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

Primary hemochromatosis is a common genetic disorder that results in inappropriate iron absorption and storage, with progressive damage to target organs. Hepatic cirrhosis and hepatocellular carcinoma are sequelae of hemochromatosis which are potentially preventable. The diagnosis may be suspected prior to target organ damage by appropriate screening tests, and is confirmed by liver biopsy. Three cases of hemochromatosis in the precirrhotic stage of the disease are presented. The pathophysiology, clinical and laboratory features and management are discussed. The high gene frequency in the general population warrants routine screening tests in asymptomatic healthy young adults. Phlebotomy is the indicated treatment for all stages of the disease.
 ...
PMID:Diagnosis and management of precirrhotic hemochromatosis. 215 80

Succinylacetone (SA) (4,6-dioxoheptanoic acid) is an abnormal metabolite produced in patients with hereditary tyrosinemia as a consequence of an inherited deficiency of fumaryl acetoacetate hydrolase activity. Patients with this disease are associated with a number of abnormalities, including aminoaciduria, proteinuria, liver failure, commonly hepatoma, and decreased GSH concentration in the liver. In the course of our studies of tyrosinemia, we found that the urine of patients with this disorder contains material(s) that absorbs light at 315 nm. We investigated the nature of the 315 nm material in detail. SA was found to react with amino acids and protein nonenzymatically, to form stable adducts at physiological temperature and pH. All SA adducts with amino acids and/or proteins exhibited an absorption peak at 315 nm. Although all amino acids reacted with SA, the most reactive amino acid was lysine (Lys), followed, in order, by glycine, methionine, phenylalanine, serine, alanine, and glutamine. SA-adducts were unstable at pH below 6, while they were made considerably more stable after reduction with NaBH4, suggesting that SA forms an adduct via Schiff base formation. High-performance liquid chromatography (HPLC) analysis of urines from patients with tyrosinemia revealed the existence of SA-glycine, SA-methionine, SA-tyrosine, and SA-phenylalanine. After digestion of urines with proteinase K, three more HPLC peaks appeared, which all corresponded to SA-Lys adducts. TLC analysis of SA-Lys showed that SA-Lys could form as many as seven different adducts. No SA-adduct peaks were observed in HPLC in urines from normal subjects, patients with other forms of aminoaciduria, or patients with the nephrotic syndrome. In addition to amino acids and proteins, SA reacted with reduced glutathione (GSH) and formed a stable adduct. These findings suggest that SA adduct formation with amino acids, GSH, and proteins is a significant process occurring in tyrosinemia, and may account for certain of the pathologic findings in this hereditary disorder.
 ...
PMID:Hereditary tyrosinemia. Formation of succinylacetone-amino acid adducts. 392 1

Fanconi's anemia is a rare genetic disorder associated with congenital deformities, infections, chromosomal abnormalities, and leukemia. This brief article describes the case of a 20 year old man affected with the disease, who was given 100 mg daily of oxymetholone to cure leukopenia and thrombocytopenia. 10 months later he died of hepatic failure. Autopsy revealed hepatoma and liver peliosis, a rare condition of unknown etiology characterized by blood-filled cysts in the liver. It is possible that in the case reported here the hepatoma could have been related to the oxymetholone treatment, which conceivably could have initiated hepatic damage.
 ...
PMID:Hepatoma and peliosis hepatis developing in a patient with Fanconi's anemia. 432 28

The clinical pattern and the pathophysiological mechanism of the hereditary disorder alpha 1-antitrypsin deficiency are outlined. It appeared that the patient described suffered not only from emphysema, cirrhosis of the liver and hepatocellular carcinoma, but also from acute haemorrhagic pancreatitis. The combination of acute pancreatitis and alpha 1-antitrypsin deficiency has not been described before. Screening of relatives is important because of possible treatment.
 ...
PMID:[Acute pancreatitis in a patient with alpha 1-antitrypsin deficiency. Is there a causal relationship?]. 841 21

Tyrosinemia, a genetic disorder of the liver and kidneys, is caused by reduced activity of fumarylacetoacetate hydrolase (FAH), the final enzyme in the degradation of tyrosine. The consequent presence of succinylacetone in urine or blood is pathognomonic of tyrosinemia and is used as a confirmatory test in the Quebec neonaral screening program. Due to a complex founder effect, the province of Quebec has an unusually high prevalence of tyrosinemia, particularly in the Saguenay-Lac Saint-Jean region (where the prevalence is 1 in 1850). Tyrosinemia has several different clinical presentations, ranging from acute liver failure with severe coagulopathy early in life, to slowly progressing cirrhosis with multiple nodules and variable renal dysfunction, to normal liver function with renal failure. Hepatocarcinoma has been found in approximately one third of cases. FAH complementary DNA has been cloned and mapped to chromosome 15q23-q25. The mutation observed in Quebec is a splice mutation at intron 12. This mutation is common and has been observed in other areas of the world as well, although more than 20 mutations causing tyrosinemia have now been described. Liver transplantation remains the definitive treatment. The author's team has carried out 28 liver transplantations (including 2 combined liver-kidney transplantations) in 25 children. The overall survival rate has been 92%; two children died as a result of primary nonfunction. The primary indications for transplantation were hepatic nodules (in 14 cases), neurological crises (6) and hepatic (3) or renal failure (2). An abnormal glomerular filtration rate (GFR) of less than 80 mL/min per 1.73 m2 was documented before transplantation in 54% of the cases. The rate normalized after liver transplantation in most patients, with rapid improvement in tubular function. However, patients with a severely low rate (less than 55 mL/min per 1.73 m2) before transplantation still had borderline renal function and poor growth after the transplantion, despite normal liver function. Therefore, for children with a consistently low GFR, careful consideration should be given to performing a combined liver-kidney transplantation, and a renal biopsy should form part of the pretransplantation evaluation.
 ...
PMID:Tyrosinemia: the Quebec experience. 888 68

Wilson's disease is a genetic disorder characterized by the accumulation of copper in the body due to a defect of biliary copper excretion. However, the mechanism of biliary copper excretion has not been fully clarified. We examined the effect of copper on the intracellular localization of the Wilson disease gene product (ATP7B) and green fluorescent protein (GFP)-tagged ATP7B in a human hepatoma cell line (Huh7). The intracellular organelles were visualized by fluorescence microscopy. GFP-ATP7B colocalized with late endosome markers, but not with endoplasmic reticulum, Golgi, or lysosome markers in both the steady and copper-loaded states. ATP7B mainly localized at the perinuclear regions in both states. These results suggest that the main localization of ATP7B is in the late endosomes in both the steady and copper-loaded states. ATP7B seems to translocate copper from the cytosol to the late endosomal lumen, thus participating in biliary copper excretion via lysosomes.
 ...
PMID:Copper does not alter the intracellular distribution of ATP7B, a copper-transporting ATPase. 1097 14

Hereditary hemochromatosis is a prevalent genetic disorder of iron hyperabsorption leading to hyperferremia, tissue iron deposition and complications including cirrhosis, hepatocarcinoma, cardiomyopathy and diabetes. Most individuals affected with hereditary hemochromatosis are homozygous with respect to a missense mutation that disrupts the conformation of HFE, an atypical HLA class I molecule (ref. 1; OMIM 235200). Mice lacking Hfe or producing a C282Y mutant Hfe protein develop hyperferremia and have high hepatic iron levels. In both humans and mice, hereditary hemochromatosis is associated with a paucity of iron in reticuloendothelial cells. It has been suggested that HFE modulates uptake of transferrin-bound iron by undifferentiated intestinal crypt cells, thereby programming the absorptive capacity of enterocytes derived from these cells; however, this model is unproven and controversial. Hepcidin, a peptide hormone (HAMP; OMIM 606464), seems to act in the same regulatory pathway as HFE. Although expression of mouse Hamp is normally greater during iron overload, Hfe-/- mice have inappropriately low expression of Hamp. We crossed Hfe-/- mice with transgenic mice overexpressing Hamp and found that Hamp inhibited the iron accumulation normally observed in the Hfe-/- mice. This argues against the crypt programming model and suggests that failure of Hamp induction contributes to the pathogenesis of hemochromatosis, providing a rationale for the use of HAMP in the treatment of this disease.
 ...
PMID:Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis. 1270 88

The consumption of excess alcohol in patients with liver iron storage diseases, in particular the iron-overload disease hereditary haemochromatosis (HH), has important clinical consequences. HH, a common genetic disorder amongst people of European descent, results in a slow, progressive accumulation of excess hepatic iron. If left untreated, the condition may lead to fibrosis, cirrhosis and primary hepatocellular carcinoma. The consumption of excess alcohol remains an important cause of hepatic cirrhosis and alcohol consumption itself may lead to altered iron homeostasis. Both alcohol and iron independently have been shown to result in increased oxidative stress causing lipid peroxidation and tissue damage. Therefore, the added effects of both toxins may exacerbate the pathogenesis of disease and impose an increased risk of cirrhosis. This review discusses the concomitant effects of alcohol and iron on the pathogenesis of liver disease. We also discuss the implications of co-existent alcohol and iron in end-stage liver disease.
 ...
PMID:Effect of alcohol on iron storage diseases of the liver. 1282 61

Copper, though essential, is highly toxic when present in excess, as in Wilson disease, a genetic disorder of hepatic copper metabolism. We hypothesized that mitochondria are a major target of copper-induced cytotoxicity in Wilson disease. We used the human hepatoma line Hep G2 to examine copper-mediated cytotoxicity and three different methods to assess organelle damage: MTT assay (mitochondria), neutral red (NR; lysosomes) and Trypan blue exclusion assay (TB; plasma membrane). For all assays, cells at approximately 60% confluence in microtitre plates were incubated with CuCl(2) (concentration range: 50-100-150-200 microM) for 24 or 48 h. Results were expressed as percent of untreated control. At 24 h, cytotoxicity as detected by NR assay was significantly higher at all concentrations of copper than for MTT or TB ( p<0.005 at all concentrations). Cytotoxicity as detected by MTT was higher than that detected by TB at all concentrations except at 200 microM (p<0.05 for 50 microM, p<0.005 for 100 microM, p = 0.001 for 150 microM). Results at 48 h were similar (NR versus others: p <0.001 MTT versus TB: NS except at 150 microM where p<0.01). We investigated reactive oxygen species (ROS) production in copper-associated hepatocytoxicity by incubating sub-confluent cells with 2('),7(')-dichlorodihydrofluorescein diacetate dye plus copper (concentration range: 0-200 microM) for 1-1.5 h. Copper, but not zinc, produced significant increases in ROS (p<0.001). In summary, Hep G2 lysosomes appeared more susceptible to Cu-mediated damage than mitochondria; the cell membrane was highly resistant to damage.
 ...
PMID:In vitro assessment of copper-induced toxicity in the human hepatoma line, Hep G2. 1513 Jun 8

Type III glycogen storage disease is a hereditary disorder with autosomal recessive transmission. It is characterized by accumulation of abnormal glycogen in the liver and, in 80% of patients, in muscle. The liver can also show fibrosis and sometimes cirrhosis. Until 2000, 9 cases of cirrhosis had been published, 3 of which showed associated hepatocarcinoma. We present the case of a 31-year-old woman, diagnosed in childhood with type III glycogen storage disease, who 30 years after onset developed a hepatocellular carcinoma with portal thrombosis in the context of advanced cirrhosis. This is the first case to be reported in the Spanish literature of type III glycogen storage disease associated with hepatocellular carcinoma.
 ...
PMID:[Type III glycogen storage disease associated with hepatocellular carcinoma]. 1637 12


1 2 3 Next >>