We have already demonstrated that inactivated, replication-defective Sendai virus particles (HVJ-E) have a powerful antitumor effect by both the generation of tumor-specific cytotoxic T cells and inhibition of regulatory T cell activity. Here, we report that HVJ-E also has an antitumor effect through non-T cell immunity. Microarray analysis revealed that direct injection of HVJ-E induced the expression of CXCL10 in established Renca tumors. CXCL10 was secreted by dendritic cells in the tumors after HVJ-E injection. Quantitative real-time RT-PCR and immunohistochemistry revealed that CXCR3+ cells (predominantly NK cells) infiltrated the HVJ-E-injected tumors. Moreover, HVJ-E injection caused systemic activation of NK cells and enhanced their cytotoxity against tumor cells. In an in vivo experiment, approximately 50% of tumors were eradicated by HVJ-E injection, and this activity of HVJ-E against Renca tumors was largely abolished by NK cell depletion using anti-asialo GM1 antibody. Since HVJ-E injection induced systemic antitumor immunity by enhancing or correcting the chemokine-chemokine receptor axis, it might be a potential new therapy for cancer.
Objectives: In order to compare the clinical efficacy of naftopidil (Naf) and tamsulosin hydrochloride (Tam), which differ in their selectivity to alpha receptor subtypes, we performed a multi-center prospective randomized controlled study. Methods: Men complaining of lower urinary tract symptoms due to benign prostatic hypertrophy, were randomized into two treatment groups: one receiving 50 mg Naftopidil daily (Naf group, n = 31 pts), and one receiving 0.2 mg Tam once daily (Tam group, n = 28 pts). Baseline symptom scores were compared to those at 2 weeks and at the end of the observation period (6-8 weeks). Results: In the Naf group at 2 weeks, the score of the daytime frequency significantly improved from 3.5 to 2.2 (P = 0.03), and the score of nocturia improved significantly from 3.5 to 2.2 (P = 0.0004), respectively. In the Tam group at 2 weeks, however, no significant improvement was noted in the increased score of daytime frequency (P = 0.1) or nocturia (P = 0.2). At 2 weeks, the storage symptom score of the frequency to the combined score of daytime frequencies and the score of nocturia was better in the Naf group (improved from 7.0 to 4.4, P = 0.0017) than in the Tam group (from 6.8 to 4.9, P = 0.08) (P < 0.05). At 6-8 weeks, the effects of the two drugs on lower urinary tract symptoms were comparable. Conclusions: Naf demonstrated a significant early response to improve storage symptoms at 2 weeks, including daytime frequency and nocturia, compared with Tam.
Sensory dysfunction could be involved in various pathogeneses in the lower urinary tract including neurogenic bladder, overactive bladder, painful bladder syndrome and neuropathy as a result of endocrine disorders. The ability to diagnose sensory function more objectively is of increasing interest to clinicians. Afferent innervations of the lower urinary tract involve myelinated (A-delta) and unmyelinated (C) fibers. The Neurometer (Neurotron, Baltimore, MD, USA) is the only reported commercially available device to evaluate afferent function by selectively depolarizing different subpopulations of afferent nerves, with 250 Hz activating A-delta fibers and 5 Hz activating C-fibers, to determine their current perception threshold (CPT) as a quantitative measure. Recently, increased evidence has suggested that measurement of CPT values of A-delta and C-fibers in the lower urinary tracts is feasible and shows significant correlation with clinical symptoms and conventional urodynamic variables, as well as the efficacy of various treatments. However, there are still controversial issues in the wider use of this technology in diagnosis and assessment of the therapeutic effectiveness of sensory dysfunction in the lower urinary tracts. In order to resolve the remaining challenges in the CPT test of the lower urinary tract, recent efforts include development of a new balloon-type electro-catheter with dual electrodes as an alternative sensory test for the bladder or urethra, which allows simultaneous performance of conventional urodynamic tests and urine collection, and future standardized techniques available for comparison with validated control values.
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