Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epirubicin is an antineoplastic agent known as an anthracycline. It acts directly on DNA by blocking its replication and transcription, so apoptosis can be induced for cancer cells. The protein expression of cancer cells will be altered due to the induction of pharmacological action of epirubicin, so it is important to pay attention to the altered profiling of proteins. Here proteomic strategy was applied to the hepatoma cells at subcellular level, comparative proteome analysis of mitochondria and nucleus were conducted between the hepatoma cells administered with epirubicin and the not-administered. Centrifugation was used for the subcellular fractionation, then 2-DE for the separation of proteins, imaging analysis for the diction of expression-altered spots, and MALDI-TOF-MS for the identification of proteins. In total, 15 proteins were found to have altered their expression after the induction of epirubicin, among them, 5 proteins showed up-regulated expression and 10 showed down-regulated expression. These altered proteins are involved in life processes of cells such as energy metabolism, protein biosynthesis, structure of cell skeleton, processing and maturation of mRNA, heat shock of cells and apoptosis.
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PMID:[Proteomic approach to the effect of epirubicin on hepatoma cells at subcellular level]. 1711 50

In rodents a high-fructose diet induces metabolic derangements similar to those in metabolic syndrome. Previously we suggested that in mouse liver an unidentified nuclear protein binding to the sterol regulatory element (SRE)-binding protein-1c (SREBP-1c) promoter region plays a key role for the response to high-fructose diet. Here, using MALDI-TOF MASS technique, we identified an X-chromosome-linked RNA binding motif protein (RBMX) as a new candidate molecule. In electrophoretic mobility shift assay, anti-RBMX antibody displaced the bands induced by fructose-feeding. Overexpression or suppression of RBMX on rat hepatoma cells regulated the SREBP-1c promoter activity. RBMX may control SREBP-1c expression in mouse liver in response to high-fructose diet.
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PMID:RBMX is a novel hepatic transcriptional regulator of SREBP-1c gene response to high-fructose diet. 1718 81

Glycosylation, a very important post-translational modification of proteins, is increasingly coming into notice. However, large-scale, throughput investigations on glycosylated proteins are few. We applied a sensitive and fast fluorescence-based multiplexed proteomics (MP) technology which included two-dimensional gel electrophoresis (2-DE) followed by the fluorescence staining of glycoprotein and mass spectrometry identification for the purpose of constructing glycoprotein databases of the typical human hepatocellular carcinoma cell lines including Hep3B cell line without metastasis and MHCC97H with highly metastatic potential as well as the control non-tumor Chang liver cell. 74+/-2 (n=3), 78+/-3 (n=3) and 72+/-5 (n=3) glycoprotein spots were detected on 2-DE gels from Chang liver, Hep3B and MHCC97H cell sample using this MP technique, respectively. In all, 80 glycoproteins from three cell lines were successfully identified via peptide mass profiling using MALDI-TOF-MS/MS and the identified glycoproteins were annotated to our databases. In addition, we also found the glycosylation pattern differences among these three cell lines. The protein glycosylation alteration would be have great significance for the diagnosis of HCC and prediction of its metastasis. This study described the construction of glycosylation patterns of proteins and glycoproteome databases of human liver cells by the novel technological platform. The glycoproteome databases also provide essential basis for following study.
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PMID:Investigation on glycosylation patterns of proteins from human liver cancer cell lines based on the multiplexed proteomics technology. 1721 54

It is known that the hepatitis B virus X protein (HBx) plays a crucial role in the pathogenesis of HCC, but the exact functions and molecular mechanisms of HBx in HCC are not well understood. In the present study, HepG2 cell lines were cultured and transfected with pEGFP-N1 and pEGFP-N1-X. Twenty-four hours after transfection, cells were harvested and total RNA was extracted using TRIzol reagent. The expression of HBx in HepG2 cell line was assayed by real-time polymerase chain reaction and was detected by Western blotting. Moreover, proteomic analysis was performed for the HepG2-pEGFP-X cells and HepG2-pEGFP control cells. The combination of 2DE and MALDI-TOF-MS/MS revealed that SEC13L1 (SEC13-like 1 isoform b), PA28 alpha (proteasome activator REG alpha), serine-threonine kinase receptor-associated protein (STRAP) and nm23/nucleoside diphosphate kinase (NME) were upregulated in HepG2-pEGFP-X cells. STRAP is known to be a WD40 domain-containing protein, which interacts with TbetaR-I and TbetaR-II and negatively regulates TGF-beta signalling, was also found increased in human cancers. NME is known to be involved in the regulation of cancer cell progression and metastasis. These results would help the understanding of how HBx maintains tumorigenicity and progression of HCC.
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PMID:The upregulation of expressed proteins in HepG2 cells transfected by the recombinant plasmid-containing HBx gene. 1730 79

Early detection is a key step for effective intervention of hepatocellular carcinoma (HCC), the lack of sensitive and specific biomarkers is a major reason for the high rate of HCC-related mortality. This report described an integrated strategy by combining SELDI-ProteinChip, sophisticated algorithm analysis, acetonitrile (ACN) pre-treatment and two-dimensional electrophoresis (2DE)-peptide mass fingerprinting (PMF) techniques to identify serological markers for the prediction of HBV-related HCC. Proteomic profiling of three groups of serum specimens from HBV-related HCC (50 cases), HBV infection (45 cases), and normal subjects (30 cases) was conducted by using SELDI-ProteinChip system and the resulting different protein peaks were subjected to stepwise statistical analyses. Three most discriminatory peaks at 5890, 11615, and 11724 Da, respectively, were screened out from the statistical algorithm and a predictive model based on the three peaks was constructed and tested using the newly enrolled serum samples. 2DE was applied to separate and compare the serum samples that were pre-treated by ACN precipitation. The protein spots obviously intensified in HCC sera in the 2DE region of 12 kDa were identified by PMF to be serum SAA, which was validated by SELDI-TOF spectra of HCC sera after immunoprecipitation using anti-SAA antibody and by Western blot experiments. Given the fact that SAA is not a specific biomarker, further attempt is being made to identify the other two most discriminatory peaks to realize the possibility of using the predictive model for HCC surveillance and prediction.
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PMID:Toward the proteomic identification of biomarkers for the prediction of HBV related hepatocellular carcinoma. 1755 78

We have observed abnormally high membrane cholesterol levels and a subsequent deficiency of oxidative energy production in mitochondria from cultured Morris hepatoma cells (MH7777). Using cholesterol affinity chromatography and MALDI-TOF Mass Spectrometry, we have identified the voltage dependent anion channel (VDAC) as a necessary component of a protein complex involved in mitochondrial membrane cholesterol distribution. VDAC is known to associate strongly with hexokinase, particularly in glycolytic cancers. By constructing an E72Q mutant form of VDAC that inhibits its binding of hexokinase, we report an increase in oxidative phosphorylation activity of MH7777 cells, as well as reduced membrane cholesterol ratios to levels near that of normal liver mitochondria. This paper demonstrates that the ability of VDAC to influence mitochondrial membrane cholesterol distribution may have implications on mitochondrial characteristics such as oxidative phosphorylation and induction of apoptosis, as well as the propensity of cancer cells to exhibit a glycolytic phenotype.
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PMID:The voltage dependent anion channel affects mitochondrial cholesterol distribution and function. 1766 30

Hepatocellular carcinoma (HCC) is a common malignant tumour. Development of HCC is a multi-step process from well-differentiated (G1), moderately differentiated (G2) to poorly differentiated (G3) phenotype. The early molecular modulators causing the onset of hepatocarcinogenesis are not fully understood. In the present study, we conducted comparative proteomics to analyze the differential proteome of G1 tumour and adjacent non-tumour tissues, with aims to identify the molecules as early tumour markers and to understand the early molecular events involved in initiation of tumorigenesis in hepatitis B virus (HBV)-infected G1 tumour. Differentially expressed proteins were identified by MALDI-TOF/TOF tandem mass spectrometry and NCBInr database interrogation. A total of 15 differentially expressed proteins with diverse biological functions were identified. Among these, 4 proteins were down-regulated, whereas the other 11 proteins were up-regulated in the G1 tumours. Two proteins, Proteasome activator subunit 1 (PA28alpha) and DJ-1, were firstly found to be down-regulated in HBV-infected G1 tumours. Down-regulations of these two proteins were further validated by Western blotting and immunohistochemistry in a panel of clinical specimens. These findings elucidate, at least in part, the molecular events underlying the mechanism and the potential roles of DJ-1 and PA28alpha in the onset of hepatocarcinogenesis.
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PMID:Proteomic identification of down-regulation of oncoprotein DJ-1 and proteasome activator subunit 1 in hepatitis B virus-infected well-differentiated hepatocellular carcinoma. 1767 84

Enhancer of zeste homolog 2 (EZH2) is suggested to be a potential therapeutic target and a diagnostic marker for cancer. Our previous study also showed the critical role of EZH2 in hepatocellular carcinoma (HCC) tumorigenesis. The present study is aimed at revealing the comprehensive downstream pathways of EZH2 by functional proteomic profiling. Lentivirus mediated RNA interference (RNAi) was employed to knockdown EZH2 in HCC cells. The 2-DE was employed to compare the expression profile difference between parental and EZH2-knockdown HCC cells. In total, 28 spots were differentially expressed during EZH2 inhibition. Among all, 18 proteins were identified by PMF with MALDI-TOF MS. Western blotting further validated upregulation of 60S acidic ribosomal protein P0 (L10E), and downregulation of two proteins with EZH2 inhibition: stathmin1 and probable protein disulfide isomerase (PDI) ER-60 precursor (ERp57). Moreover, L10E was downregulated with overexpression of EZH2 in hepatocytes, and L10E reversed the effect of EZH2 on cell proliferation, suggesting it a downstream target of EZH2. The comprehensive and comparative analyses of proteins associated with EZH2 could further our understanding on the downstream signal cascade of EZH2 leading to tumorigenesis.
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PMID:Proteomic analysis of EZH2 downstream target proteins in hepatocellular carcinoma. 1767 62

Cytotoxic and apoptosis-inducing effects of the alkaloid emetine from Psychotria ipecacuanha (Rubiaceae) were studied in human cell lines. In Jurkat T-cells emetine leads to phosphatidylserine exposure, mitochondrial depolarisation, and DNA fragmentation. Furthermore, activation of several caspases (caspase-3, -9/6, and -8) was demonstrated in a fluorescent caspase assay. Bcl-2 over-expressing cells are less sensitive to emetine while caspase-8-deficient Jurkat T-cells react similarly to wild-type cells. This indicates that apoptosis induction is mediated via the mitochondrial pathway. By using hepatoma cell lines with differing p53 expression, it was concluded that p53 does not seem to play a role in apoptosis induction by emetine. Alterations of protein profiles during emetine-induced apoptosis were analysed by 2D-PAGE and MALDI-TOF-MS. A new protein spot was apparent after treatment with emetine: It could be identified as the N-terminal fragment lamin B1, which is released after cleavage by caspase-6.
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PMID:Characteristics of apoptosis induction by the alkaloid emetine in human tumour cell lines. 1791 75

We present a novel method that combines ant colony optimization with support vector machines (ACO-SVM) to select candidate biomarkers from MALDI-TOF serum profiles of hepatocellular carcinoma (HCC) patients and matched controls. The method identified relevant mass points that achieve high sensitivity and specificity in distinguishing HCC patients from healthy individuals. The results indicate that the MALDI-TOF technology could provide the means to discover novel biomarkers for HCC.
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PMID:Ant colony optimization for biomarker identification from MALDI-TOF mass spectra. 1794 38


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