL). These cases were divided into 5 groups, according to the position and size of the stones, and each group then followed a specific regimen, either ESWL monotherapy or a combined treatment comprising an initial ESWL treatment followed by PCNL or vice versa. ESWL monotherapy provided satisfactory results only in the group with pelvic stones (54.5% success rate), with 2.16 stone treatments/renal unit, and only with calculi smaller than 2.5 cm. The groups with multiple stones or staghorn calculi were treated with a combined treatment of ESWL and PCNL and had success rates of 50 and 67%, respectively. However, the group in which PCNL was followed by ESWL showed a clear advantage over the group in which ESWL was administered before PCNL, since it required a smaller number of ESWL treatments (1,5 stone treatments/renal unit as compared to 4.3 stone treatments/renal unit). Finally, attempts for ESWL in situ in the few cases of ureteral stones proved unsuccessful.

Urothelial Carcinoma of the Urinary Bladder in Young Adults: Presentation, Clinical behavior and Outcome

Introduction. There is not much evidence regarding clinical behavior of bladder cancer in younger patients. We evaluated clinical characteristics, tumor recurrence and progression in patients younger than 40 years old with urothelial bladder carcinoma. Methods. We retrospectively reviewed the medical records of 31 patients less than 40 years old who were firstly managed with bladder urothelial carcinoma in our department. Data were analysed with the Chi-square test. Results. Mean age was 31.7 years. Mean followup was 38.52 months (11–72 months). Nineteen (61%) patients were diagnosed with GII and 2 (6%) patients with GIII disease. Five (16%) patients presented with T1 disease. Three (9%) patients with invasive disease underwent cystectomy and adjuvant chemotherapy and one developed metastatic disease. Ten (32%) patients recurred during followup with a disease free recurrence rate of 65% the first 2 years after surgery. From those, 1 patient progressed to higher stage and three to higher grade disease. No patient died during followup. Conclusions. Bladder urothelial carcinoma in patients younger than 40 years is usually low stage and low grade. Management of these patients should be according to clinical characteristics and no different from older patients with the same disease.