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)

Liver-cell dysplasia is a well known histological entity with preneoplastic significance in experimental hepatic carcinogenesis. However, while the association of liver-cell dysplasia with hepatitis B virus can be considered as established, it is still controversial whether this lesion represents a premalignant condition in cirrhotic patients. Efforts have been made to render its morphological assessment more reliable, but no firm conclusions can be drawn from the available clinical studies, which are mainly retrospective or based on autopsy series. Preliminary results from a prospective study argue that liver-cell dysplasia is associated with an increased risk to hepatocellular carcinoma. The emergence of liver-cell dysplasia as a preneoplastic lesion in cirrhotic patients will have some impact in the future on their management, including selection for closer monitoring in early detection of hepatocellular carcinoma and for liver transplantation.
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PMID:Liver-cell dysplasia and hepatocellular carcinoma. 131 75

A study was conducted to investigate the inhibitory effects of acidic retinoid (trimethylmethoxyphenyl analog of retinoic acid ethylester or TMMP) and polyprenoic acid (3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid or E-5166) on the development of hepatoma induced by 3'-methyl-N, N-dimethyl-4-aminoazobenzene (3'-MeDAB) in rats. Morphometric analysis of liver specimens was employed to evaluate the antitumor effects of the compounds in detail, and revealed significant decreases in the number and area of tumors in the TMMP- and E-5166-treated groups. As for adverse effects, retarded growth and marked hypertriglyceridemia were observed only in TMMP-treated rats. During the hepatocarcinogenesis, cellular retinoid-binding protein, F-type or CRBP(F) and cellular retinoic acid-binding protein or CRABP newly appeared in the tumor tissue, particularly in hyperplastic nodules which are the precancerous state of hepatoma. These results suggest that the polyprenoic acid is a good candidate for clinical chemoprevention of hepatoma, targetting its precancerous stage when intracellular receptors for acidic retinoid have emerged.
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PMID:Inhibitory effects of synthetic acidic retinoid and polyprenoic acid on the development of hepatoma in rats induced by 3'-methyl-N, N-dimethyl-4-aminoazobenzene. 321 38

Donryu male albino rats were fed a diet containing 0.064% 3'-methyl-4-dimethylaminoazobenzene (MDAB) for 21 weeks. During the ensuing rat liver carcinogenesis, changes in the concentrations of methylglyoxal, D-lactate and glutathione as well as activities of glyoxalase I and II in liver and plasma were examined. After the start of the diet, hepatic contents of methylglyoxal and D-lactate increased to about 7 and 3 times that of the control, respectively. However, after 21 weeks the D-lactate content decreased from the elevated level, but remained at a higher level of 1.4 times the control. The hepatic glyoxalase I activity increased 1.2 to 1.7 times over the control during carcinogenesis, while glyoxalase II activity increased 160% during the precancerous state and decreased to 55% of control at 21 weeks. the hepatic level of reduced glutathione (GSH) increased and peaked after 4 weeks of the MDAB diet and decreased thereafter to 57% of the control level after 21 weeks. Both pyruvate and L-lactate levels increased in the liver and plasma of MDAB-fed rats when rats had obvious symptoms of hepatoma.
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PMID:Changes in concentrations of methylglyoxal, D-lactate and glyoxalase activities in liver and plasma of rats fed a 3'-methyl-4-dimethylaminoazobenzene-rich diet. 890 2

We developed a novel and efficient cDNA subtraction method to isolate rat hepatocellular carcinoma (HCC)-related genes. cDNAs from Solt-Farber procedure-driven HCCs were synthesized on Latex beads. The subtraction was accomplished by a simple centrifugation, PCR amplification, and dot blot screening. Among 2000 clones from the subtracted cDNA library, one clone with a full-length HCC-related cDNA was eventually obtained. Sequence analysis of this clone showed it to exhibit 90 and 60% similarity with the rat cysteine sulfinic acid decarboxylase (CSAD) and mammalian glutamic acid decarboxylases (GAD), respectively. Differences between our sequence data on CSAD and those reported previously were observed at two positions, which arose from a single amino acid substitution and frame shift mutation. The CSAD expression was restricted to the liver and kidney of rats. During hepatocarcinogenesis, expression of the CSAD mRNA and its protein was stimulated in the precancerous liver and maintained its high expression afterward. Interestingly, a high level of anti-CSAD autoantibody was detected in the HCC-bearing rats. The titer of anti-CSAD autoantibodies in these rats was 30-200 times higher than that in normal rats. The anti-CSAD autoantibody appeared in the precancerous state and was maintained afterward, and its pattern of appearance was similar to that of CSAD mRNAs and proteins. Thus, we propose that the high-titer CSAD autoantibody resulted from increased CSAD gene expression in the liver due to stimulation by the HCC. These results remind us of human autoimmune diseases including insulin-dependent diabetes mellitus and stiff-man syndrome, which are caused by autoantibodies against GAD.
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PMID:Overexpression of cysteine sulfinic acid decarboxylase stimulated by hepatocarcinogenesis results in autoantibody production in rats. 891 62

Cirrhosis of the liver can be regarded as premalignant state, since more than 80 percent of hepatocellular carcinoma (HCC) in the western world develop in a cirrhotic liver. The risk to develop this malignancy depends on the activity of the underlying cirrhosis, its etiology and the duration of the disease. Patients suffering from cirrhosis of the liver due to HBV-, HCV- or HDV-infection and patients with genetic hemochromatosis exhibit a high risk for HCC. This risk is further increased by cocarcinogens, such as alcohol, nicotine and toxins. Ultrasound and AFP-studies aim to diagnose HCC early. The sensitivity of AFP in the serum is remarkably low (about 64%). In contrast a normal AFP-concentration (< 20 ng/ml) carries a high negative prognostic value (> 90%). Patients suspected to suffer from HCC according to the results of screening procedures should be subjected to additional radiologic investigations, such as CT-arterioportography or lipiodol-angiography.
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PMID:[Cirrhosis of the liver as a precancerous condition]. 984 85

We have recently demonstrated by Northern blot and RT-PCR that the mRNA expression of the alpha-chemokine hIRH/SDF-1alpha is reduced in hepatocellular carcinoma (HCC), several digestive tract cancers and premalignant colon adenomas, and that its receptor CXCR4 mRNA expression is reduced in HCC. Here we investigate the expression of CXCR4 mRNA expression in several digestive tract cancers and hepatitis C viral (HCV) infected liver, a premalignant condition. There was no difference in the CXCR4 mRNA expression in colon, esophageal or gastric cancers compared to non-cancerous tissues. This is significantly different from the reduced expression we have seen with hepatocellular carcinoma (p<0.05). To better refine regional tumor or hepatic cytokine mRNA analysis within a biopsy sample we describe a micro-isolation technique for RNA extraction from portal and triad areas of liver biopsies or other small malignant or non-malignant biopsy samples suitable for use in RT-PCR and differential display reactions. In HCV liver biopsies, the expression of hIRH and its receptor CXCR4 mRNA, corrected for G3PDH, was not significantly different from that of control non-HCV (steatosis) biopsies. CXCR4 is expressed on leukocytes and its expression was predicted to correlate with hepatic inflammation. CXCR4 receptor mRNA expression did correlate significantly with that of its ligand hIRH/SDF-1alpha (p=0.001), and with the severity of fibrosis (p<0.05), but not with portal inflammation (p<0.10), piecemeal necrosis (p<0.10), lobular inflammation (p>0.10), the presence of lymphoid aggregates (p>0.10), or the total histological activity index (p=0.07). There was no difference in expression of hIRH or CXCR4 between responders and non-responders to interferon (IFN) treatment, while as a control, the responder group of patients did show a higher expression of IFNalpha receptor than the non-responder group (p=0.05).
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PMID:CXCR4 mRNA expression in colon, esophageal and gastric cancers and hepatitis C infected liver. 1020 Mar 42

Differentiating primary sclerosing cholangitis (PSC) from cholangiocarcinoma (CC) can be a diagnostic challenge with major therapeutic implications. In case of advanced or symptomatic PSC, liver transplantation (OLTx) can be life saving with excellent long-term outcome. However, the outcome of CC diagnosed prior or during OLTx is dismal. PSC is a premalignant condition associated with a risk of developing cholangio- or hepatocellular carcinoma in > 15% of patients. Imaging diagnoses should be integrated into the further clinical data. It is the sudden, rapid and irreversible deterioration of the patient's condition, and the rapid progression of cholangiographic abnormalities, which may strongly point towards a malignancy or a malignant evolution in case of PSC. Brush cytology, (guided) biopsy, and tumor markers such as Ca 19.9 and CEA levels can be of some help, but confirmation of malignancy is often associated with a poor outcome and exclusion from liver transplantation. Clinical deterioration of the PSC patient and signs indicating advanced liver damage are a justification to evaluate patients for liver transplantation. Early transplantation should be considered in appropriate patients.
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PMID:Primary sclerosing cholangitis and cholangiocarcinoma as a diagnostic and therapeutic dilemma. 1043 94

Liver transplantation for hepatocellular carcinoma (HCC) in patients with cirrhosis is a radical treatment of the tumor and associated precancerous state. It is potentially curative in a proportion of patients. The outcomes of early studies of liver transplantation in this indication were initially unfavorable. Selection of transplant candidates at an early stage, in the absence of extrahepatic spread, gives better survival than surgical resection and alternative nonsurgical treatments. Transarterial chemoembolization can be used for preoperative control of the disease. Adjuvant chemotherapy may be indicated in the postoperative period for the prevention of recurrence in patients with histologic features of invasiveness in the surgical specimen. Liver transplantation as the treatment of choice for early HCC in screening programs in cirrhotic patients may become limited by graft availability as the numbers of hepatitis C-related cases increase. Resection may be indicated if the waiting time is likely to be long.
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PMID:Liver transplantation for hepatocellular carcinoma. 1051 10

Several age-related changes occur in the structure and functions of the liver. The volume of the liver decreases, despite an increase in the size of hepatocytes, suggesting loss of liver cells. There are decreases in hepatic blood flow, the synthesis of urea and cholesterol, and the metabolism of drugs. Moreover, the regenerative capacity of liver becomes less efficient. Certain caveats are important when treating older patients with liver disease. Strict dietary restrictions, such as a low protein diet, should be avoided in the elderly (unless the patient is encephalopathic) because these patients are often undernourished to start with. Similarly, strict salt restriction should be enforced with caution, since it makes food less palatable and may take away what little desire such patients have to eat. Diuretic doses should be adjusted carefully because of greater risks of azotaemia and electrolyte disturbances in the elderly. Extra vigilance should be exercised in the early detection of infections that are more likely to occur in patients with cirrhosis. For example, spontaneous bacterial peritonitis can be missed in the elderly because of poor systemic (fever, abdominal tenderness) and laboratory responses (leucocytosis). In patients presenting with acute variceal bleeding, it is better to err on the side of underhydration than overhydration because of the risk of congestive heart failure. Vasopressin should be avoided in the elderly, since this drug has a high probability of precipitating an ischaemic event. Older patients do not tolerate beta-blockers as well as younger individuals and may require other treatment strategies for the prevention of variceal rebleeding episodes. Hepatic encephalopathy, especially the milder form, needs careful assessment because it can be easily confused with senile dementia syndromes. Cirrhosis is a premalignant condition and patients are at increased risk of developing hepatocellular carcinoma (HCC), a tumour seen predominantly in the elderly. All patients with cirrhosis should be maintained on a lifelong screening programme consisting of a 6-monthly assessment of alpha-fetoprotein and an imaging study, since early detection provides the only hope for cure of HCC. The only definitive treatment of cirrhosis is liver transplantation. Advanced age is not a contraindication to transplantation, and survival in older patients (aged >60 years) is comparable to that in younger individuals.
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PMID:Drug treatment of the complications of cirrhosis in the older adult. 1158 44

Cirrhosis of the liver has to be regarded as a premalignant condition independent of its etiology. The annual risk of developing HCC in cirrhosis is between 1% and 6%. Surveillance-programs have been introduced to detect early stages of HCC in order to improve mortality. However, only controlled trials will answer the question of the efficacy of such programs. Studies on the potential benefit of surveillance-programs comparing survival in surveilled and unsurveilled patients are so far lacking. It seems clear, however, that surveillance-programs can detect small tumors, often unfocal and potentially treatable by a curative approach. Moreover, the etiology (HBV, HCV, genetic hemochromatosis) and activity of liver cirrhosis as measured by serum-transaminases, liver histology (small-cell dysplasia and atypical regenerative nodules), Child-Pugh-stage and the concentration of alpha-fetoprotein at the beginning of a surveillance-program--all these factors reflect a high risk of developing HCC in an individual patient. Until programs are introduced on the basis of randomized, controlled trials of surveillance vs. usual care (with liver-related, specific deaths and all-cause-mortality as end-points) it seems reasonable to screen high-risk patients semi-annually by liver ultrasound and determination of AFP-concentration in the serum.
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PMID:[Hepatocellular carcinoma: risk groups--screening]. 1223 79


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