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Articles by E Harada
Total Records ( 2 ) for E Harada
  H Suzuki , E Yamamoto , M Nojima , M Kai , H. o Yamano , K Yoshikawa , T Kimura , T Kudo , E Harada , T Sugai , H Takamaru , T Niinuma , R Maruyama , H Yamamoto , T Tokino , K Imai , M Toyota and Y. Shinomura
 

Altered expression of microRNA (miRNA) is strongly implicated in cancer, and recent studies have shown that the silencing of some miRNAs is associated with CpG island hypermethylation. To identify epigenetically silenced miRNAs in gastric cancer (GC), we screened for miRNAs induced by treatment with 5-aza-2’-deoxycytidine and 4-phenylbutyrate. We found that miR-34b and miR-34c are epigenetically silenced in GC and that their downregulation is associated with hypermethylation of the neighboring CpG island. Methylation of the miR-34b/c CpG island was frequently observed in GC cell lines (13/13, 100%) but not in normal gastric mucosa from Helicobacter pylori-negative healthy individuals. Transfection of a precursor of miR-34b and miR-34c into GC cells induced growth suppression and dramatically changed the gene expression profile. Methylation of miR-34b/c was found in a majority of primary GC specimens (83/118, 70%). Notably, analysis of non-cancerous gastric mucosae from GC patients (n = 109) and healthy individuals (n = 85) revealed that methylation levels are higher in gastric mucosae from patients with multiple GC than in mucosae from patients with single GC (27.3 versus 20.8%; P < 0.001) or mucosae from H. pylori-positive healthy individuals (27.3 versus 20.7%; P < 0.001). These results suggest that miR-34b and miR-34c are novel tumor suppressors frequently silenced by DNA methylation in GC, that methylation of miR-34b/c is involved in an epigenetic field defect and that the methylation might be a predictive marker of GC risk.

  H Nakagawa , Y Morikawa , Y Mizuno , E Harada , T Ito , K Matsui , Y Saito and H. Yasue
 

Background— Coronary spasm plays an important role in the pathogenesis of ischemic heart disease. However, similarities and differences between coronary spasm and atherosclerosis are not known. We examined the angiographic characteristics of coronary spasm in comparison with those of atherosclerosis.

Methods and Results— Thirty-two left anterior descending arteries, 11 left circumflex arteries, and 23 right coronary arteries with spasm and atherosclerotic plaque were analyzed for the localization of spasm in comparison with that of plaque in 47 patients (38 men and 9 women, mean age 66.8±10.3 yrs). Spasm predominantly occurred at the branch point as compared with plaque in each of the 3 arteries (76.7% versus 23.3%, P<0.0001; 72.7% versus 9.1%, P<0.039; and 60.0% versus 10.0%, P=0.002, in the left anterior descending, left circumflex, and right coronary arteries, respectively). Spasm involved the proximal segment less frequently as compared with plaque in each of the 3 arteries (56.7% versus 93.3%, P<0.0001; 18.2% versus 81.8%, P=0.016; and 15.0% versus 75.0%, P<0.0001 in the left anterior descending, left circumflex, and right coronary arteries, respectively). Most spasms occurred at the nonplaque site in each of the 3 arteries (73.3%, P=0.018; 100%, P<0.0001; and 75.0%, P=0.041 in the left anterior descending, left circumflex, and right coronary arteries, respectively).

Conclusion— Coronary spasm preferentially occurred at branch points and nonplaque sites, whereas the atherosclerotic lesion was predominantly localized at the nonbranch points of the curved proximal segments. Coronary spasm may thus be a manifestation of a distinct type of arteriosclerosis different from the lipid-laden coronary atherosclerosis.

 
 
 
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