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)

Recently, the therapeutic guideline has been mentioned in opportunistic infection of the compromised host, and many observations regarding complication of infection in these hosts have been reported. However, there were few reports in the relationship between infection and immune function or nutritional status. In this study, we confirmed that the nutritional status influences immune function in patients with lung cancer, hepatoma and renal failure, and that malnutrition markedly reduces their immunity. In patients after operation who where the pre-operative assessment of the nutritional status was performed an attempt to improve the nutritional status has been already made to improve their prognosis. Therefore, we emphasize that the management of the nutritional status even in hosts with many other diseases is thought to be important in protection against infection and prognosis of the disease.
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PMID:[Complication of infection in malnutritional status]. 969 66

Familiar Amyloid Polyneuropathy (FAP), an autosomal dominant inherited multisystemic disorder was first observed by Corino de Andrade, a Portuguese neurologist, in 1939. This disease of Portuguese origin was probably spread by fishermen, mainly to Sweden and Japan. It is characterized by a progressive peripheral polyneuropathy and autonomic neuropathy (erectile sexual disfunction, gastrointestinal disfunction, bladder dysfunction and cardio vascular disease) and malnutrition. There are neural and systemic amiloid deposits. Type I FAP, of Portuguese origin, is the most common variety. The amyloid protein is the variant transthyretin (TTR) in which methionine (MET) is a substitute for valine in position 30 (TTR MET 30). It is mainly produced by the liver (90%) and, in small amounts, by the choroidal plexus. Symptoms usually start in the 3rd and 4th decade of life and the patients usually die within 10-15 years. From the therapeutic options--plasmapheresis, immunoadsorption and liver transplantation; the latter seems to be the only one, which stops the production of TTR MET 30 in a permanent way, by means of the liver. The lack of any other effective therapy and the success of the first liver transplantation performed in Sweden arouse great hope. So far, around 300 patients have been transplanted all over the world. A hundred and thirty of them were transplanted in Portugal. A Kaplan Meier survival curve of the Portuguese patients shows a survival rate of 78% at 5 years. However, in spite of the progression of the disease being halted, the irreversibility of some neurological lesions seems to persist. This fact raises the problem of the timing of the transplantation. It seems that the patients should be transplanted as soon as the symptoms start, since mortality and severe morbidity seems to mainly involve those in whom symptomatic disease has lasted longer than six years. As the explanted liver is a morphologic normal liver, a sequential (domino) transplant has been carried out in 16 cases so far done--by one of the authors (ALF) on patients with either hepatocellular carcinoma or liver metastatic disease.
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PMID:Liver transplantation for familial amyloid polyneuropathy. 984 68

Many patients with liver cirrhosis are in a state of protein and energy malnutrition and require careful nutritional support. Our research has revealed that approximately 30% of the patients have protein-energy malnutrition, 40% protein malnutrition, and 10% energy malnutrition; 20% are in a normal nutritional state. Supplementation with branched-chain amino acids alleviates chronic liver failure, improves the protein nutritional state, and subsequently prolongs survival. In contrast, therapeutic modalities for energy malnutrition have not yet been fully elucidated and await further studies. Improved survival of the cirrhotic patients essentially brings a higher incidence of hepatocellular carcinoma (HCC). A synthetic analogue of vitamin A (acyclic retinoid or 4,5-dehydrogeranyl geranoic acid) prevents at least the development of second primary tumors after curative treatment of preceding HCC. The mechanism of this cancer chemo-prevention is clonal deletion of premalignant and latent malignant cells by the retinoid. We describe our clinical experiences with these two nutritional pharmacotherapies of chronic liver diseases and review their basic mechanisms.
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PMID:Nutritional pharmacotherapy of chronic liver disease: from support of liver failure to prevention of liver cancer. 1077 8

Removal of choline from the diet results in accumulation of triglycerides in the liver, and chronic dietary deficiency produces a non-genotoxic model of hepatocellular carcinoma. An early event in choline deficiency is the appearance of oxidized lipid, DNA and protein, suggesting that increased oxidative stress may facilitate neoplasia in the choline deficient liver. In this study, we find that mitochondria isolated from rats fed a choline-deficient, L-amino acid defined diet (CDAA) demonstrate impaired respiratory function, particularly in regard to complex I-linked (NADH-dependent) respiration. This impairment in mitochondrial electron transport occurs coincidentally with alterations in phosphatidylcholine metabolism as indicated by an increased ratio of long-chain to short-chain mitochondrial phosphatidylcholine. Moreover, hydrogen peroxide (H(2)O(2)) generation is significantly increased in mitochondria isolated from CDAA rats compared with mitochondrial from normal rats, and the NADH-specific yield of H(2)O(2) is increased by at least 2.5-fold. These findings suggest an explanation for the rapid onset of oxidative stress and energy compromise in the choline deficiency model of hepatocellular carcinoma and indicate that dietary choline withdrawal may be a useful paradigm for the study of mitochondrial pathophysiology in carcinogenesis.
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PMID:Dietary choline restriction causes complex I dysfunction and increased H(2)O(2) generation in liver mitochondria. 1078 22

Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease. It was first identified in 1989, as being distinct from hepatitis A and hepatitis B. The HCV does not attack the immune system, but rather causes an inflammatory reaction that is localized within the liver, involving the entire organ. About 80% of patients with acute hepatitis C will develop chronic HCV, of which about 20-30% will progress to cirrhosis and its consequences, over 10-20 years. After 20-40 years, a smaller proportion of patients with chronic disease will develop hepatocellular carcinoma. The course and outcome of the disease vary considerably. In some individuals, spontaneous remission occurs over a few years; in others, the disease is more severe, progressing to cirrhosis and end-stage liver disease. Despite biochemical and pathological confirmation of the diagnosis, patients are often asymptomatic for many years. Hepatic failure occurs late in the disease. Factors suggesting a poor prognosis include high serum transaminase levels, active cirrhosis on liver biopsy, and an increased viral load (HCV RNA), as well as associated medical conditions such as alcoholic liver disease, hepatitis B viral (HBV) infection, or human immunodeficiency virus (HIV). Nutrition has been recognized as a prognostic indicator in patients with chronic liver failure. However, standardized approaches for the diagnosis and classification of malnutrition in this population have not been consistently applied before implementing nutrition intervention. Common criteria for the assessment of malnutrition, weight and body mass index (BMI) for example, do not give accurate data in patients with chronic liver disease, complicated by ascites and edema. In addition, the chronic inflammatory reaction of liver failure progresses slowly, so that subtle nutritional deficits are not obvious at early stages of the disease. A review of the literature has been undertaken to identify current nutritional guidelines for patients with hepatitis C as well as chronic hepatitis.
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PMID:Nutritional guidelines for persons infected with the hepatitis C virus: a review of the literature. 1151 51

Arsenic (As) is one of the most important environmental global toxicants. In various countries and for decades people have been and currently are exposed to inorganic As through geogenically contaminated drinking water. An increased incidence of diseases mediated by this toxic element is the consequence of long-term exposure. Despite past extensive research on the toxicology of As, many questions remained unanswered, making risk assessment difficult. For instance, it is still not known how the carcinogenicity of As is mechanistically operative. Moreover, there is an increasing debate on whether the metabolic methylation of As has to be considered a detoxification process. Furthermore, it is historically documented that long-term intake of small amounts of As can lead to an acquired increased tolerance to its acute toxicity. It is not known whether this tolerance may be associated with a reduced chronic toxicity as well. In contrast to nonhuman cells, the selection of As-induced self-tolerance in human cells in vitro had been unsuccessful until now. However, we recently selected As-resistant human hepatoma HepG2 sublines that have low-level tolerance to As. Besides an approximately twofold elevated resistance to As cytotoxicity, this tolerance was associated with a significantly suppressed induction of As-mediated genotoxicity, which was evident in the cytokinesis-block micronucleus test. Additional questions arise when we consider several factors suspected to modulate the long-term toxicity of arsenic in vitro, variables that may either enhance or suppress the environmental genotoxicity and carcinogenicity of the metalloid. Besides malnutrition, these are single nutritional factors such as selenium and possible drinking water co-contaminants such as antimony. For instance, in the case of selenium, we could show that antimony (III) is able to suppress As genotoxicity. Taken together, research answers in many fields of As toxicology are needed in order to reduce the uncertainties in risk assessment of environmental As.
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PMID:Unanswered questions in arsenic toxicology. 1179 39

Apart from infectious or viral hepatitis, other most common non-infectious causes of hepatitis are alcohol, cholestatic, drugs and toxic materials. The most common mode that leads to liver injuries is antituberculosis drug-induced hepatitis. The severity of drug-induced liver injury varies from minor nonspecific changes in hepatic structure to fulminant hepatic failure, cirrhosis and liver cancer. Patients receiving antitubercular drug frequently develop acute or chronic hepatitis. The time required for the metabolites to reach hepatotoxic levels is much earlier with isoniazid plus rifampicin treatment than isoniazid alone and this has been shown to be synergistic rather than additive. Antituberculosis drug (ATT)-inducible cytochrome P-4502E1 (CYP2E1) is constitutively expressed in the liver. Recent studies show that polymorphism of the N-acetyltransferase 2 (NAT2) genes and glutathione-S-transferase (GST) are the major susceptibility risk factors for ATT-induced hepatitis. The hepatic NAT and GST are involved in the metabolism of several carcinogenic arylamines and drugs. The NAT2 enzyme has a genetic polymorphism in human. N-acetyltransferase 2 genes (NAT2) have been identified to be responsible for genetic polymorphism of slow and rapid acetylation in humans. Slow acetylators of NAT2 prove to develop more severe hepatotoxicity than rapid acetylators making it a significant risk factor. Deficiency of GST activity, because of homozygous null mutations at GSTM1 and GSTT1 loci, may modulate susceptibility to drug and xenobiotic-induced hepatotoxicity. Polymorphisms at GSTM1, GSTT1 and NAT2 loci had been linked to various forms of liver injury, including hepatocellular carcinoma.
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PMID:Antituberculosis drug-induced hepatitis: risk factors, prevention and management. 1533 88

In some patients with non-islet-cell tumor hypoglycemia (NICTH), a high molecular weight form of IGF-II (big IGF-II) derived from tumors is present in the circulation and might be associated with recurrent hypoglycemia. In this study, in order to survey the clinical characteristics of patients with IGF-II producing NICTH, we analyzed the medical records of 78 patients with NICTH (M/F 44/34, age 62+/-1.8, range; 9-86 years.) whose serum contained a large amount of big IGF-II. Hepatocellular carcinoma and gastric carcinoma were the most common causes of NICTH. The diameters of the tumors were more than 10 cm in 70% of the patients. Basal immunoreactive insulin (IRI) levels were less than 3 microU/dl in 79% of the patients. Hypoglycemic attack was the onset of disease in 31 of 65 cases (48%), but the tumor was revealed prior to the occurrence of hypoglycemia in 34 cases (52%). Twenty-five of 47 (53%) patients had decreased serum potassium levels. These data suggested that hypoinsulinemic hypoglycemia associated with the presence of a large tumor supports the diagnosis of IGF-II producing NICTH. Hypokalemia was associated with hypoglycemia in some patients. The BMI (21.4+/-0.6 kg/m2) and serum total protein levels (6.6+/-0.1g/dl) were preserved at the occurrence of first hypoglycemic attack suggesting that malnutrition might not be the main cause of hypoglycemia in most patients.
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PMID:Clinical features of insulin-like growth factor-II producing non-islet-cell tumor hypoglycemia. 1686 May 83

Deficiency of circulating alpha-1-antitrypsin (AAT) is the most widely recognized abnormality of a proteinase inhibitor that causes lung disease. AAT-deficiency is caused by mutations of the AAT gene that lead to AAT protein retention in the endoplasmic reticulum (ER). Moreover, the mutant AAT accumulated in the ER predisposes the homozygote to severe liver injuries, such as neonatal hepatitis, juvenile cirrhosis, and hepatocellular carcinoma. Despite the fact that mutant AAT protein is subject to ER-associated degradation (ERAD), yeast genetic studies have determined that the ubiquitination machinery, Hrd1/Der3p-cue1p-Ubc7/6p, which plays a prominent role in ERAD, is not involved in degradation of mutant AAT. Here we report that gp78, a ubiquitin ligase (E3) pairing with mammalian Ubc7 for ERAD, ubiquitinates and facilitates degradation of ATZ, the classic deficiency variant of AAT having a Z mutation (Glu 342 Lys). Unexpectedly, gp78 over-expression also significantly increases ATZ solubility. p97/VCP, an AAA ATPase essential for retrotranslocation of misfolded proteins from the ER during ERAD, is involved in gp78-mediated degradation of ATZ. Surprisingly, unlike other ERAD substrates that cause ER stress leading to apoptosis when accumulated in the ER, ATZ, in fact, increases cell proliferation when over-expressed in cells. This effect can be partially inhibited by gp78 over-expression. These data indicate that gp78 assumes multiple unique quality control roles over ATZ, including the facilitation of degradation and inhibition of aggregation of ATZ.
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PMID:Ubiquitin ligase gp78 increases solubility and facilitates degradation of the Z variant of alpha-1-antitrypsin. 1697 36

The aims of this study were the isolation and identification of Nocardia spp. from clinical samples of immunocompromised patients and patients with underlying diseases, and determination of antibiotic susceptibilities of the isolates. A total of 234 patients (172 male, 62 female; mean age: 58.6 +/- 15.9 years) of whom 126 (53.8%) with malignancy and 108 (46.2%) with other underlying diseases (pulmonary diseases, rheumatologic disorders, diabetes mellitus, chronic renal disfunction, cerebrovascular disorders and malnutrition) were included to the study. Biochemical characteristics, growth properties and antibiotic susceptibility patterns were used for the identification of the isolates. The distribution of specimens were as follows; sputum (124), tracheal aspirate (54), pleural fluid (27), bronchoalveolar lavage (23), abscess material (7) and lung biopsy (1) material. Nocardia spp were isolated from four out of 234 patients (1.7%), and two of them were identified as N. farcinica, one as N. asteroides and one as N. otitidiscaviarum. All of the four patients have had predisposing factors (hepatocellular carcinoma/diabetes mellitus; antiphospholipid syndrome/steroid use; nephrotic syndrome/ steroid use; chronic obstructive lung disease/lung cancer?), with a mean age of 52.5 years, and of them two were male. Nocardiosis has been presented as pulmonary infection in two of the cases, and brain and soft tissue abscesses in one of each patient. Kirby-Bauer disk diffusion, E-test and broth microdilution methods were used in order to detect the antibiotic susceptibilities of the strains. All isolates were found susceptible to imipenem and amikacin and resistant to erythromycin and ampicillin. One N. asteroides isolate was found susceptible to trimetoprim-sulphamethoxazole (TMP-SMX), whereas two N. farcinica and one N. otitidiscaviarum strains were resistant. The antibiotics to which N. farcinica isolates were susceptible were ceftriaxone and cefotaxime. As a result, since there is an increase in the number of immunocompromised patients recently, Nocardia spp. should be considered in such patients, and TMP-SMX should be used with care for empirical therapy.
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PMID:[Nocardia spp. isolated from immunocompromised patients in Trakya University Medical Faculty Hospital and their antibiotic susceptibilities]. 1817 71


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