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

The serum level of CA 19-9 elevated exponentially in gastrointestinal carcinoma and the specificity of CA 19-9 was extraordinarily high. The sensitivity of CA 19-9 to pancreas, bile duct, hepatocellular and metastatic liver carcinoma was 75%, 79%, 22%, and 82% each. TPA seems to be useful as a screening tumor maker of gastrointestinal carcinoma, because the sensitivity was very high (84%) in every gastrointestinal carcinoma. IAP increased in pancreas and bile duct carcinoma and reflected immunological status of tumor bearing host. 5'-NPD-V was useful tumor marker not only of hepatocellular carcinoma but also pancreas and bile duct carcinoma.
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PMID:[Clinical evaluation of CA 19-9, TPA, IAP and 5'-NPD-V as tumor markers of hepatocellular, bile duct and pancreas carcinoma]. 241 64

In order to study the clinical significance of IAP and ASP, we have measured serum concentration of IAP and ASP in patients with different cancer types including digestive organs, head and neck. Significantly higher correlation (coefficient of correlation = 0.924) was found between IAP and ASP. IAP and ASP levels were elevated in about 60-80% of cancer from digestive organs except hepatocellular carcinoma, and in about 56-100% of head and neck tumor. There was no correlation between IAP, ASP and various tumor markers (CEA, CA19-9, AFP) in all malignancies except pancreatic cancer. There was positive correlation between CEA and IAP, ASP in pancreatic cancer. IAP and ASP levels were significantly higher in patients with cancer having evidence of disease than the patients with cancer who had no evidence of disease, and so the determination of IAP and ASP was clinically useful for the diagnosis of tumor existence. At the time of diagnosis of recurrence, the levels of IAP and ASP were elevated in about 70% of patients with cancer recurrence. There was a definite relation between IAP, ASP and the gastric cancer stage. In later state (stage III and IV), serum IAP and ASP levels were significantly higher than the levels of stage I and II. In hepatocellular carcinoma without liver cirrhosis, the levels of IAP and ASP were higher than the patients with cirrhosis. The determination of IAP and ASP seems to be useful for monitoring clinical course, judgement of therapeutic effects.
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PMID:[Clinical evaluation of serum immunosuppressive acidic protein (IAP) and acid soluble glycoproteins (ASP) in patients with malignant tumors]. 248 24

In order to study the clinical significance of ASP and IAP, we have measured serum concentration of ASP and IAP in 259 patients with inflammatory diseases, non-inflammatory diseases, autoimmune diseases and liver diseases. Significantly higher correlation (coefficient of correlation = 0.922) was found between ASP and IAP. There were good correlation between ASP, IAP levels and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP). Coefficient of correlation were 0.705 and 0.673 between ESR and ASP, IAP; 0.621 and 0.623 between CRP and ASP,IAP, respectively. There were food correlations between ASP levels and thrombo test (TT) and hepaplastin test (HPT). The positive rate and mean concentration of ASP, IAP in patients with inflammatory diseases were significantly higher than noninflammatory diseases. It is suggested that serum ASP, IAP could be one of the useful indicator for evaluating the clinical course of patients with inflammatory diseases. Serum concentration of ASP, IAP in patients with chronic liver diseases were lower than normal subjects, especially serum levels in patients with decompensated liver cirrhosis and chronic hepatitis (active) were significantly lower than normal subjects. In patients with hepatoma with cirrhosis, serum levels of ASP, IAP were significantly lower than the hepatoma patients without cirrhosis. The determination of ASP, IAP in liver diseases seems to be useful for evaluating the severity of diseases, the effects of therapy and the forecast of prognosis.
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PMID:[Clinical significance of serum acid soluble glycoproteins (ASP) and immunosuppressive acidic protein (IAP) in inflammatory diseases and liver diseases]. 248 30

NK activity in acute viral hepatitis, chronic hepatitis, liver cirrhosis (LC), metastatic liver cancer and hepatocellular carcinoma (HCC) was preserved and had no significant change compared with the normal control in each disease. In acute hepatitis, NK activity was higher in convalescent phase than in acute phase. Although in LC and HCC, some liver functions such as total bilirubin, the rate of ICG 15' excretion, AFP and IAP did not have significant correlation with NK activity, advanced cases according to Child's classification and E factor which was anatomical extent of HCC in liver showed significantly low NK activity. The low NK activity group advanced much more in Child's classification, performance status, stage and E factor of HCC than high NK activity group significantly. According to those facts, LC or HCC is not a single entity of disease in view point of NK activity. NK activity may change in accordance with the advancement of hepatic disease and reserve function of the liver in LC and HCC.
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PMID:[NK activity in various liver diseases--especially the relation between NK activity and reserve function of the liver in liver cirrhosis and hepatocellular carcinoma]. 255 27

The death receptor Fas transduces apoptotic death signaling mediated by caspases. In the present study, human hepatoma HepG2 cells showed the Fas-mediated apoptosis mediated by caspase, especially caspase 3, only in the presence of actinomycin D. Interestingly, cytosolic proteins extracted from intact HepG2 cells induced caspase 3 inactivation. Our results reveal that this inactivation was triggered by the direct inhibition of activated caspase 3 by IAP gene family ILP. In addition, a 53 kDa protein was co-immunoprecipitated with anti-human caspase 3 antibody from intact HepG2 cells. This protein was a complex-protein of procaspase 3 and the cell cycle regulator p21WAF1 (p21). P21 bound to only procaspase 3, but not to activated caspase 3. We also demonstrate that p21 protein-loaded HepG2 cells resist to Fas-mediated apoptosis even in the presence of actinomycin D. Here we report that caspase 3 inactivation for the resistance to Fas-mediated apoptosis is induced by a procaspase 3/p21 complex formation and direct inhibition of activated caspase 3 by ILP.
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PMID:Resistance to Fas-mediated apoptosis: activation of caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP. 974 72

The second mitochondria-derived activator of caspase, Smac, is an apoptosis-related protein. Smac releases inhibition of the IAP family from caspase-3 to induce apoptosis. Smac is expressed in some malignant tumor cells and is released from mitochondria into the cytosol after death receptor stimulation to promote apoptosis of tumor cells. In this study, we found down-regulated Smac protein expression in hepatocellular carcinoma (HCC) tissues, compared to that in non-tumor hepatic tissues. Simultaneously, caspase-3 expression also decreased in HCC tissues. HCC cell lines did not undergo apoptosis after TRAIL stimulation, although Smac was expressed in these HCC cells. Ectopic Smac alone did not induce cell death, but could sensitize HCC cells to TRAIL stimulation. With over-expression of Smac in HCC cells, TRAIL induced by 10% HCC cell death. The role of Smac in apoptosis signaling pathway in HCC cells warrants further study.
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PMID:Over-expression of Smac promotes TRAIL-induced cell death in human hepatocellular carcinoma. 1279 4

Integrin-associated protein (IAP or CD47) is expressed in a variety of tissues, including the nervous system and immune system. To understand how cells control the expression of the IAP gene, we cloned the 5'-proximal region of the human IAP gene and investigated IAP promoter activity by transient transfection. RT-PCR confirmed the expression of IAP transcripts in human neuroblastoma IMR-32 and hepatoma HepG2 cells. Deletion analysis identified a core promoter of the human IAP gene located between nucleotide positions -232 and -12 relative to the translation initiation codon in these two cell lines. Site-directed mutagenesis and gel electrophoretic mobility shift assay identified a alpha-Pal/NRF-1 binding element within the IAP core promoter. Supershift assays using the alpha-Pal/NRF-1 antiserum confirmed the binding of this transcription factor on the alpha-Pal/NRF-1 site. Overexpression of the DNA binding domain of alpha-Pal/NRF-1 in cells enhanced DNA-alpha-Pal/NRF-1 binding in vitro. Furthermore, overexpression of full-length alpha-Pal/NRF-1 significantly enhanced IAP promoter activity while overexpression of dominant-negative mutant reduced promoter activity both in the cultured human cell lines and primary mouse cortical cells. These results revealed that alpha-Pal/NRF-1 is an essential transcription factor in the regulation of human IAP gene expression.
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PMID:Alpha-Pal/NRF-1 regulates the promoter of the human integrin-associated protein/CD47 gene. 1474 77

The serious result of hepatitis B (HBV) virus infection is development of hepatocellular carcinoma (HCC). However, the reason of development of HCC in HBV infected patients is still unclear. Recently, the suppression of cell apoptosis is found to relate with the development of cell carcinogenesis, therefore, the expression of apoptosis inhibitor in the virus related cancer line such as hepatoma cell line HepG2.215 was investigated. There are at least six Human apoptosis inhibitors (IAP) have been identified now. They are cIAP1, cIAP2, XIAP, NAPI, survivin and pIAP. Using gene-assay technology, we have recently compared the expression of IAPs in the HepG2.215 cells that persistently expresses Hepatitis B virus by integrated HBV genome with its parent cell line HepG2. The results suggest that there was obviously increase of cIAP2 and cIAP1 in the HepG2.215 cells versus HepG2 cells. Those observations imply a possibility of long time HBV infection could induce the over-expressing apoptosis inhibitors, furthermore, causing the liver cancer. The high expression of cIAP1 and cIAP2 in HBV expressing cells was confirmed by RT-PCR and Northern blot analysis. However, we did not find the change of NIAP and suvivin in HepG2.215 cells. In contrast, the expression of XIAP was down in the HepG2.215 cells comparing with HepG2 cells. How HBV triggers the over-expression of apoptosis inhibitor is unclear. Transient transfection of HepG2 cells with the plasmids expressing different HBV proteins such as S, M, L, X and core proteins did not give a decisive conclusion. Further study is going on now.
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PMID:High level expression of apoptosis inhibitor in hepatoma cell line expressing Hepatitis B virus. 1596 37

The hepatitis B virus X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). The relationship was examined between HBV antigens and IAP (inhibitor of apoptosis) family in development of HCC. The expression levels of HBV antigens (HBsAg, HBcAg, and HBxAg) and members of the IAP family (survivin, XIAP, cIAP-1, and cIAP-2) were detected immunohistochemically in tissues from 34 cases of HCC and 30 cases of liver cirrhosis. The positive rate of survivin was higher than these three molecules in all three tissue types (P < 0.05). The positive rates of HBxAg and survivin were high in HCC (76.5% and 88.2%), paratumor (85.3% and 91.2%), and liver cirrhosis (100% and 93.3%) tissues, with no significant differences between the survivin- and HBxAg-positive rates (each P > 0.05). To examine the effect of HBx on survivin expression, plasmid pCMV-X (encoding the HBx gene) was transfected transiently with or without plasmid pcDNA3-sur (encoding the survivin gene) into H7402 hepatoma cells and L-O2 human normal liver cells. Cells over-expressing HBx alone showed increased apoptosis along with a dose-dependent increase in survivin levels. However, co-expression of survivin inhibited the HBx-induced apoptosis. To examine the effect of HBx on survivin in hepatoma cells without apoptosis, plasmid pCMV-X was transfected stably into human hepatoma H7402 cells and L-O2 cells. These H7402-X and L-O2-X cells showed high-level expression of both HBx and survivin, but did not show apoptosis. The addition of pSilencer 3.0-X, an RNAi vector targeting the HBx gene, reduced the expression levels of survivin protein in H7402-X cells. Collectively, these data demonstrate that HBx upregulates survivin expression in hepatoma tissues, suggesting that HBx and survivin may both be involved in carcinogenesis of HCC.
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PMID:Hepatitis B virus X protein upregulates survivin expression in hepatoma tissues. 1617 17

The ubiquitin-proteasome pathway is responsible for regulating cell cycle proteins, tumor-suppressor molecules, oncogenes, transcription factors, and pro- and anti-apoptotic proteins. The aim of this study is to evaluate the effects of proteasome inhibitors on human hepatocellular carcinoma (HCC) cells. HCC cells SK-Hep1, HLE and HepG2 were treated with the proteasome inhibitors MG132 and MG115. Our data showed that both inhibitors induce apoptosis in the three cell types tested in a dose-dependent manner. Moreover, subtoxic levels of MG132 and MG115 sensitized HCC cells to TRAIL-induced apoptosis. To investigate the mechanism of increased TRAIL sensitivity in HCC cells, we first examined surface expression of TRAIL and its receptors. MG132 upregulated TRAIL and its receptors (TRAIL-R1 and -R2) in SK-Hep1 and HLE, whereas MG115 upregulated them in SK-Hep1. MG132 downregulated expression of X-linked inhibitor of apoptosis protein (XIAP) in SK-Hep1 and HLE, and of survivin in all three cell-types. MG115 downregulated expression of XIAP in SK-Hep1, and survivin in SK-Hep1 and HepG2. Furthermore, MG132 downregulated phospho-AKT and its downstream target phospho-BAD, indicating that MG132 activated the mitochondrial apoptosis pathway by inhibiting phosphorylation of AKT and BAD. In conclusion, proteasome inhibitors induced apoptosis and augmented TRAIL sensitivity via both the IAP family and AKT pathways. Thus, combining proteasome inhibitors with a TRAIL agonist may provide a new therapeutic strategy for HCC.
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PMID:Proteasome inhibition sensitizes hepatocellular carcinoma cells to TRAIL by suppressing caspase inhibitors and AKT pathway. 1652 Jun 54


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