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Articles by H Zembutsu
Total Records ( 3 ) for H Zembutsu
  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.

  H Akaza , K Kawai , T Tsukamoto , T Fujioka , Y Tomita , T Kitamura , S Ozono , T Miki , S Naito , H Zembutsu and Y. Nakamura
  Objective

In our previous study, a combination therapy of interleukin-2 and interferon- was found to be more effective than monotherapy, especially for lung metastasis. In order to determine the genetic markers of those who positively responded, a multi-institutional open study was conducted on the patients with lung metastasis. In this paper, the clinical response to our combination therapy is reported.

Methods

Untreated patients with lung metastasis were enrolled in this study. Patients received interleukin-2 (0.7 x 106 U/day) and interferon- (6 x 106 IU/day): interleukin-2, 5 days a week and interferon-, 3 days a week for the first 8 weeks, and then both interleukin-2 and interferon-, 2 or 3 days a week for 16 additional weeks.

Results

Forty-two patients were able to be evaluated for response. The overall positive response rate was 35.7% (15 of 42) including 2 patients with complete response. Progression-free patients were observed more frequently in patients with lung metastasis only (80.6%) than those with lung plus other organ metastasis (54.5%). Tumor shrinkage was observed in 81.0% (34 of 42) of patients. Progression-free survival rate at 200 days was 63.6%. Toxicities observed were primarily flu-like symptoms due to the cytokines and were typical of those observed with each single agent.

Conclusions

Combination therapy of interleukin-2 and interferon- was confirmed to be effective for renal cell carcinoma patients with lung metastasis. Identification of genetic markers is now ongoing with the tissue samples from this trial.

 
 
 
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