The Japanese Society of Internal Medicine Acta Medica Okayama 0918-2918 61 8 2022 Clinicopathological Characteristics of Superficial Barrett's Adenocarcinoma in a Japanese Population: A Retrospective, Multicenter Study 1115 1123 EN Kenta Hamada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromitsu Kanzaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Miyahara Department of Internal Medicine, Hiroshima City Hospital Masahiro Nakagawa Department of Internal Medicine, Hiroshima City Hospital Hirokazu Mouri Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Motowo Mizuno Department of Gastroenterology and Hepatology, Kurashiki Central Hospital Sakuma Takahashi Department of Gastroenterology, Kagawa Prefectural Central Hospital Shinichiro Hori Department of Endoscopy, National Hospital Organization Shikoku Cancer Center Junichiro Nasu Department of Internal Medicine, Okayama Saiseikai General Hospital Takao Tsuzuki Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital Jiro Miyaike Department of Internal Medicine, Saiseikai Imabari Hospital Ryuta Takenaka Department of Internal Medicine, Tsuyama Chuo Hospital Kenji Yamauchi Department of Gastroenterology, Mitoyo General Hospital Sayo Kobayashi Department of Internal Medicine, Fukuyama City Hospital Tatsuya Toyokawa Department of Gastroenterology, National Hospital Organization Fukuyama Medical Center Masafumi Inoue Department of Gastroenterology, Japanese Red Cross Okayama Hospital Mamoru Nishimura Department of Internal Medicine, Okayama City Hospital Minoru Matsubara Department of Internal Medicine, Sumitomo Besshi Hospital Jun Tomoda Department of Internal Medicine, Akaiwa Medical Association Hospital Yasushi Yamasaki Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiro Kawahara Department of Practical Gastrointestinal Endoscopy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Okada Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Gut Study Group 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. <br> 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). <br> Patients Consecutive patients who had pathological T1 BAs resected by ER or surgery from January 2003 <br> 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). <br> 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. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0815-9319 27 10 2012 Des-gamma-carboxyl prothrombin is associated with tumor angiogenesis in hepatocellular carcinoma 1602 1608 EN Minoru Matsubara Hidenori Shiraha Jyunro Kataoka Masaya Iwamuro Shigeru Horiguchi Shin-ichi Nishina Nobuyuki Takaoka Masayuki Uemura Akinobu Takaki Shinichiro Nakamura Yoshiyuki Kobayashi Kazuhiro Nouso Kazuhide Yamamoto 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. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0020-7136 131 11 2012 Runt-related transcription factor 3 reverses epithelial-mesenchymal transition in hepatocellular carcinoma 2537 2546 EN Shigetomi Tanaka Hidenori Shiraha Yutaka Nakanishi Shin-Ichi Nishina Minoru Matsubara Shigeru Horiguchi Nobuyuki Takaoka Masaya Iwamuro Junro Kataoka Kenji Kuwaki Hiroaki Hagihara Junichi Toshimori Hideki Ohnishi Akinobu Takaki Shinichiro Nakamura Kazuhiro Nouso Takahito Yagi Kazuhide Yamamoto 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. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1471-2407 11 2011 Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis EN Yutaka Nakanishi Hidenori Shiraha Shin-ichi Nishina Shigetomi Tanaka Minoru Matsubara Shigeru Horiguchi Masaya Iwamuro Nobuyuki Takaoka Masayuki Uemura Kenji Kuwaki Hiroaki Hagihara Junichi Toshimori Hideki Ohnishi Akinobu Takaki Shinichiro Nakamura Yoshiyuki Kobayashi Kazuhiro Nouso Takahito Yagi Kazuhide Yamamoto 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. No potential conflict of interest relevant to this article was reported.