Dysregulated Fatty Acid Metabolism in Hepatocellular Carcinoma

( Ming-da Wang ),( Jun Han ),( Hao Xing ),( Han Zhang ),( Zheng Wang ),( Zhen-li Li ),( Liang Lei ),( Chao Li ),( Feng Shen ),( Tian Yang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Studies are urgently needed on it molecular pathogenesis and biological characteristics of hepatocellular carcinoma (HCC). Dysregulation of fatty acid (FA) metabolism, in which aberrant activation of oncogenic signaling pathways alters the expression and activity of lipid-metabolizing enzymes, is an emerging hallmark of cancer cells, and it may be involved in HCC development and progression. Methods: We summarize the characteristics of FA metabolism in HCC, focusing on the pathways of FA synthesis, oxidation, uptake and transport. We also provide a brief review of the relationship between NAFLD and HCC development. Results: The current review summarizes the dysregulated FA metabolism in HCC and pathways through which this dysregulation may regulate HCC survival and growth. Aberrant activation of oncogenic signaling pathways regulates the expression and activity of lipid-metabolizing enzymes, thus reprogramming FA metabolism to promote HCC development and progression. Intracellular FAs are required for biosynthesis of most biological membrane lipids and signaling molecules, and are also used to provide energy to support HCCs survival and proliferation, when necessary, through β-oxidation process. HCC cells can employ appropriate metabolic pathways as different situation demands. Intrahepatic cholangiocarcinoma (ICC) and HCC exhibits differential requirement for de novo lipogenesis and distinct response to therapeutic approaches focusing on inhibition of exogenous FA uptake. Non-alcoholic fatty liver disease related obesity and diabetes have increasingly emerged as two major factors responsible for the rise in prevalent of HCC. Conclusions: Our understanding of dysregulated FA metabolism and associated signaling pathways may contribute to the development of novel and efficient anti-tumor approaches for patients with HCC.

Catalytic reduction of CO2 to HCO2 by nanoscale nickel-based bimetallic alloy under atmospheric pressure

Yi Zhao,Tianhao Wang,Yongbin Wang,Runlong Hao,Han Wang,Yuhong Han 한국공업화학회 2019 Journal of Industrial and Engineering Chemistry Vol.77 No.-

Carbon dioxide (CO2) was converted into formate (HCO2) in a catalytic reduction system mainlycomposed of potassium borohydride (KBH4) and nanoscale bimetallic nickel–copper alloy (NBN–C), inwhich, the average CO2 conversion efficiency of 41.92% was obtained under the optimal experimentalconditions, with a HCO2selectivity of 53.42%. Various characterization methods were employed toinvestigate the physicochemical properties of NBN–C and the results indicated that NBN–C was a coreshellmesoporous catalyst with key active sites containing Ni0 and Cu0, at which the catalytic reduction ofCO2 took place. The reaction mechanism was proposed based on these characterizations and relevantliteratures.

Risk Factors, Patterns, and Outcomes of Late Recurrence after Liver Resection for Patients with Hepatocellular Carcinoma (Analysis of a Multicenter Cohort over 15 Years)

( Xin-fei Xu ),( Jiong-jie Yu ),( Ju-dong Li ),( Hao Xing ),( Jun Han ),( Zhen-li Li ),( Han Wu ),( Han Zhang ),( Jian-hong Zhong ),( Yi- Sheng Huang ),( Ya-hao Zhou ),( Ting-hao Chen ),( Hong Wang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Late recurrence (> 2 years) after liver resection of hepatocellular carcinoma (HCC) is usually considered as multi-centric tumors or de novo cancer formation. We aimed to investigate risk factors, patterns and outcomes of late recurrence after HCC resection. Methods: From a multicenter database from 2001 to 2015, 734 patients who were alive and recurrence-free at 2 years after curative resection of initial HCC were enrolled into this retrospective study. Univariate and multivariate Cox-regression analysis were used to identify independent risk factors of late recurrence. Patterns, treatments and outcomes of late recurrence were investigated and analyzed. Results: During a median follow-up of 78.0 months after surgery, 303 patients (41.3%) developed late recurrence. Multivariate analysis revealed that cirrhosis, macroscopic vascular invasion, satellites, and tumor size > 5cm were independent risk factors of late recurrence. Among them, 273 (90.1%) were sole intrahepatic recurrence, 30 (9.9%) were concurrent intrahepatic and extrahepatic recurrence, and none of them was sole extrahepatic recurrence; 165 (54.4%) patients received curative treatments for recurrent HCC, including re-resection, transplantation and local ablation. Multivariate analysis showed regular postoperative surveillance and receiving curative treatments were two independent protective factors of prolonging survival for those patients with late recurrence. Conclusions: Late recurrence is correlated with cirrhosis and certain tumor-related characteristics of initial HCC. The patterns of late recurrence suggest that postoperative surveillance after 2 years of surgery could be adjusted and more targeted. Regular postoperative surveillance improves the probability to receive curative treatments again, yielding to better outcomes for patients with late recurrence.

Is Surgical Resection Justified for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus? (A Systematic Review and Meta-Analysis)

( Liang Lei ),( Xin-fei Xu ),( Jiong-jie Yu ),( Ju-dong Li ),( Zhen-li Li ),( Jun Han ),( Han Zhang ),( Hao Xing ),( Han Wu ),( Ming-da Wang ),( Chao Li ),( Zheng Wang ),( Feng Shen ),( Meng-chao Wu ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is very poor. According to the BCLC treatment recommendations, sorafenib or other palliative treatment (PT) is recommended as the first-line therapy when it happens. In real world, however, a significant number of selected patients with HCC and PVTT suffered from surgical resection (SR). Methods: PubMed, Embase, Medline and Cochrane library were searched for studies comparing SR with PT (including TACE, sorafenib, etc.) for HCC with PVTT, which were published before September 2017. Results: 4,810 patients from 7 studies were enrolled in this meta-analysis, which divided into the SR group (n = 2,344) and the PT group (n = 2476). When compared with the PT group, the pooled hazard ratio (HR) for the 1, 3 and 5-year OS rates of the SR group were 0.56 (95% CI 0.52-0.60, P=0.03), 0.56 (95% CI 0.53-0.59, P<0.001) and 0.55 (95% CI 0.54-0.57, P<0.001). For subgroup analysis, when compared with the mere TACE group, the pooled HR for the 1, 3 and 5-year OS rates of the SR group were 0.54 (95% CI 0.43-0.67, P=0.81), 0.75 (95% CI 0.65-0.87, P=0.25) and 0.76 (95% CI 0.67-0.88, P=0.25). Conclusions: This meta-analysis demonstrated SR had better OS than TACE or other palliative therapy for HCC with PVTT. SR may be suitable as the first-line treatment for selected patients with resectable HCC and removable PVTT.

Sex Differences in Early and Late Recurrence after Liver Resection of Hepatocellular Carcinoma (A Multicenter Study from China)

( Jiong-jie Yu ),( Ju-dong Li ),( Xin-fei Xu ),( Zhen-li Li ),( Jun Han ),( Hao Xing ),( Han Wu ),( Jian-hong Zhong ),( Yi-sheng Huang ),( Ya- Hao Zhou ),( Ting-hao Chen ),( Hong Wang ),( Wei-min Gu ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: There is a striking sex difference in the incidence of hepatocellular carcinoma (HCC), with a strong predominance for males. However, the impact of sex on the incidence of recurrence after curative resection of HCC remains controversial. Herein, we assess sex differences in the risks of recurrence and mortality for patients undergone curative resection of HCC. Methods: Data from 1,435 HCC patients undergone curative resection (1,228 males and 207 females) between 2004 and 2014 at five institutions in China were retrospectively analyzed. Patients’ baseline characteristics, operative variables, and rates of early recurrence (≤ 2 years after resection), late recurrence (> 2 years) and cancer-specific mortality (CSM) were evaluated and compared. Multivariable competing-risks regression analyses were performed to identify predictors associated with CSM, early and late recurrence. Results: The early recurrence rates between males and females were similar (43.3% vs. 42.0%, P=0.728), but the late recurrence and CSM rates in males were higher when compared to females (17.2% vs. 11.2%, P=0.044; 42.8% vs. 34.3%, P=0.022). Multivariable competing-risks regression analyses revealed no sex difference in early recurrence; however, males had significantly higher late recurrence rate [hazard ratio (HR), 1.752; 95% CI, 1.145-2.682; P=0.010] and CSM rate (HR, 1.307; 95% CI, 1.015-1.683; P=0.038) than females. Conclusions: Males had significantly higher late recurrence and CSM rates after curative resection of HCC than females. This suggests postoperative surveillance for HCC recurrence be varied by sex, especially for patients without recurrence at 2 years after resection.

RESONANT DYNAMICS OF GEARED ROTOR SYSTEM SUBJECTED TO CHANGING OIL-BEARING STIFFNESS DUE TO EXTERNAL LOADs

Hao Zhang,Qingkai Han,Meiling Wang 한국신재생에너지학회 2014 AFORE Vol.2014 No.-

Non-structural 5A protein of hepatitis C virus induces a range of liver pathology in transgenic mice

Wang, Ai-Guo,Lee, Dong-Seok,Moon, Hyung-Bae,Kim, Jin-Man,Cho, Kyung-Hyun,Choi, Soo-Ho,Ha, Hye-Lin,Han, Ying-Hao,Kim, Dae-Ghon,Hwang, Soon B.,Yu, Dae-Yeul John Wiley Sons, Ltd. 2009 The Journal of pathology Vol.219 No.2

<P>Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). However, the mechanism of HCV pathogenesis is not well understood. Our previous in vitro studies suggested that non-structural 5A (NS5A) protein may play an important role in liver pathogenesis. To elucidate the mechanism of HCV-induced liver pathogenesis, we investigated the histopathological changes of liver in transgenic mice harbouring the NS5A gene. We generated transgenic mice harbouring HCV NS5A gene under the control of hepatitis B virus (HBV) enhancer. Pathological changes were analysed by immunohistochemical staining and western blot analysis. Lipid composition and reactive oxygen species (ROS) production in NS5A transgenic mice were analysed. HCV NS5A transgenic mice developed extraordinary steatosis over 6 months old and induced HCC in some mice. NS5A was co-localized with apolipoprotein A-I in fatty hepatocytes. In addition, the extraordinarily high levels of ROS, NF-κB and STAT3 were detected in hepatocytes of NS5A transgenic mice. These data suggest that NS5A, independent of other HCV viral proteins, may play an important role in the development of hepatic pathologies, including steatosis and hepatoceullular carcinoma in transgenic mice. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</P>

Expression of the RERG Gene is Gender-Dependent in Hepatocellular Carcinoma and Regulated by Histone Deacetyltransferases

Wang, Ai-Guo,Fang, Wan,Han, Ying-Hao,Cho, Sang-Mi,Choi, Jong Young,Lee, Kee Ho,Kim, Wook Hwan,Kim, Jin Man,Park, Moon Gi,Yu, Dae-Yeul,Kim, Nam-Soon,Lee, Dong-Seok The Korean Academy of Medical Sciences 2006 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.21 No.5

<P>Ras-related, estrogen-regulated, and growth-inhibitory gene (RERG) is a novel gene that was first reported in breast cancer. However, the functions of RERG are largely unknown in other tumor types. In this study, RERG expression was analyzed in hepatocellular carcinomas of human patients using reverse transcriptase PCR analysis. In addition, the possible regulation of RERG expression by histone deacetyltransferases (HDACs) was studied in several cell lines. Interestingly, the expression of RERG gene was increased in hepatocellular carcinoma (HCC) of male patients (57.9%) but decreased in HCC of females (87.5%) comparison with paired peri-tumoral tissues. Moreover, RERG gene expression was increased in murine hepatoma Hepa1-6 cells, human breast tumor MDA-MB-231 cells, and mouse normal fibroblast NIH3T3 cells after treated by HDAC inhibitor, trichostatin A. Our results suggest that RERG may function in a gender-dependent manner in hepatic tumorigenesis and that the expression of this gene may be regulated by an HDAC-related signaling pathway.</P>

A Hybrid Modular Multilevel Converter Topology with an Improved Nearest Level Modulation Method

Wang, Jun,Han, Xu,Ma, Hao,Bai, Zhihong The Korean Institute of Power Electronics 2017 JOURNAL OF POWER ELECTRONICS Vol.17 No.1

In this paper, a hybrid modular multilevel converter (MMC) topology with an improved nearest level modulation method is proposed for medium-voltage high-power applications. The arm of the proposed topology contains N series connected half-bridge submodules (HBSMs), one full-bridge submodule (FBSM) and an inductor. By exploiting the FBSM, half-level voltages are obtained in the arm voltages. Therefore, an output voltage with a 2N+1 level number can be generated. Moreover, the total level number of the inserted submodules (SMs) is a constant. Thus, there is no pulse voltage across the arm inductors, and the SM capacitor voltage is rated. With the proposed voltage balancing method, the capacitor voltage of the HBSM is twice the voltage of the FBSM, and each IGBT of the FBSM has a relatively low switching frequency and an equalized conduction loss. The capacitor voltage balancing methods of the two kinds of SMs are implemented independently. As a result, the switching frequency of the HBSM is not increased compared to the conventional MMC. In addition, according to a theoretical calculation of the total harmonic distortion of the electromotive force (EMF), the voltage quality with the presented method can be significantly enhanced when the SM number is relatively small. Simulation and experimental results obtained with a MMC-based inverter verify the validity of the developed method.

RNA sequencing reveals that Prx II gene knockout can down-regulate the allograft rejection of dermal mesenchymal stem cells

Han Ying-Hao,Mao Ying-Ying,Yu Nan-Nan,Jin Mei-Hua,Jin Ying-Hua,Wang Ai-Guo,Zhang Yong-Qing,Shen Gui-Nan,Cui Yu-Dong,Yu Li-Yun,Lee Dong-Seok,Jo Yu-Jin,Sun Hu-Nan,Kwon Jeongwoo,권태호 한국응용생명화학회 2020 Applied Biological Chemistry (Appl Biol Chem) Vol.63 No.3

In this study, we used RNA sequencing (RNA-seq) to analyze and compare bulk cell samples from wild-type (WT) dermal mesenchymal stem cells (DMSCs) (n = 3) and Prx II knockout DMSCs (n = 3). The purpose of the study was to elucidate the role of Prx II on allogeneic immune rejection of transplanted DMSCs. The results revealed differential expression of 472 genes (176 up-regulated and 296 down-regulated; p ≤ 0.05) between the PrxII+/+ (WT) and PrxII−/− sample groups. When highly regulated genes were categorized according to the Gene Ontology (GO) molecular function classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the PrxII−/− samples showed a robust downward trend in allograft rejection. The study identified 43 all immunologically rejected differentially expressed genes, of which 41 showed lower expression in the PrxII−/− vs. PrxII+/+ (WT) samples. These findings suggest that Prx II gene knockout may down-regulate the allograft rejection that occurs during DMSCs transplantation and improve the survival rate of DMSCs in the host. This study provides a new perspective on the clinical treatment of stem cell transplantation.