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

In this study we examined the case histories of 163 living and 82 deceased adult Finnish patients with acute hepatic porphyria. There were 184 patients with acute intermittent porphyria and 61 patients with variegate porphyria. Among the 124 of the 163 living patients, who were traced 1984-1985, no hepatocellular carcinoma was found. Among the 82 deceased patients the cause of death was porphyria in 29 (36%), cardiovascular disease in 23 (29%) and hepatocellular carcinoma in 7 (9%). Of the 7 patients with hepatocellular carcinoma, 6 had acute intermittent porphyria and one had variegate porphyria. In acute hepatic porphyria, as compared with the total population, the calculated risk of hepatocellular carcinoma is increased 61-fold.
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PMID:Acute hepatic porphyria and hepatocellular carcinoma. 283 25

A retrospective case-control study of 100 elderly patients admitted to Goroka Hospital was undertaken. Chronic disease with cor pulmonale was the commonest condition diagnosed in this group (22%) and lobar pneumonia was the commonest infection (17%). Cancer occurred in only 5% of subjects, and in all of these patients, hepatocellular carcinoma was diagnosed. No cases of degenerative cardiovascular disease were observed. Mean hospital stay was 12.9 days.
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PMID:Elderly ailing Highlanders of Papua New Guinea. 696 36

Carcinogens occur naturally in the foods we eat, including a number of HCAs that have been identified in foods (beef, pork, poultry and fish) as a result of cooking. These compounds are formed during the normal cooking process by the reaction of creatine with various amino acids. The HCAs have been identified as a result of their high mutagenic activity in the Ames test. The HCAs can be separated into two types, the nonimidazole and the imidazole type, the latter of which is the predominant type present in Western foods. Both types of HCAs have been found to be carcinogenic in rodent bioassays. Of the three imidazole compounds presently under evaluation in nonhuman primates, IQ has been found to be a potent carcinogen, inducing hepatocellular carcinoma in a majority of the animals in approximately one-seventh of their life span. In addition, a high proportion of the nonhuman primates also had focal IQ-induced myocardial lesions as observed by both light and electron microscopic findings. This information, along with other toxicology data on the HCAs, much of which is cited in this paper, allows the inference to be made that HCAs may be a risk factor for both cancer and cardiovascular disease in humans.
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PMID:Carcinogens in foods: heterocyclic amines and cancer and heart disease. 759 10

The well documented association between high plasma levels of lipoprotein(a) (Lp(a)) and cardiovascular disease might be mediated by the lysine binding of apolipoprotein(a) (apo(a)), the plasminogen-like, multikringle glycoprotein in Lp(a). We employed a mutational analysis to localize the lysine-binding domains within human apo(a). Recombinant apo(a) (r-apo(a)) with 17 plasminogen kringle IV-like domains, one plasminogen kringle V-like domain, and a protease domain or mutants thereof were expressed in the human hepatocarcinoma cell line HepG2. The lysine binding of plasma Lp(a) and r-apo(a) in the culture supernatants of transfected HepG2 cells was analyzed by lysine-Sepharose affinity chromatography. Wild type recombinant Lp(a) (r-Lp(a)) revealed lysine binding in the range observed for human plasma Lp(a). A single accessible lysine binding site in Lp(a) is indicated by a complete loss of lysine binding observed for r-Lp(a) species that contain either a truncated r-apo(a) lacking kringle IV-37, kringle V, and the protease or a point-mutated r-apo(a) with a Trp-4174-->Arg substitution in the putative lysine-binding pocket of kringle IV-37. Evidence is also presented for additional lysine-binding sites within kringles 32-36 of apo(a) that are masked in Lp(a) as indicated by an increased lysine binding for the point mutant (Cys-4057-->Ser), which is unable to assemble into particles. An important role of these lysine-binding site(s) for Lp(a) assembly is suggested by a decreased assembly efficiency for deletion mutants lacking either kringle 32 or kringles 32-35.
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PMID:Identification of two functionally distinct lysine-binding sites in kringle 37 and in kringles 32-36 of human apolipoprotein(a). 789 Jul 60

The final decade of the century confirms the importance of latest generation progestogens in terms of decreased risks associated with the use of doses of ethinyl estradiol of 50 gamma or more, equally effective in contraception of this type. These new combination very considerably limit the untoward effects seen in the past regarding carbohydrate and lipid metabolism, as well as cardiovascular disease. Concerning carcinogenesis, the long term protective effect against carcinomas of the endometrium and ovary is now accepted, while studies of breast cancer are not unanimous in their condemnation, the same applying to the risk of hepatocarcinoma. Regulation of cycles is satisfactory and the vaginal flora little affected. Moderate and stable fibroids seem to be well controlled, the same applying to mucosal hyperplasia. Pregnancy, particularly rare, is not influenced unfavourably and the effect on lactation appears to be nil. Provided that regular monitoring is ensured and contraindications are respected, age does not appear to be an absolute limiting factor to its use but the risk of concomitant smoking remains.
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PMID:[Current status of estrogen-progestational contraception]. 797 41

Because of the frequent occurrence of premature cardiovascular disease in patients with non-insulin-dependent, type II diabetes mellitus (NIDDM), the attenuated fibrinolytic activity of plasma from type II diabetic patients with increased concentrations of plasminogen activator inhibitor type-1 (PAI-1), and the fact that insulin stimulates synthesis of PAI-1 by human hepatic cells in vitro, we and others have hypothesized that accelerated vascular disease in type II diabetes may result in part from impaired fibrinolysis secondary to excessive elaboration of PAI-1 stimulated by insulin. Alternatively, the hyperglycemia associated with type II diabetes could influence the synthesis and secretion of PAI-1 directly. The present study was performed to determine whether PAI-1 secretion is or is not sensitive to the prevailing concentration of glucose in the conditioned medium of endothelial and liver cells, which are thought to be the major sources of circulating PAI-1 in vivo. Confluent cells were exposed to 0, 2.8, 5.6, 11.1, or 22.2 mmol/L (0, 50, 100, 200, or 400 mg/dL) glucose in medium without serum and subsequently to media with or without insulin (7.3 nmol/L). Secretion of PAI-1 by highly differentiated human hepatoma (Hep G2) cells did not increase as a function of increasing concentrations of glucose, whether or not insulin was present. In contrast, with pig aortic endothelial cells, the secretion of PAI-1 increased significantly with extracellular glucose with or without insulin. The increases in PAI-1 were specific (as shown by metabolic labeling experiments) and not attributable to osmotic effects (as shown by replacement of glucose by sorbitol).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Augmentation of synthesis of plasminogen activator inhibitor type-1 in arterial endothelial cells by glucose and its implications for local fibrinolysis. 824 Nov 3

The endocrine physiology of the climacteric supports a rationale for the concomitant replacement of androgen and estrogen following menopause. Clinical and research experience with estrogen-androgen hormone replacement therapy, as well as androgen-only therapy, suggests that the health benefit offered by androgen replacement exceeds the potential risk when treatment is properly managed. In this review, we concentrate on the effects of oral alkylated androgens. The virilizing effects (e.g., hirsutism, acne, voice change, and alopecia) of oral androgens are typically dose and duration dependent; androgen replacement at doses < or = 10 mg once daily administered for prolonged periods (> 6 months) produces masculinization effects that generally abate with dose reduction or discontinuation of treatment. No clinical sequelae or irreversible pathophysiologic effects have been associated with any virilization that may occur. Changes in lipoprotein metabolism associated with oral estrogen-androgen use include reduced total cholesterol levels and reduced high-density lipoprotein cholesterol levels which may reduce the long-term risk of cardiovascular disease. No clinically identifiable risk with respect to other cardiovascular variables, such as blood pressure, has been associated with the longterm administration of low doses of oral androgen. With regard to liver toxicity, reports of jaundice, peliosis hepatis, and hepatocellular carcinoma are extremely rare at the dose levels of androgen used in hormone replacement therapy, although individual sensitivity to the potential hepatotoxic effects of oral alkylated and nonalkylated androgen may vary considerably. Daily dosing with oral alkylated androgen in combination with estrogen is well tolerated. Retrospective and prospective studies involving the use of androgens alone and in combination with estrogens demonstrate that concerns about the adverse effects of androgen use associated with supraphysiologic, self-escalated doses in men do not apply to the much lower doses combined with estrogens for hormone replacement in postmenopausal women.
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PMID:Androgen and estrogen-androgen hormone replacement therapy: a review of the safety literature, 1941 to 1996. 922 Feb 5

We evaluated the risk of development of second primary cancers, with particular reference to subsequent hepatocellular carcinoma (HCC), in 592 patients diagnosed as non-Hodgkin's lymphoma (NHL), at Osaka Medical Center for Cancer and Cardiovascular Diseases. During 1978-1994, 2,163 person-years of observation were accrued, and 27 of the patients developed a second primary cancer, yielding an observed-to-expected ratio (O/E) of 1.53 [95% confidence interval (CI) = 1.01-2.23]. Significant excess risk was noted for primary liver cancer (PLC; O/E = 4.36, 95% CI = 1.99-8.28; O = 9) and non-lymphocytic leukemia (O/E = 26.17, 95% CI = 5.26-76.46; O = 3). The excess risk of PLC was relatively constant within the first 10 years after the NHL diagnosis. Patients who received chemotherapy as the NHL treatment had a significantly increased risk of PLC (O/E = 5.91, 95% CI = 2.70-11.23; O = 9). Their clinical reports indicated that all nine patients with PLC were diagnosed as HCC, and eight of them had clinical and/or histologic evidence of cirrhosis at the time of HCC diagnosis. None of the nine patients had a history of blood transfusion between the first NHL treatment and the diagnosis of HCC. These findings suggested that Japanese NHL patients might have an increased risk of developing HCC, and they indicated the importance of medical surveillance for liver malignancies, as well as subsequent leukemias. Possible explanations for the excess risk of subsequent HCC are discussed.
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PMID:Second primary cancers following non-Hodgkin's lymphoma in Japan: increased risk of hepatocellular carcinoma. 926 30

Hyperhomocysteinemia and insulin resistance are independent factors for cardiovascular disease. Most of the angiotoxic effects of homocysteine are related to the formation of homocysteine thiolactone and the consequent increase in oxidative stress. The oxidative stress has also been shown to impair insulin action, therefore leading to insulin resistance. In order to study a putative direct effect of homocysteine on insulin signaling, we have characterized the molecular counter-regulation of the early events in the signal transduction of the insulin receptor, and the metabolic end-point of glycogen synthesis. We employed HTC rat hepatoma cells transfected with the human insulin receptor. A 10 min exposure to homocysteine thiolactone (50 microM) resulted in a significant inhibition of insulin-stimulated tyrosine phosphorylation of the insulin receptor beta-subunit and its substrates IRS-1 and p60-70, as well as their association with the p85 regulatory subunit of phosphatidylinositol 3-kinase. These effects led to impairment of the insulin-stimulated phosphatidylinositol 3-kinase activity, which plays a central role in regulating insulin action. Thus, insulin-stimulated glycogen synthesis was also inhibited by homocysteine thiolactone. To investigate whether oxidative stress was mediating the counter-regulatory effect of homocysteine thiolactone on insulin signaling, we preincubated the cells (5 min) with 250 microM glutathione prior to the incubation with homocysteine (10 min) and subsequent insulin challenge. Glutathione completely abolished the effects of homocysteine thiolactone on insulin-receptor signaling and restored the insulin-stimulated glycogen synthesis. In conclusion, these data suggest that homocysteine thiolactone impairs insulin signaling by a mechanism involving oxidative stress, leading to a defect in insulin action.
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PMID:Homocysteine thiolactone inhibits insulin signaling, and glutathione has a protective effect. 1146 79

C-reactive protein (CRP) is a major acute-phase protein in humans. Elevated plasma CRP levels are a risk factor for cardiovascular disease. CRP is predominantly expressed in hepatocytes and is induced by interleukin-1 (IL-1) and IL-6 under inflammatory situations, such as the acute phase. Fibrates are hypolipidemic drugs that act through the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-alpha). Fibrates have been shown to reduce elevated CRP levels in humans, but the molecular mechanism is unknown. In this study, we demonstrate that different PPAR-alpha activators suppress IL-1-induced, but not IL-6-induced, expression of CRP in primary human hepatocytes and HuH7 hepatoma cells. Induction of CRP expression by IL-1 occurs at the transcriptional level. Site-directed mutagenesis experiments show that IL-1 induces CRP expression through 2 overlapping response elements, the binding sites for CCAAT-box/enhancer-binding protein-beta (C/EBP-beta) and p50-nuclear factor-kappaB (p50-NFkappaB). Cotransfection of C/EBP-beta and p50-NFkappaB enhances CRP promoter activity, and coimmunoprecipitation experiments indicate that the increase in CRP promoter activity by IL-1 is related to the generation and nuclear accumulation of C/EBP-beta-p50-NFkappaB complexes. Interestingly, PPAR-alpha activators reduce the formation of nuclear C/EBP-beta-p50-NFkappaB complexes, and thereby CRP promoter activity, by 2 mechanisms. First, PPAR-alpha increases IkappaB-alpha expression and thus prevents p50-NFkappaB translocation to the nucleus. Second, fibrates decrease hepatic C/EBP-beta and p50-NFkappaB protein levels in mice in a PPAR-alpha-dependent way. Our findings identify C/EBP-beta and p50-NFkappaB as novel targets for PPAR-alpha and provide a molecular explanation for the reduction of plasma CRP levels by fibrates.
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PMID:Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFkappa B-C/EBP-beta complex formation. 1239 63


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