Miyagi, Japan
Miyagi, Japan

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Ito A.,Tohoku University | Shintaku I.,Tohoku University | Satoh M.,Sen en General Hospital | Ioritani N.,Sendai Shakai Hoken Hospital | And 19 more authors.
Journal of Clinical Oncology | Year: 2013

Purpose: We evaluated the efficacy of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). Patients and Methods: From December 2005 to November 2008, 77 patients clinically diagnosed with UUT-UC from 11 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were preoperatively enrolled in this study. Patients were randomly assigned to receive or not receive a single instillation of THP (30 mg in 30 mL of saline) into the bladder within 48 hours after nephroureterectomy. Cystoscopy and urinary cytology were repeated every 3 months for 2 years or until the occurrence of first bladder recurrence. Results: Seventy-two patients were evaluable for efficacy analysis, 21 of whom had a subsequent bladder recurrence. Significantly fewer patients who received THP had a recurrence compared with the control group (16.9% at 1 year and 16.9% at 2 years in the THP group v 31.8% at 1 year and 42.2% at 2 years in the control group; log-rank P = .025). No remarkable adverse events were observed in the THP-treated group. Based on multivariate analysis, THP instillation (hazard rate [HR], 0.26; 95% CI, 0.07 to 0.91; P = .035) and open surgery (HR, 0.28; 95% CI, 0.09 to 0.84; P = .024) were independently predictive of a reduced incidence of bladder recurrence. Conclusion: In this prospective randomized phase II study, a single intravesical instillation of THP seemed to reduce bladder recurrence after nephroureterectomy. A phase III, large-scale, multicenter study is needed to confirm these observations. © 2013 by American Society of Clinical Oncology.


Aizawa T.,Tohoku University | Ozawa H.,Tohoku University | Kusakabe T.,Tohoku University | Nakamura T.,Tohoku University | And 8 more authors.
Journal of Orthopaedic Science | Year: 2012

Many studies have been reported on recurrent lumbar disc herniations covering several pathological conditions. In those studies, reoperation rate of revised disc excisions was calculated by simple division between the number of reoperations and that of the total primary disc excisions. To determine the real reoperation rate, strict definition of pathologies, a large number of patients, a long observation period, and survival function method are necessary. Methods Between 1988 and 2007, 5,626 patients with disc excision were enrolled by the spine registration system of the Department of Orthopaedic Surgery, Tohoku University, Japan. Among them, 192 had revised disc surgery, and we obtained data of 186 patients whose clinical features were assessed and reoperation rates analyzed using the Kaplan-Meier method. Results In total, 205 disc herniations were excised in the revision surgery (including contralateral herniation at the same level and new herniation at a different level), and 101 were real recurrent herniations (recurrence at the same level and side as the primary herniation). The kappa coefficient of the spinal level and side between the primary and revision surgeries was 0.41, indicting moderate correlations. Real recurrent herniations showed shorter intervals between primary and revision surgeries. Male patients with surgery at a younger age carried a higher risk of reoperation. In the revision surgery, transligamentous extrusion was significantly more common than other types of herniation. On Kaplan-Meier analysis, the reoperation rate of overall revised excisions was 0.62% at 1 year, 2.4% at 5 years, 4.4% at 10 years, and 5.9% after 17 years. That of real recurrent herniations was 0.5%, 1.4%, and 2.1%, respectively, and 2.8% after 15.7 years. Conclusion Reoperation rate of real recurrent herniations calculated using survival function method gradually increased year by year, from 0.5% at 1 year after primary surgery to 2.8% at 15.7 years. © The Japanese Orthopaedic Association 2012.


Wang H.,Zhejiang Cancer Hospital | Cai Z.,Zhejiang University | Yang F.,Zhejiang University | Luo J.,Zhejiang Cancer Hospital | And 3 more authors.
Urology | Year: 2014

Objective To evaluate the therapeutic efficacy of AxdAdB-3 with Arg-Gly-Asp (RGD)-fiber modification (AxdAdB3-F/RGD), which enables integrin-dependent infection in bladder cancers. Methods Flow cytometric analysis was applied to evaluated adenovirus-mediated gene transduction into various cells. The cytopathic effects of AxdAdB3-F/RGD were evaluated in bladder cancer cell lines and a normal bladder mucosa-derived cell line (HCV29) with AxCAZ3-F/RGD (control) or AxdAdB-3. The efficacy of bladder instillation therapy with AxdAdB3-F/RGD for orthotopic bladder cancer was investigated in nude mice. Results Expression of coxsackievirus adenovirus receptor (CAR) and integrins (αvβ3 and αvβ 5) vary in different bladder cancer cell lines. The susceptibility of various cell lines to adenovirus was associated with the expression of CAR. AxdAdB-3 was more cytopathic in CAR-positive bladder cancer cells than in CAR-negative cells, whereas AxdAdB3-F/RGD caused effective oncolysis in both CAR-positive and CAR-negative bladder cancer cells. AxdAdB3-F/RGD was not cytotoxic to HCV29 cells. Direct instillation of AxdAdB3-F/RGD into the bladder of the orthotopic model, established by CAR-deficient human bladder cancer cells, inhibited tumor growth and led to significantly elongated survival. Conclusion E1A and E1B double-restricted oncolytic adenovirus with RGD fiber modification has enhanced infectivity and oncolytic effects to CAR-deficient bladder cancers, suggesting the therapeutic potential of AxdAdB3-F/RGD for bladder cancers. © 2014 Published by Elsevier Inc.


Satoh M.,Sen en General Hospital | Nakano O.,Sen en General Hospital | Kuwahara M.,Sen en General Hospital | Ito A.,Tohoku University | Arai Y.,Tohoku University
Japanese Journal of Cancer and Chemotherapy | Year: 2011

The two regimens of treatment consisted of either cisplatin and gemcitabine or methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC), which has been widely adopted for muscle-invasive bladder cancer. But because of its potential toxicity, its tolerability has been troublesome, especially for very elderly patients. Herein, we report a bladder cancer case with multiple metastases which were controlled by low-dose UFT. At the same time, the chemosensitivity of 5-FU combined with uracyl or 5-chloro-2, 4-dihydroxypyridine (CDHP). Four invasive bladder cancer cell lines were evaluated with a collagen gel droplet embedded drug sensitivity test (CD-DST). Three of four cell lines showed an increasing sensitivity to 5-FU with the combination of uracil or CDHP. Examinations with CD-DST may provide important scientific evidence for determining suitable chemotherapy for patients with advanced bladder cancer.


Wang H.,Tohoku Pharmaceutical University | Wang H.,Zhejiang Cancer Hospital | Isaji T.,Tohoku Pharmaceutical University | Isaji T.,Sen en General Hospital | And 13 more authors.
Urology | Year: 2013

Objective: To investigate the therapeutic effects of exogenous gangliosides GM3 on human bladder cancer cell lines and the severe combined immunodeficiency mouse model of orthotopic bladder cancer. Materials and Methods: Human bladder cancer cell lines YTS-1, T24, 5637, and KK47 were used in the study. In vitro cytotoxicity of GM3 was assessed using the cell counting kit-8. Cell adhesion was determined using a spreading assay. Phosphorylation of epidermal growth factor receptor was determined by Western blotting. In vivo, the orthotopic bladder cancer model was established using severe combined immunodeficiency mice and GM3 was administered intravesically by way of a transurethral catheter. Results: GM3 inhibited the proliferation of all the bladder cancer cell lines tested. The addition of GM3 decreased cell adhesion and epidermal growth factor-dependent phosphorylation of epidermal growth factor receptor. Direct instillation of GM3 into the bladder of the orthotopic model significantly inhibited tumor growth. Conclusion: Our results suggest exogenous GM3 as a potential therapeutic agent for treating bladder cancer. © 2013 Elsevier Inc. All Rights Reserved.


PubMed | Tohoku University, Sen en General Hospital, Zhejiang Cancer Hospital and Zhejiang University
Type: Journal Article | Journal: Urology | Year: 2014

To evaluate the therapeutic efficacy of AxdAdB-3 with Arg-Gly-Asp (RGD)-fiber modification (AxdAdB3-F/RGD), which enables integrin-dependent infection in bladder cancers.Flow cytometric analysis was applied to evaluated adenovirus-mediated gene transduction into various cells. The cytopathic effects of AxdAdB3-F/RGD were evaluated in bladder cancer cell lines and a normal bladder mucosa-derived cell line (HCV29) with AxCAZ3-F/RGD (control) or AxdAdB-3. The efficacy of bladder instillation therapy with AxdAdB3-F/RGD for orthotopic bladder cancer was investigated in nude mice.Expression of coxsackievirus adenovirus receptor (CAR) and integrins (v3 and v5) vary in different bladder cancer cell lines. The susceptibility of various cell lines to adenovirus was associated with the expression of CAR. AxdAdB-3 was more cytopathic in CAR-positive bladder cancer cells than in CAR-negative cells, whereas AxdAdB3-F/RGD caused effective oncolysis in both CAR-positive and CAR-negative bladder cancer cells. AxdAdB3-F/RGD was not cytotoxic to HCV29 cells. Direct instillation of AxdAdB3-F/RGD into the bladder of the orthotopic model, established by CAR-deficient human bladder cancer cells, inhibited tumor growth and led to significantly elongated survival.E1A and E1B double-restricted oncolytic adenovirus with RGD fiber modification has enhanced infectivity and oncolytic effects to CAR-deficient bladder cancers, suggesting the therapeutic potential of AxdAdB3-F/RGD for bladder cancers.

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