Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
 
Articles by A Sato
Total Records ( 9 ) for A Sato
  T Arimura , N Inagaki , T Hayashi , D Shichi , A Sato , K Hinohara , M Vatta , J. A Towbin , T Chikamori , A Yamashina and A. Kimura
  Aims

Z-band alternatively spliced PDZ-motif protein (ZASP)/Cypher is a Z-disc component of which several dilated cardiomyopathy (DCM)-associated mutations have been reported. Most of the mutations were found in exons 4 and 10 of ZASP/Cypher gene LDB3 and both exons were expressed preferentially in the heart. The aim of this study was to investigate the functional alteration of ZASP/Cypher caused by the DCM-associated mutations.

Methods and results

The yeast-two-hybrid method was used to identify the protein bound to a domain encoded by exon 4 of LDB3. Interaction of ZASP/Cypher with the binding protein was investigated in relation to the functional alterations caused by LDB3 mutations. Localization of the ZASP/Cypher-binding protein was examined at the cellular level in rat cardiomyocytes. Phosphoglucomutase 1 (PGM1), a metabolic enzyme involved in glycolysis and gluconeogenesis, was identified as a protein interacting with ZASP/Cypher. PGM1 bound to ZASP/Cypher at the domains encoded by exons 4 and 10. Two LDB3 mutations in exon 4 (Ser189Leu and Thr206Ile) and another mutation in exon 10 (Ile345Met) reduced the binding to PGM1. PGM1 showed diffuse localization in the cytoplasm of rat cardiomyocytes under standard culture conditions, and distribution at the Z-discs was observed under stressed culture conditions. Binding of endogenous PGM1 and ZASP/Cypher was found to be enhanced by stress in rat cardiomyocytes.

Conclusion

ZASP/Cypher anchors PGM1 to Z-disc under conditions of stress. The impaired binding of PGM1 to ZASP/Cypher might be involved in the pathogenesis of DCM.

  Y Kanemitsu , T Kato , Y Shimizu , Y Inaba , Y Shimada , K Nakamura , A Sato , Y Moriya and for the Colorectal Cancer Study Group (CCSG) of Japan Clinical Oncology Group
 

A randomized controlled trial is being conducted in Japan to compare hepatectomy alone with hepatectomy followed by adjuvant chemotherapy as treatment in patients with curatively resected liver metastases from colorectal cancer to improve survival with intensive chemotherapy. Between 42 and 70 days after liver resection, patients are randomly assigned to either hepatectomy alone or hepatectomy followed by 12 cycles of modified FOLFOX6 (mFOLFOX6) regimen. A total of 300 patients (including 78 patients in Phase II) will be accrued from 38 institutions within 3 years. The primary endpoint is treatment compliance at nine courses of mFOLFOX6 regimen in Phase II and disease-free survival in Phase III. The secondary endpoints are overall survival, incidence of adverse events and patterns of recurrence.

  K Ito , H Yoshii , J Asakuma , A Sato , A Horiguchi , M Sumitomo , M Hayakawa and T. Asano
  Objective

Renal cell carcinoma (RCC) with a high-nucleolar-grade component is considered to be an aggressive type of tumor. In the present study, we evaluated the impact of the presence of the worst-nucleolar-grade component and also tried to determine predictors for recurrence and prognosis in patients with the worst grade component.

Methods

We evaluated 314 patients with RCC. A three-graded system was used for nucleolar grading, the patients were classified into four groups according to the presence of the worst nucleolar grade (Grade 3) and the occupancy of each grade, and clinicopathological factors and clinical outcomes were compared. In patients of Grade 3 components (Groups 1 and 2), factors influencing on prognosis and recurrence were evaluated by multivariate analysis.

Results

There was no significant difference in clinicopathological factors between Group 1 (with Grade 3-dominant tumors) and Group 2 (with tumors in which Grade 1 or 2 was dominant and there were Grade 3 components). Neither did cause-specific survival or recurrence-free survival differ significantly between those two groups. In multivariate analysis, only distant metastasis was an independent predictor for prognosis in all patients with Grade 3 components. Moreover, an elevated C-reactive protein (CRP) level (≥1 mg/dl) was the only independent predictor of recurrence in N0M0 patients.

Conclusions

Regardless of dominancy, the presence of the worst grade component has a significant clinical impact in RCC patients. N0M0 patients whose RCC has worst-grade components but whose CRP levels are <1 are expected to have longer recurrence-free intervals and to survive longer than those whose CRP levels are higher.

  H Kato , A Sato , H Fukuda , Y Kagami , H Udagawa , A Togo , N Ando , O Tanaka , M Shinoda , H Yamana and S. Ishikura
  Objective

The study objective was to evaluate the efficacy and toxicity of chemoradiotherapy with 5-fluorouracil (5-FU) plus cisplatin in patients with Stage I esophageal squamous cell carcinoma (ESCC). The primary endpoint was proportion of complete response (%CR).

Methods

Patients with Stage I (T1N0M0) ESCC, aged 20–75 years, without indication of endoscopic mucosal resection were eligible. Treatment consisted of cisplatin 70 mg/m2 (day 1) and 5-FU 700 mg/m2/day (days 1–4) combined with 30 Gy radiotherapy (2 Gy/day, 5 days/week, days 1–21). The cycle was repeated twice with 1-week split. Salvage surgery was recommended for residual tumor or local recurrence.

Results

From December 1997 to June 2000, 72 patients were enrolled. No ineligible patient or major protocol violation was observed. There were 63 CRs for %CR of 87.5% [95% confidence interval (CI): 77.6–94.1]. Six patients with residual tumor successfully underwent esophagectomy. There was no Grade 4 toxicity. Four-year survival proportion was 80.5% (95% CI: 71.3–89.7), and 4-year major relapse-free survival proportion was 68% (95% CI: 57.3–78.8) (mucosal recurrence removed by endoscopy was not counted as an event).

Conclusions

High CR proportion and survival proportion with mild toxicity suggest that this regimen could be considered as a candidate of new standard treatment to be compared with surgery in patients with Stage I ESCC.

  W Koizumi , T Akiya , A Sato , K Yamaguchi , T Sakuyama , N Nakayama , S Tanabe , K Higuchi , T Sasaki , T Sekikawa and The Tokyo Cooperative Oncology Group (TCOG GI Group)
  Objective

A multicenter trial was conducted to evaluate the efficacy and safety of paclitaxel every 2 weeks in patients with advanced or recurrent gastric cancer who had previously received fluoropyrimidine-based chemotherapy.

Methods

The subjects were patients with gastric cancer who had disease progression or recurrence while receiving fluoropyrimidine-based chemotherapy. All patients had adequate major organ functions with an Eastern Cooperative Oncology Group performance status (PS) of 0–2. Paclitaxel 140 mg/m2 was administered intravenously on days 1 and 15 of a 4-week cycle. The primary endpoint was the response rate. Secondary endpoints were progression-free survival (PFS), overall survival and safety.

Results

Response was assessable in 40 of 41 enrolled patients. Their median age was 63 (range: 48–77) years, and PS was 0 in 22 patients, 1 in 13 and 2 in 5. Previous treatment included S-1 (1 M tegafur–0.4 M gimestat–1 M otastat potassium) monotherapy in 32 patients and S-1-based combination therapy in 5. The median number of administered courses of paclitaxel was 3.5 (1–14). The response rate was 17.5% (95% confidence interval: 7.3–32.8%, partial response: 7, stable disease: 21, progressive disease: 10 and not evaluable: 2). The disease control rate was 70.0%, the median PFS was 111 days and the median overall survival was 254 days. Major adverse events of Grade 3 or 4 were neutropenia (27.5%), anemia (12.5%), diarrhea (2.5%) and sensory neuropathy (2.5%).

Conclusions

Biweekly paclitaxel seemed to be one of the useful chemotherapies after failure of fluoropyrimidine-based treatment in patients with advanced or recurrent gastric cancer.

  T Doi , N Boku , K Kato , Y Komatsu , K Yamaguchi , K Muro , Y Hamamoto , A Sato , W Koizumi , N Mizunuma and H. Takiuchi
  Objective

The addition of bevacizumab to fluoropyrimidine-based combination chemotherapy as first-line therapy for metastatic colorectal cancer results in clinically significant improvements in patient outcome. However, clinical trials have been conducted primarily in Caucasian patients with only a small proportion of Asian patients. This Phase I/II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab in Japanese patients with metastatic colorectal cancer.

Methods

Patients with previously untreated, measurable metastatic colorectal cancer received bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1, plus capecitabine 1000 mg/m2 twice daily on days 1–14, every 3 weeks. A three-step design evaluated in: step 1, initial safety of XELOX in six patients; step 2, initial safety of XELOX plus bevacizumab in six patients; and step 3, efficacy and safety in a further 48 patients. The primary study endpoints were safety and response rate.

Results

No dose-limiting toxicity occurred during Steps 1 and 2. Fifty-eight patients were enrolled in Steps 2 and 3 and received XELOX plus bevacizumab. In the 57 patients assessed for response, the overall response rate was 72% (95% confidence interval, 58.5–83.0). Median progression-free survival was 11.0 months (95% confidence interval, 9.6–12.5) and median overall survival was 27.4 months (95% confidence interval, 22.0–not calculated). Eight patients (14%) underwent surgery with curative intent. The most common grade 3/4 adverse events were neurosensory toxicity (17%) and neutropenia (16%).

Conclusions

XELOX plus bevacizumab is effective and has a manageable tolerability profile when given to Japanese patients with metastatic colorectal cancer.

  M Yamada , R Tatsumi , K Yamanouchi , T Hosoyama , S. i Shiratsuchi , A Sato , W Mizunoya , Y Ikeuchi , M Furuse and R. E. Allen
 

Skeletal muscle regeneration and work-induced hypertrophy rely on molecular events responsible for activation and quiescence of resident myogenic stem cells, satellite cells. Recent studies demonstrated that hepatocyte growth factor (HGF) triggers activation and entry into the cell cycle in response to mechanical perturbation, and that subsequent expression of myostatin may signal a return to cell quiescence. However, mechanisms responsible for coordinating expression of myostatin after an appropriate time lag following activation and proliferation are not clear. Here we address the possible role of HGF in quiescence through its concentration-dependent negative-feedback mechanism following satellite cell activation and proliferation. When activated/proliferating satellite cell cultures were treated for 24 h beginning 48-h postplating with 10–500 ng/ml HGF, the percentage of bromodeoxyuridine-incorporating cells decreased down to a baseline level comparable to 24-h control cultures in a HGF dose-dependent manner. The high level HGF treatment did not impair the cell viability and differentiation levels, and cells could be reactivated by lowering HGF concentrations to 2.5 ng/ml, a concentration that has been shown to optimally stimulate activation of satellite cells in culture. Coaddition of antimyostatin neutralizing antibody could prevent deactivation and abolish upregulation of cyclin-dependent kinase (Cdk) inhibitor p21. Myostatin mRNA expression was upregulated with high concentrations of HGF, as demonstrated by RT-PCR, and enhanced myostatin protein expression and secretion were revealed by Western blots of the cell lysates and conditioned media. These results indicate that HGF could induce satellite cell quiescence by stimulating myostatin expression. The HGF concentration required (over 10–50 ng/ml), however, is much higher than that for activation, which is initiated by rapid release of HGF from its extracellular association. Considering that HGF is produced by satellite cells and spleen and liver cells in response to muscle damage, local concentrations of HGF bathing satellite cells may reach a threshold sufficient to induce myostatin expression. This time lag may delay action of the quiescence signaling program in proliferating satellite cells during initial phases of muscle regeneration followed by induction of quiescence in a subset of cells during later phases.

  A Sato , M Mishima , A Nagai , S. Y Kim , Y Ito , T Hakoshima , J. G Jee and K. Kitano
 

Bloom syndrome is a rare genetic disorder characterized by severe growth retardation and cancer predisposition. The disease is caused by a loss of function of the Bloom syndrome protein (BLM), a member of the RecQ family of DNA helicases. Here we report on the first 3D structure of a BLM fragment, a solution structure of the C-terminal helicase-and-ribonuclease D-C-terminal (HRDC) domain from human BLM. The structure reveals unique features of BLM HRDC that are distinct from the HRDC domain of Werner syndrome protein. In particular, BLM HRDC retains many acidic residues exposed to the solvent, which makes the domain surface extensively electronegative. Consistent with this, fluorescence polarization assays showed an inability of isolated BLM HRDC to interact with DNA substrates. Analyses employing ultracentrifugation, gel-filtration, CD spectroscopy and dynamic light scattering showed that the BLM HRDC domain exists as a stable monomer in solution. The results show that BLM HRDC is a compact, robust and acidic motif which may play a distinct role apart from DNA binding.

 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility