1.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.
2.A Case of Glomerulonephritis Associated with Staphylococcal Retroperitoneal Abscess.
Joo Won BYUN ; Hyoung Joon LEE ; Yeun Jong CHOI ; Jin Soo KIM ; Hyo Youl KIM ; Byoung Geun HAN ; Eun Young LEE ; Seung Ok CHOI
Korean Journal of Nephrology 1998;17(5):818-822
The development of renal glomerular lesions secondary to severe visceral infection (pulmonary, pleural, retroperitoneal or hepatic abscess) is not generally appreciated. Such patients resemble those with infective endocarditis. The suggested pathogenetic mechanisms by which infection can cause glomerular damage are immunologic interaction, direct toxicity of a bacterial products, and some other triggering factors; However, direct correlation between the infectious and immunologic events has not been demonstrated. The histopathologic findings of infectious glomerulonephritis are variable, and these findings, as well as the clinical abnormalities, may resolve with effective antimicrobial therapy or abscess drainage. We experienced a case of glomerulonephritis and acute renal failure due to staphylococcal retroperitoneal abscess. The patient was a 58-year-old man who presented with abdominal and back pain. We performed an abdominal CT scan which showed a retroperitoneal abscess which was proven to be a staphylococcal infection upon percutaneous abscess drainage. Furthermore, we performed a renal biopsy in order to investigate hematuria, RBC casts, and proteinuria. Pathologic findings revealed postinfectious glomerulonephritis. Abscess drainage and sensitive antibiotics were administered, after which his symptoms and urinary abnormalities disappeared, and the retroperitoneal abscess subsided. Here, we report a case of a staphylococcal retroperitoneal abscess which led to postinfectious glomerulonephritis and acute renal failure along with a brief review of the literatures.
Abscess*
;
Acute Kidney Injury
;
Anti-Bacterial Agents
;
Back Pain
;
Biopsy
;
Drainage
;
Endocarditis
;
Glomerulonephritis*
;
Hematuria
;
Humans
;
Middle Aged
;
Proteinuria
;
Staphylococcal Infections
;
Tomography, X-Ray Computed
3.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
4.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.
5.Foods Inducing Typical Gastroesophageal Reflux Disease Symptoms in Korea.
Jung Wan CHOE ; Moon Kyung JOO ; Hyo Jung KIM ; Beom Jae LEE ; Ji Hoon KIM ; Jong Eun YEON ; Jong Jae PARK ; Jae Seon KIM ; Kwan Soo BYUN ; Young Tae BAK
Journal of Neurogastroenterology and Motility 2017;23(3):363-369
BACKGROUND/AIMS: Several specific foods are known to precipitate gastroesophageal reflux disease (GERD) symptoms and GERD patients are usually advised to avoid such foods. However, foods consumed daily are quite variable according to regions, cultures, etc. This study was done to elucidate the food items which induce typical GERD symptoms in Korean patients. METHODS: One hundred and twenty-six Korean patients with weekly typical GERD symptoms were asked to mark all food items that induced typical GERD symptoms from a list containing 152 typical foods consumed daily in Korea. All patients underwent upper gastrointestinal endoscopy followed by 24-hour ambulatory esophageal pH monitoring. The definition of “GERD” was if either of the 2 studies revealed evidence of GERD, and “possible GERD” if both studies were negative. RESULTS: One hundred and twenty-six cases (51 GERD and 75 possible GERD) were enrolled. In 19 (37.3%) of 51 GERD cases and in 17 (22.7%) of 75 possible GERD cases, foods inducing typical GERD symptoms were identified. In the GERD group (n = 19), frequent symptom-inducers were hot spicy stews, rice cakes, ramen noodles, fried foods, and topokki. In the possible GERD group (n = 17), frequent symptom-inducers were hot spicy stews, fried foods, doughnuts, breads, ramen noodles, coffee, pizza, topokki, rice cakes, champon noodles, and hotdogs. CONCLUSIONS: In one-third of GERD patients, foods inducing typical symptoms were identified. Hot spicy stews, rice cakes, ramen noodles, fried foods, and topokki were the foods frequently inducing typical symptoms in Korea. The list of foods frequently inducing typical GERD symptoms needs to be modified based on their own local experiences.
Bread
;
Coffee
;
Endoscopy, Gastrointestinal
;
Esophageal pH Monitoring
;
Gastroesophageal Reflux*
;
Humans
;
Korea*
;
Symptom Assessment
6.Experience on Emotional Support of Hospital Nurses.
Hyun Joo PARK ; Bok Yae CHUNG ; Ok Hee KIM ; Yun Kyung KIM ; Hyo Ja AN ; Young Nae LEE ; Hye Sun BYUN ; Kyung Soon JEONG ; Ji Youn KIM
Journal of Korean Academy of Adult Nursing 2008;20(6):852-865
PURPOSE: This study was designed to explore what experiences nurses had while caring and providing emotional support for patients. METHODS: Participants were eight nurses working at hospitals for more than one year. Data were collected from June, 2006 to January, 2007 through in-depth interview by using tape-recordings. Data were analysed with the phenomenological method proposed by Colazzi(1978). RESULTS: From significant statements, 4 clustered themes, 7 themes and 23 sub-themes were extracted from the essential meaning of the emotional experience of hospital nurses. The 4 clustered themes were 'movement of mind', 'affection and service for patients', 'worthwhile and conflict' and 'control oneself'. The 7 themes were 'special feeling', 'rapport formation', 'consideration', 'human interaction', 'value discovery', 'loss of volition', and 'keep to balance'. CONCLUSION: Although nurses had tough experiences for providing care for patients' emotional support, they had also experienced spiritual maturity from its experience. The result of this study would contribute for nurses not only to care for patients who need emotional support but also to develop knowledge in nursing.
Humans
7.Factors associated with pulmonary toxicity after myeloablative conditioning using fractionated total body irradiation.
Hwa Kyung BYUN ; Hong In YOON ; Jaeho CHO ; Hyun Ju KIM ; Yoo Hong MIN ; Chuhl Joo LYU ; June Won CHEONG ; Jin Seok KIM ; Hyo Sun KIM ; Soo Jeong KIM ; Andrew Jihoon YANG ; Byung Min LEE ; Won Hee LEE ; Joongyo LEE ; Ki Jung AHN ; Chang Ok SUH
Radiation Oncology Journal 2017;35(3):257-267
PURPOSE: Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic pneumonia syndrome (IPS), are serious side effects of total body irradiation (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical factors associated with IP and IPS following TBI. MATERIALS AND METHODS: Fifty-eight patients with hematologic malignancies who underwent TBI before allogeneic hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary toxicities were diagnosed based on either radiographic evidence or reduced pulmonary function, and were subdivided into IP and IPS based on the presence or absence of concurrent infection. RESULTS: Pulmonary toxicities developed in 36 patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly associated with increased treatment-related mortality (p = 0.028) and decreased survival (p = 0.039). Multivariate analysis revealed that the risk of developing IPS was significantly higher in patients who received stem cells from a matched unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] = 12.67; 95% confidence interval [CI], 1.46–110.30). Combining other conditioning agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064; HR = 6.19; 95% CI, 0.90–42.56). CONCLUSION: IP and IPS involve different risk factors and distinct pathogeneses that should be considered when planning treatments before and after TBI.
Cyclophosphamide
;
Hematologic Neoplasms
;
Hematopoietic Stem Cell Transplantation
;
Humans
;
Mortality
;
Multivariate Analysis
;
Pneumonia
;
Risk Factors
;
Siblings
;
Stem Cell Transplantation
;
Stem Cells
;
Tissue Donors
;
Unrelated Donors
;
Whole-Body Irradiation*
8.Factors associated with pulmonary toxicity after myeloablative conditioning using fractionated total body irradiation.
Hwa Kyung BYUN ; Hong In YOON ; Jaeho CHO ; Hyun Ju KIM ; Yoo Hong MIN ; Chuhl Joo LYU ; June Won CHEONG ; Jin Seok KIM ; Hyo Sun KIM ; Soo Jeong KIM ; Andrew Jihoon YANG ; Byung Min LEE ; Won Hee LEE ; Joongyo LEE ; Ki Jung AHN ; Chang Ok SUH
Radiation Oncology Journal 2017;35(3):257-267
PURPOSE: Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic pneumonia syndrome (IPS), are serious side effects of total body irradiation (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical factors associated with IP and IPS following TBI. MATERIALS AND METHODS: Fifty-eight patients with hematologic malignancies who underwent TBI before allogeneic hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary toxicities were diagnosed based on either radiographic evidence or reduced pulmonary function, and were subdivided into IP and IPS based on the presence or absence of concurrent infection. RESULTS: Pulmonary toxicities developed in 36 patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly associated with increased treatment-related mortality (p = 0.028) and decreased survival (p = 0.039). Multivariate analysis revealed that the risk of developing IPS was significantly higher in patients who received stem cells from a matched unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] = 12.67; 95% confidence interval [CI], 1.46–110.30). Combining other conditioning agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064; HR = 6.19; 95% CI, 0.90–42.56). CONCLUSION: IP and IPS involve different risk factors and distinct pathogeneses that should be considered when planning treatments before and after TBI.
Cyclophosphamide
;
Hematologic Neoplasms
;
Hematopoietic Stem Cell Transplantation
;
Humans
;
Mortality
;
Multivariate Analysis
;
Pneumonia
;
Risk Factors
;
Siblings
;
Stem Cell Transplantation
;
Stem Cells
;
Tissue Donors
;
Unrelated Donors
;
Whole-Body Irradiation*
9.Effect of Aspiration Thrombectomy on Microvascular Dysfunction in ST-Segment Elevation Myocardial Infarction With an Elevated Neutrophil Count.
Hye Young LEE ; Jeong Hoon KIM ; Byung Ok KIM ; Yoon Jung KANG ; Hyo Seung AHN ; Mee Won HWANG ; Kyoung Min PARK ; Young Sup BYUN ; Choong Won GOH ; Kun Joo RHEE
Korean Circulation Journal 2011;41(2):68-75
BACKGROUND AND OBJECTIVES: Aspiration thrombectomy (AT) during primary percutaneous coronary intervention (PCI) is an effective adjunctive therapy for ST-segment elevation myocardial infarction (STEMI). An elevated neutrophil count in STEMI is associated with microvascular dysfunction and adverse outcomes. We evaluated whether AT can improve microvascular dysfunction in patients with STEMI and an elevated neutrophil count. SUBJECTS AND METHODS: Seventy patients with STEMI undergoing primary PCI from August 2007 to February 2009 in our institution were classified by tertiles of neutrophil count on admission (<5,300/mm3, 5,300-7,600/mm3, and >7,600/mm3). The angiographic outcome was post-procedural thrombolysis in myocardial infarction (TIMI) flow grade. Microvascular dysfunction was assessed by TIMI myocardial perfusion (TMP) grade and ST-segment resolution on electrocardiography 90 minutes after PCI. The clinical outcome was major adverse cardiac event (MACE), defined as cardiac death, re-infarction, and target lesion revascularization at 9 months. RESULTS: There were no significant differences in the clinical characteristics and pre- and post-procedural TIMI flow grades between the neutrophil tertiles. As the neutrophil count increased, a lower tendency toward TMP grade 3 (83% vs. 52% vs. 54%, p=0.06) and more persistent residual ST-segment elevation (>4 mm: 13% vs. 26% vs. 58%, p=0.005) was observed. The 9-month MACE rate was similar between the groups. On subgroup analysis of AT patients (n=52) classified by neutrophil tertiles, the same tendency toward less frequent TMP grade 3 (77% vs. 56% vs. 47%, p=0.06) and persistent residual ST-segment elevation (>4 mm: 12% vs. 28% vs. 53%, p=0.05) was observed as neutrophil count increased. CONCLUSION: A higher neutrophil count at presentation in STEMI is associated with more severe microvascular dysfunction after primary PCI, which is not improved with AT.
Death
;
Electrocardiography
;
Humans
;
Myocardial Infarction
;
Neutrophils
;
Percutaneous Coronary Intervention
;
Perfusion
;
Thrombectomy
;
Thymidine Monophosphate
10.Effect of Aspiration Thrombectomy on Microvascular Dysfunction in ST-Segment Elevation Myocardial Infarction With an Elevated Neutrophil Count.
Hye Young LEE ; Jeong Hoon KIM ; Byung Ok KIM ; Yoon Jung KANG ; Hyo Seung AHN ; Mee Won HWANG ; Kyoung Min PARK ; Young Sup BYUN ; Choong Won GOH ; Kun Joo RHEE
Korean Circulation Journal 2011;41(2):68-75
BACKGROUND AND OBJECTIVES: Aspiration thrombectomy (AT) during primary percutaneous coronary intervention (PCI) is an effective adjunctive therapy for ST-segment elevation myocardial infarction (STEMI). An elevated neutrophil count in STEMI is associated with microvascular dysfunction and adverse outcomes. We evaluated whether AT can improve microvascular dysfunction in patients with STEMI and an elevated neutrophil count. SUBJECTS AND METHODS: Seventy patients with STEMI undergoing primary PCI from August 2007 to February 2009 in our institution were classified by tertiles of neutrophil count on admission (<5,300/mm3, 5,300-7,600/mm3, and >7,600/mm3). The angiographic outcome was post-procedural thrombolysis in myocardial infarction (TIMI) flow grade. Microvascular dysfunction was assessed by TIMI myocardial perfusion (TMP) grade and ST-segment resolution on electrocardiography 90 minutes after PCI. The clinical outcome was major adverse cardiac event (MACE), defined as cardiac death, re-infarction, and target lesion revascularization at 9 months. RESULTS: There were no significant differences in the clinical characteristics and pre- and post-procedural TIMI flow grades between the neutrophil tertiles. As the neutrophil count increased, a lower tendency toward TMP grade 3 (83% vs. 52% vs. 54%, p=0.06) and more persistent residual ST-segment elevation (>4 mm: 13% vs. 26% vs. 58%, p=0.005) was observed. The 9-month MACE rate was similar between the groups. On subgroup analysis of AT patients (n=52) classified by neutrophil tertiles, the same tendency toward less frequent TMP grade 3 (77% vs. 56% vs. 47%, p=0.06) and persistent residual ST-segment elevation (>4 mm: 12% vs. 28% vs. 53%, p=0.05) was observed as neutrophil count increased. CONCLUSION: A higher neutrophil count at presentation in STEMI is associated with more severe microvascular dysfunction after primary PCI, which is not improved with AT.
Death
;
Electrocardiography
;
Humans
;
Myocardial Infarction
;
Neutrophils
;
Percutaneous Coronary Intervention
;
Perfusion
;
Thrombectomy
;
Thymidine Monophosphate