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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diethylnitrosamine (DEN) was administered to rats as a single dose, which is known not to give rise to liver tumours without subsequent promotion. Iron dextran (Fe/Dex) was then administered parenterally to the animals, to induce iron overload. At 3 and 6 months after the final Fe/Dex treatments, livers were examined quantitatively for the numbers of the placental form of glutathione-S-transferase (GST-P) expressing foci, the area occupied by these foci and their size distribution. The results demonstrate that iron not only increased the number of foci after DEN initiation in the rat liver, but that the area occupied by these lesions increased significantly between 3 and 6 months after initiation. There is no evidence that iron increased the number of GST-P expressing foci present in rats not exposed to DEN. This indicates that iron did not act as an initiator in this rodent model of liver cancer. The increase in the area of the liver occupied by the foci in iron and DEN treated rats was due to an increase in the size of the foci, as well as to an increase in the number of foci. This is the first demonstration that iron can act as a promoter of DEN initiated hepatocytes. It also demonstrates that fibrogenesis is not an absolute requirement for the promotion, by iron, of liver foci in the rat, and that this could also be the case for iron overload in man. Iron may also act as a promoter of already initiated hepatocytes in the development of human liver cancer, as it does in the rat.
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PMID:Iron promotes DEN initiated GST-P foci in rat liver. 906 62

To demonstrate the usefulness of iron colloid-enhanced MR images in differentiating hepatocellular carcinoma (HCC) from hyperplastic nodules (HN), microautoradiographs of chemically induced rat liver tumours were prepared 4 h after intravenous injection of chondroitin sulphate iron colloid (CSIC) labelled with 59Fe by the dipping technique. 20 Wistar rats were allocated into three groups: (1) a normal group, 10; (2) an HN group, 5; and (3) a liver cancer (LC) group, 5. In the I.C group, a diet containing 0.06% 3'-methydiaminobenzine tetrahydro-chloride (DAB) was administered for 3 months. In the HN group, a diet containing 0.025% acetylaminofluorene (AAF) was administered for 4 months. Non-labelled CSIC was intravenously injected into five rats in the normal group, and pseudomicroautoradiographs were prepared using the same technique (normal cold group). 50 sites for examination were randomly selected for each of the normal liver tissue, HN, well-differentiated HCC (HCC-W), and moderately to poorly-differentiated HCC (HCC-MP). The number of Kupffer cell-like macrophages and the photosensitized area ratio (PAR) per field of view were calculated. There was no significant difference in either the number of Kupffer cell-like macrophages or the PAR between HN and normal liver tissue. Although there was no significant difference in the number of these cells between groups HN and HCC-W, the PAR in group HCC-W was significantly lower than that in group HN (p = 0.045). In HCC-MP, both their number (p = 0.003) and the PAR (p = 1.18 x 10(-9)) were significantly lower than in group HCC-W. However, the PAR in HCC-MP was significantly higher than those in the normal cold group (p = 0.019). Iron colloid-enhanced MRI is useful for differentiating HCC from HN, and for diagnosing the degree of HCC differentiation.
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PMID:Usefulness of iron colloid-enhanced MRI in differentiating experimental hepatocellular carcinoma from hyperplastic nodules in rats: analysis by microautoradiography. 913 70

In a Swedish cohort of workers (n = 6,454) from seven aluminum foundries and three secondary aluminum (scrap) smelters there was no overall excess risk of cancer among male or female workers less than 85 years of age (males: 325 observed cases, standardized incidence ratio (SIR) 1.02, 95% confidence interval (CI) 0.91-1.13; females: 22 cases, SIR = 0.95, 95% CI = 0.60-1.44). In male workers, however, significantly elevated risk estimates were observed for cancer of the lung (51 cases; SIR = 1.49, 95% CI = 1.11-1.96), anorectal cancer (33 cases; SIR 2.13, 95% CI = 1.47-2.99), and sinonasal cancer (4 cases; SIR = 4.70, 95% CI = 1.28-12.01). There was no increase of urinary bladder or liver cancer. Lung cancer risks were highest in workers with a short duration of employment (< 5 years) suggesting determinants of risk related to socioeconomic factors rather than the occupational environment under study, but there were also indications of a lung cancer hazard from sand casting of aluminum for 10 years or more (SIR = 2.10, 95% CI = 1.01-3.87). The increase in anorectal cancer could not be etiologically related to occupational determinants of risk. Sand casting of aluminum aside, the cancer risk in secondary aluminum smelting seems to be lower than in primary aluminum smelting and in iron and steel founding, respectively.
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PMID:Cancer morbidity in workers at aluminum foundries and secondary aluminum smelters. 932 70

Cirrhotic patients with hereditary hemochromatosis (HHC) have an increased risk of primary liver cancer (PLC). The purpose of this study was to determine the prevalence of primary liver cancer in patients with HHC undergoing orthotopic liver transplantation (OLT). Five liver transplant centers were surveyed; clinical and pathological data on 37 patients with HHC undergoing OLT were retrospectively collected and analyzed. The diagnosis of HHC was established by a combination of serum transferrin-iron saturation, hepatic iron index (HII), and/or pattern of liver iron staining. The diagnosis of HHC had been unsuspected before OLT in 13 of 37 (35%). Primary liver cancer was found in the explants of 10 of 37 patients (27%) and was unsuspected in 7 of 10 (70%); 8 were hepatocellular carcinoma, and 2 were cholangiocarcinoma; foci of hepatocyte dysplasia were found in 6 additional patients. Mean (+/- SEM) hepatic iron content and HII in 20 patients without prior phlebotomy or bleeding were 17.2 mg/g dry weight (+/- 2.9) and 5.5 (+/- 0.8), respectively. The overall 1-year survival rate after OLT in the 37 HHC patients was 58% (v 55% for HHC patients with PLC). We draw the following conclusions: (1) the diagnosis of HHC is often unsuspected before OLT, and HHC should be evaluated pretransplantation by direct and indirect markers; (2) HHC patients undergoing OLT have a high prevalence of primary liver cancer, the majority being unsuspected; and (3) HHC patients have poorer than average survival after OLT, which cannot be explained solely by the presence of concomitant PLC.
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PMID:Primary liver cancer and survival in patients undergoing liver transplantation for hemochromatosis. 934 73

We examined a new MR technique for obtaining 3D-MRA images of the liver that simultaneously depicts HCC and the portal and hepatic veins. Five patients with clinically suspected HCC were studied with superparamagnetic iron oxide (SHU-555A) used as a negative contrast medium for the liver. In our study, a 3D-rotational display was provided on the CTR monitor from 2D-TOF images by computed reconstruction, clearly showing HCC and portal and hepatic veins on the same image. Our method was found to be of great value in planning surgery of the liver.
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PMID:[Three-dimensional MR angiography of HCC and portal and hepatic veins using superparamagnetic iron oxide]. 955 52

Most of copper present in rat plasma and liver binds to caeruloplasmin and metallothionein, respectively, and is not redox active. However, free forms of copper including loosely bound forms to other molecules are redox active. We assessed the free copper in Long-Evans rats with a cinnamon-like coat color (LEC rats), an animal model of Wilson disease and liver cancer. Compared to those of control rats, the liver and plasma of LEC rats showed a marked elevation of free copper, especially at the stage of acute hepatitis, in parallel with an increase of total copper levels in the livers and a decrease of plasma caeruloplasmin (ferroxidase I) activity. At the onset of jaundice, the total copper levels, however, decreased in liver, but increased in plasma, while free copper levels in both liver and plasma remained higher. Free iron levels in both liver and plasma were also determined and did not change significantly, except for the case of plasma in jaundiced rats. The data are consistent with a proposal in which increased levels of redox active free copper in the liver of LEC rats catalyze Fenton-type reactions, producing a large flux of hydroxyl radicals that would play an important role in the observed liver dysfunction, leading to acute hepatitis, and finally, hepatocarcinoma. This is the first demonstration that the free copper may participate in the pathophysiology of the LEC rats and Wilson disease.
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PMID:A marked increase in free copper levels in the plasma and liver of LEC rats: an animal model for Wilson disease and liver cancer. 970 24

The purpose of this study was to compare small and ultrasmall superparamagnetic iron oxide particles (SPIO and USPIO, respectively) as MR contrast agents for the evaluation of focal hepatic disease. In two different patient groups (SPIO [n = 53], USPIO [n = 27]), with focal liver disease (metastases, hepatocellular carcinoma [HCC], hepatocellular adenoma [HCA], and focal nodular hyperplasia [FNH]), spin-echo T1- and T2-weighted images (T1WI, T2WI) were obtained at 1.0T, before and after intravenous contrast administration. The percentage signal-to-noise ratio (SNR) change and lesion-to-liver contrast (LLC) were measured and statistically compared. The liver decreased in signal intensity (SI) after SPIO administration (-28%) and increased after USPIO administration (+16%) on T1WI. On T2WI, the liver decreased in SI on postcontrast images with both agents (-78% SPIO, -73% USPIO). This difference was not statistically significantly different (P < or = .07). Both SPIO and USPIO provided >500% improvement in LLC on T2WI. On T1WI, LLC was increased in metastases (120%) and HCC (325%) with SPIO. Post-USPIO, LLC was increased on T1WI only in metastases (>500%). Both SPIO and USPIO show excellent hepatic uptake, presumed secondary to reticuloendothelial activity, based on the degree of %SI change seen in the liver after administration of contrast on T2WI. However, USPIO preparations exhibit blood pool activity that may aid in further characterization of focal liver lesions, as is evidenced by their greater T1 effect in the liver and in some focal liver lesions.
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PMID:MRI in focal liver disease: a comparison of small and ultra-small superparamagnetic iron oxide as hepatic contrast agents. 978 44

The complications of iron overload in hemochromatosis can be avoided by early diagnosis and appropriate management. Therapeutic phlebotomy is used to remove excess iron and maintain low normal body iron stores, and it should be initiated in men with serum ferritin levels of 300 microg/L or more and in women with serum ferritin levels of 200 microg/L or more, regardless of the presence or absence of symptoms. Typically, therapeutic phlebotomy consists of 1) removal of 1 unit (450 to 500 mL) of blood weekly until the serum ferritin level is 10 to 20 microg/L and 2) maintenance of the serum ferritin level at 50 microg/L or less thereafter by periodic removal of blood. Hyperferritinemia attributable to iron overload is resolved by therapeutic phlebotomy. When applied before iron overload becomes severe, this treatment also prevents complications of iron overload, including hepatic cirrhosis, primary liver cancer, diabetes mellitus, hypogonadotrophic hypogonadism, joint disease, and cardiomyopathy. In patients with established iron overload disease, weakness, fatigue, increased hepatic enzyme concentrations, right upper quadrant pain, and hyperpigmentation are often substantially alleviated by therapeutic phlebotomy. Patients with liver disease, joint disease, diabetes mellitus and other endocrinopathic abnormalities, and cardiac abnormalities often require additional, specific management. Dietary management of hemochromatosis includes avoidance of medicinal iron, mineral supplements, excess vitamin C, and uncooked seafoods. This can reduce the rate of iron reaccumulation; reduce retention of nonferrous metals; and help reduce complications of liver disease, diabetes mellitus, and Vibrio infection. This comprehensive approach to the management of hemochromatosis can decrease the frequency and severity of iron overload, improve quality of life, and increase longevity.
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PMID:Management of hemochromatosis. Hemochromatosis Management Working Group. 986 45

Population screening for hemochromatosis done by using the transferrin saturation test has been advocated by experts to permit the initiation of therapeutic phlebotomy before the onset of clinical disease. The discovery of a gene associated with hemochromatosis has made DNA testing another option for screening and diagnosis. In this paper, U.S. Preventive Services Task Force criteria are used to evaluate the evidence for the usefulness of population screening done by using iron measures or genetic testing. Published clinical research offers little evidence to suggest that population screening for hemochromatosis done by using genetic testing improves clinical outcomes. Although one recently discovered mutation, C282Y, accounts for 60% to 92% of cases of the disease in series of patients with hemochromatosis, uncertainties remain about the clinical penetrance of various genotypes; the accuracy of genetic testing; and the ethical, legal, and social effects of genetic testing. Before population screening for hemochromatosis done by using transferrin saturation testing can be recommended, laboratory standardization needs to be addressed and questions about risk for clinical disease in asymptomatic persons with mutations or early biochemical expression of disease require resolution. Evidence from case series suggests that hemochromatosis may be associated with liver cancer, other liver disease, diabetes, bradyarrhythmias, and arthritis. In all studies but one, however, estimation of the magnitude and significance of this risk is limited by lack of adequate comparison groups. The need for population data to answer questions about penetrance among asymptomatic persons should not impede efforts to increase the detection and treatment of hemochromatosis in persons found to have elevated iron measures a family history of hemochromatosis, or consistent early signs and symptoms of the disease.
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PMID:Iron overload, public health, and genetics: evaluating the evidence for hemochromatosis screening. 986 50

Oxidative DNA damage and its repair in primary rat hepatocyte cultures was investigated following 4 h of incubation with the toxic iron chelate, ferric nitrilotriacetate (Fe-NTA), in the presence or absence of the potent protective flavonoid myricetin (25-50-100 microM). Seven DNA base oxidation products were quantified in DNA extracts by gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring mode. Concomitantly, DNA repair capacity of hepatocytes was estimated by the release of oxidized-base products into culture media, using the same GC-MS method. A genotoxic effect of Fe-NTA (100 microM) in hepatocytes was evidenced by a severe increase in DNA oxidation over basal levels, with accumulation in cellular DNA of five oxidation products derived from both purines and pyrimidines. This prooxidant effect of iron was also noted by an induction of lipid peroxidation, estimated by free malondialdehyde production. Addition of increasing concentrations of myricetin (25-50-100 microM) simultaneously with iron prevented both lipid peroxidation and accumulation of oxidation products in DNA. Moreover, as an activation of DNA repair pathways, myricetin stimulated the release of DNA oxidation bases into culture media, especially of purine-derived oxidation products. This removal of highly mutagenic oxidation products from DNA of hepatocytes might correspond to an activation of DNA excision-repair enzymes by myricetin. This was verified by RNA blot analysis of DNA polymerase beta gene expression which was induced by myricetin in a dose-dependent manner. This represented a novel and original mechanism of cytoprotection by myricetin against iron-induced genotoxicity via stimulation of DNA repair processes. Since iron-induced DNA damage and inefficient repair in hepatocytes could be related to genotoxicity and most probably to hepatocarcinogenesis, modulation of these processes in vitro by myricetin might be relevant in further prevention of liver cancer derived from iron overload pathologies.
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PMID:Repair of iron-induced DNA oxidation by the flavonoid myricetin in primary rat hepatocyte cultures. 1040 9


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