Spandidos Publications Acta Medica Okayama 2049-9434 13 5 2020 Human NINEIN polymorphism at codon 1111 is associated with the risk of colorectal cancer 45 EN Yukiko Yasuda Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Sakai Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sachio Ito Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaori Sasai Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akisada Ishizaki Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiya Okano Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seito Kawahara Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshimi Jitsumori Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nagahide Matsubara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Shimizu Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Katayama Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences NINEIN serves an essential role in centrosome function as a microtubule organizing center, and in the reformation of the interphase centrosome architecture following mitosis. In the present study, the association between NINEIN Pro1111Ala (rs2236316), a missense single nucleotide polymorphism, and the risk of colorectal cancer (CRC), related to smoking and alcohol consumption habits in 200 patients with CRC and 1,141 cancer‑free control participants were assessed in a case‑control study performed in Japan. The results showed that the NINEIN Ala/Ala genotype compared with the Pro/Pro genotype was significantly more associated with an increased risk of CRC, and the males with the Ala/Ala genotype exhibited a significantly increased risk of CRC compared with those with Pro/Pro and Pro/Ala genotypes. Stratified analyses of the Ala/Ala genotype with CRC risk further showed an increased association in never/light drinkers (<23 g of ethanol/day), in male never/light drinkers and in male patients with rectal cancer. These findings suggest that the genetic variant of the NINEIN Pro1111Ala polymorphism has a significant effect on CRC susceptibility in the Japanese population. No potential conflict of interest relevant to this article was reported.

Blackwell Acta Medica Okayama 0013-9580 49 3 2007 Rasmussen encephalitis associated with SCN1A mutation 521 526 EN Iori Ohmori Departments of Cellular Physiology, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama University Mamoru Ouchida Departments of Molecular Genetics, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama University Katsuhiro Kobayashi Departments of Child Neurology, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama University Yoshimi Jitsumori Takushi Inoue Departments of Child Neurology, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama University Kenji Shimizu Departments of Molecular Genetics, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama University Hideki Matsui Departments of Cellular Physiology, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama University Yoko Ohtsuka Departments of Child Neurology, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama University Yoshihiro Maegaki Division of Child Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University Mutations in the SCN 1 A gene, encoding the neuronal voltage-gated sodium channel alpha1 subunit, cause SMEI, GEFS+, and related epileptic syndromes. We herein report the R1575C-SCN 1 A mutation identified in a patient with Rasmussen encephalitis. R1575C were constructed in a recombinant human SCN 1 A and then heterologously expressed in HEK293 cells along with the human beta1 and beta2 sodium channel accessory subunits. Whole-cell patch-clamp recording was used to define biophysical properties. The R1575C channels exhibited increased channel availability and an increased persistent sodium current in comparison to the wild-type. These defects of electrophysiological properties can result in neuronal hyperexitability. The seizure susceptibility allele may influence the pathogenesis of Rasmussen encephalitis in this case. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 71 1 2017 Human RAD 17 Polymorphism at Codon 546 Is Associated with the Risk of Colorectal Cancer 59 68 EN Yukiko Yasuda Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Sakai Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sachio Ito Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaori Sasai Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nagahide Matsubara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mamoru Ouchida Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Katayama Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Shimizu Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/54826 Human RAD17 acts as an activator of checkpoint signals in response to DNA damage. Here we evaluated the association of hRAD17 Leu546Arg (rs1045051), a missense single nucleotide polymorphism, with the risk of colorectal cancer (CRC) in relation to smoking and alcohol consumption habits in 212 CRC patients and 1,142 cancer-free controls in a case-control study conducted in Japan. The results showed that the hRAD17 Leu/Arg genotype compared to the Leu/Leu genotypes was significantly associated with the protective effect on CRC risk with the adjusted odds ratio (OR) of 0.68 [95% confidence interval (CI): 0.49−0.95, p=0.024], and the males with the Arg/Arg genotype had a greater risk of CRC compared to those with the Leu/Leu and Leu/Arg genotypes (OR=1.87, 95%CI 1.03−3.40, p=0.04). In stratified studies, the protective effect of the Leu/Arg genotype on CRC risk was markedly higher in the light smokers (< 20 pack years) (OR=0.61, 95%CI 0.40−0.94, p=0.024) and the rectal cancer patients (OR=0.49, 95%CI 0.31−0.78, p=0.003). The risk of the Arg/Arg genotype was associated with heavy smoking (≥ 20 pack-years) (OR=2.24, 95%CI 1.09−4.61, p=0.03). These findings suggest that the genetic variant of hRAD17 Leu546Arg polymorphism has a significant effect on CRC susceptibility in Japanese. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 65 5 2011 Single Nucleotide Polymorphism WRN Leu1074Phe Is Associated with Prostate Cancer Susceptibility in Chinese Subjects 315 323 EN Lei Wang Haruki Kaku Peng Huang Kexin Xu Kai Yang Jiheng Zhang Ming Li Liping Xie Xiaofeng Wang Akiko Sakai Masami Watanabe Yasutomo Nasu Kenji Shimizu Hiromi Kumon Yanqun Na Original Article 10.18926/AMO/47013 Deficiencies in the human DNA repair gene WRN are the cause of Werner syndrome, a rare autosomal recessive disorder characterized by premature aging and a predisposition to cancer. This study evaluated the association of WRN Leu1074Phe (rs1801195), a common missense single nucleotide polymorphism in WRN, with prostate cancer susceptibility in Chinese subjects. One hundred and forty-seven prostate cancer patients and 111 male cancer-free control subjects from 3 university hospitals in China were included. Blood samples were obtained from each subject, and the single nucleotide polymorphism WRN Leu1074Phe was genotyped by using a Snapshot assay. The results showed that WRN Leu1074Phe was associated with the risk of prostate cancer in Chinese men and that the TG/GG genotype displayed a decreased prevalence of prostate cancer compared with the TT genotype (OR＝0.58, 95%CI:0.35-0.97, p＝0.039). Through stratified analysis, more significant associations were revealed for the TG/GG genotype in the subgroup with diagnosis age <_ 72 yr (OR＝0.27, 95%CI:0.12-0.61, p＝0.002) and in patients with localized diseases (OR＝0.36, 95%CI:0.19-0.70, p＝0.003). However, no statistically significant difference was found in the subgroup with age ＞72 yr or in patients with advanced diseases. We concluded that the genetic variant Leu1074Phe in the DNA repair gene WRN might play a role in the risk of prostate cancer in Chinese subjects. No potential conflict of interest relevant to this article was reported.

Wiley-Liss, Inc. Acta Medica Okayama 0020-7136 112 1 2004 Tumor-specific exon creation of the HELLS/SMARCA6 gene in non-small cell lung cancer 8 13 EN Masaaki Yano Mamoru Ouchida Hisayuki Shigematsu Noriyoshi Tanaka Koichi Ichimura Kazuyasu Kobayashi Yasuhiko Inaki Shinichi Toyooka Kazunori Tsukuda Nobuyoshi Shimizu Kenji Shimizu In an attempt to identify tumor suppressor genes on chromosome 10 in non-small cell lung cancers, we isolated 10 types of splicing variants of the HELLS/ SMARCA6 gene transcripts. HELLS/SMARCA6 is a novel member of SNF2 family, which is implicated in cellular function like chromatin remodeling. Variant 1 was an alternatively spliced isoform containing an insertion of a 44-ntd intronic sequence between exons 3 and 4, giving rise to a premature termination of translation. The expression of the variant 1 was detected exclusively in the lung cancer specimens (11 of 43 cases, 26%), but was not detected in corresponding normal tissues. D10S520 marker in the proximity of the HELLS/SMARCA6 gene showed prevalent allelic loss (41%) as compared with flanking markers (25-31%). These results suggest that loss of function of HELLS/SMARCA6 by allelic loss and aberrant proteins by tumor-specific exon creation may result in epigenetic deregulation, leading the lung cells to malignancy or its progression. No potential conflict of interest relevant to this article was reported.

Elsevier Ireland Ltd. Acta Medica Okayama 0304-3835 224 2 2005 Significant growth suppression of synovial sarcomas by the histone deacetylase inhibitor FK228 in vitro and in vivo 311 319 EN Tatsuo Ito Mamoru Ouchida Yuki Morimoto Aki Yoshida Yoshimi Jitsumori Toshifumi Ozaki Hiroshi Sonobe Hajime Inoue Kenji Shimizu About 97% of synovial sarcomas harbor the SYT-SSX fusion gene by chromosomal translocation. We found that the histone deacetylase (HDAC) inhibitor FK228 significantly suppressed the growth of synovial sarcoma cells as compared with that of osteosarcoma. The 50% growth inhibition IC50 value we obtained for FK228 was 0.02-0.2 nM, and it indicates that its suppression effect on synovial sarcoma cells is the highest of any of the HDAC inhibitors yet reported. It was not likely that the growth suppression of FK228 depends on the doubling time of these cells. Introduction of SYT-SSX cDNA into HEK293 cells enhanced the sensitivity of the cells for FK228. Immunostaining of the FK228-treated cells using an anti-acetyl-histone H3 antibody showed that FK228 inhibits deacetylation of histone. In a mice assay, the growth of synovial sarcoma cells was markedly inhibited by FK228 treatment, and the invasion of tumors into surrounding tissues was suppressed. These results suggest that FK228 may be useful in developing therapeutic strategies to treat synovial sarcoma. No potential conflict of interest relevant to this article was reported.

岡山実験動物研究会 Acta Medica Okayama 13 1996 細胞癌化の機構 11 18 EN Kenji Shimizu No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 114 3 2003 ヒト癌における遺伝子異常の検索と遺伝子診断 309 323 EN No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 00301558 119 2 2007 食道扁平上皮癌の発癌過程におけるDNAメチル化の役割 113 117 EN Tatsuhiro Ishii Jun Murakami Kenji Notohara Hiromi Sasamoto Takeshi Kambara Yasuhiro Shirakawa Yoshio Naomoto Mamoru Ouchida Kenji Shimizu R. Jass Jeremy Nagahide Matsubara Noriaki Tanaka No potential conflict of interest relevant to this article was reported.