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Prognosis of hepatocellular carcinoma expressing cytokeratin 19:Comparison with other liver cancers

World Journal of Gastroenterology 2012年第34期18卷 4751-4757页

作者： Jung Il Lee Jin-Woo Lee Joon Mee kim ja kyung kim Hyun Jung Chung Young Soo kim Department of Internal Medicine School of MedicineInha UniversityIncheon 400-711South Korea Department of Pathology School of MedicineInha UniversityIncheon 400-711South Korea Department of Internal Medicine Yonsei University College of MedicineGangnam Severance HospitalSeoul 135-720South Korea

AIM:To investigate whether expressing biliary phenotype predicted poor outcome after the surgical treatment in primary liver cancers. METHODS:Out of 204 patients that underwent liver resection due to hepatocellular carcinoma (HCC), liver specimens of 70 patients with HCC were evaluated for biliary components by cytokeratin (CK) 19 immunostain (CK19 - HCC and CK19 + HCC). CK19 positivity was defined as membranous and/or cytoplasmic expression in ≥ 5% of tumor cells with moderate or strong intensity. Patients with other primary liver cancers, such as com- bined HCC and cholangiocarcinoma (cHCC-CC), intrahe- patic cholangiocarcinoma (ICC) who received curative liver resection, were also included in the study. Clinical characteristics of CK19-HCC and CK19 + HCC patients, including survival outcome after curative liver resection, were compared with that of cHCC-CC and ICC patients. RESULTS: The overall survival (OS) rate of CK19 - HCC(n = 49) after the curative surgical treatment was 90.7%, and 80.4% at 1 and 5 years after the resection. OS rate of CK19 + HCC (n = 21) was 74.3%, 28.9% and OS rate of cHCC-CC (n = 22) was 66.7%, 32.2% at 1 and 5 years after the surgery. For ICC (n = 19), 1 and 5-year-OS rate was 50.2% and 14.3% after the cura-tive resection. The OS rates of CK19 + HCC and cHCC-CC were significantly lower than that of CK19-HCC, but higher than the OS rate of ICC (P = 0.000). There was no statistically significant difference in OS rate between CK19 + HCC and cHCC-CC. The disease free survival (DFS) rate of CK19-HCC was 72.0% and 54.5% at 1 and 3 years after the surgical treatment. DFS rate of CK19 + HCC was 53.3%, 34.3% and DFS rate of cHCC- CC was 51.5%, 39.2% at 1 and 3 years after the resection. For ICC, 1 and 3-year-DFS rate was 28.0% and 14.0% after the curative resection. DFS rate of CK19-HCC was significantly higher than that of ICC (P = 0.017), but marginally higher than DFS rate of either CK19 + HCC or cHCC-CC (P = 0.097, P = 0.089, respec-tively).

关键词： Cytokeratin 19 Hepatocellular carcinoma Intrahepatic cholangiocarcinoma Liver cancers Hepa-tectomy

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Comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer:a phase II trial of pembrolizumab

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Oncology Research 2025年第1期33卷 57-65页

作者： RYUL kim JOO kyung PARK MINSUK KWON MINAE AN JUNG YONG HONG JOON OH PARK SUNG HEE LIM SEUNG TAE kim Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Division of Gastroenterology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Department of Hematology-Oncology Ajou University School of MedicineSuwon-siGyeonggi-doKorea Samsung Advanced Institute of Health Science and Technology Sungkyunkwan University School of MedicineSeoulKorea

Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid ***,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still *** and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line ***:All patients had microsatellite stable(MSS)type *** of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab *** analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor ***,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated ***:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.

关键词： Pembrolizumab Whole-exome sequencing Whole-transcriptome sequencing Biliary tract cancer

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Efficacy of Pegylated Interferon Monotherapy versus Sequential Therapy of Entecavir and Pegylated Interferon in Hepatitis B e Antigen-Positive Hepatitis B Patients： A Randomized, Multicenter, Phase IIIb Open-Label Study （POTENT Study）

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Chinese Medical Journal 2018年第14期131卷 1645-1651页

作者： Dae Won Jun Sang Bong Ahn Tae Yeob kim Joo Hyun Sohn Sang Gyune kim Se Whan Lee Byung Ho kim Dong Joon kim ja kyung kim Hyoung Su kim Seong Gyu Hwang Won Choong Choi Won Young Tak Heon Ju Lee Ki Tae Yoon Byung Cheol Yun Sung Wook Lee Soon Koo Baik Seung Ha Park Ji Won Park Sol Ji Park Ji Sung Lee Department of Internal Medicine Hanyang University Seoul Hospital Hanyang University Seou104763 Korea Department of Internal Medicine Nowon Eulji Hospital Eulji University Seou101830 Korea Department of Internal Medicine Hanyang University Guri Hospital Hanyang University Guri 11923 Korea Department of Internal Medicine SoonChunHyang University Bucheon Hospital SoonChunHyang University Bucheon 14584 Korea Department of Internal Medicine SoonChunHyang University Cheonan Hospital SoonChunHyang University Cheonan 31151 Korea Department of Internal Medicine Kyung Hee University Hospital Kyung Hee University Seoul 02453 Korea Department of Internal Medicine Chuncheon Sacred Heart Hospital Hallym University Chuncheon 24252 Korea Department of Internal Medicine Kangdong Sacred Heart Hospital Hallym University Seou105355 Korea Department of Internal Medicine Gangnam Severance Hospital Yonsei University Seou106273 Korea Department of Internal Medicine CHA Bundang Medical Center CHA University Seongnam 13496 Korea Department of Internal Medicine Sanggye Paik Hospital Inje University Seoul 01757 Korea Department of Internal Medicine Kyungpook National University Hospital Kyungpook National University Daegu 41944 Korea Department of Internal Medicine Yeungnam University Medical Center Yeungnam University Daegu 42415 Korea Department of Internal Medicine Pusan National University Yangsan Hospital Pusan National University Yangsan 50612 Korea Department of Internal Medicine Kosin University Gospel Hospital Kosin University Pusan 49267 Korea Department of Internal Medicine Dong A University Medical Center Dong A University Pusan 49201 Korea Department of Internal Medicine Wonju Severance Christian Hospital Yonsei University Wonju 26426 Korea Department of Internal Medicine Haeundae Paik Hospital Inje University Pusan 48108 Korea Department of Internal Medicine Hallym University Sacred Heart Hospital Hallym University Anyang 14068 Korea Department of Cli

Background： Until now, various types of combined therapy with nucleotide analogs and pegylated interferon （Peg-INF） in patients with hepatitis B patients have been tried. Howe6ver, studies regarding the benefits of de novo combination, late-add on, and sequential treatmentare very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment. Methods： Between June 2010 and June 2015, hepatitis 13 e antigen （HBeAg）-positive patients （n = 162） received Peg-IFN for 48 weeks （mono-treatment group, n = 81） and entecavir （ETV） for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy （sequential treatment group, n = 81）. The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher＇s exact test, and regression ***： HBeAg seroconversion rate （18.2% vs. 18.2%, t = 0.03, P = 1.000） and seroclearance rate （19.7% vs. 19.7%, t = 0.03, P = 1.000） were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase （ALT） normalization （45.5% vs. 54.5%, t = 1.12, P = 0.296） and serum hepatitis B virus （HBV）-DNA 〈2000 U/L （28.8% vs. 28.8%, t = 0.10, P = 1.000） was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate （HBeAg seroconversion and serum HBV-DNA 〈2000 U/L） was not different in the two groups （12.1% vs. 16.7%, t = 1.83, P = 0.457）. Baseline HBV-DNA level （7 log10 U/ml vs. 7.5 log10 U/ml, t = 1.70, P = 0.019） and hepatitis B surface antigen titer （3.6 log10 U/ml vs. 4.0 log10 U/ml, t = 2.19, P = 0.020） were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively. Conclusions： The current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

关键词： Entecavir Hepatitis B Peginterferon Alfa-2a

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Insulinotrophic and hypolipidemic effects of Ecklonia cava in streptozotocin-induced diabetic mice

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Asian Pacific Journal of Tropical Medicine 2012年第5期5卷 374-379页

作者： Mi-ja kim Hye kyung kim Department of Food and Biotechnology Hanseo UniversitySeosan 356-706Republic of Korea Department of Pharmacology school of MedicineKyunghee UniversitySeoul 130-701Republic of Korea

Objective:To explore the anti-diabetic activity of Ecklonia cava(EC) in streptozotocin(STZ)-induced diabetic ***:Diabetes was induced by a single intraperitoneal injection of STZ(90 mg/kg).Normal and diabetic mice were treated with 0%,3%,and 5%EC diet for 4 weeks. Serum glucose and insulin concentrations,serum lipid profile,oral glucose tolerance test,and liver and pancreaticβ-cell histopathological observations were *** addition,in vitro glucose-induced insulin secretion was determined using pancreaticβ-islet ***:EC supplementation significantly and dose-dependently decreased serum glucose concentration, and improved glucose homeostasis in diabetic mice by preventing loss ofβ-cell mass resulting in increase of insulin *** triglyceride and total cholesterol concentrations in the serum and liver were markedly reduced by EC treatment in STZ-diabetic ***,LDL-,and HDL-cholesterol levels were ameliorated in EC supplemented diabetic *** steatosis induced by STZ was ameliorated by EC ***,in vitro insulinotrophic effect of EC extract was observed in pancreaticβ-***:This study demonstrated that EC is a potent and efficacious hypoglycemic and hypolipidemic agent,and prevents the loss ofβ-cell mass resulting in increase of insulin secretary capacity.

关键词： Diabetes Streptozotocin Insulin Lipid profile Pancreaticβ-cell

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Decadal Changes in Climatological Intraseasonal Fluctuation of Subseasonal Evolution of Summer Precipitation over the Korean Peninsula in the mid-1990s

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Advances in Atmospheric Sciences 2011年第3期28卷 591-600页

作者： WonMoo kim Jong-Ghap JHUN kyung-ja HA Masahide kimOTO School of Earth and Environmental Sciences/Research Institute of Oceanography Seoul National University151-742Korea Divison of Earth Environmental System Pusan National University609-735Korea Atmosphere and Ocean Research Institute University of Tokyo277-8564Japan

Decadal changes in the subseasonal evolution and the phase-locked climatological intraseasonal fluctuation of summertime rainfall over the Korean Peninsula before and after the mid-1990s are *** activity and the migration speed of the monsoon rain band over the East Asian region are altered in the recent decade,resulting in the drier conditions in late spring and the earlier onset of *** early August when a climatological monsoon break was clear in the earlier decade,the precipitation has increased dramatically with a meridional *** response to the enhanced convection over the South China Sea and southeastern China provides a favorable condition for more precipitation in early August through the changes in moisture transport and tropical cyclone passage.

关键词： decadal change intraseasonal fluctuation East Asian summer monsoon

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Impact of Fusobacterium nucleatum in the gastrointestinal tract on natural killer cells

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World Journal of Gastroenterology 2021年第29期27卷 4879-4889页

作者： Yeon Ji kim Bu kyung kim Seun ja Park jae Hyun kim Institute of Gastroenterology Kosin University College of MedicineBusan 49267Spain Department of Internal Medicine Kosin University College of MedicineBusan 49267South Korea

BACKGROUND Gut microbial dysbiosis contributes to the development and progression of colorectal cancer(CRC).Natural killer(NK)cells are involved in early defense mechanisms to kill infective pathogens and tumor cells by releasing chemokines and *** better understand the relationship between the gut microbiome and CRC,it was hypothesized here that a high abundance of Fusobacterium nucleatum(***)in the gastrointestinal tract could cause reduced NK cell *** To identify associations between gastrointestinal tract *** levels and NK cell *** In vitro experiments were performed on NK cells treated with ***,Peptostreptococcus anaerobius,and Parvimonas micra to identify the effects of gut microbiome species on NK *** 24 and 48 h of treatment,NK cell counts were *** parallel studies,C57BL/6 mice were given broadspectrum antibiotics in their drinking water to reduce resident gut *** 3 wk,the mice received the various bacterial species or phosphate-buffered saline(PBS)via oral gavage every 2 d for 6 *** the study end,blood samples were acquired to perform NK cell activity assessment and cytokine *** tissues were collected and analyzed via immunohistochemistry(IHC).RESULTS The data show that after 3 wk of broad-spectrum antibiotic treatment,levels of total bacteria and *** were markedly decreased in *** of *** significantly decreased NK cell activity relative to the activities of cells from mice treated with antibiotics only and *** administration of *** decreased the proportion of NK46+cells based on IHC staining and increased the production of interleukin-1βand tumor necrosis factor-α.CONCLUSION High levels of *** in the gastrointestinal tract reduced NK cell activity in mice,and the decrease in NK cell activity might be affected by increased proinflammatory cytokines after *** treatment.

关键词： Fusobacterium nucleatum Natural killer cells Colorectal cancer

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Association between Tropical Convection and Boreal Wintertime Extratropical Circulation in 1982/83 and 1988/89

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Advances in Atmospheric Sciences 2003年第4期20卷 593-603页

作者： ja-Yeon MOON kyung-ja HA Climate Research Laboratory Meteorological Research InstituteSeoul156-720KoreaDepartment of Atmospheric SciencesPusan National UniversityPusan609-735Korea

Boreal wintertime extratropical circulation is studied in relation to the tropical convection during the 1982/83 El Niño and 1988/89 La Niña. The anomaly structure of 1982/83 and 1988/89 over the extratropics reveals remarkably different features as the longitudinal tropical forcing region changes. The Rossby wave source (Positive) shows the largest maximum over East Asia in both years due to the persistent heating from the western Pacific warm pool area. However, the sink term shows contrasting features over the subtropics and extratropics between the two years. In the El Niño year, enhanced tropical convection over the eastern Pacific produces the Rossby wave sink at 10°N and shifted eastward over the North Pacific, while in the La Niña year, the sink area is shifted westward over the North Pacific. The contrasting features between the two events in mean-eddy interaction appears especially over the downstream area of the East Asian Jet. The extension (retraction) of the meanflow eastward (westward) to the east (west) of the dateline is related with the effect of the westward (eastward) E-vector and the strengthening (weakening) of the negative anomalies of the barotropic growth of kinetic energy. Hence, almost opposite characteristics between the two events can explain the close relationship of tropical convection and the extratropical internal variability.

关键词： tropical convection extratropical circulation rossby wave source mean-eddy interaction

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Lactic Acid Fermentation from Coffee Ground Waste Hydrolysate by Lactobacillus rhamnosus

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Journal of Renewable Materials 2019年第4期7卷 365-372页

作者： ja-Ryong Koo Hye Min Park Se kyung kim Hyun Shik Yun Department of Biological Engineering Inha UniversityIncheon 22212Korea Institute of Industrial Biotechnology Inha University Research and Business FoundationIncheon 22212Korea

Lactic acid is an important organic acid that is widely used in the food,pharmaceutical,and cosmetic *** acid was produced from coffee ground waste which contains fermentable sugars and is increasingly generated from our daily dietary *** 114 strains of Lactobacillus species,Lactobacillus rhamnosus ATCC 10863 was selected for the production of lactic acid from coffee ground *** alkali pretreatment and saccharification,cellulose and hemicellulose in coffee ground waste were converted into fermentable *** experiments were conducted at various alkali solution,concentrations,and *** pretreatment with 35 g/L of KOH at 121oC for 60 min,the highest concentration of fermentable sugars was *** optimum concentration of Viscozyme L was 2%when saccharification was proceeded at 55oC for 7 *** productivity of lactic acid fermentation was the highest(0.59 g/L/h)at 100 g of coffee ground waste(1x concentration),whereas the lactic acid concentration was the highest at 600 g of coffee ground waste(6x concentration).As the concentration of coffee ground increased,the lactic acid concentration was also increased,however,the amount was not proportional to the coffee ground waste *** this study,it was found that coffee ground waste could be used as a culture medium for Lactobacillus rhamnosus ATCC 10863 through pretreatment and saccharification for the production of lactic acid.

关键词： Coffee ground waste Lactobacillus rhamnosus lactic acid fermentable sugars saccharification alkali pretreatment

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Promoter hypomethylation and reactivation of MAGE-A1 and MAGE-A3 genes in colorectal cancer cell lines and cancer tissues

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World Journal of Gastroenterology 2006年第35期12卷 5651-5657页

作者： kyung-Hee kim Jin-Sung Choi Il-Jin kim ja-Lok Ku jae-Gahb Park Laboratory of Cell Biology Korean Cell Line Bank Cancer Research Institute Seoul National University College of Medicine Seoul 110-744 Korea Laboratory of Cell Biology Korean Cell Line Bank Cancer Research Institute Seoul National University College of Medicine Seoul 110-744

AIM： To verify the expression and methylation status of the MAGE-A1 and MAGE-A3 genes in colorectal cancer tissues and cancer cell lines. METHODS： We evaluated promoter demethylation status of the MAGE-A1 and MAGE-A3 genes by RT-PCR analysis and methylation-specific PCR （MS-PCR）, as well as sequencing analysis, after sodium bisulfite modification in 32 colorectal cancer cell lines and 87 cancer tissues. RESULTS： Of the 32 cell lines, MAGE-A1 and MAGE-A3 expressions were observed in 59% and 66%, respectively. Subsequent to sodium bisulfite modification and MSPCR analysis, the promoter hypomethylation of MAGE-A1 and MAGE-A3 was confirmed in both at 81% each. Promoter hypomethylation of MAGE-A1 and MAGE-A3 in colorectal cancer tissues was observed in 43% and 77%, respectively. Hypomethylation of MAGE-A1 and MAGE-A3 genes in corresponding normal tissues were observed in 2% and 6%, respectively. CONCLUSION： The promoter hypomethylation of MAGE genes up-regulates its expression in colorectal carcinomas as well as in gastric cancers and might play a significant role in the development and progression of human colorectal carcinomas.

关键词： MAGE-A1 MAGE-A3 Promoter Hypomethylation Colorectal cancer

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Promoter hypermethylation and loss of CD133 gene expression in colorectal cancers

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World Journal of Gastroenterology 2010年第25期16卷 3153-3160页

作者： You-kyung Jeon Sung-Hee kim Seung-Ho Choi kyung-Hee kim Byong-Chul Yoo ja-Lok Ku jae-Gahb Park Laboratory of Cell Biology Cancer Research Institute Seoul National University College of Medicine Seoul 110-799 South Korea Colorectal Cancer Branch Research Institute National Cancer Center Goyang 411-764 Gyeonggi South Korea

AIM: To understand CD133 promoter hypermethyl-ation and expression in 32 colorectal cancer cell lines. METHODS: Nucleic acid was isolated from 32 colorectal cancer cell lines and CD133 expression levels were measured by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. Promoter methylation status of the CD133 gene was analyzed with a methylation-specific PCR after sodium-bisulfi te modification and by clonal sequencing analysis. The correlation between expression and promoter methylation of CD133 gene was confirmed with treatment of 5-aza-2’-deoxycytidine. RESULTS: We measured CD133 expression levels in 32 colorectal cancer cell lines. RT-PCR analysis showed undetectable or low levels of CD133 expression in 34.4%of cell lines. To verify the relation between CD133 expression and methylation status of the CD133 gene promoter in colorectal carcinogenesis, CD133 gene promoter hypermethylation was analyzed in 32 cancer cell lines. Promoter hypermethylation was detected in 13 (40.6%) of the cell lines using methylation specificPCR and confirmed by bisulfite sequencing analysis. Treatment of 11 of the cell lines with the demethylation agent 5-aza-2’-deoxycytidine recovered CD133 expression in most of them. CONCLUSION: Transcriptional repression of CD133 is caused by promoter hypermethylation of the CD133 CpG islands in some of colorectal cancer cell lines. The study may contribute to the understanding of the role of CD133 inactivation in the progression of colorectal cancers.

关键词： CD133 Promoter Hypermethylation Colorectal cancer Sodium bisulfite modification

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