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Articles by S. Takashima
Total Records ( 5 ) for S. Takashima
  N Katsumata , T Watanabe , H Minami , K Aogi , T Tabei , M Sano , N Masuda , J Andoh , T Ikeda , T Shibata and S. Takashima
 

Background: This randomized, multicenter, phase III trial compared doxorubicin plus cyclophosphamide (AC), single-agent docetaxel (D), and an alternating regimen of AC and docetaxel (AC–D) as first-line chemotherapy in metastatic breast cancer (MBC).

Patients and methods: Patients with MBC resistant to endocrine therapy were entered in a randomized study to receive either six cycles of AC (doxorubicin 40 mg/m2 plus cyclophosphamide 500 mg/m2), D (60 mg/m2), or alternating treatment with AC–D (i.e. three cycles of AC and three cycles of D). Treatment was administered every 3 weeks.

Results: A total of 441 patients were entered in a randomized study. Response rates were 30% for AC, 41% for D, and 35% for AC–D. The median times to treatment failure (TTFs) were 6.4, 6.4, and 6.7 months (one-sided log-rank test, P = 0.13 for AC versus D, P = 0.14 for AC versus AC–D) and median overall survival (OS) was 22.6, 25.7, and 25.0 months (P = 0.09 for AC versus D, P = 0.13 for AC versus AC–D) in the AC, D, and AC–D, respectively.

Conclusion: There was no difference in the TTF among the three arms. However, there was a trend toward a better response and better OS in the D than in the AC.

  D Takabatake , N Taira , F Hara , T Sien , S Kiyoto , S Takashima , K Aogi , S Ohsumi , H Doihara and S. Takashima
  Objective

The 7-year follow-up of the US oncology 9735 trial demonstrated the superiority of TC [docetaxel (DTX)/cyclophosphamide (CPA)] to doxorubicin/CPA therapy. To introduce TC therapy in Japan, the verification of the safety and tolerability is essential. We performed a collaborative prospective safety study with Okayama University to introduce TC therapy.

Methods

The subjects were 53 patients aged from 33 to 67 years at intermediate risk based on the St Gallen risk classification who underwent radical surgery for primary breast cancer between August 2007 and December 2008. As post-operative adjuvant chemotherapy, four cycles of TC (DTX 75 mg/m2 + CPA 600 mg/m2) were administered at 3-week intervals. Adverse events were evaluated based on National Cancer Institute—Common Terminology Criteria for Adverse Events ver. 3.0. The safety and completion rate were evaluated as the primary and secondary endpoints, respectively.

Results

Regarding hematological toxicity, Grade (G) 4 neutropenia occurred in 71.7% and G3 in 26.4%. G3–4 leukopenia developed in 32.1% and 56.6%, respectively, G4 anemia in 1.9% and G1–2 anemia in 26.4%. Regarding non-hematological toxicity, systemic malaise, skin eruption, edema, myalgia, arthralgia and nausea were noted in most patients. The completion rate was 94.3%, dose reduction was necessary in 7.5% and granulocyte colony-stimulating factor (G-CSF) support was required in 17.0%. On comparison between patients aged 65 years or older and younger than 65 years, the completion rate, dose reduction and incidence of febrile neutropenia (FN) were higher in the elderly patients. G-CSF support was more often needed in this subgroup.

Conclusions

TC therapy is tolerable for Japanese patients, but attention should be paid to the development of FN and neutropenia. The completion rate was lower in the elderly patients, showing that tolerability was not necessarily favorable.

  S Ohsumi , K Shimozuma , S Morita , F Hara , D Takabatake , S Takashima , N Taira , K Aogi and S. Takashima
  Objective

To determine if health-related quality-of-life (QOL) differences existed between breast cancer (BC) survivors receiving mastectomy and those receiving breast-conserving treatment (BCT). Factors associated with QOL in long-term BC survivors were also identified.

Methods

One hundred patients who had previously undergone BC surgery and were alive without recurrence for >5 years were asked to answer the patient-administered questionnaires to assess their QOL (Functional Assessment of Cancer Therapy scale-Breast: FACT-B) and psychological distress (Hospital Anxiety and Depression Scale: HADS). Of them, 93 responded to the questionnaires affirmatively.

Results

Although none of the QOL scores were related to the surgical procedures, statistically significant relationships were found between age and the scores of FACT-General and social/family well-being (SWB), and between the educational status and scores of SWB in univariate analyses. There was no statistically significant relationship between psychological distress and each factor examined. In multivariate analyses, significant correlations were established between scores of the FACT-BC subscale (FACT-BCS) and the type of surgery and between those on the FACT SWB subscale and age at study or educational status. Namely, patients who had undergone BCT, younger patients and patients with higher educational background scored higher QOL.

Conclusions

Among the BC survivors, those who underwent BCT experienced significantly but slightly better QOL than those who received mastectomy in FACT-BCS assessments. Younger patients and patients with higher educational backgrounds experienced significantly better SWB.

  Y Suzuki , Y Tokuda , Y Fujiwara , H Iwata , Y Sasaki , S Saji , K Aogi , Y Nambu , A Suri , T Saeki and S. Takashima
  Objective

This Phase II study was conducted to evaluate efficacy and safety of gemcitabine monotherapy in anthracycline and taxane pre-treated Japanese metastatic breast cancer patients.

Methods

At Step 1, twelve patients were divided into two groups of six patients each and the dose-limiting toxicity was evaluated at gemcitabine 1000 and 1250 mg/m2 to determine the dose for Step 2. At Step 2, an additional 56 patients were assessed for efficacy and safety of gemcitabine monotherapy. Patients were treated with gemcitabine on days 1 and 8 of a 21-day cycle and explored incidence of adverse events graded by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, overall response rate (RR), time to progression disease and overall survival time.

Results

Gemcitabine 1250 mg/m2 was determined as the dose for Step 2. Adverse events reported in this study were similar in type, frequency and toxicity grades as seen in other tumor types. Of the 62 patients at 1250 mg/m2, 1 complete response (1.6%), 4 partial response (6.5%) and 20 stable disease (32.3%) were achieved, yielding an RR of 8.1% (95% CI: 2.7%, 17.8%). Median time to progression was 92.0 days (range: 29–651 days). The median survival time was 17.8 months (95% CI: 14.9 months to incalculable).

Conclusion

Gemcitabine at 1250 mg/m2 on days 1 and 8 of a 21-day cycle was tolerable and can be a salvage treatment option for Japanese metastatic breast cancer patients previously treated with anthracyclines and taxanes.

  J Seino , K Ishii , T Nakano , N Ishida , M Tsujimoto , Y Hashimoto and S. Takashima
 

Using the basic local alignment search tool (BLAST) algorithm to search the Oryza sativa (Japanese rice) nucleotide sequence databases with the Arabidopsis thaliana UDP-galactose transporter sequences as queries, we found a number of sequences encoding putative O. sativa UDP-galactose transporters. From these, we cloned four putative UDP-galactose transporters, designated OsUGT1, 2, 3 and 4, which exhibited high sequence similarity with Arabidopsis thaliana UDP-galactose transporters. OsUGT1, 2, 3 and 4 consisted of 350, 337, 345 and 358 amino acids, respectively, and all of these proteins were predicted to have multiple transmembrane domains. To examine the UDP-galactose transporter activity of the OsUGTs, we introduced the OsUGTs’ expression vectors into UDP-galactose transporter activity-deficient Lec8 cells. Our results showed that transfection with OsUGT1, 2 and 3 resulted in recovery of the deficit phenotype of Lec8 cells, but transfection with OsUGT4 did not. The results of an in vitro nucleotide sugar transport assay of OsUGTs, carried out with a yeast expression system, suggested that OsUGT4 is a UDP-glucose transporter rather than a UDP-galactose transporter. Although plants have multiple UDP-galactose transporter genes, phylogenic analysis indicates that plant UDP-galactose transporter genes are not necessarily evolutionary related to each other.

 
 
 
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