The Korean Journal of Internal Medicine Vol. 29, No. 5 (Suppl. 1)
WCIM 2014 SEOUL KOREA 477
Slide Session
S-GIO-06 GI Oncology
Malat-1 Promote Invasion and Migration of Gastric Cancer
Chan Hyuk Park1, Jung Hwa Lee1, Na Keum Lee1, Yong Chan Lee1, Sang Kil Lee1 Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Institute of Gastroen- terology, Yonsei University College of Medicine, Korea1
Background: Gastric cancer is one of the major causes of cancer death worldwide;
however, the mechanism of carcinogenesis is complex and poorly understood. Recently long non-coding was emerged as promoters of metastasis in various cancers including gastric cancer. Here we investigated the impact of lung adenocarcinoma transcript-1 (MALAT-1) on apoptosis, cell proliferation and cell cycle to dissect the carcinogenesis of gastric cancer and examined mechanism of invasion and metastasis.
Methods: Expression of MALAT-1 and U6 was determined by SYBR qRT-PCR in twen- ty two gastric cancer cell lines and fi fty fresh cancer tissues and adjacent tissues.
Down regulation of MALAT-1 was confi rmed by two different siRNAs. Cell counts and proliferation was determined after treatment of siRNAs. FACS using PI/Annexin-V staining carried out. Scratch wound healing assay and the matrigel invasion assay was done.
Results: The expression of MALAT-1 was signifi cantly elevated in various gastric can- cer cell lines and gastric cancer tissues compared to normal (P<0.01). SiR-MALAT-1 significantly reduced viable AGS cell and induces apoptosis (p<0.05). Deep invasion of tumor (advanced T stages) was more common in the high level of MALAT-1 group (p<0.05). siR-MALAT-1 signifi cantly decreased the AGS cell invasiveness and migration.
siR-MALAT-1 reduced expression of snail and N-cadherin and elevated E-cadherin.
Conclusions: MALAT-1 was involved in gastric carcinogenesis via inhibition of apopto- sis and promoted invasiveness via epithelial-to-mesenchymal transition.
S-GIO-07 GI Oncology
Abdominal Obesity is Inversely Related to the Size of Colorectal Cancer
Taek Gun Jeong1, Sun-Young Lee1, Hee Sun Park2, Hye Seung Han3, Dae Yong Hwang4 Department of Internal Medicine, Konkuk University School of Medicine, Korea1, Department of Radiol- ogy, Konkuk University School of Medicine, Korea2, Department of Pathology, Konkuk University School of Medicine, Korea3, Department of Surgery, Konkuk University School of Medicine, Korea4 Background/Aims: Obesity is known to be related to colorectal cancer (CRC). The aim of this study was to establish the characteristics of CRC relative to the degree of ab- dominal obesity.
Methods: CRC patients who agreed on analysis including microsatellite instability af- ter the surgical resection were included in the study. Abdominal obesity was measured on computed tomography (CT) images obtained using a multidetector CT unit (Light- Speed VCT XT or LightSpeed Pro 16, GE Healthcare, Milwaukee, WI, USA). CT image data sets were transferred to a workstation (Rapidia, INFINITT, Seoul, Korea). A single slice at the level of the umbilicus was selected for the analysis of visceral fat and sub- cutaneous fat areas.
Results: In total, 153 CRC patients were analyzed. The volume of visceral fat was inversely related to depth (Spearman’s rho=-0.208, p=0.010), size (Spearman’s rho=- 0.252, p=0.002) and volume (Spearman’s rho=-0.223, p=0.006) of the CRC. The vol- ume of subcutaneous fat was positively associated with female gender (Spearman’s rho=0.495, p<0.001), volume of visceral fat (Spearman’s rho=0.516, p<0.001), and body mass index (BMI, Spearman’s rho=0.565, p<0.001). Both the volume of subcu- taneous fat and BMI were inversely related to the CRC depth (p=0.047 and p=0.021), size (p=0.001 and p<0.001) and volume (p=0.006 and p=0.001). Of these signifi cant factors, female gender (p=0.012 and p<0.001) and smaller size of CRC (p=0.001 and p=0.037) were independently correlated with larger amounts of visceral fat and sub- cutaneous fat, respectively.
Conclusion: Subjects with a larger amount of abdominal fat tend to have a smaller CRC than those without abdominal obesity. Visceral fat and subcutaneous fat appear to slow the growth of CRCs, enabling tumors to be detected in a smaller size.
S-GIO-08 GI Oncology
HDAC Inhibitors Induce Epithelial-Mesenchymal Transition in Colonic Carcinoma Cells
Ki Bae Kim1, Joo Young Lee1, Mi Jin Kim1, Jae Geun Park1, Joung-Ho Han1, Soon Man Yoon1, Hee Bok Chae1, Seon Mee Park1, Sei Jin Youn1
Chungbuk National University Hospital, Korea1
Background: The effects of histone deacetylase (HDAC) inhibitors on the epitheli- al-mesenchymal transition (EMT) differ in various cancers. We investigated the EMT phenotypes in four colonic cancer cells when challenged with HDAC inhibitors Trichos- tatinA (TSA) and Valproic acid (VPA) with or without transforming growth factor-ß1 (TGF-ß1) treatment.
Methods: Four colonic cancer cells with different phenotypes in tumorigenicity, mi- crosatellite stability, and DNA mutation were used. EMT phenotypes were measured by the expression of E-cadherin and Vimentin using Western blot, immunofl uorescence, quantitative real time RT-PCR following treatment with TSA (100nM or 200nM) or VPA (0.5mM) with or without TGF-ß1 (5ng/ml) for 24 hours. Biological EMT pheno- types also measured by cell morphology, migration and invasion assay.
Results: TSA or VPA induced mesenchymal features in colon carcinoma cells by de- crease E-cadherin and increase Vimentin expression in the mRNA and protein levels.
Confocal microscopy revealed membranous attenuation or nuclear translocation of E-cadherin and enhanced expression of Vimentin. These responses occur after 6 hours and increased till 24 hours. Colon cancer cells changed from round or rectangular shapes to spindle shapes and increased migration and invasion by TSA or VPA treat- ment. The susceptibility to EMT changes induced by TSA or VPA was comparable in microsatellite stable cells (SW480 and HT29) and microsatellite unstable cells (DLD1 and HCT116). EMT changes were augmented by dual treatment with TSA or VPA and TGF-ß1.
Conclusion: TSA or VPA induce a mesenchymal phenotype in colonic carcinoma cells and these effects were augmented in the presence of TGF-ß1. HDAC inhibitors need careful caution for application as new anticancer drugs in colonic cancers.
K-UG-01 Upper GI Tract
Analysis of Gastric Microbiota by Pyrosequencing According to Helicobacter pylori Infection in Gastric Cancer
Hyun Jin Jo1, Nayoung Kim1, Jaeyeon Kim1, Ji Hyun Park2, Ryoung Hee Nam1, Yeong- Jae Seok3, Yeon-Ran Kim3, Joo Sung Kim2, Jung Mogg Kim4, Dong Hoo Lee1, Hyun Chae Jung2
Department of Internal Medicine, Seoul National University Bundang Hospital, Korea1, Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Korea2, Department of Biological Sciences and Institute of Microbiology, Seoul National University, Korea3, De- partment of Microbiology, College of Medicine, Hanyang University, Korea4
Background: Diverse microbiota of stomach has begun to be revealed by modern technique but our understanding is still in the early stages.We aimed to compare the differences of microbiota between groups according to disease state and Helicobacter pylori (HP) infection, and to investigate the role of microbiota in the gastric carcino- genesis.
Methods: Subjects were divided into four groups as follows; HP(-) control group (n=13), HP(+) control group (n=16), HP(-) cancer group (n=19), and HP (+) cancer group (n=15).
Gastric microbiota was assessed by barcoded 454-pyrosequencing of the 16S rRNA gene in the level of phylum, genus and species including nitrosating or nitrate reducing bacteria (NB). Differences were investigated according to biopsy site and type of sam- ple. In addition, the change of microbiota was followed-up focusing on the NB.
Results: The major phyla were Proteobacteria, Firmicutes, Actinobacteria, Bacterioi- detes and Fusobacteria, in order in all subgroups. Cancer group had proportionately fewer Proteobacteria and larger Actinobacteria compared to control. NB signifi cantly increased in the HP(+) cancer than in HP(+) control or HP(-) cancer groups. NB other than HP (nonHP-NB) was two times higher in cancer group than control group but it did not reach statistical signifi cance (10.3% vs. 5.1% in HP(-), P=0.985; 7.2% vs. 3.9%
in HP(+), P=0.453). NonHP-NB increased as time went but this phenomenon was pre- vented by HP eradication in HP(+) control group.
Conclusions: Though the pattern of phylum confi guration was similar in all subgroups, the composition of genus level showed differences in gastric cancer. The increase of nonHP-NB over time could be prevented by HP eradication therapy.
