Comparison of Liver Transplantation and Liver Resection for Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus Type I and Type II

Jia-Yu Lv,Ning-Ning Zhang,Ya-Wei Du,Ying Wu,Tian-Qiang Song,Ya-Min Zhang,Yan Qu,Yu-Xin Liu,Jie Gu,Ze-Yu Wang,Yi-Bo Qiu,Bing Yang,Da-Zhi Tian,Qing-Jun Guo,Li Zhang,Ji-San Sun,Yan Xie,Zheng-Lu Wang,Xin 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.1

Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellularcarcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involvedand divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were comparedbefore and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR(p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longermedian RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335,respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase(AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion: LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels>200 ng/mL.

Lentivirus-mediated microRNA-124 gene-modified bone marrow mesenchymal stem cell transplantation promotes the repair of spinal cord injury in rats

Jia-Lin Song,Wei Zheng,Wei Chen,Yun Qian,Yuan-Ming Ouyang,Cun-Yi Fan 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Our study aims to explore the effects of lentivirus-mediated microRNA-124 (miR-124) gene-modified bone marrow mesenchymal stem cell (BMSC) transplantation on the repair of spinal cord injury (SCI) in rats. BMSCs were isolated from the bone marrow of rats. The target gene miR-124 was identified using a luciferase-reporter gene assay. Seventy-two rats were selected for construction of the SCI model, and the rats were randomly divided into the blank group, sham group, SCI group, negative control (NC) group, overexpressed miR-124 group and si-PDXK group. The mRNA expression of miR-124 and the mRNA and protein expression of pyridoxal kinase (PDXK) were detected by quantitative real-time polymerase chain reaction and western blotting. The locomotor capacity of the rats was evaluated using the Basso, Beattie and Bresnahan (BBB) scale. Brdu, neuron-specific enolase (NSE), neurofilament (NF) and microtubule-associated protein 2 (MAP2) were detected using immunohistochemistry. The expression levels of thyrotropin-releasing hormone (TRH), prostacyclin (PGI2) and gangliosides (GM) were measured using an enzyme-linked immunosorbent assay. PDXK was identified as the target gene of miR-124. The overexpressed miR-124 group exhibited higher miR-124 expression than the SCI, NC and si-PDXK groups. Compared with the SCI and NC groups, the PDXK expression was downregulated in the overexpressed miR-124 and si-PDXK groups, and the BBB scores were significantly increased 7, 21 and 35 days after transplantation. The double-labeled positive cell densities (Brdu+NSE/NF/MAP2) and the expression levels of TRH, PGI2 and GM in the overexpressed miR-124 group were significantly higher than those in the NC and SCI groups. These results indicated that miR-124 targeted PDXK to accelerate the differentiation of BMSCs into neurocytes and promote SCI repair.

Therapeutic Effects and Adverse Drug Reactions are Affected by Icotinib Exposure and CYP2C19 and EGFR Genotypes in Chinese Non-Small Cell Lung Cancer Patients

Chen, Jia,Zheng, Xin,Liu, Dong-Yang,Zhao, Qian,Wu, Yi-Wen,Tan, Fen-Lai,Wang, Yin-Xiang,Jiang, Ji,Hu, Pei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

Genome-wide Analysis of Aberrant DNA Methylation for Identification of Potential Biomarkers in Colorectal Cancer Patients

Fang, Wei-Jia,Zheng, Yi,Wu, Li-Ming,Ke, Qing-Hong,Shen, Hong,Yuan, Ying,Zheng, Shu-Sen Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Background: Colorectal cancer is one of the leading causes of mortality worldwide. Genome wide analysis studies have identified sequence mutations causing loss-of-function that are associated with disease occurrence and severity. Epigenetic modifications, such DNA methylation, have also been implicated in many cancers but have yet to be examined in the East Asian population of colorectal cancer patients. Methods: Biopsies of tumors and matched non-cancerous tissue types were obtained and genomic DNA was isolated and subjected to the bisulphite conversion method for comparative DNA methylation analysis on the Illumina Infinium HumanMethylation27 BeadChip. Results: Totals of 258 and 74 genes were found to be hyper- and hypo-methylated as compared to the individual's matched control tissue. Interestingly, three genes that exhibited hypermethylation in their promoter regions, CMTM2, ECRG4, and SH3GL3, were shown to be significantly associated with colorectal cancer in previous studies. Using heatmap cluster analysis, eight hypermethylated and 10 hypomethylated genes were identified as significantly differentially methylated genes in the tumour tissues. Conclusions: Genome-wide methylation profiling facilitates rapid and simultaneous analysis of cancerous cells which may help to identify methylation markers with high sensitivity and specificity for diagnosis and prognosis. Our results show the promise of the microarray technology in identification of potential methylation biomarkers for colorectal cancers.

Effect of Glucagon-like Peptide 2 on Tight Junction in Jejunal Epithelium of Weaned Pigs though MAPK Signaling Pathway

Yu, Changsong,Jia, Gang,Jiang, Yi,Deng, Qiuhong,Chen, Zhengli,Xu, Zhiwen,Chen, Xiaolin,Wang, Kangning Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.5

The glucagon-like peptide 2 (GLP-2) that is expressed in intestine epithelial cells of mammals, is important for intestinal barrier function and regulation of tight junction (TJ) proteins. However, there is little known about the intracellular mechanisms of GLP-2 in the regulation of TJ proteins in piglets' intestinal epithelial cells. The purpose of this study is to test the hypothesis that GLP-2 regulates the expressions of TJ proteins in the mitogen-activated protein kinase (MAPK) signaling pathway in piglets' intestinal epithelial cells. The jejunal tissues were cultured in a Dulbecco's modified Eagle's medium/high glucose medium containing supplemental 0 to 100 nmol/L GLP-2. At 72 h after the treatment with the appropriate concentrations of GLP-2, the mRNA and protein expressions of zonula occludens-1 (ZO-1), occludin and claudin-1 were increased (p<0.05). U0126, an MAPK kinase inhibitor, prevented the mRNA and protein expressions of ZO-1, occludin, claudin-1 increase induced by GLP-2 (p<0.05). In conclusion, these results indicated that GLP-2 could improve the expression of TJ proteins in weaned pigs' jejunal epithelium, and the underlying mechanism may due to the MAPK signaling pathway.

Cross-immunizing potential of tumor MAGE-A epitopes recognized by HLA-A*02:01-restricted cytotoxic T Lymphocytes

( Ze Min Huang ),( Zheng Cai Jia ),( Jun Tang ),( Yi Zhang ),( Yi Tian ),( Dong Jing Ni ),( Fang Wang ),( Yu Zhang Wu ),( Bing Ni ) 생화학분자생물학회(구 한국생화학분자생물학회) 2012 BMB Reports Vol.45 No.7

Almost all melanoma cells express at least one member of the MAGE-A antigen family, making the cytotoxic T cells (CTLs) epitopes with cross-immunizing potential in this family attractive candidates for the broad spectrum of anti-melanoma immunotherapy. In this study, four highly homologous peptides (P264: FLWGPRALA, P264I9: FLWGPRALI, P264V9: FLWGPRALV, and P264H8: FLWGPRAHA) from the MAGE-A antigens were selected by homologous alignment. All four peptides showed high binding affinity and stability to HLA-A*02:01 molecules, and could prime CTL immune responses in human PBMCs and in HLA-A*02:01/Kb transgenic mice. CTLs elicited by the four epitope peptides could cross-lyse tumor cells expressing the mutual target antigens, except MAGE-A11 which was not tested. However, CTLs induced by P264V9 and P264I9 showed the strongest target cell lysis capabilities, suggesting both peptides may represent the common CTL epitopes shared by the eight MAGE-A antigens, which could induce more potent and broad-spectrum antitumor responses in immunotherapy. [BMB Reports 2012; 45(7): 408-413]

Improvement of energy storage performance in PbZr0.52Ti0.48O3/PbZrO3 multilayer thin films via regulating PbZrO3 thickness

Yang Fei,Shi Yu Jia,Lin Lin,Chen Jing Yao,Hou Meng Zhe,Yu Ke Xin,Zhang Yi Han,Yuan Zheng,Li Xiao Fang,Hu Yan Chun,Shang Jun,Yin Shao Qian,Wang Xian Wei 한국물리학회 2023 Current Applied Physics Vol.50 No.-

In this work, to prepare the PbZr0.52Ti0.48O3(PZT)/PbZrO3(PZ) multilayer films, PZ films and PZT films were spin-coated on LaNiO3/SiO2/Si substrates in sequence by the sol-gel method, and the PZ films were prepared using PZ precursor solution with different concentrations. After each spin-coating, PZ layer and PZT layer were annealed with rapid thermal annealing (RTA) technique at 650 ◦C and 550 ◦C, respectively. The crystal structures, microstructures and electrical properties of the films with different PZ film thickness were comprehensively investigated. The PZ films with different thickness showed perovskite phase. The PZT films on crystallized PZ films exhibited the coexistence of pyrochlore phase and perovskite phase at the annealing temperature of 550 ◦C. The PZT/PZ multilayer films with 0.2 M PZ precursor solution exhibit typical anti-ferroelectricity with double hysteresis loops, while other multilayer films exhibit nearly linear loops. In addition, the recoverable energy storage density increases with the increase of the film thickness and reaches the maximum value 32.4 J/ cm3 in the PZT/PZ multilayer films with 0.4 M PZ precursor solution. Therefore, the ferroelectric properties of the PZT/PZ multilayer films could be regulated by different PZ film thickness, which effectively further enhances the energy storage performance.

Effects of microRNA-135a on the epithelial–mesenchymal transition, migration and invasion of bladder cancer cells by targeting GSK3β through the Wnt/β-catenin signaling pathway

Xia-Wa Mao,Jia-Quan Xiao,Zhong-Yi Li,Yi-Chun Zheng,Nan Zhang 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

This study investigated the effects of microRNA-135a (miR-135a) targeting of glycogen synthase kinase 3β (GSK3β) on the epithelial–mesenchymal transition (EMT), migration and invasion of bladder cancer (BC) cells by mediating the Wnt/β-catenin signaling pathway. BC and adjacent normal tissues were collected from 165 BC patients. Western blotting and quantitative realtime PCR were used to detect the expression of GSK3β, β-catenin, cyclinD1, E-cadherin, vimentin and miR-135a in BC tissues and cells. Cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, small interfering RNA (siRNA)-GSK3β or miR-135a inhibitors+siRNA-GSK3β groups. miR-135a, β-catenin, cyclinD1 and vimentin expression increased, while GSK3β and E-cadherin expression decreased in BC tissues compared with adjacent normal tissues. Compared with the blank and NC groups, the expression of miR-135a, β-catenin, cyclinD1 and vimentin was higher, and cell proliferation, migration, invasion and tumor growth were increased in the miR-135a mimics and siRNA-GSK3β groups. These groups showed an opposite trend in GSK3β and E-cadherin expression and cell apoptosis. The miR-135a inhibitors group was inversely correlated with the blank and NC groups. It was concluded that miR-135a accelerates the EMT, invasion and migration of BC cells by activating the Wnt/β-catenin signaling pathway through the downregulation of GSK3β expression.

Optical Properties of Zinc-oxide Films Determined Using Spectroscopic Ellipsometry with Various Dispersion Models

Zhong-Hong Dai,Jie Shao,Yi-Ming Chen,Yu-Xiang Zheng,Jia-Da Wu,Liang-Yao Chen,Rong-Jun Zhang 한국물리학회 2009 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.55 No.3

In this work, we have studied the optical properties of wurtizite zinc-oxide films grown on silicon (100) substrates by means of pulsed laser deposition (PLD). Spectroscopic ellipsometry and three dispersion models, namely, the Sellmeier, Cauchy, and Forouhi-Bloomer models, were applied for determining the optical constants of the ZnO thin films. A comparison was made between two samples that were deposited for 30 minutes (sample I) and 60 minutes (sample II), respectively. X-ray diffraction analysis indicates that there are two types of preferred-orientation, i.e., (101) and (100) orientations for sample I and II, respectively. Results show that the Cauchy model gives the best fit for the samples with least root mean square error (RMSE) whereas the Forouhi-Bloomer model is most suitable for the data analysis in both the transparent and the absorption regions. The optical properties extracted from different dispersion models have been compared with the data reported in the literature. The results given in this work show that different dispersion models should be applied to obtain the optical constants In this work, we have studied the optical properties of wurtizite zinc-oxide films grown on silicon (100) substrates by means of pulsed laser deposition (PLD). Spectroscopic ellipsometry and three dispersion models, namely, the Sellmeier, Cauchy, and Forouhi-Bloomer models, were applied for determining the optical constants of the ZnO thin films. A comparison was made between two samples that were deposited for 30 minutes (sample I) and 60 minutes (sample II), respectively. X-ray diffraction analysis indicates that there are two types of preferred-orientation, i.e., (101) and (100) orientations for sample I and II, respectively. Results show that the Cauchy model gives the best fit for the samples with least root mean square error (RMSE) whereas the Forouhi-Bloomer model is most suitable for the data analysis in both the transparent and the absorption regions. The optical properties extracted from different dispersion models have been compared with the data reported in the literature. The results given in this work show that different dispersion models should be applied to obtain the optical constants

Identification of interacting proteins of retinoid-related orphan nuclear receptor gamma in HepG2 cells

( Ze Min Huang ),( Jun Wu ),( Zheng Cai Jia ),( Yi Tian ),( Jun Tang ),( Yan Tang ),( Ying Wang ),( Yu Zhang Wu ),( Bing Ni ) 생화학분자생물학회 (구 한국생화학분자생물학회) 2012 BMB Reports Vol.45 No.6

The retinoid-related orphan nuclear receptor gamma (RORγ) plays critical roles in regulation of development, immunity and metabolism. As transcription factor usually forms a protein complex to function, thus capturing and dissecting of the RORγ protein complex will be helpful for exploring the mechanisms underlying those functions. After construction of the recombinant tandem affinity purification (TAP) plasmid, pMSCVpuro RORγ-CTAP(SG), the nuclear localization of RORγ-CTAP(SG) fusion protein was verified. Following isolation of RORγ protein complex by TAP strategy, seven candidate interacting proteins were identified. Finally, the heat shock protein 90 (HSP90) and receptor-interacting protein 140 (RIP140) were confirmed to interplay with RORγ by co-immunoprecipitation. Interference of HSP90 or/and RIP140 genes resulted in dramatically decreased expression of CYP2C8 gene, the RORγ target gene. Data from this study demonstrate that HSP90 and RIP140 proteins interact with RORγ protein in a complex format and function as co-activators in the RORγ-mediated regulatory processes of HepG2 cells. [BMB Reports 2012; 45(6): 331-336]