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OBJECTIVE To assess the efficacy of silodosin as second-line α-blocker monotherapy in patients with lower urinary tract symptoms as a result of benign prostatic hyperplasia. METHODS Men who were given an α-blocker other than silodosin for ≥8 weeks, aged ≥50 years, had a total International Prostate Symptom Score ≥13 and quality of life index ≥4 were enrolled. After treatment with 8 mg/day silodosin for 8 weeks, symptoms and treatment satisfaction were assessed. If the patients still complained and hoped for readministration of the first-line α-blocker, the previous medication was administered again for 8 weeks in the case of persisting symptoms, and efficacy was again evaluated. RESULTS A total of 73 patients were enrolled and analyzed at 8 weeks. Silodosin administration significantly improved the International Prostate Symptom Score and Overactive Bladder Symptom Score. The quality of life index was improved by at least 1 point in 49.3% patients, and its mean change was significantly greater in the group with previous naftopidil treatment than in those with tamsulosin. A total of 59 patients hoped to continue silodosin, and 13 requested administration of the first-line α-blocker. Previously taking naftopidil and having a shorter duration of prior α-blocker treatment at baseline were associated with silodosin continuation. Although prior α-blocker readministration in the 13 patients did not show significant efficacy, six preferred to continue the previous α-blocker. CONCLUSIONS Silodosin represents an effective second-line α-blocker monotherapy, even in those who still have moderate lower urinary tract symptoms.

An 81-year-old man with castration-resistant prostate cancer experienced general fatigue while receiving enzalutamide treatment. In some patients we encountered the enzalutamide treatment had to be interrupted or the dose decreased because of this adverse effect. We evaluated the patient's general fatigue using the Cancer Fatigue Scale (CFS) score and clarified the quantitative information about his general fatigue. In order to maintain the optimal dose, we advised the patient to take enzalutamide at night. This alleviated the adverse effect, and he could maintain the optimal dose of this medicine. We compared the CFS score before and after switching to nighttime treatment and found improvement. This is the first report of a CFS-based evaluation of the improvement in general fatigue caused by enzalutamide by switching to nighttime treatment.

Objectives To evaluate urine loss ratio after catheter removal as a predictive factor of urinary continence after radical prostatectomy. Methods A total of 190 patients who had undergone retropubic radical prostatectomy were evaluated. Urine loss ratio was measured using the 24-h pad test during 7 consecutive days after removal of urethral catheters. Continence rates at 1, 3, 6 and 12 months after operation were evaluated with the urinary function domain of the University of California, Los Angeles Prostate Cancer Index. The desirable urine loss ratio for continent condition at 12 months after the operation was calculated. As desirable target urine loss ratio continence at 12 months was determined by using logistic analysis. Results Continence rates of all patients at 1, 3, 6 and 12 months after surgery were 13%, 37.8%, 58.9%, and 85.8%, respectively. Continence rates of patients who achieved ≤1% of urine loss ratio within 7 days or ≤5% urine loss ratio within 3 days after catheter removal was 100% at 12 months. Logistic regression analysis proved these urine loss ratio values were significant predictors of continence at 12 months. Conclusions Urine loss ratio after catheter removal within 7 days is a significant determinant of urinary continence after radical prostatectomy. This parameter could have clinical usefulness to estimate future recovery of urinary continence.

Objectives To determine the efficacy of two α1-adrenoceptor antagonists with different affinities for α1-adrenoceptor subtypes, silodosin and naftopidil, in the treatment of premature ejaculation. Methods This was a prospective, open-label, multicenter trial. A total of 26 patients with untreated acquired premature ejaculation were enrolled. Premature ejaculation was defined based on the International Society for Sexual Medicine recommendation. Patients self-administered on demand silodosin 4 mg or naftopidil 25 mg 1 h before intercourse, alternating drugs at least three times each. Clinical global impression change for premature ejaculation, premature ejaculation profile, and intravaginal ejaculation latency time were evaluated at baseline and during treatment. Results Due to clinical global impression change, 24 patients (92%) and 12 patients (46%) reported improvement in their own premature ejaculation problems under silodosin and nafitopidil administration, respectively. Silodosin treatment produced a significantly higher improvement rate compared with naftopidil (P = 0.0002). Objectively, silodosin significantly prolonged intravaginal ejaculation latency time compared with baseline and naftopidil (P < 0.01). Mean intravaginal ejaculation latency times were 1.9, 4.1, and 7.6 min at baseline, control and with silodosin, respectively. The rate of reduced semen volume during silodosin treatment was higher than during naftopidil treatment. There were no adverse systemic effects in either group. Conclusions Silodosin, a highly selective α1A-adrenoceptor antagonist, produces greater improvements in premature ejaculation profiles and related symptoms along with intravaginal ejaculation latency time in acquired premature ejaculation patients with or without erectile dysfunction. This result supports the clinical use of silodosin as an alternative treatment for premature ejaculation.

Premature ejaculation is a common sexual problem, as is erectile dysfunction. We evaluated silodosin, a highly selective α1A-adrenoceptor antagonist, as a new treatment option for premature ejaculation. α1-Adrenoceptor antagonists are widely used for lower urinary tract symptoms, and clinical studies on silodosin have shown excellent clinical efficacy for lower urinary tract symptoms. However, compared with other α1-adrenoceptor antagonists, silodosin appeared to suppress ejaculation in a relatively higher percent of trial participants. This suppression of ejaculation by silodosin suggested its potential for treating premature ejaculation. Consequently, we evaluated the feasibility of off-label silodosin as a new treatment option for premature ejaculation. Eight patients suffering premature ejaculation were treated with silodosin. Silodosin (4 mg) was given 2 h before sexual intercourse. Intravaginal ejaculatory latency time, premature ejaculation profile item, clinical global impression change in premature ejaculation and systemic adverse events were recorded. Intravaginal ejaculatory latency time was significantly prolonged (from 3.4 min to 10.1 min, P = 0.003). All patients answered better (much better) or slightly better for their own premature ejaculation problem compared with pretreatment condition in the clinical global impression change. Premature ejaculation profile also significantly improved. Two (25%), three (37.5%) and seven patients (87.5%) experienced anejaculation, reduced semen volume and discomfort during orgasm, respectively. However, these problems were not of major concern for the participants. No systemic adverse effects were reported. The current results support the possible use of silodosin as a new treatment option for premature ejaculation, and suggest that a placebo controlled study assessing its clinical usefulness would be worthwhile.

Murine leukemia virus (MLV)-based replication-competent retrovirus (RCR) vectors have been shown to mediate efficient, selective, and persistent tumor transduction, thereby achieving significant therapeutic benefit in a wide variety of cancer models. To further augment the efficiency of this strategy, we have developed a delivery method employing a gutted adenovirus encoding an RCR vector (AdRCR); thus, tumor cells transduced with the adenoviral vector transiently become RCR vector producer cells in situ. As expected, high-titer AdRCR achieved significantly higher initial transduction levels in human cancer cells both in vitro and in vivo, as compared to the original RCR vector itself. Notably, even at equivalent initial transduction levels, more secondary RCR progeny were produced from AdRCR-transduced cells as compared to RCR-transduced cells, resulting in further acceleration of subsequent RCR replication kinetics. In pre-established tumor models in vivo, prodrug activator gene therapy with high-titer AdRCR could achieve enhanced efficacy compared to RCR alone, in a dose-dependent manner. Thus, AdRCR hybrid vectors offer the advantages of high production titers characteristic of adenovirus and secondary production of RCR in situ, which not only accelerates subsequent vector spread and progressive tumor transduction, but can also significantly enhance the therapeutic efficacy of RCR-mediated prodrug activator gene therapy.

Transplantation of many tissues requires histocompatibility matching of human leukocyte antigens (HLA) to prevent graft rejection, to reduce the level of immunosuppression needed to maintain graft survival, and to minimize the risk of graft-versus-host disease, particularly in the case of bone marrow transplantation. However, recent advances in fields of gene delivery and genetic regulation technologies have opened the possibility of engineering grafts that display reduced levels of HLA expression. Suppression of HLA expression could help to overcome the limitations imposed by extensive HLA polymorphisms that restrict the availability of suitable donors, necessitate the maintenance of large donor registries, and complicate the logistics of procuring and delivering matched tissues and organs to the recipient. Accordingly, we investigated whether knockdown of HLA by RNA interference (RNAi), a ubiquitous regulatory system that can efficiently and selectively inhibit the expression of specific gene products, would enable allogeneic cells to evade immune recognition. For efficient and stable delivery of short hairpin-type RNAi constructs (shRNA), we employed lentivirus-based gene transfer vectors, which provide a delivery system that can achieve integration into genomic DNA, thereby permanently modifying transduced graft cells. Our results show that lentivirus-mediated delivery of shRNA targeting pan-Class I and allele-specific HLA can achieve efficient and dose-dependent reduction in surface expression of HLA in human cells, associated with enhanced resistance to alloreactive T lymphocyte-mediated cytotoxicity, while avoiding MHC-non-restricted killing. We hypothesize that RNAi-induced silencing of HLA expression has the potential to create histocompatibility-enhanced, and, eventually, perhaps "universally" compatible cellular grafts.

Background A 29-year-old male patient presented with a history of painless enlargement of the left hemiscrotum. Investigations Laboratory tests for β-human chorionic gonadotrophin, α-fetoprotein, and lactate dehydrogenase, physical examination, and CT of the chest, abdomen and pelvis. Histologic examination, nerve-sparing retroperitoneal lymph-node dissection. Diagnosis Paratesticular rhabdomyosarcoma with lymph node metastasis. Management Inguinal radical orchiectomy and adjuvant chemotherapy for 48 weeks. Radiotherapy and additional chemotherapy were administered following local recurrence.

We previously reported that gelsolin gene expression is reduced in various tumors. In an effort to gain further insights into the mechanism of gelsolin downregulation in tumors, we examined the in vivo properties of the gelsolin promoter in urinary bladder cancer cell lines. Neither mutation nor hypermethylation were responsible for gene silencing at the promoter. After exposure to trichostatin A (TSA), a histone deacetylase inhibitor, gelsolin promoter activity was markedly enhanced in the cancer cells not in cells derived from normal tissue. Chromatin immunoprecipitation (ChIP) assays revealed that both histones H3 and H4 were hypoacetylated in the promoter region of the cancer cells, and the accumulation of acetylated histones were detected by TSA treatment. In vivo footprinting analysis revealed the presence of dimethylsulfate (DMS) hypersensitive site in the untranslated region around nucleotide -35 only in the cancer cells but not in cells derived from normal tissue, and analysis of KMnO4 reactive nucleotides showed that the stem loop structure could be formed in vivo of the cancer cells. This novel stem loop structure may play a part in regulating the transcription of the gelsolin gene in the cancer cells. .. These results suggest that nucleosome accessibility through histone deacetylation and structural changes (DMS hypersensitivity and stem loop structure) in the promoter region form the basis of the mechanism leading to the silencing of gelsolin gene in human bladder cancer.

Background: Intravesical bacillus Calmette-Guerin (BCG) therapy has been proven to be effective in the prophylaxis and treatment of superficial bladder cancer. However, several complications of BCG therapy have been reported. The aim of this study was to clarify the impact of BCG treatment-related side effects on the clinical outcome of patients with superficial urothelial cancer. Methods: We reviewed the medical records of 33 patients who underwent BCG instillation therapy in our department. After complete endoscopic tumor resection, intravesical or intrapelvic instillation of BCG (80 mg of the Tokyo strain) was performed every week for 8 weeks. BCG treatment-related side effects were classified as minor (persistence of symptoms or low-grade fever for less than 48 h) or major (persistence of symptoms or low-grade fever for more than 48 h, or high fever). Risk factors for major side effects and relationships between the occurrence of major side effects and subsequent tumor progression were evaluated. Results: In total, there were 43 courses of intravesical and intrapelvic instillations of BCG in 33 patients, 20 (46%) of which were associated with major side effects. Risk factors associated with the occurrence of major side effects could not be detected. Subsequent tumor progression was observed in 3 of the 16 patients (19%) with major side effects and in 10 of the 17 patients (59%) without them. Nine patients who discontinued BCG therapy because of major side effects experienced no tumor progression. Progression-free survival was significantly higher in patients with major side effects than in those without them. Conclusions: These results suggest that BCG therapy should be discontinued whenever major side effects occur, because this does not necessarily lead to an unfavorable outcome regarding tumor progression.

Unmatched human leukocyte antigens (HLA) expressed by allogeneic donor cells are the major target for immunological rejection. In order to reduce the immunogenicity of allograft cells, we have developed lentiviral vectors for delivery of short hairpin ribonucleic acid (shRNA) against Class I HLA. This approach was evaluated in both an established human embryonic kidney cell line and primary human CD34+ hematopoietic stem/progenitor cells. Target cells transduced with lentiviral vectors expressing either HLA-A*0201 allele-specific or HLA-A, -B, -C consensus sequence-specific shRNA showed effective knockdown of cell surface HLA expression. Mixed lymphocyte-target cell reactions showed significantly reduced interferon-gamma production from alloreactive cytotoxic T lymphocytes and significantly reduced levels of target cell apoptosis after shRNA-mediated knockdown of HLA expression and target cell survival correlated with vector transduction efficiency. Furthermore, increasing resistance to complement-dependent cytotoxicity mediated by anti-HLA antibodies was observed to correlate with increasing levels of shRNA vector transduction in primary human CD34+ cells. Notably, non-HLA restricted killing by lymphokine-activated killer cells was not incurred after HLA knockdown. These data demonstrate the potential for genetic engineering strategies targeting incompatible HLA alleles to reduce both cellular and humoral responses and enable graft survival after transplantation of allogeneic cells and tissues.

Lymphoepithelioma-like carcinoma (LELC), best known to occur in the nasopharynx, can arise in a variety of sites, such as the salivary gland, thymus, lung, stomach, skin and uroepithelium. Primary LELC of the uroepithelium is very rare and there is only limited information in the published reports. We managed a case of a 75-year-old woman who presented with nausea and gross painless hematuria. She was treated with laparoscopic nephroureterectomy and was diagnosed with a T1N1M0 LELC of the renal pelvis. Unlike nasopharyngeal lymphoepithelioma, immunohistochemical analysis of this urinary LELC was negative for the Epstein-Barr virus. Herein we report on one more case of primary LELC of the renal pelvis and review of the published reports, particularly those concerning Epstein-Barr virus expressions. Recognition of this tumor and complete resection are essential for saving patients.

Background Therapeutic gene transfer is currently being evaluated as a potential therapy for inflammatory bowel disease. This study investigates the safety and therapeutic benefit of a locally administered lentiviral vector encoding murine interleukin-10 in altering the onset and relapse of dextran sodium sulfate induced murine colitis. Methods Lentiviral vectors encoding the reporter genes firefly-luciferase and murine interleukin-10 were administered by intrarectal instillation, either once or twice following an ethanol enema to facilitate mucosal uptake, on Days 3 and 20 in Balb/c mice with acute and relapsing colitis induced with dextran sulfate sodium (DSS). DSS colitis was characterized using clinical disease activity, macroscopic, and microscopic scores. Bioluminescence optical imaging analysis was employed to examine mucosal lentiviral vector uptake and transgene expression. Levels of tumor necrosis factor-α and interleukin-6 in homogenates of rectal tissue were measured by ELISA. Biodistribution of the lentiviral vector to other organs was evaluated by real time quantitative PCR. Results Mucosal delivery of lentiviral vector resulted in significant transduction of colorectal mucosa, as shown by bioluminescence imaging analysis. Lentiviral vector-mediated local expression of interleukin-10 resulted in significantly increased levels of this cytokine, as well as reduced levels of tumor necrosis factor-α and interleukin-6, and significantly reduced the clinical disease activity, macroscopic, and microscopic scores of DSS colitis. Systemic biodistribution of locally instilled lentiviral vector to other organs was not detected. Conclusions Topically-delivered lentiviral vectors encoding interleukin-10 safely penetrated local mucosal tissue and had therapeutic benefit in this DSS model of murine colitis.

To evaluate urine loss ratio after catheter removal as a predictive factor of urinary continence after radical prostatectomy.A total of 190 patients who had undergone retropubic radical prostatectomy were evaluated. Urine loss ratio was measured using the 24-h pad test during 7 consecutive days after removal of urethral catheters. Continence rates at 1, 3, 6 and 12 months after operation were evaluated with the urinary function domain of the University of California, Los Angeles Prostate Cancer Index. The desirable urine loss ratio for continent condition at 12 months after the operation was calculated. As desirable target urine loss ratio continence at 12 months was determined by using logistic analysis.Continence rates of all patients at 1, 3, 6 and 12 months after surgery were 13%, 37.8%, 58.9%, and 85.8%, respectively. Continence rates of patients who achieved ≤1% of urine loss ratio within 7 days or ≤5% urine loss ratio within 3 days after catheter removal was 100% at 12 months. Logistic regression analysis proved these urine loss ratio values were significant predictors of continence at 12 months.Urine loss ratio after catheter removal within 7 days is a significant determinant of urinary continence after radical prostatectomy. This parameter could have clinical usefulness to estimate future recovery of urinary continence.

Erectile dysfunction following radical prostatectomy (RP) is still a significant burden as a post-operative morbidity, despite advances in nerve-sparing techniques and penile (erectile function) rehabilitation (PR) programs. We assessed the effects of stimulation with the masturbation device "EGG" on enhancement of erectile response along with administration of phospho diesterase type 5 inhibitor. We also studied the change of self-esteem and motivation for continuation of PR after stimulation with EGG. Eight nonresponders for PDE5-I who underwent retropubic RP were enrolled. Patients' median age was 71.5 years old. No patients received adjuvant therapy for prostate cancer. The patients' erectile response in the penile rehabilitation session (masturbation) with PDE5-I＋manual stimulation and PDE5-I＋stimulation with EGG were evaluated by erection hardness score (EHS). Changes of self-esteem and motivation for penile rehabilitation were assessed by the self-esteem subscale of the Self-Esteem and Relationship (SEAR) questionnaire and one original question, respectively. PDE5-I ＋ stimulation with EGG significantly enhanced EHS compared to PDE5-I＋manual stimulation in the eight patients (p＝0.027). Transformed score of self-esteem subscale score of SEAR questionnaire was significantly increased in the PR session with EGG compared to the PR session with manual stimulation (p＝0.043). Six patients who showed a better erectile response with EGG retained motivation for continuation of PR. PDE5-I＋stimulation with EGG improved the erectile response in post-RP patients. EGG as a masturbation device may have a potential for contribution to successful PR.

To determine the follow-up schedule in patients with non-muscle-invasive bladder cancer who had remained recurrence-free for 5 or more years, we retrospectively reviewed 258 patients with Ta and T1 bladder cancer who had been free of recurrence for at least 5 years. Of these 258 patients, subsequent recurrences developed in 100 patients. In spite of our recommendation that cystoscopic follow-up be done at 12-month intervals for patients who remained recurrence-free for more than 5 years, 45 had been followed at intervals of more than 12 months (range, 13-77 months) when the recurrences were found. Of 100 recurrent tumors, 20 (20.0%) showed bladder muscle invasion. Muscle-invasive cancer was identified more often in the patients with cytoscopic intervals of more than 12 months than in those of less than 12 months (35.6% versus 7.3%). Therefore, we recommend that cystoscopy be performed at intervals of less than 12 months in patients with non-muscle invasive bladder cancer for recurrence detection before tumors become muscle invasive, even when patients remain free of recurrence for a long period.

To analyze expectations for sexual life after radical prostatectomy in patients and their partners, and its influence on sexual motivation and bothers in the postoperative period.A total of 162 patients who underwent retropubic radical prostatectomy and their partners were evaluated. The patients' sexual function, sexual bother and expectations for postoperative sexual life were assessed prospectively at baseline, and at 1, 3, 6 and 12 months after radical prostatectomy. The partner was asked questions about postoperative sexual life before the operation. Sexual function and sexual bother were evaluated by the University of California Los Angeles Prostate Cancer Index. Expectations for postoperative sexual life were studied using three ad hoc questions.The rate of having sexual intercourse and adequate penile rigidity for vaginal penetration at baseline was 29.0% and 21.6%, respectively. A significantly higher rate of patients considered "sexual life is important" (patient 35.2%, partner 13.0%), hoped for "preservation of erectile function" (patient 66.0%, partner 33.3%) and accepted "use of phosphodiesterase type 5 inhibitor" (patient 65.4%, partner 43.2%) compared with their partners (P 0.001). Patients who had partners with a negative sexual attitude lost sexual motivation 1 year after operation. However, patients with cooperative partners maintained sexual motivation, although they felt greater sexual bother 1 year after radical prostatectomy.There was a significant dissociation in perspectives of postoperative sexual life between patients undergoing radical prostatectomy and their partners. Partners' low expectations are associated with patients' low sexual bother and motivation. Partners' cooperative attitude might contribute to maintaining patients' sexual desire and motivation.

Premature ejaculation is a common sexual problem, as is erectile dysfunction. We evaluated silodosin, a highly selective α1A-adrenoceptor antagonist, as a new treatment option for premature ejaculation. α1-Adrenoceptor antagonists are widely used for lower urinary tract symptoms, and clinical studies on silodosin have shown excellent clinical efficacy for lower urinary tract symptoms. However, compared with other α1-adrenoceptor antagonists, silodosin appeared to suppress ejaculation in a relatively higher percent of trial participants. This suppression of ejaculation by silodosin suggested its potential for treating premature ejaculation. Consequently, we evaluated the feasibility of off-label silodosin as a new treatment option for premature ejaculation. Eight patients suffering premature ejaculation were treated with silodosin. Silodosin (4 mg) was given 2 h before sexual intercourse. Intravaginal ejaculatory latency time, premature ejaculation profile item, clinical global impression change in premature ejaculation and systemic adverse events were recorded. Intravaginal ejaculatory latency time was significantly prolonged (from 3.4 min to 10.1 min, P = 0.003). All patients answered better (much better) or slightly better for their own premature ejaculation problem compared with pretreatment condition in the clinical global impression change. Premature ejaculation profile also significantly improved. Two (25%), three (37.5%) and seven patients (87.5%) experienced anejaculation, reduced semen volume and discomfort during orgasm, respectively. However, these problems were not of major concern for the participants. No systemic adverse effects were reported. The current results support the possible use of silodosin as a new treatment option for premature ejaculation, and suggest that a placebo controlled study assessing its clinical usefulness would be worthwhile.

Leiomyosarcoma is a malignant soft-tissue cancer arising from tissues containing smooth muscle. It commonly occurs in the gastrointestinal system and retroperitoneum, but is rare in the genito-urinary system. We experienced a case of primary testicular leiomyosarcoma. A 71-year-old man presented with painless swelling of the right scrotal contents for 4 months. A high orchiectomy was performed. Histological examination revealed primary testicular leiomyosarcoma. The patient did not receive any adjuvant therapy. Seven months after the operation, there has been no recurrence. Cases of primary intratesticular leiomyosarcoma are rare. To the best of our knowledge, only sixteen cases have been reported in the literature.

Testing immunotherapeutic strategies for prostate cancer has been impeded by the lack of relevant tumor models in immunocompetent animals. This opportunity is now provided by the recent development of prostate specific PTEN knockout mice, which show spontaneous development of true adenocarcinoma arising from prostate epithelium and more faithfully recapitulate the human disease than any previous model. We investigated the feasibility of using tumor cells derived from this model to test tumor vaccination and adoptive immunotherapeutic strategies for prostate cancer.PTEN-CaP8 adenocarcinoma cells derived from the biallelic PTEN knockout prostate cancer model were used to vaccinate nontumor bearing litter mates. Tumor specific effector cells were generated from splenocytes of vaccinated mice by mixed lymphocyte-tumor reactions, and antiproliferative effects and cytokine generation were examined in vitro. The effect of vaccination or adoptive immunotherapy on luciferase marked PTEN-CaP8 subcutaneous tumors was monitored by tumor volumetric measurements and noninvasive bioluminescence imaging.Vaccination of litter mate mice with irradiated PTEN-CaP8 cells showed a significant prophylactic effect against the subsequent tumor challenge. Effector cells harvested from vaccinated litter mates showed significant interferon-gamma secretion upon co-incubation with PTEN-CaP8 target cells and they were capable of efficient target cell growth inhibition in vitro. Intratumor adoptive transfer of effector cells resulted in significant growth inhibition of preestablished prostate tumors in vivo.The PTEN knockout model serves as a highly useful model in which to investigate tumor cell vaccination and adoptive immunotherapeutic strategies in the context of true adenocarcinoma of the prostate. This model should accelerate efforts to develop effective immunotherapies for human prostate cancer.

Lymphoepithelioma-like carcinoma (LELC), best known to occur in the nasopharynx, can arise in a variety of sites, such as the salivary gland, thymus, lung, stomach, skin and uroepithelium. Primary LELC of the uroepithelium is very rare and there is only limited information in the published reports. We managed a case of a 75-year-old woman who presented with nausea and gross painless hematuria. She was treated with laparoscopic nephroureterectomy and was diagnosed with a T1N1M0 LELC of the renal pelvis. Unlike nasopharyngeal lymphoepithelioma, immunohistochemical analysis of this urinary LELC was negative for the Epstein-Barr virus. Herein we report on one more case of primary LELC of the renal pelvis and review of the published reports, particularly those concerning Epstein-Barr virus expressions. Recognition of this tumor and complete resection are essential for saving patients.

Gelsolin is an actin regulatory protein that is undetectable or reduced in human bladder tumors compared with normal epithelial cells. Whether the over expression of gelsolin could inhibit tumor growth was investigated in an orthotopic bladder cancer nude mouse model using recombinant adenovirus encoding wild-type gelsolin (Ad-GSN).The 2 human bladder cancer cell lines KU-7 and UMUC-2 were transduced with Ad-GSN in vitro. Flow cytometric analysis was done to examine the cell cycle after transducing the adenovirus. Cell growth was compared with control groups of these cells transduced with adenovirus containing the Escherichia coli beta-galactosidase gene Ad-betagal. In vivo KU-7 cells were introduced into the bladder of nude mice (day 0), followed by 3 injections into the urethra (days 2 to 4) with Ad-GSN or Ad-betagal (1 x 10 pfu). At 8 days after initial adenovirus exposure (day 10) each bladder was sectioned and stained, and the mass of the tumor was digitally determined.Bladder cancer cell growth (KU-7 and UMUC-2) was inhibited after these cells were transduced with Ad-GSN in vitro. Based on flow cytometric analysis over expression of gelsolin may cause these cells to arrest or delay at the G2/M phase of the cell cycle. In the orthotopic bladder cancer model the mass of the tumor was approximately 90% less in Ad-GSN treated animals than in controls.Ad-GSN provides a significant tumor suppressive effect on human bladder cancer cells in this orthotopic nude mouse model. Adenovirus mediated over expression of gelsolin may be useful therapy for human bladder cancer.

Replicating murine leukemia virus (RMLV)-based vectors can propagate specifically within actively dividing cancer cells and achieve highly efficient and tumor-selective gene delivery. However, in view of the known potential for retroviral integration-mediated genotoxicity, additional mechanisms to target the virus specifically to cancer cells are desirable. To further improve their tumor specificity and safety profile, we have developed RMLV vectors regulated by two different tissue-specific promoters. We generated GFP-expressing RMLV vectors ACE-emd (wild type), ACE-At-emd (regulated by ARR2PB promoter, a synthetic variant of the probasin promoter which exhibits high specificity for androgen receptor (AR)-positive prostate cancer cells) and ACE-PSES-emd (regulated by PSES promoter, an androgen-independent promoter which is highly active in PSA/PSMA-positive prostate cancer cells, both in the presence and absence of androgen). We also developed ACE-yCD, ACE-At-yCD and ACE-PSES-yCD carrying the yeast cytosine deaminase (yCD) prodrug-activator gene, which converts the nontoxic prodrug 5-fluorocytosine (5FC) into the chemotoxin 5-fluorouracil. These vectors were first in vitro tested in both prostate (LNCaP, MDA PCa 2b and PC-3) and non-prostate (293T) cell lines in the presence and absence of androgen. RMLV vector ACE-At-emd exhibited high specificity and robust replication in AR-positive prostate cancer cell lines, but only in the presence of androgen. RMLV vector ACE-PSES-emd exhibited high specificity for PSA/PSMA-positive prostate cancer cell line both in the presence and absence of androgen. For in vivo studies, male nude mice were inoculated subcutaneously with LNCaP cells (AR-positive, PSA/PSMA-positive) in Matrigel. RMLV vectors expressing GFP were injected intratumorally, and tumors were analyzed by flow cytometry 2 and 4 weeks after vector injection. The results showed that both ARR2PB- and PSES-regulated RMLV vectors achieve efficient gene delivery to LNCaP s.c. tumors in vivo. Cytotoxic activity of RMLV-yCD vectors was examined in vitro in LNCaP cells in the presence and absence of 5FC after virus infection. Cell-specific expression of each vector correlated with reduced cell viability compared to uninfected cells after 5FC treatment. We are now conducting studies to evaluate therapeutic efficacy vs. potential genotoxicity of these vectors for prodrug-activator gene therapy in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5393. doi:10.1158/1538-7445.AM2011-5393

Epigenetic silencing of the tumor-suppressing gelsolin gene involves histone deacetylation of its promoter region in human urinary bladder cancer