Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Yasue kimura Last modified date:2020.06.26

Associate Professor / Department of Surgery and Sciences, Graduate School of Medical Sciences / Faculty of Medical Sciences

1. Kimura Y, Oki E, Ando K, Saeki H, Kusumoto T, Maehara Y. , Incidence of Venous Thromboembolism Following Laparoscopic Surgery for Gastrointestinal Cancer: A Single-Center, Prospective Cohort Study.
, World J Surg. , 10.1007/s00268-015-3234-y., 2016.02.
2. Kimura Y, Oki E, Yoshida A, Aishima S, Zaitsu Y, Ohtsu H, Ando K, Ida S, Saeki H, Morita M, Kusumoto T, Oda Y, Maehara Y.  , Significance of accurate human epidermal growth factor receptor-2 (HER2) evaluation as a new biomarker in gastric cancer. , Anticancer Res., 2014.08.
3. Kimura Y, Oda S, Egashira A, Kakeji Y, Baba H, Nakabeppu Y, Maehara Y. , A variant form of hMTH1, a human homologue of E. coli mutT gene, correlates with somatic mutation in p53 tumour suppressor gene in gastric cancer patients. , Journal of Medical Genetics. 41:e57,2004. , 10.1136/jmg.2003.013268, 41, 5, 2004.10, Oxidative damage to diverse physiological molecules, including proteins, lipids, and nucleic acids, is an inevitable outcome of various cellular activities in living organisms. In particular, some oxidised forms of nucleotides cause miscoding of genetic information, and have therefore been present as a major threat for cells. Multigene systems to counteract such oxidative damage have evolved in diverse organisms. In E coli, several mutants designated ‘mutator’ have been isolated, and in these cells the mutation rate is significantly elevated, due to disruption of genes regulating the spontaneous mutation rate on the genome. Previous studies using these mutators have identified three genes that function in the system to counteract mutagenic oxidative damage. The mutT− strain is one of the mutators that exhibit the highest spontaneous mutation rate. Maki H et al have shown that the product of the mutT gene hydrolyses an oxidised form of guanine nucleotides, 8-oxo-2′-deoxyguanosine 5′-triphosphate (8-oxo-dGTP).1 8-oxo-dGTP incorporated into the genome stably pairs with adenine as well as cytosine in the template strand, accumulation of this oxidised form of guanine nucleotides leads to an increase in base substitution mutations—that is, A:T to G:C and G:C to T:A transversions. In the mutT− strain, the rate for A:T to C:G transversion is indeed elevated 1000 fold over the wild type level.2 The other two genes that function in cooperation with mutT are mutM (fpg) and mutY, both of which encode a DNA glycosylase to excise deleterious bases on the genome.3 The former excises 8-oxo-guanine in the opposite site of cytosine on the genome, the latter removing adenine that pairs with 8-oxo-guanine. Thus, even in cells lacking MUT, G:C to T:A transversions are suppressed low.4 Multiplicity of cellular anti-mutagenic systems guarantees the spontaneous mutation rate on the genome at an extremely low level.

Several mammalian counterparts of these E coli genes are now known. MTH1 is the first identified mammalian homologue of E coli mutT.5 The human MTH1 gene, hMTH1, has been described in detail.6 Altered function of hMTH1 and consequent elevation of the mutation rate may be an attractive hypothesis for various human diseases, particularly cancer. In several human diseases, including some common malignancies, the nucleotide sequence of hMTH1 has been explored.6 However, no apparent mutations were found. Instead, a single nucleotide polymorphism (SNP) at the first nucleotide of codon 83, which results in amino acid change from valine (V83: GTG) to methionin (M83: ATG), has been found, and the incidence of the M83 allele is relatively frequent in healthy controls (allele frequency  =  0.09).7 In mice, an mutT homologue has been identified and designated Mth1. MTH1-null mice, in which Mth1 is homozygously disrupted, have been reported.8 Although the estimated increase in the mutation rate was only twice that in wild type counterparts, relatively frequent tumourigenesis was observed in the liver, lung, and stomach of the animals.9 In patients with liver and lung cancer, sequence of hMTH1 has been determined.7 However, no relevant sequence alterations were found, and the M83 allele is not also frequent in patients with these malignancies. .