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Articles by S Hirohashi
Total Records ( 2 ) for S Hirohashi
  T Kubo , Y Kuroda , H Shimizu , A Kokubu , N Okada , F Hosoda , Y Arai , Y Nakamura , H Taniguchi , K Yanagihara , I Imoto , J Inazawa , S Hirohashi and T. Shibata
 

The tyrosine kinase (TK) family is an important regulator of signaling pathways that control a variety of physiological and pathological conditions, and a substantial proportion of TK genes are genetically altered in cancer. To clarify the somatic mutation profile of TK genes and discover potential targets for gastric cancer (GC) therapy, we undertook a systematic screening of mutations in the kinase domains of all human TK genes (636 exons of 90 genes) in 17 GC cell lines and 52 microdissected primary GCs with poorly differentiated histology. We identified 26 non-synonymous alterations (22 genes in total) that included 11 sequence alterations in cell lines and 15 somatic mutations in primary tumors. Recurrent mutations were found in four genes including a known oncogene (NTRK3), the Src kinase family (LTK and CSK) and a potential Wnt signal activator (ROR2). In addition, we analyzed copy number alterations of all the TK gene loci in the same cohort samples by array-based comparative genomic hybridization analysis and identified 24 high-level amplifications and two homozygous deletions. Both sequence alteration and frequent copy number aberration were detected in two TK genes (HCK and ERBB2), strongly suggesting that they encode potential oncogenes in GC. Our focused and integrated analyses of systemic resequencing and gene copy number have revealed the novel onco-kinome profile of GC and pave the way to a comprehensive understanding of the GC genome.

  K Kikuta , M Gotoh , T Kanda , N Tochigi , T Shimoda , T Hasegawa , H Katai , Y Shimada , Y Suehara , A Kawai , S Hirohashi and T. Kondo
  Objective

The clinical course of gastrointestinal stromal tumor (GIST) spans a wide spectrum from a curable disorder to a highly malignant disease that leads to metastasis and death. To develop prognostic modalities for GIST patients, we developed a mouse monoclonal antibody against pfetin, the prognostic value of which has been previously reported.

Methods

The reactivity of the monoclonal antibody against pfetin was examined by western blotting and immunohistochemistry.

Results

Western blotting demonstrated that the monoclonal antibody was specific to pfetin. The immunohistochemical study demonstrated that the 5-year disease-free survival rate was 93.2% and 94.5% for GIST patients with pfetin-positive tumors and 70.0% and 80.7% for those with pfetin-negative tumors in the 159 cases from the National Cancer Center Hospital (P < 0.0001) and in the 100 cases from Niigata University Medical and Dental Hospital (P < 0.0001), respectively. Uni- and multivariate analyses revealed that pfetin expression was a powerful prognostic factor among the clinico-pathological parameters examined.

Conclusions

These results establish pfetin as a practical prognostic marker for GIST patients after surgery. Pfetin may also present a novel therapeutic target to prevent recurrence of GIST.

 
 
 
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