1.HOTAIR Induces Methylation of PCDH10, a Tumor Suppressor Gene, by Regulating DNMT1 and Sponging with miR-148b in Gastric Adenocarcinoma
Seung In SEO ; Jung-Ho YOON ; Hyo Joo BYUN ; Sang Kil LEE
Yonsei Medical Journal 2021;62(2):118-128
Purpose:
HOX transcript antisense intergenic RNA (HOTAIR), as a long non-coding RNA, has been reported to regulate carcinogenesis by epigenetic mechanism in various cancers. Protocadherin 10 (PCDH10) is one of the well-known tumor suppressor genes, and is frequently methylated in gastric cancers (GC). We aimed to investigate the detailed pathway of how HOTAIR contributes to the target gene in gastric carcinogenesis.
Materials and Methods:
We investigated the mechanism of HOTAIR on carcinogenesis and metastasis of GC. Methylation-specific PCR was performed to identify the interaction between HOTAIR and PCDH10. In addition, we investigated the interaction between miR-148b and HOTAIR by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.
Results:
The expression of HOTAIR was significantly upregulated in GC tissues (p<0.05) and GC cell lines (p<0.01), while PCDH10 was downregulated in GC tissues (p<0.05). The knockdown of HOTAIR (si-HOTAIR1 and 2) significantly upregulated the mRNA/protein expression of PCDH10 and reduced the methylation of PCDH10 compared to the control in MKN 28 and MKN 74. Si-HOTAIR1 and 2 significantly reduced DNA methyltransferase 1 (DNMT1) expression, and overexpression of HOTAIR increased DNMT1 expression. In RIP, we found that miR-148b interacted with HOTAIR. Si-HOTAIRs increased miR-148b expression, and miR-148b mimic inversely reduced HOTAIR expression. Si-HOTAIRs and miR-148b mimic reduced DNMT1 expression and increased PCDH10 expression compared to the control.
Conclusion
This study demonstrated that HOTAIR interacts with miR-148b and DNMT1, eventually leading to PCDH10 methylation, which contributes to the progression of GC. Our findings provide a better understanding for detailed pathway of HOTAIR in epigenetic mechanism of GC.
2.LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2in Gastric Cancer
Hyo Joo BYUN ; Jung-Ho YOON ; Sang Kil LEE
Yonsei Medical Journal 2020;61(11):923-934
Purpose:
The mechanisms of Wnt/β-catenin pathway signaling and abnormal expression of tumor suppressor genes is not well known in gastric cancer (GC). Long non-coding RNA (lncRNA) has recently been identified as a possible link therein. In this study, we investigated the role of lung cancer associated transcript 1 (LUCAT1) in GC.
Materials and Methods:
The expression of LUCAT1 in GC cell lines and 100 tissue samples was examined by qRT-PCR. Two different siRNAs were used for knockdown of LUCAT1 expression. Cell viability was assessed by MTT assay. To analyze metastasis, scratch wound-healing assay, a Matrigel invasion assay, and colony formation assay were performed. Apoptosis was analyzed by PI/Annexin-V staining. To check the methylation status in tumor suppressor genes, methylation-specific PCR was carried out.Western blot was performed to detect epithelial-mesenchymal transition and apoptosis markers upon silencing of LUCAT1 (siLUCAT1).
Results:
LUCAT1 expression in GC cell lines and tissues was significantly elevated, compared to that in normal gastric cells and adjacent non-tumor tissues (p<0.001). Two different siRNAs for LUCAT1 reduced cell proliferation, invasion, and migration, compared to siCT (p<0.05), and these reductions were restored by pcDNA-LUCAT1 (p<0.05). siLUCAT1 elicited upregulation of the expression of CXXC4 and SFRP2. The expression of H3K27me3 was reduced by siLUCAT1, and this reduction was correlated with methylation of CXXC4 and SFRP2. Inhibition of LUCAT1 up-regulated EZH2 expression and resulted in demethylation of CXXC4 and SFRP2 through the Wnt/β-catenin signaling pathway.
Conclusion
We concluded that LUCAT1 induces methylation ofCXXC4 and SFRP2, thereby regulating Wnt/β-catenin signaling in GC.
3.Clinical Usefulness of ¹â¸F-FC119S Positron-Emission Tomography as an Auxiliary Diagnostic Method for Dementia: An Open-Label, Single-Dose, Evaluator-Blind Clinical Trial
Inki LEE ; Hae Ri NA ; Byung Hyun BYUN ; Ilhan LIM ; Byung Il KIM ; Chang Woon CHOI ; In Ok KO ; Kyo Chul LEE ; Kyeong Min KIM ; Su Yeon PARK ; Yu Keong KIM ; Jun Young LEE ; Seon Hee BU ; Jung Hwa KIM ; Hee Seup KIL ; Chansoo PARK ; Dae Yoon CHI ; Jeong Ho HA ; Sang Moo LIM
Journal of Clinical Neurology 2020;16(1):131-139
BACKGROUND:
AND PURPOSE: The aim of this study was to determine the diagnostic performance and safety of a new ¹â¸F-labeled amyloid tracer, ¹â¸F-FC119S.
METHODS:
This study prospectively recruited 105 participants, comprising 53 with Alzheimer's disease (AD) patients, 16 patients with dementia other than AD (non-AD), and 36 healthy controls (HCs). In the first screening visit, the Seoul Neuropsychological Screening Battery cognitive function test was given to the dementia group, while HC subjects completed the Korean version of the Mini Mental State Examination. Individuals underwent ¹â¸F-FC119S PET, ¹â¸F-fluorodeoxyglucose (FDG) PET, and brain MRI. The diagnostic performance of ¹â¸F-FC119S PET for AD was compared to a historical control (comprising previously reported and currently used amyloid-beta PET agents), ¹â¸F-FDG PET, and MRI. The standardized uptake value (SUV) ratio (ratio of the cerebral cortical SUV to the cerebellar SUV) was measured for each PET data set to provide semiquantitative analysis. All adverse effects during the clinical trial periods were monitored.
RESULTS:
Visual assessments of the ¹â¸F-FC119S PET data revealed a sensitivity of 92% and a specificity of 84% in detecting AD. ¹â¸F-FC119S PET demonstrated equivalent or better diagnostic performance for AD detection than the historical control, ¹â¸F-FDG PET (sensitivity of 80.0% and specificity of 76.0%), and MRI (sensitivity of 98.0% and specificity of 50.0%). The SUV ratios differed significantly between AD patients and the other groups, at 1.44±0.17 (mean±SD) for AD, 1.24±0.09 for non-AD, and 1.21±0.08 for HC. No clinically significant adverse effects occurred during the trial periods.
CONCLUSIONS
¹â¸F-FC119S PET provides high sensitivity and specificity in detecting AD and therefore may be considered a useful diagnostic tool for AD.
4.Management of Clinical T1N0M0 Esophageal Cancer
Andrew J YANG ; Seo Hee CHOI ; Hwa Kyung BYUN ; Hyun Ju KIM ; Jinhyun CHOI ; Yong Chan LEE ; Sang Kil LEE ; Kyung Ran PARK ; Chang Geol LEE
Gut and Liver 2019;13(3):315-324
BACKGROUND/AIMS: Endoscopic resection is a standard treatment for stage T1a esophageal cancer, with esophagectomy or radical radiation therapy (RT) performed for stage T1b lesions. This study aimed to compare treatment outcomes of each modality for clinical stage T1 esophageal cancer. METHODS: In total, 179 patients with clinical T1N0M0-stage esophageal cancer treated from 2006 to 2016 were retrospectively evaluated. Sixty-two patients with clinical T1a-stage cancer underwent endoscopic resection. Among 117 patients with clinical T1b-stage cancer, 82 underwent esophagectomy, and 35 received chemoradiotherapy or RT. We compared overall survival (OS) and recurrence-free survival (RFS) rates for each treatment modality. RESULTS: The median follow-up time was 32 months (range, 1 to 120 months). The 5-year OS and RFS rates for patients with stage T1a cancer receiving endoscopic resection were 100% and 85%, respectively. For patients with stage T1b, the 5-year OS and RFS rates were 78% and 77%, respectively, for the esophagectomy group; 80% and 44%, respectively, for the RT alone group; and 96% and 80%, respectively, for the chemoradiation group. The esophagectomy group showed significantly higher RFS than the RT alone group (p=0.04). There was no significant difference in RFS between the esophagectomy and chemoradiation groups (p=0.922). Grade 4 or higher treatment-related complications occurred in four patients who underwent esophagectomy. CONCLUSIONS: Endoscopic resection appeared to be an adequate treatment for patients with T1a-stage esophageal cancer. The multidisciplinary approach involving chemoradiation was comparable to esophagectomy in terms of survival outcome without serious complications for T1b-stage esophageal cancer.
Chemoradiotherapy
;
Esophageal Neoplasms
;
Esophagectomy
;
Follow-Up Studies
;
Humans
;
Radiotherapy
;
Retrospective Studies
5.Long Noncoding RNA N-BLR Upregulates the Migration and Invasion of Gastric Adenocarcinoma
Young Hoon YOUN ; Hyo Joo BYUN ; Jung Ho YOON ; Chan Hyuk PARK ; Sang Kil LEE
Gut and Liver 2019;13(4):421-429
BACKGROUND/AIMS: Gastric cancer is one of the most common malignant tumors worldwide with poor prognosis due to a lack of effective treatment modalities. Recent research showed that a long noncoding RNA named N-BLR modulates the epithelial-to-mesenchymal transition (EMT) process in colorectal cancer. However, the biological role of N-BLR in gastric cancer still remains to be explored. The aim of this study was to investigate the possibility of N-BLR as an EMT modulator in gastric cancer. METHODS: The expression of N-BLR was measured by quantitative polymerase chain reaction in fresh gastric cancer tissue, paired adjacent normal tissues and cell lines. Fresh gastric tissues, paired samples obtained by surgery and clinical data were collected prospectively. Knockdown of N-BLR was induced by small interfering RNA (siRNAs). Cell number and viability were assessed after treatment with siRNAs. The ability of N-BLR to promote metastasis was measured using migration and invasion assays. Additionally, an inverse correlation between N-BLR and miR-200c was measured by TaqMan microRNA assays. Western blotting was performed to detect EMT and apoptosis markers upon knockdown of N-BLR. RESULTS: N-BLR expression was significantly elevated in gastric cancer cell lines and tissues compared to that in a normal gastric cell line and adjacent normal tissues (p<0.01). Two different siRNAs significantly reduced cell proliferation of gastric cancer cells compared to the siCT. siRNAs for N-BLR significantly suppressed migration and invasion in AGS and MKN28 cells. N-BLR expression was inversely correlated with miR-200c, which is known to regulate EMT. CONCLUSIONS: In this study, we confirmed N-BLR as a regulator of the EMT process in gastric cance
Adenocarcinoma
;
Apoptosis
;
Blotting, Western
;
Cell Count
;
Cell Line
;
Cell Proliferation
;
Colorectal Neoplasms
;
MicroRNAs
;
Neoplasm Metastasis
;
Polymerase Chain Reaction
;
Prognosis
;
Prospective Studies
;
RNA, Long Noncoding
;
RNA, Small Interfering
;
Stomach Neoplasms
6.Idiopathic Hypereosinophilic Syndrome Presenting As a Single Mass in the Liver.
Kil Chan OH ; Sang Hoon PARK ; Seung Hoon BAEK ; Chul Hee PARK ; Tae Ho HAHN ; Dong Keun LEE ; Jong Eun YEON ; Jong Hyeok KIM ; Kwan Soo BYUN ; Choong Kee PARK ; Chang Hong LEE
The Korean Journal of Gastroenterology 2004;43(1):61-65
Hypereosinophilic syndrome is characterized by persistent blood eosinophilia of 1,500/mm3 or more in the absence of known causes and multiorgan dysfunction by eosinophil-related tissue damage. In Korea, some cases of hypereosinophilic syndrome with hepatic involvement have been described with prolonged benign clinical courses. Most of them were diffuse or multifocal lesions in imaging studies, and any case presenting as a large single mass lesion has not been described. Herein we report a case of hypereosinophilic syndrome with hepatic involvement in a 48-year-old woman who presented with a giant single mass. By abdominal CT scan, a lobulated well-margined heterogenous mass lesion was detected in the left lateral segment of the liver. Liver biopsy revealed severe eosinophilic infiltration and centrilobular necrosis of hepatocytes. The lesion completely disappeared after steroid administration for eleven months.
English Abstract
;
Eosinophils/pathology
;
Female
;
Humans
;
Hypereosinophilic Syndrome/*diagnosis
;
Liver/pathology
;
Liver Diseases/*diagnosis/pathology
;
Middle Aged
7.Diffusion-weighted MR Imaging of Bone Marrow in the Spine: Differentiations of Metastatic Compression Fracture,Benign Compression Fracture, & Spondylitis.
Byung Hak RHO ; Woo Mok BYUN ; Won Gyu PARK ; Sang Ho AN ; Kil Ho CHO ; Jae Kyo LEE ; Jae Ho CHO ; Mi Soo HWANG ; Jay Chun JANG
Journal of the Korean Radiological Society 2000;43(3):349-355
PURPOSE: To determine the findings of diffusion-weighted magnetic resonance (MR) imaging of acute and chronic benign compression fracture, metastatic compression fracture, and spondylitis, and to differentiate between them. MATERIALS AND METHODS: Forty-nine cases with vertebral compression fractures (17 metastatic, 16 acute osteo-porotic, 11 old osteoporotic, 5 acute traumatic) and seven with spondylitis (4 tuberculous, 3 pyogenic) underwent MR imaging. All cases were classified as belonging to one of four groups: A: acute osteoporotic and traumatic, B: metastatic, C: old osteoporotic, or D: spondylitic. For MR imaging, a 1.5-T scanner (Magnetom Vision, Siemens, Erlangen, Germany) was used, and the diffusion-weighted imaging sequence was based on reversed fast imaging with steady-state precession (PSIF) and a relatively low b value of about 150 sec/mm 2. Signal intensity characteristics were evaluated in terms of the contrast ratio (CR) and signal-to-noise ratio (SNR) of bone marrow. RESULTS: Diffusion-weighted MR imaging showed that signal intensity in group A was hypointense to adjacent normal vertebral bodies, but in group B, hyperintensity was noted. In group C, signal intensity was variable, while in group D, hyperintensity was again noted. Diffusion-weighted imaging revealed that in group A, bone marrow CR had a negative value, while in groups B and D, this value was positive (p < .01). The SNR of group D was lower than that of group B, but the difference was not statistically significant (p > .01). CONCLUSION: Diffusion-weighted MR imaging revealed that the signal intensity of metastatic compression fracture and spondylitis was hyperintense to adjacent normal vertebral bodies, that of acute benign compression fracture was hypointense, and that of chronic benign compression fracture was variable. This modality is therefore useful for differentiating between metastatic compression fracture, spondylitis and acute benign compression fracture.
Bone Marrow*
;
Fractures, Compression*
;
Magnetic Resonance Imaging*
;
Signal-To-Noise Ratio
;
Spine*
;
Spondylitis*
8.CT Features of Peritonitis associated with Continuous Ambulatory Peritoneal Dialysis.
Ji Young YUN ; Jae Young BYUN ; Sang Hoon LEE ; Tae Ahn KWON ; Yeon Kil KIM ; Young Ok KIM ; Kyung Sup SONG
Journal of the Korean Radiological Society 1999;40(1):95-98
PURPOSE: To evaluate the CT findings of peritonitis associated with continuous ambulatory peritonealdialysis(CAPD). MATERIALS AND METHODS: We retrospectively analyzed CT scans of 14 symptomatic patients withperitonitis after CAPD. Diffuse abdominal pain was present in 11, fever in two, and abdominal mass with vomitingin one. The mean duration of CAPD ranged from 10 months to 5 years(mean : 3.9 years). On abdominal CT, weevaluated the presence and location of ascites, bowel wall thickening, cocoon formation, the pattern ofenhancement of peritoneal thickening, the presence of calcifications in the peritoneum, and mesenteric and omentalchange. RESULTS: On enhanced CT, multiloculated ascites was observed in all cases(n=14) ; it was located mainlyin the pelvic cavity with small multi-loculated fluid collections in the peritoneal cavity (n=13), including thelesser sac(n=3). In one patient, ascites was located in the space between the greater omentum and anteriorperitoneal surface. CT showed ileus in 12 cases, small bowel wall thickening in 11, and cocoon formation in five.Uneven but smooth thickening of the peritoneum, with contrast enhancement, was seen in eight cases, and in five ofthese, peritoneal thickening was more prominent in the anterior peritoneum. Other findings included reticularopacity in two cases, hematoma of the rectus muscle in one, and umbilical hernia in one. CONCLUSION:Multiloculated fluid collection, ileus, small bowel wall thickening, uneven but smooth peritoneal thickening, andcocoon formation appear to be CT features of CAPD peritonitis.
Abdominal Pain
;
Ascites
;
Dialysis
;
Fever
;
Hematoma
;
Hernia, Umbilical
;
Humans
;
Ileus
;
Omentum
;
Peritoneal Cavity
;
Peritoneal Dialysis, Continuous Ambulatory*
;
Peritoneum
;
Peritonitis*
;
Retrospective Studies
;
Tomography, X-Ray Computed
9.An Analytic Study for Incidence of Childhood Leukemia in Pusan City, Korea.
Soon Yong LEE ; Jong Bum SHIN ; Ick Ho SUNG ; Jae Sun PARK ; Young Ho LEE ; Young Tak LIM ; Jin Ho CHUN ; Kil Seo KIM ; Sung Won KIM ; Sung Taek KIM ; Heui Jin KIM ; Byung Do NAM ; Soon Ok BYUN ; Jin Kil PARK ; Son Sang SEO ; Young Suk JEON ; Kyong Suk CHO ; So Young HUH
Korean Journal of Pediatric Hematology-Oncology 1998;5(1):81-88
BACKGROUND: Cancer is the second cause of childhood death following accident, and leukemia is the most frequent childhood cancer in Korea. For the desirable control of childhood leukemia, of which the mortality is still high, the basic data for the incidence has a great importance. This is the second report from the data during 1991~1995 following the first one that analyzed the data from 328 cases of childhood leukemia during 1981~1990 in the same area, Pusan city, Korea. METHODS: The data were obtained from 138 new cases(84 males and 54 females from 0 to 15 years old) of childhood leukemia who had been living in the city of Pusan and were admitted to the 4 university hospitals and 11 general hospitals from 1991 to 1995. The cases were confirmed by CBC and bone marrow examination. RESULTS: The crude annual incidence rate per 100,000 population varied 1.50~5.30, 2.59~6.00 and 1.58~2.61 in the age group of 0~4 years, 5~9 years and 10~14 years, respectively. The standardized annual incidence rate per 100,000 population varied from 2.05 to 3.46(male 2.96~4.89, female 0.98~3.57). Sex ratio(male to female) was 1.58:1, 1.44:1, and 1.82:1 in total cases, ALL and AML, respectively, while incalculable in CML. By the major types of childhood leukemia, the cases were composed of 105 ALL (76.1%), 31 AML(22.5%), 2 CML(1.4%). CONCLUSION: It was concluded that the annual incidence rate of childhood leukemia per 100,000 population in Pusan city during 1991~1995 was similar to that of previous report during 1981~1990, while the proportion of ALL had tendency to increase up to that of United States, in contrast to the low proportions of ALL in the previous reports.
Bone Marrow Examination
;
Busan*
;
Female
;
Hospitals, General
;
Hospitals, University
;
Humans
;
Incidence*
;
Korea*
;
Leukemia*
;
Male
;
Mortality
;
United States
10.Brain MRI Findings of Spontaneous Intracranial Hypotension.
Won Kyu PARK ; Woo Mok BYUN ; Yang Gu JOO ; Jae Ho CHO ; Kil Ho CHO ; Mi Soo HWANG ; Bok Hwan PARK ; Sang Jin LEE
Journal of the Korean Radiological Society 1997;37(3):385-391
PURPOSE: To evaluate brain MRI findings of spontaneous intracranial hypotension. MATERIALS AND METHODS: A retrospective review of MRI findings was conducted on six patients with clinically proven spontaneous intracranial hypotension ; no patient had history of previous spinal puncture. Follow-up MRI was available in two patients, and to detect CSF leakage, radionuclide cisternography (n=5), myelography (n=1), and MR myelography (n=1) were performed. RESULTS: On contrast-enhanced T1WI, diffuse dural enhancement was seen in all cases, subdural hematoma or hygroma was seen in four cases, pituitary gland prominence in four, dural sinus dilatation in four, downward displacement of cerebellar tonsil in two, downward displacement of iter in one, and suprasellar and prepontine cistern effacement in two. In no patient was abnormal CSF leakage found. CONCLUSION: Although dural enhancement, as seen on MRI, is not specific, diffuse enhancement of dura matter accompanying by subdural hematoma, hygroma, pituitary gland prominence, dural sinus dilatation, downward displacement of the cerebellar tonsil, or suprasellar and prepontine cistern effacement can strongly suggest intracranial hypotension.
Brain*
;
Dilatation
;
Follow-Up Studies
;
Hematoma, Subdural
;
Humans
;
Intracranial Hypotension*
;
Lymphangioma, Cystic
;
Magnetic Resonance Imaging*
;
Myelography
;
Palatine Tonsil
;
Pituitary Gland
;
Retrospective Studies
;
Spinal Puncture

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