Our study confirms the excellent clinical outcome of transvesical prostatectomy, and rapid improvement of most subjective and objective parameters during the 4 weeks after surgery. Bladder hypertrophy appears to be significantly reduced after prostate surgery. The urodynamic results in patients who underwent open surgery probably represent the maximum obtainable relief of obstruction and should be considered the reference standard to which all other treatments, including transurethral resection, should aspire.
BackgroundCancer cell adopts peculiar metabolic strategies aimed to sustain the continuous proliferation in an environment characterized by relevant fluctuations in oxygen and nutrient levels. Monocarboxylate transporters MCT1 and MCT4 can drive such adaptation permitting the transport across plasma membrane of different monocarboxylic acids involved in energy metabolism.MethodsRole of MCTs in tumor-stroma metabolic relationship was investigated in vitro and in vivo using transformed prostate epithelial cells, carcinoma cell lines and normal fibroblasts. Moreover prostate tissues from carcinoma and benign hypertrophy cases were analyzed for individuating clinical-pathological implications of MCT1 and MCT4 expression.ResultsTransformed prostate epithelial (TPE) and prostate cancer (PCa) cells express both MCT1 and MCT4 and demonstrated variable dependence on aerobic glycolysis for maintaining their proliferative rate. In glucose-restriction the presence of L-lactate determined, after 24 h of treatment, in PCa cells the up-regulation of MCT1 and of cytochrome c oxidase subunit I (COX1), and reduced the activation of AMP-activated protein kinase respect to untreated cells. The blockade of MCT1 function, performed by si RNA silencing, determined an appreciable antiproliferative effect when L-lactate was utilized as energetic fuel. Accordingly L-lactate released by high glycolytic human diploid fibroblasts WI-38 sustained survival and growth of TPE and PCa cells in low glucose culture medium. In parallel, the treatment with conditioned medium from PCa cells was sufficient to induce glycolytic metabolism in WI-38 cells, with upregulation of HIF-1a and MCT4. Co-injection of PCa cells with high glycolytic WI-38 fibroblasts determined an impressive increase in tumor growth rate in a xenograft model that was abrogated by MCT1 silencing in PCa cells. The possible interplay based on L-lactate shuttle between tumor and stroma was confirmed also in human PCa tissue where we observed a positive correlation between stromal MCT4 and tumor MCT1 expression.ConclusionsOur data demonstrated that PCa progression may benefit of MCT1 expression in tumor cells and of MCT4 in tumor-associated stromal cells. Therefore, MCTs may result promising therapeutic targets in different phases of neoplastic transformation according to a strategy aimed to contrast the energy metabolic adaptation of PCa cells to stressful environments.
Introduction Significantly more women reporting stress urinary incontinence (SUI) or low urinary tract symptoms complained of sexual dysfunction than a general healthy female population. The use of a tension-free vaginal tape (TVT), placed transvaginally under the mid-urethra, ensures to reacquire continence but could affect sexual function. Aim This study aimed to determine if a suburethral tape for the correction of SUI could interfere with sexual activity. Methods Of 108 patients, 37 underwent positioning of a tension free vaginal tape through a retropubic approach (TVT), and 71 through a transobturator approach from outside to inside (TOT). Main Outcome Measures All patients enrolled had a complete urodynamic study and were invited to answer the Female Sexual Function Index questionnaire and our personal questionnaire, before surgery, after 1 month, and then at 3-month intervals. Results Of the 108 patients, 67% of the women experienced incontinence during intercourse, 96% during penetration, and 4% on orgasm. The cure rate for SUI was 97.1%. Sixty-two women (87%) with TOT placement and 31 (84%) with TVT were satisfied with the operation as regards sexual function, 68 (96%) and 29 (78%), respectively, with TOT and TVT had an improvement of urinary symptoms with resolution of urinary leakage during intercourse, after a 12.3-month follow-up. Just one patient treated with a TOT approach and two with the TVT complained of low grade of leakage. Of the 101 sexually active women, 90.1% reported a significant improvement in their sexual life, 9.9% referred a poor sexual activity not due to surgical intervention. Conclusions In the surgical treatment of SUI, it is important to think about the patients' future sexual life and inform them that the great part of women can expect to improve their quality of life.
The activation of epidermal growth factor receptor (EGF-R) plays a key role in the promotion of proliferation and invasion in prostatic carcinoma (PCa). Gefitinib (Iressa; ZD1839), an orally active EGF-R tyrosine kinase inhibitor, has shown an important anti-proliferative activity in tumors expressing EGF-R both in vitro and in vivo. Our aim was to elucidate the role of gefitinib in the modulation of the metastatic spread of PCa cells. The therapeutic role of gefitinib was investigated by evaluating the proliferative and invasive ability of the PCa cell line PC3 and of its high metastatic sub-line, PCb2, by in vitro assays and intracardiac injection in nude mice. The inhibitory effect of gefitinib was tested in vivo by injecting PCa cells subcutaneously or in the left ventricle of nude mice and by administrating daily 150 mg/kg of gefitinib. While xenograft growth was equally reduced in all PCa lines (about 50%), the bone metastasis formation was inhibited especially for the high metastatic PCb2 sub-line (81%) in comparison to PC3 cells (47%). The comparative in vitro analysis among PCa cell lines showed that PCb2 cells were more sensitive to the inhibitory effect of gefitinib in their invasive ability compared to parental PC3 cells but not in their proliferation rate. Moreover, PCb2 cells demonstrated an increased invasive ability in vitro in response to bone stromal cell conditioned medium (BCM). The simultaneous presence of 0.1 ng/ml gefitinib was sufficient to reduce the number of invaded cells in the presence of both EGF and BCM. The molecular characterization of the highly aggressive PCa sub-lines demonstrated that this phenomenon was associated with an increment in uPA/uPAR axis but not in EGF-R expression. In conclusion, our data suggest that the use of gefitinib as a therapeutic agent may be indicated in the control of PCa spreading to bone.
One of the major obstacles in the treatment of hormone-refractory prostate cancer (HRPC) is the development of chemoresistant tumors. The aim of this study is to evaluate the role of azacitidine as chemosensitizing agent in association with docetaxel (DTX) and cisplatin using two models of aggressive prostate cancer, the 22rv1, and PC3 cell lines. Azacitidine shows antiproliferative effects associated with increased proportion of cells in G0/G1 and evident apoptosis in 22rv1 cells and increased proportion of cells in G2/M phase with the absence of acute cell killing in PC3 cells. In vivo, azacitidine (0.8 mg/kg i.p.) reduced tumor proliferation and induced apoptosis in both xenografts upmodulating the expression of p16INKA, Bax, Bak, p21/WAF1, and p27/KIP1, and inhibiting the activation of Akt activity and the expression of cyclin D1, Bcl-2, and Bcl-XL. In vitro treatments with azacitidine lead to upregulation of cleaved caspase 3 and PARP. BCl2 antagonists, such as HA-14-1, enhanced the effects of azacitidine in these two prostate cancer models. In addition, azacitidine showed synergistic effects with both DTX and cisplatin. In vivo this agent caused tumor growth delay without complete regression in xenograft systems. Azacitidine sensitized PC3 and 22rv1 xenografts to DTX and cisplatin treatments. These combinations were also tolerable in mice and superior to either agent alone. As DTX is the standard first-line chemotherapy for HRPC, the development of DTX-based combination therapies is of great interest in this disease stage. Our results provide a rationale for clinical trials on combination treatments with azacitidine in patients with hormone-refractory and chemoresistant prostate tumors.
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