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Notch1 and Notch4 are markers for poor prognosis of hepatocellular carcinoma

Hepatobiliary & Pancreatic Diseases International 2013年第3期12卷 286-294页

作者： Soomin Ahn Jiyeon Hyeon cheol-keun park Department of Pathology Samsung Medical Center Sungkyunkwan University School of Medicine

BACKGROUND: Notch signaling is critical to physiologic angiogenesis and has been implicated in tumor angiogenesis and metastasis. Notch signaling was reported to exert either oncogenic or tumor-suppressive function in hepatocellular carcinoma (HCC) tumorigenesis. However, the prognostic significance of Notch receptors in HCC remains uncertain. In this study, we investigated the roles of Notch receptors in the prognosis of HCC. METHODS: We investigated the expressions of Notch receptors in tumor tissue microarrays of 288 patients with primary HCC who had undergone curative resection using immunohistochemistry. Additionally, prognostic factors of HCC were examined by univariate and multivariate analyses. The median follow-up period was 97.1 months. Tumor recurrence was detected in 189 patients (65.6%), and 99 (34.4%) died of HCC. RESULTS: Cytoplasmic expression of Notch1, cytoplasmic expression of Notch3, coexistent nuclear expression of Notch3, and cytoplasmic Notch4 overexpression were observed in 145 (50.3%), 60 (20.8%), 17 (5.9%), and 172 (59.7%) of the 288 HCCs, respectively. Multivariate analyses revealed that Notch1 expression (P=0.029), Edmondson grade Ⅲ (P=0.038), and higher BCLC stage (P<0.001) were independent predictors of shorter disease-free survival. Cytoplasmic Notch3 expression tended to be an independent predictor of shorter disease-free survival (P=0.055). Notch1 expression (P=0.039), Notch4 overexpression (P=0.012), and higher BCLC stage (P<0.001) were independent predictors of shorter disease-specific survival. On univariate analysis, Notch1 expression tended to show an unfavorable influence on disease-specific survival (P=0.063) and Notch4 overexpression did not show an unfavorable influence on disease-specific survival (P=0.103). CONCLUSIONS: Notch1 expression might be an independent predictor of both shorter disease-free survival and shorter disease-specific survival in HCC patients after curative resection. Notch4 overexpression might be

关键词： Notch1 Notch4 hepatocellular carcinoma recurrence survival

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Smad3 and its phosphoisoforms are prognostic predictors of hepatocellular carcinoma after curative hepatectomy

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Hepatobiliary & Pancreatic Diseases International 2012年第1期11卷 51-59页

作者： Seok-Hyung Kim Soomin Ahn cheol-keun park Department of Pathology Samsung Medical CenterSungkyunkwan University School of Medicine

BACKGROUND:Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis,which correlate with recurrence after surgical treatment and poor *** may be an unusual cancer affected by continuous inflammation that can lead to consistent upregulation of transforming growth factor-β (TGF-β).Chronic inflammation shifts hepatocytic TGF-β signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L *** this study,we investigated the functional roles of Smad3 and its phosphoisoforms in the progression of ***:Tumor tissue microarrays of samples from 272 HCC patients who underwent curative surgical resection were used to detect the expression of Smad3,Smad4,pSmad3C (S423/425),pSmad3L (T179),pSmad3L (S204),and pSmad3L (S213).Disease-specific death was defined as 1) tumor occupying more than 80% of the liver,2) portal venous tumor thrombus (PVTT) proximal to the second bifurcation,3) obstructive jaundice due to tumor,4) distant metastases,or 5) variceal hemorrhage with PVTT proximal to the first *** the time of analysis,tumor recurrence was detected in 184 (67.6%) patients,and 96 (35.3%) had died of ***:Nuclear and cytoplasmic localization of Smad3,and nuclear localization of Smad4 were observed in 18.0%,9.9%,and 9.2% of HCCs,*** rates of Smad3 phosphoisoform-immunoreactive HCC varied according to the location of phosphorylation:pSmad3C (S423/425) 8.1%,pSmad3L (T179) 2.6%,pSmad3L (S204) 2.2%,and pSmad3L (S213) 10.3%.Multivariate analyses revealed that pSmad3C (S423/425) (P=0.022) was an independent predictor of longer recurrence-free ***3L (S213) (P=0.006),intrahepatic metastasis,multicentric occurrence,and liver cirrhosis were independent predictors of shorter recurrence- free *** Smad3 (P=0.006),larger tumor size,and intrahepatic metastasis were independent predictors of shorter disease-specific *** pSmad3L (S213) did not sh

关键词： Smad3 pSmad3C (S423/425) pSmad3L (S213) hepatocellular carcinoma hepatectomy survival

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Expression of prothymosin α predicts early recurrence and poor prognosis of hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2015年第2期14卷 171-177页

作者： Sang Yun Ha Dae Hyun Song Soo Hyun Hwang Soo Youn Cho cheol-keun park Department of Pathology Samsung Medical CenterSungkyunkwan University School of Medicine

BACKGROUND：Prothymosinα（PTMA）is a nuclear oncoprotein-transcription factor essential for cell cycle progression and *** was overexpressed in several human malignancies including hepatocellular carcinoma（HCC）.However,the prognostic significance of PTMA protein expression in HCC remains *** the present study,we evaluated PTMA protein expression by immunohistochemistry in order to elucidate the prognostic roles of PTMA in HCC ***： By immunohistochemistry, we investigated the expression of PTMA protein in tumor tissue from 226 HCC patients who underwent curative hepatectomy. Univariate and multivariate analyses were performed to evaluate its predic- tive value for tumor recurrence and survival of patients. The median follow-up period was 120 months. RESULTS： PTMA expression was observed in 162 （71.7%） of the 226 HCC patients and was significantly associated with higher Edmondson grade, microvascular invasion, intrahe- patic metastasis, higher American Joint Committee on Cancer （AJCC） T-stage, and lower albumin level. PTMA expression was an independent predictor of early recurrence （P=0.001）. PTMA expression showed an unfavorable influence on recurrence- free survival （RFS）（P〈0.001）. Subgroup analysis showed that among patients with tumor size _〈5.0 cm （140 patients）, patients at AJCC T-stage I （95 patients） and patients with a-fetoprotein ≤20 ng/mL （83 patients）, the differences in RFS between PTMA- positive and PTMA-negative groups were also statistically sig- nificant （P=0.017, P=0.002 and P=0.002, respectively）. In addi- tion, PTMA expression was an independent predictor of shorter RFS （P=0.011）. PTMA expression showed an unfavorable influ- ence on overall survival （P=0.014）, but was not an independent predictor of shorter overall survival （P=0.161）. CONCLUSIONS： PTMA protein expression might be a novel predictor of early recurrence and RFS in HCC patients, even those at early stage or with a-fetoprotein-negative after curative hep

关键词： prothymosin a hepatocellular carcinoma recurrence

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Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 353-360页

作者： Seogsong Jeong Sun Jae park Seong Kyun Na Sang Min park Byung-cheol Song Yun Hwan Oh Department of Biomedical Sciences Seoul National University Graduate SchoolSeoul 03080Korea Department of Biomedical Informatics CHA University School of MedicineCHA UniversitySeongnam 13488Korea Department of Internal Medicine Inje University College of MedicineSeoul 50834Korea Department of Family Medicine Seoul National University HospitalSeoul National University College of MedicineSeoul 03080Korea Department of Internal Medicine Jeju National University HospitalJeju National University College of MedicineJeju 63241Korea Department of Family Medicine Jeju National University HospitalJeju National University College of MedicineJeju 63241Korea Department of Family Medicine Chung-Ang University Gwangmyeong HospitalChung-Ang University College of MedicineGwangmyeong 14353Korea

Background:The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease(K-NAFLD)score was recently developed with the intent to operationally define nonalcoholic fatty liver disease(NAFLD).However,there remained an external validation that confirmed its diagnostic performance,especially in patients with alcohol consumption or hepatitis virus ***:Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®.Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score,fatty liver index(FLI),and hepatic steatosis index(HSI).Results:K-NAFLD-moderate[adjusted odds ratio(aOR)=2.53,95%confidence interval(CI):1.13-5.65]and K-NAFLD-high(aOR=4.14,95%CI:1.69-10.13)groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics,and FLI-moderate and FLI-high groups revealed aORs of 2.05(95%CI:1.22-3.43)and 1.51(95%CI:0.78-2.90),*** addition,the HSI was less predictive for Fibroscan®-defined fatty *** K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection,and the adjusted area under curve values were comparable between K-NAFLD and ***:Externally validation of the K-NAFLD and FLI showed that these scores may be a useful,noninvasive,and non-imaging modality for the identification of fatty *** addition,these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

关键词： Nonalcoholic fatty liver disease Fatty liver index Hepatic steatosis index

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Chemical and mechanical properties of stainless, environment-friendly, and nonflammable Mg alloys (SEN alloys): A review

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Journal of Magnesium and Alloys 2024年第3期12卷 841-872页

作者： Jong Un Lee Hyun Ji Kim Sang-cheol Jin Ye Jin Kim Young Min Kim Bong Sun You Jun Ho Bae Sung Hyuk park Advanced Metals Division Korea Institute of Materials ScienceChangwon 51508Republic of Korea Department of Materials Science and Metallurgical Engineering Kyungpook National UniversityDaegu 41566Republic of Korea Missile Research Institute Agency for Defense DevelopmentDaejeon 34060Republic of Korea

This review article provides overall understanding of stainless,environment-friendly,and nonflammable Mg alloys(SEN alloys)recently developed at the Korea Institute of Materials *** alloys are produced by adding small amounts of Ca and Y(each<1 wt%)into commercial Mg–Al based alloys,resulting in exceptional ignition and corrosion resistances and impressive mechanical *** main advantages of SEN alloys are as follows.(1)A dense multi-oxide layer of SEN alloys comprising MgO,CaO,and Y_(2)O_(3) impedes the outward dispersion of Mg vapor and the inward penetration of O_(2) during oxidation,thereby enhancing the oxidation and ignition resistances.(2)The presence of Ca-and Y-based second-phase particles in SEN alloys can enhance their corrosion resistance because Ca-containing particles prevent the spread of corrosion,and the replacement of Al-containing particles with less noble ones containing Y(e.g.,Al–Mn–Y or Al–Y particles)retards corrosion.(3)The addition of minor amounts of Ca and Y renders excellent mechanical properties due to improved strengthening *** enhanced properties are attributed to more pronounced dynamic recrystallization and grain refining behaviors caused by the second-phase particles during extrusion.(4)Despite the presence of various types of second-phase particles,the fatigue properties of SEN9 alloys are similar to those of commercial AZ91 alloys.(5)Simultaneous introduction of Ca and Y suppresses the formation of Mg17Al12 discontinuous precipitates during aging,leading to the enhanced elongation of aged SEN alloys.(6)Adding mischmetal into the SEN9 alloy leads to a six-fold enhancement in ***,the studies conducted on SEN alloys demonstrate their excellent ignition and corrosion resistances and mechanical properties,which broaden the industrial applications of Mg alloys by addressing their inherent weaknesses.

关键词： SEN magnesium alloy Corrosion resistance Ignition resistance Mechanical properties Extrudability.

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Diagnosis of gastric epithelial neoplasia:Dilemma for Korean pathologists

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World Journal of Gastroenterology 2011年第21期17卷 2602-2610页

作者： Joon Mee Kim Mee-Yon Cho Jin Hee Sohn Dae Young Kang cheol keun park Woo Ho Kim So-Young Jin Kyoung Mee Kim Hee Kyung Chang Eunsil Yu Eun Sun Jung Mee Soo Chang Jong Eun Joo Mee Joo Youn Wha Kim Do Youn park Yun Kyung Kang Sun Hoo park Hye Seung Han Young Bae Kim Ho Sung park Yang Seok Chae Kye Won Kwon Hee Jin Chang The Gastrointestinal Pathology Study Group of Korean Society of Pathologists Department of Pathology Inha University Hospital Department of Pathology Yonsei University Wonju College of Medicine Wonju Christian Hospital Department of Pathology Sungkyunkwan University School of MedicineKangbuk Samsung Medical Center Department of Pathology Chungnam National University College of Medicine Department of Pathology Sungkyunkwan University School of MedicineSamsung Medical Center Department of Pathology Seoul National University College of Medicine Department of Pathology Soonchunhyang University Hospital Department of Pathology Kosin University College of Medicine Department of Pathology University of Ulsan College of MedicineAsan Medical Center Department of Pathology The Catholic University of KoreaSeoul St.Mary's Hospital Department of Pathology Seoul National University Boramae Hospital Department of Pathology Eulji General Hospital Department of Pathology Inje University Ilsan Paik Hospital Department of Pathology Kyunghee University College of Medicine Department of Pathology Pusan National University College of Medicine Department of Pathology Inje University Seoul Paik Hospital Department of Pathology Korea Cancer Center Hospital Department of Pathology Konkuk University Medical Center Department of Pathology Ajou University School of Medicine Department of Pathology Chonbuk National University Medical School Department of Pathology Korea University College of Medicine Department of Pathology Bundang Jesaeng Hospital Department of Pathology National Cancer Center The Korean Society of Pathologists 4FThe Korean Medical Association BuildingSeoul 140-721South Korea

The histopathological diagnosis of gastric mucosal biopsy and endoscopic mucosal resection/endoscopic submucosal dissection specimens is important,but the diagnostic criteria,terminology,and grading system are not the same in the East and West.A structurally invasive focus is necessary to diagnose carcinoma for most Western pathologists,but Japanese pathologists make a diagnosis of cancer based on severe dysplastic cytologic atypia irrespective of the presence of *** the Vienna classification was introduced to reduce diagnostic discrepancies,it has been difficult to adopt due to different concepts for gastric epithelial neoplastic *** pathologists experience much difficulty making a diagnosis because we are influenced by Japanese pathologists as well as Western *** is geographically close to Korea,and academic exchanges are ***,Korean doctors are familiar with Western style medical *** a result,the terminology,definitions,and diagnostic criteria for gastric intraepithelial neoplasia are very heterogeneous in *** solve this problem,the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has made an effort and has suggested guidelines for differential diagnosis:(1) a diagnosis of carcinoma is based on invasion;(2) the most important characteristic of low grade dysplasia is the architectural pattern such as regular distribution of crypts without severe branching,budding,or marked glandular crowding;(3) if nuclear pseudostratification occupies more than the basal half of the cryptal cells in three or more adjacent crypts,the lesion is considered high grade dysplasia;(4) if severe cytologic atypia is present,careful inspection for invasive foci is necessary,because the risk for invasion is very high;and(5) other structural or nuclear atypia should be evaluated to make a final decision such as cribriform pattern,papillae,ridges,vesicular nuclei,high nuclear/cytoplasmic ratio,loss

关键词：病理诊断粘膜上皮理学家胃粘膜韩国学术交流活动发育不良细胞学

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Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules

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World Journal of Gastroenterology 2005年第14期11卷 2072-2079页

作者： Seung Oe Lim Sung Gyoo park Jun-Hi Yoo Young Min park Hie-Joon Kim Kee-Taek Jang Jae Won Cho Byung Chul Yoo Gu-Hung Jung cheol keun park School of Biological Sciences Seoul National University SeoulKorea Hepatology Center and Laboratory of Hepatocarcinogenesis Bundang Jesaeng General Hospital KyungkidoKorea School of Chemistry Seoul National University SeoulKorea Department of Pathology Samsung Medical Center Sungkyunkwan University School of MedicineSeoulKorea General Surgery Samsung Medical Center Sungkyunkwan University School of MedicineSeoulKorea Internal Medicine Samsung Medical Center Sungkyunkwan University School of MedicineSeoulKorea

AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the differential expression of HSPs in multistep hepatocarcinogenesis. It was the purpose of this study to monitor the expression of HSPs in multistep hepatocarcinogenesis and to evaluate their prognostic significance in hepatitis B virus (HBV)related ***: Thirty-eight HCC and 19 DN samples were obtained from 52 hepatitis B surface antigen-positive Korean patients. Immunohistochemical and dot immunoblot analyses of HSP27, HSP60, HSP70, HSP90, glucoseregulated protein (GRP)78, and GRP94 were performed and their expression at different stages of HCC development was statistically ***: Expression of HSP27, HSP70, HSP90, GRP78, and GRP94 increased along with the stepwise progression of hepatocarcinogenesis. Strong correlation was found only in GRP78 (Spearman's r= 0.802). There was a positive correlation between the expressions of GRP78, GRP94, HSP90, or HSP70 and prognostic factors of HCC. Specifically, the expression of GRP78, GRP94, or HSP90 was associated significantly with vascular invasion and intrahepatic ***: The expressions of HSPs are commonly up-regulated in HBV-related HCCs and GRP78 might play an important role in the stepwise progression of HBVrelated hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.

关键词：热负荷蛋白基因表达乙型肝炎病毒肝细胞癌发育异常结节

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Parameter estimation for building energy models using GRcGAN

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Building Simulation 2023年第4期16卷 629-639页

作者： Hansol Shin cheol-Soo park Department of Architecture and Architectural Engineering College of EngineeringSeoul National UniversitySeoul08826R.O.Korea Institute of Construction and Environmental Engineering Institute of Engineering ResearchCollege of EngineeringSeoul National UniversitySeoul08826R.O.Korea

Parameter estimation methods can be classified into(1)manual(trial-and-error),(2)numerical optimization(optimization,sampling),(3)Bayesian inference(Bayes filter,Bayesian calibration),and(4)machine learning(generative model).Bayesian calibration has been widely used because it can capture stochastic nature of uncertain ***,the results of Bayesian calibration could be biased by(1)the prior distribution assumed by the expert’s subjective judgment;(2)the likelihood function that cannot always describe the true likelihood;and(3)the posterior distribution approximation method,such as the Markov Chain Monte Carlo,which requires significant computation *** overcome this,a new approach using a generator-regularized continuous conditional generative adversarial network(GRcGAN)is presented in this *** target parameters of the DOE reference building model were *** was trained to estimate uncertain parameters using simulated monthly electricity and gas *** can successfully estimate five uncertain parameters based on 1,000 training data *** proposed approach presents a potential for stochastic parameter estimation.

关键词： generative adversarial networks generative model parameter estimation inverse problem model calibration parameter uncertainty

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Comprehensive analysis of two-dimensional charge transport mechanism in thin-film transistors based on random networks of single-wall carbon nanotubes using transient measurements

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Nano Research 2022年第2期15卷 1524-1531页

作者： Hyeonwoo Shin Sang-Joon park Byeong-cheol Kang Tae-Jun Ha Department of Electrical Engineering and Computer Science Inter-university Semiconductor Research CenterSeoul National UniversitySeoul 08826Korea Department of Electronic Materials Engineering Kwangwoon UniversitySeoul 01897Korea

Understanding charge transport mechanisms in thin-film transistors based on random networks of single-wall carbon nanotubes(SWCNT-TFTs)is essential for further advances to improve the potential for various nanoelectronic ***,a comprehensive investigation of the two-dimensional(2D)charge transport mechanism in SWCNT-TFTs is reported by analyzing the temperature-dependent electrical characteristics determined from the direct-current and non-quasi-static transient measurements at 80-300 *** elucidate the time-domain charge transport characteristics of the random networks in the SWCNTs,an empirical equation was derived from a theoretical trapping model,and a carrier velocity distribution was determined from the differentiation of the transient ***,charge trapping and de-trapping in shallow-and deep-traps in SWCNT-TFTs were analyzed by investigating charge transport based on their trapping/de-trapping *** comprehensive analysis of this study provides fundamental insights into the 2D charge transport mechanism in TFTs based on random networks of nanomaterial channels.

关键词： single-wall carbon nanotube random networks two-dimensional(2D)charge transport time-domain transient measurements charge trapping/de-trapping shallow-/deep-traps

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Scale-invariant machine-learning model accelerates the discovery of quaternary chalcogenides with ultralow lattice thermal conductivity

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npj Computational Materials 2022年第1期8卷 455-466页

作者： Koushik Pal cheol Woo park Yi Xia Jiahong Shen Chris Wolverton Department of Materials Science and Engineering Northwestern UniversityEvanstonIL60208USA

We design an advanced machine-learning(ML)model based on crystal graph convolutional neural network that is insensitive to volumes(i.e.,scale)of the input crystal structures to discover novel quaternary chalcogenides,AMM′Q3(A/M/M'=alkali,alkaline earth,post-transition metals,lanthanides,and Q=chalcogens).These compounds are shown to possess ultralow lattice thermal conductivity(κ_(l)),a desired requirement for thermal-barrier coatings and *** screening the thermodynamic stability of~1 million compounds using the ML model iteratively and performing density-functional theory(DFT)calculations for a small fraction of compounds,we discover 99 compounds that are validated to be stable in *** several DFT-stable compounds,we calculate theirκl using Peierls–Boltzmann transport equation,which reveals ultralowκ_(l)(<2 Wm^(−1)K^(−1)at room temperature)due to their soft elasticity and strong phonon *** work demonstrates the high efficiency of scale-invariant ML model in predicting novel compounds and presents experimental-research opportunities with these new compounds.

关键词： ultralow thermal invariant

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