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

The possible association between the risk of liver cancer and the levels of magnesium in drinking water from municipal supplies was investigated in a matched cancer case-control study in Taiwan. All eligible liver-cancer deaths (9166 cases) of Taiwan residents from 1994 through 1998 were compared with deaths from other causes (9166 controls). The levels of magnesium in the drinking water of these residents were also determined. Data on magnesium levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation (TWSC). The control group consisted of people who died from other causes, and the controls were pair-matched to the cases by year of birth and death. The adjusted odd ratios for the relationship between magnesium levels in drinking water and liver cancer were not statistically significant. Confounding variables, hepatitis B and C infection for example, are probably most likely in the genesis of liver cancer.
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PMID:Magnesium in drinking water and the risk of death from liver cancer. 1263 76

Seven new nitrogen heterocycle porphyrins, 5,10,15,20-tetra[4-(N-pyrrolidinyl)phenyl]porphine (TBPPH(2)), 5,10,15,20-tetra[4-(4'-ethylpiperazinyl)phenyl]porphine (TEPPH(2)), 5,10,15,20-tetra [4-(4'-butylpiperazinyl)phenyl]porphine (TUPPH(2)), 5,10,15,20-tetra[4-(4'-heptylpiperazinyl) phenyl]porphine (THPPH(2)), 5-[4-(4'-ethylpiperazinyl)phenyl]-10,15,20-triphenylporphine (MEPPH(2)), 5-[4-(4'-buthylpiperazinyl)phenyl]-10,15,20-triphenylporphine (MUPPH(2)) and piperazine bridge porphine dimer N,N'-di(5,10,15,20-tetraphenylporphinato)piperazine (DiPPH(2)) have been synthesized by the direct condensation of nitrogen heterocycle substituted benzaldehydes with pyrrole. Each porphine bears one or four substituted pyrrolidine or piperazine moieties that have been used as drugs. Their structures were characterized by elementary analysis, MS, 1H NMR, IR and UV-vis. These nitrogen heterocycle porphyrins aggregates in water and THF solution were studied by the spectrophotofluorimetry. The anticancer activity of these porphines for the liver cancer cells, the stomach tumor cells and the nasopharyngeal carcinoma cancer cells were tested by the MTT assay. Compared with cis-platinum (cis-Pt) and 5-Fluorouracil (5-Fu), the nitrogen heterocycle porphyrins have the better biological activity and might have potential application in medicine.
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PMID:Study on synthesis, characterization and biological activity of some new nitrogen heterocycle porphyrins. 1265 60

The use of many halogenated alkanes such as carbon tetrachloride (CCl4), chloroform (CHCl3) or iodoform (CHI3), has been banned or severely restricted because of their distinct toxicity. Yet CCl4 continues to provide an important service today as a model substance to elucidate the mechanisms of action of hepatotoxic effects such as fatty degeneration, fibrosis, hepatocellular death, and carcinogenicity. In a matter of dose,exposure time, presence of potentiating agents, or age of the affected organism, regeneration can take place and lead to full recovery from liver damage. CCl4 is activated by cytochrome (CYP)2E1, CYP2B1 or CYP2B2, and possibly CYP3A, to form the trichloromethyl radical, CCl3*. This radical can bind to cellular molecules (nucleic acid, protein, lipid), impairing crucial cellular processes such as lipid metabolism, with the potential outcome of fatty degeneration (steatosis). Adduct formation between CCl3* and DNA is thought to function as initiator of hepatic cancer. This radical can also react with oxygen to form the trichloromethylperoxy radical CCl3OO*, a highly reactive species. CCl3OO* initiates the chain reaction of lipid peroxidation, which attacks and destroys polyunsaturated fatty acids, in particular those associated with phospholipids. This affects the permeabilities of mitochondrial, endoplasmic reticulum, and plasma membranes, resulting in the loss of cellular calcium sequestration and homeostasis, which can contribute heavily to subsequent cell damage. Among the degradation products of fatty acids are reactive aldehydes, especially 4-hydroxynonenal, which bind easily to functional groups of proteins and inhibit important enzyme activities. CCl4 intoxication also leads to hypomethylation of cellular components; in the case of RNA the outcome is thought to be inhibition of protein synthesis, in the case of phospholipids it plays a role in the inhibition of lipoprotein secretion. None of these processes per se is considered the ultimate cause of CCl4-induced cell death; it is by cooperation that they achieve a fatal outcome, provided the toxicant acts in a high single dose, or over longer periods of time at low doses. At the molecular level CCl4 activates tumor necrosis factor (TNF)alpha, nitric oxide (NO), and transforming growth factors (TGF)-alpha and -beta in the cell, processes that appear to direct the cell primarily toward (self-)destruction or fibrosis. TNFalpha pushes toward apoptosis, whereas the TGFs appear to direct toward fibrosis. Interleukin (IL)-6, although induced by TNFalpha, has a clearly antiapoptotic effect, and IL-10 also counteracts TNFalpha action. Thus, both interleukins have the potential to initiate recovery of the CCl4-damaged hepatocyte. Several of the above-mentioned toxication processes can be specifically interrupted with the use of antioxidants and mitogens, respectively, by restoring cellular methylation, or by preserving calcium sequestration. Chemicals that induce cytochromes that metabolize CCl4, or delay tissue regeneration when co-administered with CCl4 will potentiate its toxicity thoroughly, while appropriate CYP450 inhibitors will alleviate much of the toxicity. Oxygen partial pressure can also direct the course of CCl4 hepatotoxicity. Pressures between 5 and 35 mmHg favor lipid peroxidation, whereas absence of oxygen, as well as a partial pressure above 100 mmHg, both prevent lipid peroxidation entirely. Consequently, the location of CCl4-induced damage mirrors the oxygen gradient across the liver lobule. Mixed halogenated methanes and ethanes, found as so-called disinfection byproducts at low concentration in drinking water, elicit symptoms of toxicity very similar to carbon tetrachloride, including carcinogenicity.
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PMID:Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. 1270 12

A liver precancerous model in rats was established with diethylnitorsamine(DEN) injected intraperitoneally as initiator and promoted by partial hepatectomy and injection of CCl4. The model was used to study the chemopreventive effect of tea polyphenols and tea pigments. A water solution of 0.1% tea polyphenols or tea pigments was given to Wistar rats as drinking water during the 56-day experiment period. A stable and sensitive early marker of liver cancer--GST-Pi positive foci or nodule was measured by a immunohistochemical method. Both tea polyphenols and tea pigments decreased the density and area of the GST-Pi foci. The expression of GST-Pi mRNA in chemical induced precancerous liver tissue was measured by Northern Blotting technique, and the expression of GST-Pi isoenzyme in liver tissue was detected by Western Blotting method. The results showed that both tea polyphenols and tea pigments effectively reduced the GST-Pi expression at both transcription and translation level. It is concluded that the inhibition of tea polyphenols and tea pigments on GST-Pi overexpression induced by chemical carinogen may be one of the mechanisms of their inhibition on the occurrence and progression of liver precancerous lesions in rats.
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PMID:[Inhibitory effects of tea polyphenols and tea pigments on liver precancerous lesions in rats]. 1271 1

The 1998 National Institute for Occupational Safety and Health (NIOSH) criteria document for metalworking fluids (MWF) is the most recent authoritative review of mortality studies of workers with these exposures. NIOSH concluded that substantial evidence exists for increased risk of cancer at several sites (larynx, rectum, pancreas, skin, scrotum, and bladder) among workers exposed to MWF before the mid-1970s, and that evidence is equivocal for cancer at several other sites, including stomach, esophagus, lung, prostate, brain, colon, and hematopoietic system. The UAW believes that systematic analysis of that body of data makes a much stronger case for stomach cancer related to MWF exposure. Since the Criteria document, the mortality experience of three of the cohorts reviewed has been either updated or reanalyzed. These updates strengthen the evidence for increased mortality from stomach and liver cancer, and non-malignant respiratory disease associated with exposure to water-based metalworking fluids. Additional toxicological data providing clear evidence for carcinogenicity of diethanolamine, a widely used ingredient, also increases the biological plausibility of these findings. Despite changes in composition of MWFs with time, and reduced exposure levels, these data contradict the notion that cancer risks have been eliminated.
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PMID:Updated epidemiology of workers exposed to metalworking fluids provides sufficient evidence for carcinogenicity. 1455 43

Strawberries contain high levels of antioxidants, which have been correlated with a decreased risk of chronic disease. To more fully characterize the antioxidant profiles and possible associated health benefits of this fruit, the total free and bound phenolic, total flavonoid, and total anthocyanin contents of eight strawberry cultivars (Earliglow, Annapolis, Evangeline, Allstar, Sable, Sparkle, Jewel, and Mesabi) were measured. Cultivar effects on phenolic contents were compared with antioxidant capacities, as measured by the total oxyradical scavenging capacity (TOSC) assay, and to antiproliferative activities, as measured by inhibition of HepG(2) human liver cancer cell proliferation in vitro. Free phenolic contents differed by 65% between the highest (Earliglow) and the lowest (Allstar) ranked cultivars. The water soluble bound and ethyl acetate soluble bound phenolic contents averaged 5% of the total phenolic content of the cultivars. The total flavonoid content of Annapolis was 2-fold higher than that of Allstar, which had the lowest content. The anthocyanin content of the highest ranked cultivar, Evangeline, was more than double that of the lowest ranked cultivar, Allstar. Overall, free phenolic content was weakly correlated with total antioxidant activity, and flavonoid and anthocyanin content did not correlate with total antioxidant activity. The proliferation of HepG(2) human liver cancer cells was significantly inhibited in a dose-dependent manner after exposure to all strawberry cultivar extracts, with Earliglow exhibiting the highest antiproliferative activity and Annapolis exhibiting the lowest. No relationship was found between antiproliferative activity and antioxidant content.
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PMID:Antioxidant and antiproliferative activities of strawberries. 1458 91

This study evaluates the chemopreventive effect of an aqueous extract of dried leaves of Ardisia compressa against liver cancer. A rat liver assay that mimics progressive forms of human disease was used as a carcinogenesis model. Forty-five male Wistar rats (180-200 g body weight) were injected intraperitoneally on day 1 with a single dose (100 mg/kg) of diethylnitrosamine (DEN), and also received via gavage 20 mg/kg acetylaminofluorene (2-AAF), on days 7, 8 and 9. The rats were randomly divided into four groups (n=15). Control groups (Group 1 and Group 2) had free access to water. Group 3 received 0.5% (w/v) of A. compressa tea for 10 days before treatment and during the study as the sole source of fluid until the rats were killed. A fourth group of 15 rats received no carcinogen or promoter but did receive 0.5%, (w/v) of A. compressa tea. All animals had 70% partial hepatectomy at day 10. The incidences of hepatocellular foci, nodules and carcinoma were significantly smaller in Group 3 than in Group 2 (P<0.01). A. compressa tea consumption alone (Group 4) did not induce the development of foci, nodules or carcinomas (P<0.01). The striking observation of this study was that consumption of A. compressa tea resulted in complete inhibition of the chemically-induced hepatocarcinogenesis in Wistar rats.
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PMID:Inhibition of liver carcinogenesis in Wistar rats by consumption of an aqueous extract from leaves of Ardisia compressa. 1487 94

Based on extensive ecological data and conducted Bayesian modeling, this paper reports on epidemiological findings concerning a possible relationship between magnesium in drinking water and carcinogenesis in human liver. Relative contributions of water quality to endemic waterborne disease for particular categories of magnesium concentration and for age groups of patients were ascertained, i.e. the smaller liver cancer morbidity is referred with a greater magnesium concentration in drinking water, both in males and females. The achieved outcomes provide statistically significant evidence of positive health effects of magnesium water supplies on this lethal disease.
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PMID:New data on ecological analysis of possible relationship between magnesium in drinking water and liver cancer. 1508 69

Trichloroethylene (TCE) is an industrial solvent and a widespread environmental contaminant. Induction of liver cancer in mice by TCE is thought to be mediated by two carcinogenic metabolites, dichloroacetate (DCA) and trichloroacetate (TCA). TCE is considered to be a relatively weak peroxisome proliferator (PP), a group of rodent hepatocarcinogens that cause adaptive responses in liver through the PP-activated receptor alpha (PPARalpha). The objectives of this study were to determine whether effects of TCE, TCA and DCA in the liver associated with carcinogenesis are mediated by PPARalpha. Male wild-type and PPARalpha-null mice were given TCE by gavage for 3 days or 3 weeks; TCA or DCA were given in the drinking water for 1 week. Increases in relative liver and kidney weights by TCE were dependent on PPARalpha whereas liver weight increases by DCA were PPARalpha-independent. Dose-dependent increases in hepatocyte proliferation observed in wild-type mice after TCE exposure as determined by BrdU-labeling of hepatocytes were PPARalpha-dependent. Transcript profiling using macroarrays containing approximately 1200 genes showed that 93% (40 out of 43) of all expression changes observed in wild-type mice upon TCE exposure were dependent on PPARalpha and included known targets of PP (Cyp4a12, epidermal growth factor receptor) and additional genes involved in cell growth. Increases in enzymes that catalyze beta- and omega-oxidation of fatty acids were dependent on PPARalpha after exposure to TCE, TCA or DCA. TCE altered a unique set of genes in the livers of PPARalpha-null mice compared to wild-type mice including those that respond to different forms of stress. These data support the hypothesis that PPARalpha plays a dominant role in mediating the effects associated with hepatocarcinogenesis upon TCE exposure.
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PMID:Role of the peroxisome proliferator-activated receptor alpha (PPARalpha) in responses to trichloroethylene and metabolites, trichloroacetate and dichloroacetate in mouse liver. 1536 85

Arsenic has been well documented as the major risk factor for development of blackfoot disease (BFD), a unique peripheral vascular disease that was once endemic to the southwestern coast of Taiwan, where residents imbibed artesian well water containing high concentrations of arsenic for more than 50yr. Long-term arsenic exposure has also been reported to be associated with increased incidence of liver cancer in a dose-responsive manner. A tap-water supply system was implemented in the early 1960s in the BFD endemic areas. Artesian well water was no longer used for drinking and cooking after the mid-1970s. The objective of this study was to examine whether liver cancer mortality rates were altered after the consumption of high-arsenic artesian well water ceased and, if so, when the reduction occurred. Standardized mortality ratios (SMRs) for liver cancer were calculated for the BFD endemic area for the years 1971-2000. Cumulative-sum techniques were used to detect the occurrence of changes in the SMRs. The study results show that mortality from liver cancer in females declined starting 9yr after the cessation of consumption of high-arsenic artesian well water. However, data show fluctuations in male liver cancer mortality rates. Based on the reversibility criterion, the association between arsenic exposure and liver cancer mortality is likely to be causal for females but not in males.
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PMID:Does arsenic exposure increase the risk for liver cancer? 1537 Dec 25


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