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

  K Iida , J Mimura , K Itoh , C Ohyama , Y Fujii Kuriyama , T Shimazui , H Akaza and M. Yamamoto
 

Down-regulation of carcinogen detoxifying enzymes might be a critical factor in tumour formation by increasing the carcinogen concentration in the target organ. Previous reports revealed that the expression of UGT1A mRNA is either lost or decreased in certain human cancer tissues, including urinary bladder cancer. To elucidate this down-regulation mechanism, we used an N-nitrosobutyl (4-hydroxybutyl) amine (BBN)-induced mouse urinary bladder carcinogenesis model. Similar to human cancer, the expressions of Ugt1a6, Ugt1a9 and total Ugt1a mRNA in the BBN-induced bladder cancer were markedly decreased compared with those of normal mice. BBN down-regulated the basal Ugt1a mRNA expression in a time-dependent manner and this was reversible in the first 2 weeks of BBN treatment. However, after 4 weeks of BBN treatment the repression became persistent after the cessation of BBN treatment. Aryl hydrocarbon receptor (AhR) regulates the constitutive and inducible expression of Ugt1a mRNA. We found that the constitutive Ugt1a mRNA expression is decreased in the bladder of AhR knockout (KO) mice. Furthermore, BBN-induced Ugt1a down-regulation was lost in AhR KO mice, and the canonical AhR target gene Cyp1a1 was similarly down-regulated by BBN in the bladder. These results demonstrate that BBN repressed Ugt1a mRNA expression via suppression of AhR signaling pathway during BBN-induced carcinogenesis.

 
 
 
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