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Articles by K Yamazaki
Total Records ( 6 ) for K Yamazaki
  N Hosono , M Kato , K Kiyotani , T Mushiroda , S Takata , H Sato , H Amitani , Y Tsuchiya , K Yamazaki , T Tsunoda , H Zembutsu , Y Nakamura and M. Kubo
 

Background: Cytochrome P450 2D6 (CYP2D6), one of the most important drug-metabolizing enzymes, has been reported to possess variation in the encoding CYP2D6 gene (cytochrome P450, family 2, subfamily D, polypeptide 6) that affects enzymatic activity. For the pharmacogenetic study of CYP2D6, accurate measurement of the dosage of the functional gene is essential; however, current genotyping techniques are insufficient because of their inability to provide the exact copy number of functional CYP2D6 genes.

Methods: We developed 3 quantitative real-time PCR (qPCR) assays for estimating the total copy number of the CYP2D6 gene, as well as 24-multiplex PCR-based real-time Invader assays (mPCR-RETINAs) for estimating the allele ratio at each variation locus. After determining the allele copy number at each locus, we estimated the frequencies of CYP2D6 alleles in a population and the diplotype in each individual by a CNVphaser (copy number variation phaser). The qPCR assays and RETINAs used for HapMap Japanese and Chinese samples were applied to 455 Japanese individuals.

Results: Forty-two individuals (9.2%) had one CYP2D6 gene copy, 207 (45.5%) had 2 copies, 161 (35.4%) had 3 copies, 40 (8.8%) had 4 copies, and 5 (1.1%) had 5 copies of the CYP2D6 gene. We found 16 different CYP2D6 alleles, with frequencies similar to those described in previous reports. In the diplotype analysis, we observed that CYP2D6*1/*1 and *1/*10-*36 were the most common diplotypes (approximately 20%) in our population.

Conclusions: Our method is the first to determine the exact number of functional CYP2D6 gene copies. We believe our method will facilitate and accelerate the detailed pharmacogenetic analysis of CYP2D6.

  S Hironaka , K Yamazaki , K Taku , T Yokota , K Shitara , T Kojima , S Ueda , N Machida , K Muro and N. Boku
  Objective

S-1 plus cisplatin is standard treatment for advanced gastric cancer in Japan. Triplet therapy with docetaxel, cisplatin and fluoropyrimidine showed a survival benefit over doublet therapy, but was associated with substantial toxicities. We investigated the maximum tolerated dose of combination chemotherapy with divided-dose docetaxel added to standard-dose S-1 plus cisplatin in advanced gastric cancer patients.

Methods

Patients with advanced gastric cancer, naive to chemotherapy or not refractory to fluoropyrimidine, were enrolled. Fixed doses of S-1 (40 mg/m2 twice daily for 3 weeks) and cisplatin (60 mg/m2 on day 1) were administered with increasing docetaxel dose levels of 20 mg/m2 (dose level 1), 25 mg/m2 (dose level 2) and 30 mg/m2 (dose level 3) on days 1, 8 and 15, or 40 mg/m2 (dose level 4) on days 1 and 15 of a 5-week cycle. Treatment cycles were repeated until disease progression, patient's refusal or unacceptable toxicity occurred.

Results

Fifteen patients were enrolled. During the first cycle, no dose-limiting toxicity was observed at dose levels 1 and 2. At dose level 3, grade 3 febrile neutropenia was seen in one patient. At dose level 4, grade 3 infection and grade 3 abdominal pain were observed. Thus, dose level 4 was determined to be the maximum tolerated dose. The response rate was 54% (7/13), and median progression-free survival and overall survival were 243 and 383 days, respectively.

Conclusions

The recommended dose of docetaxel added to standard-dose S-1 (80 mg/m2 days 1–21) plus cisplatin (60 mg/m2 day 1) was 40 mg/m2 on days 1 and 15 of a 5-week cycle.

  T Shukuya , H Yasui , N Boku , Y Onozawa , A Fukutomi , K Yamazaki , K Taku , T Kojima and N. Machida
  Objectives

Peritoneal metastasis is one of the major sites of disease progression of pancreatic cancer. There have been few trials in the second-line setting after gemcitabine failure because patients can hardly be candidates for chemotherapy after failure in the first-line chemotherapy, especially those with malignant ascites. The safety and efficacy of weekly paclitaxel therapy was evaluated for pancreatic cancer patients with malignant ascites in this retrospective study.

Methods

The subjects of this retrospective study were 23 advanced pancreatic cancer patients with malignant ascites who received weekly paclitaxel therapy after gemcitabine failure. Paclitaxel (80 mg/m2, div. for 1 h) was administered on Days 1, 8 and 15, every 4 weeks.

Results

While the disease control rate was 35%, decrease of ascites was obtained in 30% of the patients and ascites control rate was 61%. The median survival time was 101 days. Toxicities were mild, although one treatment-related death occurred.

Conclusions

Weekly paclitaxel therapy may be useful treatment option for pancreatic cancer patients with malignant ascites after gemcitabine failure.

  D Shindo , K Takahashi , Y Murakami , K Yamazaki , S Deguchi , H Suga and Y. Kondo
 

The double-probe piezodriving specimen holder that was recently developed by some of the present authors is modified to introduce a laser irradiation port in one of its two arms. As a result, the new specimen holder consists of a piezodriving probe and a laser irradiation port, both of which can be three-dimensionally controlled by using piezoelectric elements and micrometers. While the piezodriving probe interacts with the specimen set in the holder in several ways, the laser beam causes photo-induced phenomena to occur. By performing electron holography using the new specimen holder, we demonstrate that it is possible to evaluate the change in the electric field resulting from the discharging effect of laser irradiation on organic photoconductors.

  A Hirata , K Yamazaki , S Hamada , Y Kamimura , H Tarao , K Wake , Y Suzuki , N Hayashi and O. Fujiwara
 

The present study provides an intercomparison of the induced quantities in a human model for uniform magnetic field exposures at extremely low frequency. A total of six research groups have cooperated in this joint intercomparison study. The computational conditions and numeric human phantom including the conductivity of tissue were set identically to focus on the uncertainty in computed fields. Differences in the maximal and 99th percentile value of the in situ electric field were less than 30 and 10 % except for the results of one group. Differences in the current density averaged over 1 cm2 of the central nerve tissue are 10 % or less except for the results of one group. This comparison suggests that the computational uncertainty of the in situ electric field/current density due to different methods and coding is smaller than that caused by different human phantoms and the conductivitys of tissue, which was reported in a previous study.

  Y Tachibana , K Sakaguchi , T Goto , H Oda , K Yamazaki and S. Iida
  Background

Although several devices for meniscal repairs have become available, a successful outcome is ultimately due to a healed meniscus on the clinical findings. The authors assessed the repair integrity after meniscal repair with the FasT-Fix device using second-look arthroscopy.

Hypothesis

Meniscal repair with the FasT-Fix will lead to arthroscopically evident healing, but some menisci will show incomplete healing even in clinically successful cases and have newly formed injuries on the meniscal substance resulting from the path of the implant.

Study Design

Case series; Level of evidence, 4.

Methods

Sixty-five consecutive patients were studied, in whom 84 menisci were subjected to all-inside meniscal repair with the FasT-Fix device in conjunction with anterior cruciate ligament reconstruction. Repair was only performed on longitudinal or double longitudinal tears within the red-red or red-white zone. The repaired menisci were evaluated by second-look arthroscopy at the time of staged hardware removal after anterior cruciate ligament reconstruction.

Results

Sixty-two meniscal tears in 46 patients were available for this study. Eight patients were found to be symptomatic and considered to be clinical failures. The clinical success rate was 83%. At second-look arthroscopy, 46 tears (74%) were healed, 9 (15%) were healed incompletely, and 7 (11%) had failed. In the failed menisci, 1 had meniscal symptoms, while the other 6 were asymptomatic. In the 9 menisci with incomplete healing, 3 were associated with nonspecific knee pain but none showed meniscal symptoms. Newly formed injuries, which occurred in an area different from the original repair site, were confirmed on the surface of 19 menisci (35%) among the healed and incompletely healed menisci. Thirty menisci (48%) displayed successful and complete healing of the original tear site without newly formed tears.

Conclusion

Meniscal repair with the FasT-Fix in conjunction with anterior cruciate ligament reconstruction resulted in complete healing in 74% of cases. Eighty-three percent of menisci were symptom-free regardless of meniscal integrity. Even when the menisci repaired are asymptomatic and considered to be a clinical success, however, there may be newly formed injuries.

 
 
 
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