Sapporo, Japan
Sapporo, Japan

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Kubo S.,Hyogo College of Medicine | Kubo S.,University of California at Los Angeles | Haga K.,University of California at Los Angeles | Haga K.,Sanjukai Hospital | And 5 more authors.
Molecular Therapy | Year: 2011

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. © The American Society of Gene & Cell Therapy.


Matsuda Y.,Sapporo Medical University | Hisasue S.-I.,Sapporo Medical University | Hisasue S.-I.,Juntendo University | Kumamoto Y.,Sapporo Medical University | And 4 more authors.
Journal of Sexual Medicine | Year: 2014

Introduction: The Erection Hardness Score (EHS) and the Sexual Health Inventory for men (SHIM) are patient-reported outcome scoring systems for erectile function. It is unclear which is more reliable for predicting the objective erectile function. Aim: The aim of this study was to evaluate whether the EHS could predict objective erectile function by measuring the maximal penile circumferential change (MPCC) with an erectometer. Methods: The study included 98 patients who visited our clinic from 2005 to 2010. The erectile function was evaluated using the SHIM, EHS, and MPCC. The MPCC was measured with the largest circumferential change of three consecutive occurrences of nocturnal penile tumescence (NPT) determined using the erectometer. Main Outcome Measures: We defined erectile dysfunction (ED) as MPCC<20mm and carried out multivariate analysis using logistic regression analysis to clarify the predictors for ED, with the variables including age, the SHIM score, and the EHS. We compared the tendency for MPCC≥20mm when EHS was 3 or more with that when EHS was 2 or less. Results: The median age of the patients was 59.5 years (range 18-83). In logistic regression analysis, the EHS was the only predictor for ED with MPCC<20mm. The mean EHS in the MPCC<20mm group was 1.64±0.20 (mean±SEM) and that in the MPCC≥20mm group was 2.46±0.13 (P=0.0018). There was a correlation between the EHS and the MPCC (correlation coefficient=0.33). In comparison with the group having an EHS of 2 or less, that with an EHS of 3 or more tended to have MPCC≥20mm (P=0.013). Conclusions: The EHS was correlated with the MPCC. The EHS represents the objective erectile function shown by the measurement of NPT. © 2014 International Society for Sexual Medicine.


Kojima Y.,Sapporo Medical University | Takasawa A.,Sapporo Medical University | Murata M.,Sapporo Medical University | Akagashi K.,Sanjukai Hospital | And 6 more authors.
Pathology International | Year: 2013

The lipid cell variant of urothelial carcinoma is a rare variant of urinary bladder cancer, comprised of lipoblast-like cells. In this report, we describe a case of the lipid cell variant of aggressive urothelial carcinoma. A 78-year-old man was admitted to the hospital because of gross hematuria. On cystoscopy, an ulcerative lesion, non-papillary architecture, was observed in the lateral wall of the bladder. Transurethral resection was performed. Histopathological findings of the bladder tumor indicated neoplastic cells forming irregular solid nests and sheets. Lipoblast-like neoplastic cells that had eccentric nuclei and cytoplasmic vacuoles were observed, not only in the resected specimen, but also in urine samples. On mucin histochemistry, the tumor cell cytoplasm contained no neutral or acidic mucus. The lipoblast-like cells were positive for cytokeratins (AE1/AE3, CK7) and adipophilin, known as a protein associated with neutral lipid synthesis. In general, it is difficult to prove the existence of intracytoplasmic lipid in formalin-fixed paraffin-embedded materials. This is the first report in which the presence of lipid in vacuoles of the lipid cell variant has been verified by immunohistochemistry. © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.


Hashimoto K.,Sapporo Medical University | Kyoda Y.,Sapporo Medical University | Tanaka T.,Sapporo Medical University | Maeda T.,Sapporo Medical University | And 6 more authors.
Laboratory Investigation | Year: 2015

Neuroendocrine (NE) cells in prostate cancer have been shown to be associated with the progression of prostate cancer. However, little is known about the molecular basis of this association. We have previously demonstrated that NE cells promote metastasis of a human prostate cancer cell line (LNCaP) with overexpression of the gelsolin gene. The purpose of this study was to investigate the interactions between NE cells and LNCaP cells and the involvement of gelsolin in contributing to the invasive potential of LNCaP cells. In addition, we examined whether neurotensin induced gelsolin-mediated invasion. We used the NE cell line NE-CS that was established from the prostate of the LPB-Tag 12T-10 transgenic mouse. Small interfering RNA (siRNA) targeting gelsolin or not targeting it was transfected into LNCaP cells. Cell invasion was assessed by Matrigel invasion assay. The supernatant of NE-CS cells and neurotensin induced the transformation of LNCaP cells. Neurotensin was observed in the supernatant of NE-CS cells but not in LNCaP cells. The siRNA targeting of gelsolin resulted in inhibition of invasion of LNCaP cells in the culture medium with neurotensin added, and in the supernatant of NE-CS cells with epidermal growth factor. The invasive potential of LNCaP cells enhanced by neurotensin or the supernatant of NE-CS cells through neurotensin receptor 1 (NTSR1) was blocked by a phospholipase Cγ inhibitor and an intracellular calcium chelator, with concomitant gelsolin suppression. This study indicates that NE cells and neurotensin induce gelsolin-mediated invasion of LNCaP cells through NTSR1 activation. © 2015 USCAP, Inc.


Sato Y.,Sanjukai Hospital | Tanda H.,Sanjukai Hospital | Nakajima H.,Sanjukai Hospital | Nitta T.,Sanjukai Hospital | And 6 more authors.
International Journal of Urology | Year: 2013

Objective: 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. Methods: 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. Results: 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. Conclusions: 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. © 2013 The Japanese Urological Association.


Sato Y.,Sanjukai Hospital | Tanda H.,Sanjukai Hospital | Nakajima H.,Sanjukai Hospital | Nitta T.,Sanjukai Hospital | And 6 more authors.
International Journal of Urology | Year: 2012

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 (4mg) was given 2h 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 3.4min to 10.1min, 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. © 2011 The Japanese Urological Association.


Sato Y.,Sanjukai Hospital | Tanda H.,Sanjukai Hospital | Nakajima H.,Sanjukai Hospital | Nitta T.,Sanjukai Hospital | And 6 more authors.
International Journal of Urology | Year: 2014

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. © 2014 The Japanese Urological Association.


PubMed | Sanjukai Hospital
Type: Journal Article | Journal: Hinyokika kiyo. Acta urologica Japonica | Year: 2012

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.


PubMed | Sanjukai Hospital
Type: Journal Article | Journal: International journal of urology : official journal of the Japanese Urological Association | Year: 2012

Premature ejaculation is a common sexual problem, as is erectile dysfunction. We evaluated silodosin, a highly selective 1A-adrenoceptor antagonist, as a new treatment option for premature ejaculation. 1-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 1-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.


PubMed | Sanjukai Hospital
Type: Journal Article | Journal: Hinyokika kiyo. Acta urologica Japonica | Year: 2013

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-Imanual stimulation and PDE5-Istimulation 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-Imanual stimulation in the eight patients (p0.027). 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 (p0.043). Six patients who showed a better erectile response with EGG retained motivation for continuation of PR. PDE5-Istimulation with EGG improved the erectile response in post-RP patients. EGG as a masturbation device may have a potential for contribution to successful PR.

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