Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A non-nucleosidic compound, Helioxanthin (HE-145), was found to suppress HBV gene expression and replication in HCC cells. To understand the molecular mode of action of HE-145 on HBV gene expression, the effects of HE-145 on four viral promoter activities using luciferase as a reporter were examined. It was found that HE-145 selectively suppresses surface antigen promoter II (SPII) and core promoter (CP) but has no effect on surface antigen promoter I (SPI) or promoter for X gene (Xp). The suppressive effects of HE-145 on either SPII or CP activity is liver-specific, since no suppressive activity of HE-145 was observed when CP or SPII promoter activity was assayed in non-liver cells such as HeLa or 293T. To examine the mode of action of HE-145, EMSA analysis revealed that HE-145 decreased the DNA-binding activity of nuclear extract of HepA2 cells to specific cis element of HBV promoter for core antigen, including peroxisome proliferator-activated receptors (PPARs), PPARs binding site (PPRE), alpha-fetoprotein transcription factor (FTF), and Sp1. Ectopic expression of PPAR gamma or HNF4 alpha partially reversed the HE-145-mediated suppression of HBV RNA. Therefore, HE-145 may represent a novel class of anti-HBV agents which selectively modulate transcriptional machinery of human liver cells to suppress HBV gene expression and replication.
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PMID:The role of helioxanthin in inhibiting human hepatitis B viral replication and gene expression by interfering with the host transcriptional machinery of viral promoters. 1824 49

We report two rare cases of hepatocellular carcinoma with invasion into the right atrium. In both our cases, the patients had liver cirrhosis and were admitted to our department due to symptoms such as worsening of the jaundice, ascites and edema of the lower extremities. The diagnosis of the HCC was established when we found high levels of alpha-fetoprotein, and the patients underwent MRI and CT-scan that were indicative of HCC. The clinical suspicion of invasion of the RA by the tumor emerged from the presence of heart-related symptoms, such as dyspnea and chest discomfort. The patients underwent two-dimensional transthoracic echocardiogram, which revealed from the sub-costal view a mobile atrial mass protruding from the inferior vena cava. In conclusion, when a patient with a history of chronic hepatic disease presents with symptoms of right heart failure one must be cautious and should bear in mind that right heart involvement from a malignant tumor may be present.
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PMID:Hepatocellular carcinoma with invasion into the right atrium. Report of two cases and review of the literature. 1825 Nov 69

Hepatocellular carcinoma is the 5th most common cancer in the world. Prognosis for this disease is poor since hepatocellular carcinoma is mostly diagnosed at an advanced stage. Serum alpha-fetoprotein (AFP) is one of the most common diagnostic markers for hepatocellular carcinoma. However, its diagnostic value is more and more questioned. Therefore, research has focussed on AFP related parameters (AFP mRNA and AFP glycoforms). The aim of this paper is to review the present knowledge on AFP and its related parameters in diagnosing and monitoring HCC. AFP related parameters can be arranged in two types: AFP mRNA and AFP glycoforms. AFP mRNA is a potentially prognostic marker and AFP mRNA assays are based on PCR techniques. The AFP glycoforms have diagnostic potential and assays are based on isoelectric focussing and lectin affinity electrophoretic methods. Up to now the diagnostic use of the AFP related parameters is limited. Although some of them are recommended as a complementary test, they cannot (yet) replace serum AFP as the golden standard of diagnostic markers for hepatocellular carcinoma.
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PMID:Diagnosing and monitoring hepatocellular carcinoma with alpha-fetoprotein: new aspects and applications. 1853 35

Previous studies identified amino acid (aa) substitutions of the hepatitis C virus core region of genotype 1b (HCV-1b core region) and elevated serum alpha-fetoprotein (AFP) levels as predictors of poor virologic response to pegylated interferon (PEG-IFN) plus ribavirin (RBV), and also as risk factors for hepatocarcinogenesis. The present study evaluated the impact of aa substitutions of HCV-1b core region on AFP, as a surrogate marker of hepatocarcinogenesis, on AFP levels in 569 Japanese patients with HCV-1b but without HCC, and investigated the predictive factors of elevated AFP (> or =11 microg/L). High AFP levels were detected in 27.4% of the patients. The rate of hepatocarcinogenesis in a group of 109 patients who received IFN monotherapy and followed-up for 15 years, was significantly higher in patients with abnormal than normal AFP. Multivariate analysis of 569 patients identified fibrosis stage (F3,4), aspartate aminotransferase (> or =76 IU/L), substitution of aa 70 (glutamine or histidine), and platelet count (<15.0 x 10(4)/microl) as significant determinants of elevated AFP. In 49 patients with abnormal AFP levels and substitutions at aa 70 who were treated with PEG-IFN + RBV, the rate of normalization of AFP was significantly lower in non-virological responders (28.6%) than in transient (71.4%) and sustained (100%) virological responders. The results indicated that substitution of aa 70 of HCV-1b core region is an important predictor of elevated AFP in non-HCC patients, and that eradication of the mutant virus normalizes AFP. The results highlight the importance of eradication of mutant type virus of aa 70 for reducing the risk of hepatocarcinogenesis.
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PMID:Substitution of amino acid 70 in the hepatitis C virus core region of genotype 1b is an important predictor of elevated alpha-fetoprotein in patients without hepatocellular carcinoma. 1855 9

Various molecular changes characterizing organ-specific carcinogenesis have been identified in human tumors; however, the molecular mechanisms of the genomic changes specific for each cancer are not well defined. A transgenic (Tg) mouse model with constitutive expression of the nucleotide-editing enzyme, activation-induced cytidine deaminase (AID), develops tumors in various organs as a result of the mutagenic activities of AID. This phenotypic character of AID Tg mice allowed us to analyze the organ-specific genetic changes in tumor-related genes commonly triggered by AID-mediated mutagenesis. Among the 80 AID Tg mice analyzed, 11 mice developed hepatocellular carcinomas, and 7 developed lung cancers. In addition, 1 developed the gastric cancer and 3 developed gastric adenomas. Organ-specific preferences for nucleotide changes were observed in some of the tumor-related genes in each epithelial tissue of the AID Tg mice. Of note, the c-myc and K-ras genes were the preferential targets of the mutagenic activity of AID in lung and stomach cancers, respectively, whereas mutations in the p53 and beta-catenin genes were commonly observed in all 3 organs. Quantitative RT-PCR analyses revealed that alpha-fetoprotein, insulin-like growth factor-2 and cyclin D1 genes were specifically upregulated in HCC, whereas upregulation of the matrix metalloproteinase-7 gene was more marked in lung cancer. Our findings suggest that AID, a DNA mutator that plays a critical role linking inflammation to human cancers, might be involved in the generation of organ-specific genetic diversity in oncogenic pathways during cancer development.
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PMID:Organ-specific profiles of genetic changes in cancers caused by activation-induced cytidine deaminase expression. 1878 63

N-linked glycosylation is prevalent in proteins destined for extracellular environments; nearly all secreted proteins are glycosylated. However, with respect to their glycosylation sites, little attention has been paid. Here, we report the analysis of N-glycosylation sites on secreted proteins of human hepatocellular carcinoma cells. For the enrichment of glycopeptides, capture methods with hydrophilic affinity (HA) and hydrazide chemistry (HC) were used complementarily. With the use of both methods in combination with nano-LC-ESI-MS/MS analysis, 300 different glycosylation sites within 194 unique glycoproteins were identified, and 172 glycosites have not been determined experimentally previously. A direct comparison between HA and HC methods was also investigated for the first time. In brief, in terms of selectivity for glycopeptides, HC is superior to HA (92.9% vs 51.3%); however, based on the number of glycosites identified, HA outweighs HC (265 vs 159). Furthermore, unavoidable contaminants such as actin and bovine serum albumin which are not N-glycosylated could be easily depleted by using this glycoproteomic strategy. As a consequence, more low-abundance and genuinely secreted proteins were identified. Among the glycoproteins identified, alpha-fetoprotein, CD44 and laminin have been reported to be implicated in HCC and its metastasis.
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PMID:Identification of N-glycosylation sites on secreted proteins of human hepatocellular carcinoma cells with a complementary proteomics approach. 1919 83

We combined data from two liver transplant centers to determine the tumor characteristics and outcomes of 51 patients transplanted with incidental hepatocellular carcinoma (iHCC) compared with 143 patients transplanted for previously known HCC (pkHCC). There were no differences in age, gender, or frequency of hepatitis C infection. Patients with iHCC were more likely to be African-American (22% vs 10%; P = .016), more likely to be screened by ultrasound (38% vs 9%; P < .001), had a lower alpha-fetoprotein (83.9 +/- 258.1 vs 572.4 +/- 2376.4 ng/mL; P = .005), and had a higher model for end-stage liver disease (MELD) score (14.3 +/- 4.1 vs 11.8 +/- 4.7; P < .001). The liver explants of patients with iHCC had smaller total tumor burden than patients with pkHCC (3.1 +/- 3.5 vs 4.1 +/- 2.6 cm; P < .001), but a similar percentage of single lesions (66% vs 65%) and tumors that met Milan criteria (76% vs 65%). Patients with iHCC had 1-, 3-, and 5-year survivals of 78%, 67%, and 58%, and 1-, 3-, and 5-year recurrence-free survivals of 90%, 87%, and 87% compared with the 1-, 3-, and 5-year survivals of 90%, 82%, and 70%, and the 1-, 3-, and 5-year tumor-free survivals of 91%, 84%, and 78% in patients with pkHCC. We concluded that patients with iHCC were more likely to be African-American, to be screened by ultrasound, to have a lower alpha-fetoprotein, and a higher MELD score. Ultrasound is not a sensitive modality for screening patients for HCC. Patients with iHCC do not have an advantage in survival over those with pkHCC.
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PMID:Incidental hepatocellular carcinoma after liver transplantation: population characteristics and outcomes. 1924 18

The number and ratio of both HBsAg- and HCV Ab-negative hepatocellular carcinoma (HCC-nonBC) cases have been steadily increasing in Japan. The aim of this study was to examine the frequency of detection of HCC-nonBC by screening methods and to elucidate the clinical characteristics of HCC-nonBC compared with those of hepatitis C and/or B virus-associated HCC (HCC-virus). We recruited 624 patients with HCC who were diagnosed between 1982 and 2007 at the Department of Gastroenterology and Hepatology, Nagasaki University Hospital. They were categorized into 2 groups as follows: i) 550 were included in the HCC-virus group: positive for HBsAg and/or positive for HCV Ab, and ii) 74 were included in the HCC-nonBC group: negative for both HBsAg and HCV Ab. The follow-up patterns until the initial detection of HCC and the survival rates were analyzed and compared between the 2 groups. Multivariate analysis identified follow-up, alcohol consumption, albumin level, total bilirubin level, alpha-fetoprotein (AFP) level, and tumor-node-metastasis (TNM) stage as independent and significant risk factors for prognosis. Among the 397 patients with HCC in TNM stage I or II, multivariate analysis identified the cause of liver disease, gender, Child-Pugh score, serum albumin level and TNM stage as independent and significant risk factors for prognosis. We reported that the poor prognoses of patients with HCC-nonBC were attributable to its late detection in an advanced condition due to the absence of a surveillance system for the early detection of HCC. However, in early-stage patients, patients with HCC-nonBC showed significantly better prognosis than those in the HCC-virus group.
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PMID:Differences in prognostic factors according to viral status in patients with hepatocellular carcinoma. 2037 46

In the treatment of hepatocellular carcinomas, therapies such as trans-arterial chemo-embolisation, trans-arterial radioembolisation, percutaneous ethanol injection and radio-frequency ablation can decrease the size (and overall viability) of the tumours, thus potentially increasing the proportion of patients qualifying for resection and transplantation. While the use of such downstaging therapies is straightforward when resection is the aim, in a similar way to other neo-adjuvant treatments in the surgery of tumours that are too large or awkwardly placed to be primarily resected the issues related to transplantation are more complex. In the context of transplantation the word "downstaging" designates not only a neo-adjuvant treatment, but also a selection strategy to allow patients who are initially outside accepted listing criteria to benefit from transplantation should the neo-adjuvant therapy be successful in reducing tumour burden. The effectiveness of downstaging as a selection strategy, at first questioned because of methodological bias in the studies that described it, has been recently demonstrated by more solid prospective investigations. Several issues however remain open, such as inclusion criteria before the strategy is implemented (size/number, surrogate markers of differentiation/vascular invasion such as alpha-fetoprotein), the choice of which downstaging therapy, the end-points of treatment, and the need and duration of a period of observation proving disease response or stabilisation before the patient can be listed. The present review discusses which treatments and strategies are available for downstaging HCC on the basis of the published literature.
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PMID:The place of downstaging for hepatocellular carcinoma. 2038 28

Sorafenib has recently been shown to be effective for the treatment of advanced hepatocellular carcinoma in randomized controlled trials. Here, we report the experience with sorafenib in 25 patients with advanced HCC under daily practice conditions. Tolerance to sorafenib was acceptable and side effects were manageable, although the ECOG performance status was reduced in all patients. The most prevalent grade 2/3 side effects were fatigue (40%) and diarrhea (24%), and withdrawal from therapy occurred in 29% of patients. Disease stabilization was documented in 60% of patients. The median treatment time was 2.7 months and overall survival was 11.0 months. No significant serum alpha-fetoprotein decline was noted at the time of the first radiological control in a subgroup of patients with baseline levels >50 ng/ml who achieved stable disease. In conclusion, in daily practice sorafenib is safe and disease stabilization can be achieved in the majority of patients. However, intolerance to sorafenib can affect treatment adherence substantially.
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PMID:Efficacy and safety of sorafenib in advanced hepatocellular carcinoma under daily practice conditions. 2056 28


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