Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic activation of the hepatocarcinogenic mycotoxin aflatoxin B(1) (AFB(1)) results in the covalent attachment of AFB(1) to serum albumin. Digestion of adducted albumin releases AFB(1)-lysine, a biomarker of exposure status. AF-albumin adducts have been most frequently measured in precipitated serum albumin using an immunoassay (ELISA); however, a sensitive and specific isotope dilution mass spectrometric (IDMS) assay for measurement of AFB(1)-lysine in serum has recently been developed. The ELISA and IDMS methods were compared using 20 human sera collected in Guinea, West Africa, where AF exposure is endemic. Measurement of AFB(1)-lysine adduct concentrations by IDMS in serum and albumin precipitated from the same sample revealed that precipitation has no effect on the measured adduct levels. The concentration of AF-albumin adducts measured by ELISA and AFB(1)-lysine measured by IDMS in 2 mg of albumin were well correlated (R = 0.88, P < 0.0001); however, AF-albumin adduct concentrations measured by ELISA were on average 2.6-fold greater than those of the AFB(1)-lysine adduct. Although these data suggest that the ELISA is measuring other AF adducts in addition to AFB(1)-lysine, these biomarkers are comparable in their ability to assess AF exposure at AF-albumin concentrations > or =3 pg AFB(1)-lysine equivalents/mg albumin. Identification of other adducts may clarify the mechanistic basis for using AF-protein biomarkers to assess exposure status in future epidemiologic studies of liver cancer.
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PMID:Quantitative comparison of aflatoxin B1 serum albumin adducts in humans by isotope dilution mass spectrometry and ELISA. 1661 31

We conducted a multicenter, randomized, controlled trial to investigate the effect of long-term oral supplementation with branched-chain amino acids (BCAA) on the event-free survival in 622 patients with decompensated cirrhosis. In the present study, the development of liver cancer was analyzed as an endpoint in particular. Subjects received either treatment with BCAA at 12g/day or dietary therapy containing the matched daily energy and protein intake. A Cox regression analysis was carried out to estimate the hazard ratios for different background factors stratified by treatment group. Liver cancer was noted in 89 patients. The risk for liver cancer was significantly higher for males, patients with concurrent diabetes mellitus, patients with an alpha-fetoprotein (AFP) level of 20ng/mL or higher, patients with higher body mass index (BMI), and patients with lower serum albumin levels. When the BCAA group and the diet group were compared for factors that interacted with the treatment arms, the risk for liver cancer was significantly reduced in the BCAA group with a BMI of 25 or higher and with an AFP level of 20ng/mL or higher. Oral supplemental treatment with BCAA may reduce the risk of liver cancer in cirrhotic patients with these specific factors.
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PMID:Overweight and obesity increase the risk for liver cancer in patients with liver cirrhosis and long-term oral supplementation with branched-chain amino acid granules inhibits liver carcinogenesis in heavier patients with liver cirrhosis. 1673 44

All-trans retinoic acid (ATRA) was incorporated into lipid emulsions in an attempt to alter its distribution characteristics and improve its inhibition of liver cancer metastasis. Lipid emulsions composed of egg phosphatidylcholine, cholesterol, and soybean oil were the optimized carriers for ATRA delivery, as shown by the submicron particle size and high incorporation efficiency. The particle size and zeta potential of ATRA incorporated into emulsions were about 133 nm and -11 mV, respectively. In vitro drug release study demonstrated that the release of ATRA from emulsions was sustained in the absence and present of bovine serum albumin, suggesting that ATRA was stable when incorporated in emulsions. After intravenous administration in mice, [3H]cholesteryl hexadecyl ether incorporated into emulsion, which is the inherent distribution of emulsions, accumulated gradually mainly in the liver. The blood concentration and hepatic accumulation of [3H]ATRA incorporated into emulsion was significantly higher than that of serum dissolving [3H]ATRA, which represent the original distribution characteristic of free ATRA. In a murine liver metastasis model by colon adenocarcinoma, the liver metastasis number and liver weight were significantly reduced and the survival time of mice was prolonged following intravenous injection of ATRA incorporated into emulsions.
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PMID:Inhibition of liver metastasis by all-trans retinoic acid incorporated into O/W emulsions in mice. 1679 Mar 29

The purpose of this study was to compare the clinical features and survival in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) and hepatitis C virus-related hepatocellular carcinoma (HCV-HCC). A total of 2820 HCC patients were included. The mean age of HBV-HCC patients was 52.5+/-13.4 years, while it was 64.8+/-8.7 years in HCV-HCC patients. The male/female ratio was 7.8 in HBV-HCC, while it was 1.7 in HCV-HCC. The mean alpha-fetoprotein level in HBV-HCC was 11,661+/-22,805 ng/mL, while it was 5079+/-15,005 ng/mL in HCV-HCC. The mean tumour size was 6.4+/-4.1 cm in HBV-HCC, while it was 4.6+/-3.1 cm in HCV-HCC. The median survival was 11.1 months in HBV-HCC, while it was 23.9 months in HCV-HCC. Compared with HBV-HCC patients, HCV-HCC patients were older, had a lower male/female ratio, lower white blood cell count, lower serum albumin level, higher serum ALT level, lower serum alpha-fetoprotein level, smaller tumour size and survived longer.
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PMID:Hepatitis B- and C-related hepatocellular carcinomas yield different clinical features and prognosis. 1692 Mar 52

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

Fe(3)O(4) nanoparticles were stabilized using different functional polysaccharides, such as chitosan (CS), O-carboxymethylchitosan (OCMCS) and (N-succinyl-O-carboxymethylchitosan (NSOCMCS) to improve their bioactivity. The release profile and the in vitro cancer cell inhibition activity of camptothecin (CPT) loaded polysaccharide modified Fe(3)O(4) nanoparticles were systematically studies. The particle size and size distribution of CPT-loaded polysaccharide modified Fe(3)O(4) nanoparticles were found to be strongly dependent on polysaccharide character. Such polysaccharide character could also affect CPT adsorption efficiency, CPT release behavior and bovine serum albumin (BSA) unspecific binding capacity. After 24 h incubation of 7721 cancer cells with CPT-loaded polysaccharide modified Fe(3)O(4) nanoparticles, significant changes in cell morphology could be discernible from phase contrast microscopy. Cytotoxicity assay showed these polysaccharide modified Fe(3)O(4) nanoparticles did not exhibit noteworthy cytotoxicity against 7721, however, the in vitro inhibition rate of CPT-loaded polysaccharide modified Fe(3)O(4) nanoparticles against 7721 liver cancer cell increased significantly in comparison with that of CPT-free drug.
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PMID:Polysaccharide surface modified Fe3O4 nanoparticles for camptothecin loading and release. 1928 31

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

The main goal of this investigation was to develop and test a new method of treatment for human hepatocellular carcinoma (HCC). We present a method of carbon nanotube-enhanced laser thermal ablation of HepG2 cells (human hepatocellular liver carcinoma cell line) based on a simple multiwalled carbon nanotube (MWCNT) carrier system, such as human serum albumin (HSA), and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. Both HepG2 cells and hepatocytes were treated with HSA-MWCNTs at various concentrations and at various incubation times and further irradiated using a 2 W, 808 nm laser beam. Transmission electron, phase contrast, and confocal microscopy combined with immunochemical staining were used to demonstrate the selective internalization of HSA-MWCNTs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. The postirradiation apoptotic rate of HepG2 cells treated with HSA-MWCNTs ranged from 88.24% (for 50 mg/L) at 60 sec to 92.34% (for 50 mg/L) at 30 min. Significantly lower necrotic rates were obtained when human hepatocytes were treated with HSA-MWCNTs in a similar manner. Our results clearly show that HSA-MWCNTs selectively attach on the albondin (aka Gp60) receptor located on the HepG2 membrane, followed by an uptake through a caveolin-dependent endocytosis process. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.
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PMID:Enhanced laser thermal ablation for the in vitro treatment of liver cancer by specific delivery of multiwalled carbon nanotubes functionalized with human serum albumin. 2128 90

Liver cancer patients are confronted with the additional risk of malnutrition because the disease is often associated with hepatitis, liver cirrhosis, and metabolic disturbances. Nutritional intervention can improve treatment outcome, but early detection is important. This study aimed to determine whether the Mini Nutritional Assessment (MNA) could effectively rate the nutritional status of patients with liver cancer in Taiwan. A total of 300 patients were evaluated for nutritional status with two modified versions of the MNA in short and long forms. MNA-Taiwan Version 1 adopted population-specific anthropometric cutpoints, whereas Version 2 replaced mid-arm and calf circumferences in place of body mass index. Predicted statuses were compared to results predicted by the Council on Nutrition Appetite Questionnaire (CNAQ) and analyzed for correlations with biochemical or cancer status parameters. Results showed that both versions of the MNA were effective in predicting nutritional status, and predictions by the short forms agreed well with those by the long forms. The nutritional scores correlated well with hemoglobin, serum albumin, C-reactive protein, r-glutamyl transpeptidase, TNM (tumor, node, metastasis) staging, and severity of cirrhosis. These results suggest that the MNA can be an effective tool for assessing the nutritional status of patients with liver cancer.
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PMID:Usefulness of the mini nutritional assessment in predicting the nutritional status of patients with liver cancer in Taiwan. 2146 83

The aflatoxins were discovered in toxic peanut meal causing "turkey X" disease, which killed large numbers of turkey poults, ducklings and chicks in the UK in the early 1960s. Extracts of toxic feed induced the symptoms in experimental animals, and purified metabolites with properties identical to aflatoxins B(1) and G(1) (AFB(1) and AFG(1)) were isolated from Aspergillus flavus cultures. Structure elucidation of aflatoxin B(1) was accomplished and confirmed by total synthesis in 1963. AFB(1) is a potent liver carcinogen in rodents, non-human primates, fish and birds, operating through a genotoxic mechanism involving metabolic activation to an epoxide, formation of DNA adducts and, in humans, modification of the p53 gene. Aflatoxins are unique among environmental carcinogens, in that elucidation of their mechanisms of action combined with molecular epidemiology provides a foundation for quantitative risk assessment; extensive evidence confirms that contamination of the food supply by AFB(1) puts an exposed population at increased risk of developing hepatocellular carcinoma (HCC). Molecular biomarkers to quantify aflatoxin exposure in individuals were essential to link aflatoxin exposure with liver cancer risk. Biomarkers were validated in populations with high HCC incidence in China and The Gambia, West Africa; urinary AFB(1)-N (7)-Guanine excretion was linearly related to aflatoxin intake, and levels of aflatoxin-serum albumin adducts also reflected aflatoxin intake. Two major cohort studies employing aflatoxin biomarkers identified their causative role in HCC etiology. Results of a study in Shanghai men strongly support a causal relationship between HCC risk and the presence of biomarkers for aflatoxin and HBV infection, and also show that the two risk factors act synergistically. Subsequent cohort studies in Taiwan confirm these results. IARC classified aflatoxin as a Group 1 human carcinogen in 1993, based on sufficient evidence in humans and experimental animals indicating the carcinogenicity of naturally occurring mixtures of aflatoxins, aflatoxin B(1), G(1) and M(1). Aflatoxin biomarkers have also been used to show that primary prevention to reduce aflatoxin exposure can be achieved by low-technology approaches at the subsistence farm level in sub-Saharan Africa. Also, in residents of Qidong, China, oral dosing with chlorophyllin, a chlorophyll derivative, prior to each meal led to significant reduction in aflatoxin-DNA biomarker excretion, supporting the feasibility of preventive measures to reduce HCC risk in populations experiencing unavoidable aflatoxin exposure. The systematic, comprehensive approach used to create the total aflatoxin database justifies optimism for potential success of preventive interventions to ameliorate cancer risk attributable to aflatoxin exposure. This strategy could serve as a template for the development, validation and application of molecular and biochemical markers for other carcinogens and cancers as well as other chronic diseases resulting from environmental exposures.
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PMID:Present and future directions of translational research on aflatoxin and hepatocellular carcinoma. A review. 2162 89


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