No abstract

Survivin, a member of the inhibitor of apoptosis protein family, is expressed in many malignant tumors including urothelial cancer but is hardly detectable in normal, differentiated adult tissues. Previously we reported CD8-positive cytotoxic T-lymphocytes (CTLs) were successfully induced by stimulation with survivin-2B80-88 peptide in vitro. We started a phase I clinical study of survivin-2B80-88 peptide vaccination for advanced urothelial cancer patients to assess the safety and efficacy of this vaccination. Nine patients were received vaccination and were evaluated for immunological evaluation, adverse events, and clinical responses. A total of 46 vaccinations were carried out. There was no severe adverse event. HLA-A24/survivin-2B80-88 peptide tetramer analysis revealed a significant increase in the peptide-specific CTL frequency after the vaccination in five patients. Slight reduction of the tumor volume was observed in one patient. Survivin-2B80-88 peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in urothelial cancer patients.

Our data demonstrate that down-regulation of HLA class I on tumor cells is an independent prognostic factor for clear cell renal cell carcinoma. This finding suggests that HLA class I restricted cytotoxic T lymphocytes have an important role in the suppression of renal cell carcinoma.

Abbreviations & AcronymsAbstract: Premature ejaculation is a common sexual problem, as is erectile dysfunction. We evaluated silodosin, a highly selective a1A-adrenoceptor antagonist, as a new treatment option for premature ejaculation. a1-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 a1-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.

Purpose: Various immune systems play important roles in the clinical efficacy of intravesical Bacillus Calmette-Guerin (BCG) instillation for bladder cancer. However, human leukocyte antigen (HLA) class I molecules on tumor cells and various immune system cells infiltrating to/around the tumor have not been evaluated, although many prognostic factors, including clinical, pathologic, and molecular ones, have been investigated. The aim of this study was to determine immunologic prognostic factors of BCG immunotherapy for bladder cancer. Experimental Design: Immunohistochemical staining for HLA class I, CD4, CD8, CD20, CD68, TIA-1, S-100, and FOXP3 was carried out on specimens from 30 patients who underwent BCG immunotherapy from whom both pretreatment and posttreatment specimens were obtained.We did univariate and multivariate analyses of factors affecting recurrence-free survival. The positive, weakly positive, and negative groups of cells that infiltrated to/around the tumor were compared with recurrence-free survival using the Kaplan-Meier method and log-rank test. Results: HLA class I was a significant prognostic factor both in univariate and multivariate analyses. The 5-year recurrence-free survivals of the patients with HLA class I^positive tumors and those with HLA class I^negative tumors were 55.7% and 19.1%, respectively (P = 0.019). There was a significant association between infiltration of CD8, CD20, and CD68-positive cells after BCG therapy and therapeutic effects. Conclusions: Our data show that expression of HLA class I molecules on tumor cells contributes significantly to the therapeutic effect of BCG immunotherapy for bladder cancer. It is suggested that CTLs may be one of main effectors in this therapy.