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Articles by T Ishii
Total Records ( 3 ) for T Ishii
  T Ishii , J Wang , W Zhang , J Mascarenhas , R Hoffman , Y Dai , N Wisch and M. Xu
 

Pruritus is a common symptom in patients with Philadelphia chromosome–negative myeloproliferative disorders (MPDs). The pathophysiology of MPD-associated pruritus is unclear. We have demonstrated that MPD mast cells (MCs) are involved by the malignant process. In the present study, we explored the hypothesis that MCs play an important role in the development of pruritogenesis in MPDs. We found that MPD MCs released significantly greater amounts of pruritogenic factors, including histamine, leukotrienes, and interleukin-31 (IL-31) than normal MCs. Elevated levels of IL-31 were also observed in MPD CD3+ cell-conditioned media. MPD MCs exhibited increased migratory behavior in response to stem cell factor or interleukin-8, which was associated with increased filamentous-actin content. Furthermore, the presence of pruritus in MPDs was statistically correlated with a greater number of MCs being generated by CD34+ cells, a greater number of MC colonies being formed by CD34+ cells, decreased apoptosis and prostaglandin D2 release by cultured MCs, and higher plasma levels of IL-31. These data demonstrate that functional abnormalities of MPD MCs probably lead to pruritogenesis in patients with MPDs. These studies provide cellular and molecular targets for the development of antipruritus drugs for patients with MPDs.

  S Abe , Y Tsuji , T Tsushima , T Kogawa , M Abe , Y Onodera , T Mizushima , T Kukitsu , T Sumiyoshi , N Yoshizaki , T Ishii and H. Kondo
  Objective

Although combination chemotherapy with 3 weeks of S-1 and cisplatin is effective for advanced gastric cancer, the toxicities of S-1 which mostly occur during the third week of administration are a major problem. To achieve fewer adverse effects with S-1 and higher dose intensity of cisplatin, we performed combination chemotherapy with 2 weeks of S-1 and cisplatin as first line. The aim of this retrospective study was to analyse the efficacy and feasibility of this regimen.

Methods

S-1 (40–60 mg depending on patient's body surface area) was given orally twice daily for 2 consecutive weeks, and 70 mg/m2 cisplatin was given intravenously on day 8, followed by a 2-week rest period.

Results

Forty-eight patients received a total of 184 courses of chemotherapy. Overall response rate was 40.6% and median survival time was 411 days. Dose intensities were 257.6 mg/m2/week for S-1 and 16.4 mg/m2/week for cisplatin. The incidences of grade 3/4 haematological toxicities were leucopenia (19%), neutropenia (29%) and anaemia (17%), and those of grade 3 non-haematological toxicities were anorexia (31%) and nausea (21%). The rate of treatment discontinuation owing to toxicity was 10%.

Conclusions

This regimen may be effective as an alternative therapy to 3 weeks of S-1 and cisplatin to reduce the toxicity of chemotherapy for advanced gastric cancer.

  G. i Sampei , S Baba , M Kanagawa , H Yanai , T Ishii , H Kawai , Y Fukai , A Ebihara , N Nakagawa and G. Kawai
 

Glycinamide ribonucleotide synthetase (GAR-syn, PurD) catalyses the second reaction of the purine biosynthetic pathway; the conversion of phosphoribosylamine, glycine and ATP to glycinamide ribonucleotide (GAR), ADP and Pi. In the present study, crystal structures of GAR-syn’s from Thermus thermophilus, Geobacillus kaustophilus and Aquifex aeolicus were determined in apo forms. Crystal structures in ligand-bound forms were also determined for G. kaustophilus and A. aeolicus proteins. In general, overall structures of GAR-syn’s are similar to each other. However, the orientations of the B domains are varied among GAR-syn’s and the MD simulation suggested the mobility of the B domain. Furthermore, it was demonstrated that the B loop in the B domain fixes the position of the β- and - phosphate groups of the bound ATP. The structures of GAR-syn’s and the bound ligands were compared with each other in detail, and structures of GAR-syn’s with full ligands, as well as the possible reaction mechanism, were proposed.

 
 
 
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