PMID- 30008864
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 16
IP  - 2
DP  - 2018 Aug
TI  - Overexpression of MTH1 and OGG1 proteins in ulcerative colitis-associated 
      carcinogenesis.
PG  - 1765-1776
LID - 10.3892/ol.2018.8812 [doi]
AB  - Oxidative stress, demonstrated by an accumulation of 8-hydroxy-2'-deoxyguanosine 
      (8-OHdG), results in DNA damage, which is normally repaired by base excision 
      repair enzymes including 8-OHdG DNA glycosylase (OGG1) and human MutY homolog 
      (MUTYH), in addition to nucleotide pool sanitizing enzymes including MutT Homolog 
      1 (MTH1). Abnormalities of this repair system are present in various cancer 
      types. The present study aimed to elucidate the clinicopathological significance 
      of altered expression levels of inducible nitric oxide synthase (iNOS), 8-OHdG, 
      OGG1, MTH1 and MUTYH in ulcerative colitis (UC) and UC-associated neoplasms. 
      Immunohistochemical staining for these markers and p53 in 23 cases of 
      UC-associated neoplasm (Group A, 14 carcinomas and nine dysplasias), 16 cases of 
      UC without neoplasm (Group B) and 17 cases of normal colon specimens (Group C) 
      was performed. Mutation analyses was conducted for KRAS proto-oncogene, GTPase 
      (K-ras), tumor protein P53 (TP53) and isocitrate dehydrogenase (NADP (+)) 1, 
      cytosolic (IDH1) genes. Immunohistochemically, the iNOS, 8-OHdG, OGG1 and MTH1 
      expression levels were increased in Groups A and B compared with Group C. The 
      OGG1 and MTH1 expression levels in Group A were also increased compared with 
      Group B. Group A and Group B exhibited increased cytoplasmic expression and 
      decreased nuclear expression of MUTYH compared with Group C. Mutations of K-ras 
      and TP53 were detected in 2/21 (9.5%) and 10/22 (45.5%) cases of Group A, 
      respectively. IDH1 mutation was not detected in any cases. These findings suggest 
      that, as a response to oxidative damage, OGG1 and MTH1 may be upregulated in UC 
      through an inflammatory condition that progresses to cancer formation. Persisting 
      oxidative damage stress may play a role in the pathogenesis of UC-associated 
      tumors.
FAU - Kumagae, Yoshiteru
AU  - Kumagae Y
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Fukuoka 812-8582, Japan.
FAU - Hirahashi, Minako
AU  - Hirahashi M
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Fukuoka 812-8582, Japan.
FAU - Takizawa, Katsumi
AU  - Takizawa K
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Fukuoka 812-8582, Japan.
FAU - Yamamoto, Hidetaka
AU  - Yamamoto H
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Fukuoka 812-8582, Japan.
FAU - Gushima, Masaki
AU  - Gushima M
AD  - Department of Medical Gastroenterology, Shimonoseki Hospital, Yamaguchi, 
      Yamaguchi 750-8520, Japan.
FAU - Esaki, Motohiro
AU  - Esaki M
AD  - Department of Medicine and Clinical Science, Surgery and Oncology, Graduate 
      School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan.
FAU - Matsumoto, Takayuki
AU  - Matsumoto T
AD  - Division of Gastroenterology, Department of Internal Medicine, School of 
      Medicine, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
FAU - Nakamura, Masafumi
AU  - Nakamura M
AD  - Department of Medicine and Clinical Science, Surgery and Oncology, Graduate 
      School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan.
FAU - Kitazono, Takanari
AU  - Kitazono T
AD  - Department of Medicine and Clinical Science, Surgery and Oncology, Graduate 
      School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan.
FAU - Oda, Yoshinao
AU  - Oda Y
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Fukuoka 812-8582, Japan.
LA  - eng
PT  - Journal Article
DEP - 20180525
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC6036322
OTO - NOTNLM
OT  - MTH1
OT  - OGG1
OT  - base excision repair enzyme
OT  - carcinoma
OT  - oxidative stress
OT  - ulcerative colitis
EDAT- 2018/07/17 06:00
MHDA- 2018/07/17 06:01
PMCR- 2018/05/25
CRDT- 2018/07/17 06:00
PHST- 2016/12/08 00:00 [received]
PHST- 2017/09/05 00:00 [accepted]
PHST- 2018/07/17 06:00 [entrez]
PHST- 2018/07/17 06:00 [pubmed]
PHST- 2018/07/17 06:01 [medline]
PHST- 2018/05/25 00:00 [pmc-release]
AID - OL-0-0-8812 [pii]
AID - 10.3892/ol.2018.8812 [doi]
PST - ppublish
SO  - Oncol Lett. 2018 Aug;16(2):1765-1776. doi: 10.3892/ol.2018.8812. Epub 2018 May 
      25.