Intravesical treatment of advanced urothelial bladder cancers with oncolytic HSV-1 co-regulated by differentially expressed microRNAs.

Urothelial bladder cancer is the most common malignancy of the urinary tract. Although most cases are initially diagnosed as non-muscle-invasive, more than 80% of patients will develop recurrent or metastatic tumors. No effective therapy exists currently for late-stage metastatic tumors. By intravesical application, local administration of oncolytic Herpes Simplex virus (oHSV-1) can provide a promising new therapy for this disease. However, its inherent neurotoxicity has been a perceived limitation for such application. In this study, we present a novel microRNA-regulatory approach to reduce HSV-1-induced neurotoxicity by suppressing viral replication in neurons while maintaining oncolytic selectivity toward urothelial tumors. Specifically, we designed a recombinant virus that utilizes differentially expressed endogenous microR143 (non-cancerous, ubiquitous) and microR124 (neural-specific) to regulate expression of ICP-4, a gene essential for HSV-1 replication. We found that expression of ICP-4 must be controlled by a combination of both miR143 and miR124 to achieve the most effective attenuation in HSV-1-induced toxicity while retaining maximal oncolytic capacity. These results suggest that interaction between miR143 and miR124 may be required to successfully regulate HSV-1 replication. Our resent study is the first proof-in-principle that miRNA combination can be exploited to fine-tune the replication of HSV-1 to treat human cancers.

[The quality of life after radical prostatectomy measured by general health questionnaire and visual analogue scales].

OBJECTIVES: The impact of radical prostatectomy on the quality of life (QOL) of patients were evaluated. MATERIALS AND METHODS: A total of 22 patients who underwent radical prostatectomy for clinically localized prostate cancer entered this study. Patients were asked to complete a questionnaire containing the general health questionnaire (GHQ) and a series of questions evaluating voiding function, incontinence and sexual dysfunction before and after the operation. In addition, the visual analogue scaled (VAS) questionnaire containing incontinence and sexual dysfunction was applied. RESULTS: No significant differences in GHQ were found between pre- and post operative status, but disease-targeted QOL such as sexual function was affected after the radical prostatectomy. In the points of incontinence and sexual dysfunction, VAS questionnaire significantly correlated with those of categorical questionnaires. CONCLUSIONS: There results suggest that GHQ is not affected, but disease-targeted QOL in some categories of sexual function is affected by radical prostatectomy, and that VAS questionnaires are not only useful for assessing the disease-targeted QOL but also easy to quantify QOL of the patients.

[Estimated numbers of patients with intractable respiratory diseases].

To estimate the number of patients with intractable respiratory diseases, we conducted a two-stage nationwide epidemiological survey in 1997. The first survey was performed at randomly sampled hospitals to identify the number of patients treated. The second survey sought detailed clinico-epidemiological data on the patients reported in the first survey. The response rates were 54% for the first survey and 62% for the second. Based on the survey findings, we derived the following nationwide estimates: 450 patients (95% confidence interval: 360-530) with chronic thromboembolic pulmonary hypertension; 230 (200-260) with primary pulmonary hypertension; 180 (150-210) with obesity-associated hypoventilation syndrome; 40 (30-50) with primary alveolar hypoventilation syndrome; 160 (140-180) with histiocytosis X; and 190 (150-230) with juvenile pulmonary emphysema.