start-ver=1.4 cd-journal=joma no-vol=61 cd-vols= no-issue=8 article-no= start-page=1115 end-page=1123 dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20220415 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinicopathological Characteristics of Superficial Barrett's Adenocarcinoma in a Japanese Population: A Retrospective, Multicenter Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective Although Barrett's adenocarcinoma (BA) remains a minor disease in Japan, its incidence has been gradually increasing. We analyzed the characteristics of BA in Japanese populations.
Methods We retrospectively reviewed medical records and analyzed the clinicopathological differences between short-segment Barrett's esophagus (SSBE) and long-segment Barrett's esophagus (LSBE), as well as metastasis. Local recurrence and metachronous lesions were analyzed only in patients who underwent endoscopic resection (ER).
Patients Consecutive patients who had pathological T1 BAs resected by ER or surgery from January 2003
Results A total of 168 patients were analyzed, including 139 with SSBE and 29 with LSBE. In total, 67% of the SSBE lesions and 32% of the LSBE lesions were located between 0 and 3 o'clock (p=0.0014). No patients who achieved pathological margin-free resection (pR0) and 17% of patients who did not achieve pR0 experienced local recurrence (p=0.0131). None of the patients without lymphovascular involvement, a poorly differentiated component, lesion size of >30 mm, and submucosal invasion of >500 mu m experienced metastasis. The 5-year cumulative incidence rate of metachronous BA after ER was 0% in patients with SSBE and 40% in patients with LSBE (p=0.0005).
Conclusion Superficial BA was likely to be detected at the right anterior wall of SSBE in the Japanese population. The risk for metachronous BA after ER was high in Japanese patients with LSBE, as in Western patients. en-copyright= kn-copyright= en-aut-name=HamadaKenta en-aut-sei=Hamada en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanzakiHiromitsu en-aut-sei=Kanzaki en-aut-mei=Hiromitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiyaharaKoji en-aut-sei=Miyahara en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NakagawaMasahiro en-aut-sei=Nakagawa en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MouriHirokazu en-aut-sei=Mouri en-aut-mei=Hirokazu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MizunoMotowo en-aut-sei=Mizuno en-aut-mei=Motowo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakahashiSakuma en-aut-sei=Takahashi en-aut-mei=Sakuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HoriShinichiro en-aut-sei=Hori en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NasuJunichiro en-aut-sei=Nasu en-aut-mei=Junichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TsuzukiTakao en-aut-sei=Tsuzuki en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MiyaikeJiro en-aut-sei=Miyaike en-aut-mei=Jiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakenakaRyuta en-aut-sei=Takenaka en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamauchiKenji en-aut-sei=Yamauchi en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=KobayashiSayo en-aut-sei=Kobayashi en-aut-mei=Sayo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=ToyokawaTatsuya en-aut-sei=Toyokawa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=InoueMasafumi en-aut-sei=Inoue en-aut-mei=Masafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=NishimuraMamoru en-aut-sei=Nishimura en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MatsubaraMinoru en-aut-sei=Matsubara en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=TomodaJun en-aut-sei=Tomoda en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=YamasakiYasushi en-aut-sei=Yamasaki en-aut-mei=Yasushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=TanakaTakehiro en-aut-sei=Tanaka en-aut-mei=Takehiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=ShirakawaYasuhiro en-aut-sei=Shirakawa en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=KawaharaYoshiro en-aut-sei=Kawahara en-aut-mei=Yoshiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=OkadaHiroyuki en-aut-sei=Okada en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=Okayama Gut Study Group en-aut-sei=Okayama Gut Study Group en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Internal Medicine, Hiroshima City Hospital kn-affil= affil-num=4 en-affil=Department of Internal Medicine, Hiroshima City Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Kurashiki Central Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Kurashiki Central Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology, Kagawa Prefectural Central Hospital kn-affil= affil-num=8 en-affil=Department of Endoscopy, National Hospital Organization Shikoku Cancer Center kn-affil= affil-num=9 en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital kn-affil= affil-num=10 en-affil=Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital kn-affil= affil-num=11 en-affil=Department of Internal Medicine, Saiseikai Imabari Hospital kn-affil= affil-num=12 en-affil=Department of Internal Medicine, Tsuyama Chuo Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterology, Mitoyo General Hospital kn-affil= affil-num=14 en-affil=Department of Internal Medicine, Fukuyama City Hospital kn-affil= affil-num=15 en-affil=Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center kn-affil= affil-num=16 en-affil=Department of Gastroenterology, Japanese Red Cross Okayama Hospital kn-affil= affil-num=17 en-affil=Department of Internal Medicine, Okayama City Hospital kn-affil= affil-num=18 en-affil=Department of Internal Medicine, Sumitomo Besshi Hospital kn-affil= affil-num=19 en-affil=Department of Internal Medicine, Akaiwa Medical Association Hospital kn-affil= affil-num=20 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=21 en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=22 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=23 en-affil=Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=24 en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=25 en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=26 en-affil= kn-affil= en-keyword=Barrett's adenocarcinoma kn-keyword=Barrett's adenocarcinoma en-keyword=endoscopic resection kn-keyword=endoscopic resection en-keyword=long -segment Barrett's esophagus kn-keyword=long -segment Barrett's esophagus en-keyword=metachronous kn-keyword=metachronous en-keyword=lesion kn-keyword=lesion en-keyword=short -segment Barrett's esophagus kn-keyword=short -segment Barrett's esophagus en-keyword=surgery kn-keyword=surgery END start-ver=1.4 cd-journal=joma no-vol=27 cd-vols= no-issue=10 article-no= start-page=1602 end-page=1608 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Des-gamma-carboxyl prothrombin is associated with tumor angiogenesis in hepatocellular carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aim: Hepatocellular carcinoma (HCC) is a hypervascular tumor, and angiogenesis plays an important role in its development. Previously, we demonstrated that des-gamma-carboxyl prothrombin (DCP) promotes both cell proliferation and migration of human umbilical vein endothelial cells (HUVECs) by inducing the autophosphorylation of kinase insert domain receptor (KDR). In the present study, DCP-associated tumor angiogenesis was assessed by comparing hypovascular and common hypervascular HCC. Methods: The solitary HCCs of 827 patients were classified into two groups according to the tumor density at the arterial phase of a dynamic computed tomography scan; the initial clinical data of patients with the hyper- and hypovascular types were compared. The HCC tissues from 95 tumors were analyzed by immunohistochemical staining for DCP and phosphorylated KDR, and intratumoral microvessel density (MVD) was analyzed to evaluate microvessel angiogenesis. Results: The serum DCP levels (320 +/- 3532 mAU/mL) and tumor size (18.4 +/- 9.0 mm) of patients with hypervascular HCC were significantly greater than those with hypovascular HCC (38.7 +/- 80 mAU/mL and 14.6 +/- 5.2 mm, P < 0.001). Immunohistochemical analysis revealed that the expressions of DCP and phospho-KDR were significantly greater in hypervascular HCC (71.4% and 31.0%, respectively) than in hypovascular HCC (7.6% and 5.7%, respectively). Intratumoral MVD was significantly correlated with DCP (r = 0.48, P < 0.0001). Conclusions: des-gamma-carboxyl prothrombin production is associated with tumor angiogenesis in HCC. en-copyright= kn-copyright= en-aut-name=MatsubaraMinoru en-aut-sei=Matsubara en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShirahaHidenori en-aut-sei=Shiraha en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KataokaJyunro en-aut-sei=Kataoka en-aut-mei=Jyunro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=NishinaShin-ichi en-aut-sei=Nishina en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakaokaNobuyuki en-aut-sei=Takaoka en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=UemuraMasayuki en-aut-sei=Uemura en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NakamuraShinichiro en-aut-sei=Nakamura en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KobayashiYoshiyuki en-aut-sei=Kobayashi en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoKazuhide en-aut-sei=Yamamoto en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=2 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=3 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=4 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=5 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=6 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=7 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=8 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=9 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=10 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=11 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=12 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=13 en-affil= kn-affil=Okayama Univ Grad Sch Med & Dent, Dept Gastroenterol & Hepatol en-keyword=des-gamma-carboxyl prothrombin kn-keyword=des-gamma-carboxyl prothrombin en-keyword=hepatocellular carcinoma kn-keyword=hepatocellular carcinoma en-keyword=intratumoral microvessel density kn-keyword=intratumoral microvessel density en-keyword=kinase insert domain receptor kn-keyword=kinase insert domain receptor END start-ver=1.4 cd-journal=joma no-vol=131 cd-vols= no-issue=11 article-no= start-page=2537 end-page=2546 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20121201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Runt-related transcription factor 3 reverses epithelial-mesenchymal transition in hepatocellular carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Loss or decreased expression of runt-related transcription factor 3 (RUNX3), a tumor suppressor gene involved in gastric and other cancers, has been frequently observed in hepatocellular carcinoma (HCC). The objective of this study was to identify the regulatory mechanism of the epithelialmesenchymal transition (EMT) by RUNX3 in HCC. Human HCC cell lines, Hep3B, Huh7, HLF and SK-Hep1, were divided into low- and high-EMT lines, based on their expression of TWIST1 and SNAI2, and were used in this in vitro study. Ectopic RUNX3 expression had an anti-EMT effect in low-EMT HCC cell lines characterized by increased E-cadherin expression and decreased N-cadherin and vimentin expression. RUNX3 expression has previously been reported to reduce jagged-1 (JAG1) expression; therefore, JAG1 ligand peptide was used to reinduce EMT in RUNX3-expressing low-EMT HCC cells. Immunohistochemical analyses were performed for RUNX3, E-cadherin, N-cadherin and TWIST1 in 33 human HCC tissues, also divided into low- and high-EMT HCC, based on TWIST1 expression. E-cadherin expression was correlated positively and N-cadherin expression was correlated negatively with RUNX3 expression in low-EMT HCC tissues. Correlations between EMT markers and RUNX3 mRNA expression were analyzed using Oncomine datasets. Similarly, mRNA expression of E-cadherin was also significantly correlated with that of RUNX3 in low-EMT HCC, while mRNA expression of JAG1 was negatively correlated with that of RUNX3. These results suggest a novel mechanism by which loss or decreased expression of RUNX3 induces EMT via induction of JAG1 expression in low-EMT HCC. en-copyright= kn-copyright= en-aut-name=TanakaShigetomi en-aut-sei=Tanaka en-aut-mei=Shigetomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShirahaHidenori en-aut-sei=Shiraha en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NakanishiYutaka en-aut-sei=Nakanishi en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishinaShin-Ichi en-aut-sei=Nishina en-aut-mei=Shin-Ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsubaraMinoru en-aut-sei=Matsubara en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakaokaNobuyuki en-aut-sei=Takaoka en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KataokaJunro en-aut-sei=Kataoka en-aut-mei=Junro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KuwakiKenji en-aut-sei=Kuwaki en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HagiharaHiroaki en-aut-sei=Hagihara en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ToshimoriJunichi en-aut-sei=Toshimori en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OhnishiHideki en-aut-sei=Ohnishi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraShinichiro en-aut-sei=Nakamura en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=YagiTakahito en-aut-sei=Yagi en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YamamotoKazuhide en-aut-sei=Yamamoto en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=2 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=8 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=9 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=10 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=11 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=12 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=13 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=14 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=15 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=16 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol affil-num=17 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol Surg Transplant & Surg Oncol affil-num=18 en-affil= kn-affil=Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol & Hepatol en-keyword=cell migration kn-keyword=cell migration en-keyword=tumor invasion kn-keyword=tumor invasion en-keyword=jagged-1 kn-keyword=jagged-1 en-keyword=E-cadherin kn-keyword=E-cadherin en-keyword=N-cadherin kn-keyword=N-cadherin END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2011 dt-pub=20110104 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background: Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC). Methods: RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis. Results: RUNX3 protein expression was frequently inactivated in the HCC cell lines (91%) and tissues (90%). RUNX3 expression inhibited 90 +/- 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 +/- 4% and 4 +/- 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation. Conclusion: RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis. en-copyright= kn-copyright= en-aut-name=NakanishiYutaka en-aut-sei=Nakanishi en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShirahaHidenori en-aut-sei=Shiraha en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishinaShin-ichi en-aut-sei=Nishina en-aut-mei=Shin-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TanakaShigetomi en-aut-sei=Tanaka en-aut-mei=Shigetomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MatsubaraMinoru en-aut-sei=Matsubara en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwamuroMasaya en-aut-sei=Iwamuro en-aut-mei=Masaya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=TakaokaNobuyuki en-aut-sei=Takaoka en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UemuraMasayuki en-aut-sei=Uemura en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KuwakiKenji en-aut-sei=Kuwaki en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HagiharaHiroaki en-aut-sei=Hagihara en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ToshimoriJunichi en-aut-sei=Toshimori en-aut-mei=Junichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OhnishiHideki en-aut-sei=Ohnishi en-aut-mei=Hideki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NakamuraShinichiro en-aut-sei=Nakamura en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KobayashiYoshiyuki en-aut-sei=Kobayashi en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=YagiTakahito en-aut-sei=Yagi en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=YamamotoKazuhide en-aut-sei=Yamamoto en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ affil-num=2 en-affil= kn-affil=Okayama Univ affil-num=3 en-affil= kn-affil=Okayama Univ affil-num=4 en-affil= kn-affil=Okayama Univ affil-num=5 en-affil= kn-affil=Okayama Univ affil-num=6 en-affil= kn-affil=Okayama Univ affil-num=7 en-affil= kn-affil=Okayama Univ affil-num=8 en-affil= kn-affil=Okayama Univ affil-num=9 en-affil= kn-affil=Okayama Univ affil-num=10 en-affil= kn-affil=Okayama Univ affil-num=11 en-affil= kn-affil=Okayama Univ affil-num=12 en-affil= kn-affil=Okayama Univ affil-num=13 en-affil= kn-affil=Okayama Univ affil-num=14 en-affil= kn-affil=Okayama Univ affil-num=15 en-affil= kn-affil=Okayama Univ affil-num=16 en-affil= kn-affil=Okayama Univ affil-num=17 en-affil= kn-affil=Okayama Univ affil-num=18 en-affil= kn-affil=Okayama Univ affil-num=19 en-affil= kn-affil=Okayama Univ END