Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver transplantation is the only effective treatment for hereditary tyrosinaemia type I (McKusick 276700). We have treated one acute and four subacute-chronic cases with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27), to prevent the formation of maleylacetoacetate and fumarylacetoacetate and their saturated derivatives. The oral daily dose was 0.1-0.6 mg/kg. The excretion of succinylacetoacetate and succinylacetone decreased from 15-103 mmol/mol creatinine to the detection limit or slightly above (ie, to 20-150 mumol/mol creatinine). The concentration of succinylacetone in plasma decreased from 5.8-43 mumol/l to the detection limit (0.1 mumol/l) over 2-5 months of treatment. The almost complete inhibition of porphobilinogen synthase in erythrocytes was abolished and the excretion of 5-aminolevulinate decreased to within or slightly above the reference range. The concentration of alpha-fetoprotein decreased in four patients to 1.3-7.5% of initially high values over 6-8 months. Improved liver function was reflected by normal concentrations of prothrombin complex and in decreased activities of alkaline phosphatase and gamma-glutamyltransferase in serum. Computed tomography revealed regression of hepatic abnormalities in three patients. One patient developed rickets 6 months before treatment and had excreted high concentrations of markers of tubular dysfunction--after 3 weeks of treatment, this excretion had disappeared. No side-effects were encountered. Inhibition of 4-hydroxyphenylpyruvate dioxygenase may prevent the development of liver cirrhosis and abolish or diminish the risk of liver cancer. Normalisation of porphyrin synthesis will eliminate the risk of porphyric crises. This type of treatment may thus offer an alternative to liver transplantation in hereditary tyrosinaemia.
 ...
PMID:Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenase. 135 48

We measured urinary levels of free L-fucose in healthy subjects, patients with benign diseases, and patients with cancer using an automated analyzer and a newly isolated L-fucose dehydrogenase, and evaluated the clinical usefulness of the results. The values obtained were corrected for urinary creatinine as micromoles per gram of creatinine. The cutoff value, set at the mean + 2SD for the healthy subjects, was 250 mumol/g.Cr. Patients with gallbladder cancer, bile-duct cancer, liver cancer, pancreatic cancer, or cirrhosis of the liver had significantly higher levels of L-fucose than the healthy subjects. The diagnostic sensitivity for these five diseases, taken together, was 68% (144/213). Specificity for the detection of cancer was calculated by use of false positives for patients with cholelithiasis, hepatitis, and pancreatitis: it was 73% (76/104). Diagnostic accuracy for these seven diseases taken together was therefore 69% (220/317). We compared the positive ratio of the L-fucose level with that of the tumor markers AFD and CA19-9. The positive ratio of an L-fucose value above the cutoff was higher than the positive ratio of either marker in bile-duct cancer, gallbladder cancer, liver cancer, and pancreatic cancer. The results suggested that the urinary levels of free L-fucose reflected the metabolism of sugar chains of glycoconjugates, and may be usefully clinically as a tumor marker.
 ...
PMID:[Clinical assessment of urinary free L-fucose levels]. 140 61

A radioimmunoassay for transforming growth factor alpha (TGF-alpha) using synthetic rat sarcoma transforming growth factor and its rabbit polyclonal antibody has been developed. Using radioimmunoassays, the urinary TGF-alpha and epidermal growth factor (EGF) concentrations in 31 patients with hepatocellular carcinoma (HCC), 15 probable HCC, four metastatic liver cancer, and 33 age, sex-matched healthy controls were determined. For the first time, we have shown that the average TGF-alpha concentration for HCC patients was 21.5 +/- 20.3 micrograms per g creatinine, significantly higher than that of healthy subjects, 4.9 +/- 2.8 micrograms per g creatinine (P less than 0.001). There was no statistical difference in the level of EGF between HCC patients and controls (40.9 +/- 29.3 versus 46.2 +/- 16.6 micrograms per g creatinine; P greater than 0.05). The ratio of EGF/TGF-alpha between HCC patients (3.37 +/- 4.42) and controls (15.5 +/- 13.0) was significantly different (P less than 0.001). Among patients, 65% (20 of 31) of HCC cases and 87% (13 of 15) of probable HCC cases showed a marked elevation of TGF-alpha levels. We found only 16% (five of 31) of HCC cases with increased EGF level. EGF excretion was inversely age related. Serum total protein concentration and alkaline phosphatase activity were positively correlated to EGF concentration (r = 0.522, P less than 0.01 and rt = 0.393, P less than 0.05, respectively). There was no correlation between biochemical functions of liver and TGF-alpha concentration in HCC patients. Our results also suggested that TGF-alpha may be a useful complementary tumor marker for management of patients with clinical manifestation of HCC who have low alpha-fetoprotein levels.
 ...
PMID:Elevation of transforming growth factor alpha and its relationship to the epidermal growth factor and alpha-fetoprotein levels in patients with hepatocellular carcinoma. 243 30

Urinary and serum pseudouridine concentrations were determined by high-performance liquid chromatography in 80 patients with primary liver cancer, 32 with benign space occupying lesions of the liver, 42 with liver cirrhosis and 40 healthy subjects. Their mean urinary and serum pseudouridine levels were 39.2 +/- 11.5 nmol/mumol creatinine and 3.4 +/- 1.3 mumol/L, 24.5 +/- 5.4 nmol/mumol creatinine and 2.5 +/- 0.5 mumol/L, 22.8 +/- 7.8 nmol/mumol creatinine and 2.3 +/- 0.4 mumol/L, 26.4 +/- 4.6 nmol/mumol creatinine and 2.3 +/- 0.4 mumol/L, respectively. Exceeding the mean plus 2SD of pseudouridine of healthy control was considered as positive value for the diagnosis of primary liver cancer. Thus the positivity of urinary and serum pseudouridine in hepatoma was 71.3% and 70.0%, respectively. The positive rate of combined pseudouridine and alpha-fetoprotein assay was 91.3% in patients with hepatoma. Besides, pseudouridine levels could elevate before positive localization and reduce to normal levels after tumor resection. The results showed that the determination of pseudouridine is of clinical significance in the diagnosis and monitoring of primary liver cancer.
 ...
PMID:Clinical value of urinary and serum pseudouridine in diagnosis and monitoring of primary liver cancer. 779 29

Epidemiological studies have shown that exposure to aflatoxin B(1) (AFB(1)) and concurrent infection with hepatitis B lead to a multiplicative risk of developing liver cancer. This chemical-viral interaction can be recapitulated in the tree shrew (Tupia belangeri chinensis). As an initial characterization of this model, the metabolism of AFB(1) in tree shrews has been examined and compared to a sensitive bioassay species, the rat. Utilizing LC/MS/MS, an unreported product, aflatoxin M(1)-N(7)-guanine (AFM(1)-N(7)-guanine), was detected in urine and hepatic DNA samples 24 h after administration of 400 microg/kg AFB(1). In hepatic DNA isolated from tree shrews, AFM(1)-N(7)-guanine was the predominant adduct, 0.74 +/- 0.14 pmol/mg DNA, as compared to 0.37 +/- 0.07 pmol/mg DNA of AFB(1)-N(7)-guanine. Conversely, in rat liver, 6.56 +/- 2.41 pmol/mg DNA of AFB(1)-N(7)-guanine and 0.42 +/- 0.13 pmol/mg DNA of AFM(1)-N(7)-guanine were detected. Rats excreted 1.00 +/- 0.21 pmol AFB(1)-N(7)-guanine/mg creatinine and 0.29 +/- 0.10 pmol AFM(1)-N(7)-guanine/mg creatinine as compared to 0.60 +/- 0.12 pmol AFB(1)-N(7)-guanine/mg creatinine and 0.69 +/- 0.16 pmol AFM(1)-N(7)-guanine/mg creatinine excreted by the tree shrew. Furthermore, tree shrew urine contained 40 times more of the hydroxylated metabolite, AFM(1), than was excreted by rats. In vitro experiments confirmed this difference in oxidative metabolism. Hepatic microsomes isolated from tree shrews failed to produce aflatoxin Q(1) or aflatoxin P(1) but formed a significantly greater amount of AFM(1) than rat microsomes. Bioassays indicated that the tree shrew was considerably more resistant than the rat to AFB(1) hepatocarcinogenesis, which may reflect the significant differences in metabolic profiles of the two species.
 ...
PMID:Identification of aflatoxin M1-N7-guanine in liver and urine of tree shrews and rats following administration of aflatoxin B1. 1297 6

We report validation of the first isotope dilution mass spectrometry method for determination of aflatoxin B(1)-N(7)-guanine (AFB(1)-N(7)-Gua), a major human aflatoxin-DNA adduct that is excreted in the urine. Measurement of urinary AFB(1)-N(7)-Gua, a biomarker of the biologically effective dose following dietary aflatoxin B(1) (AFB(1)) exposure, has helped identify AFB(1) as a risk factor in the development of hepatocellular carcinoma, a common cancer worldwide. Triple-quadrupole mass spectrometry, coupled with the use of a stable isotope-labeled internal standard (AFB(1)-N(7)-(15)N(5)-Gua) and better solid phase extraction and immunoaffinity column chromatography, have enabled us to greatly improve accuracy, precision, specificity, and sensitivity over previously published determinations. The limit of quantitation for AFB(1)-N(7)-Gua was 0.8 pg/20 mL urine (0.07 pg/mg creatinine). The method was validated for accuracy and precision over the range of 0.8-25 pg/20 mL urine, with between-day and within-day reproducibility for analysis of six aliquots of a human urine sample containing 6.0 pg/20 mL measured at <6% coefficient of variation. AFB(1)-N(7)-Gua concentrations were measured in 20 human urine samples collected in a region with known aflatoxin exposure. The mean concentration of AFB(1)-N(7)-Gua, measured in 16/20 urine samples with levels above the method's limit of quantitation, was 2.9 pg/20 mL urine (0.28 pg/mg creatinine) with a range of <0.8-7.2 pg/20 mL urine (0.04-65 pg/mg creatinine). With improved accuracy and precision, this sensitive biomarker for recent human exposure to AFB(1) will be especially useful for measuring the efficacy of planned interventions to reduce aflatoxin-related liver cancer in AFB(1)-exposed populations.
 ...
PMID:Quantification of aflatoxin-B1-N7-Guanine in human urine by high-performance liquid chromatography and isotope dilution tandem mass spectrometry. 1697 23

(1) An estimated 15% to 25% of patients with chronic hepatitis B die of complications of the disease, such as cirrhosis and liver cancer. (2) In 2000, interferon monotherapy was the first-line treatment for chronic hepatitis B. This article examines the results of trials of peginterferon and nucleoside/nucleotide analogues (adefovir, entecavir, lamivudine), through a systematic review of the literature based on standardised Prescrire methodology. (3) We found no significant new data on interferon alfa administered subcutaneously three times a week: this treatment leads to sustained eradication of HBe antigen (reflecting a lack of viral replication) in 20% to 40% of patients. Adverse effects include a flu-like syndrome, potentially severe psychiatric disorders, and haematological and thyroid problems. (4) A trial comparing peginterferon alfa-2a once a week with interferon alfa-2a three times a week in about 300 patients showed that peginterferon alfa was at least as effective as interferon alfa-2a but that it increased the risk of neutropenia. (5) Three randomised controlled trials show that adding lamivudine to peginterferon does not increase the effect on viral load. Two trials show that peginterferon alfa-2a monotherapy is more effective than lamivudine monotherapy at 48 weeks. (6) In a randomised placebo-controlled trial in more than 600 cirrhotic patients, lamivudine (100 mg/day) reduced the risk of clinical progression in 10% of patients after three years of treatment. (7) The adverse effects of lamivudine are generally mild. Viral resistance occurs frequently and can limit its use. (8) Randomised controlled trials of adefovir dipivoxil show that it is effective after lamivudine failure, and that viral resistance tends to occur later than with lamivudine. When used as first-line treatment, adefovir dipivoxil is virologically effective for at least two years in about 25% of patients. Fewer follow-up data are available for adefovir dipivoxil than for lamivudine. Adefovir dipivoxil is nephrotoxic, meaning that blood creatinine levels must be monitored. (9) Entecavir was more effective than lamivudine on viral load and histological inflammation in three comparative trials lasting 96 weeks. However, entecavir may be carcinogenic. (10) In short, the treatment options for patients with chronic hepatitis B improved significantly between 2000 and 2007. Peginterferon alfa is now the first choice treatment, followed by adefovir dipivoxil or lamivudine as second-line treatment and by entecavir as a last resort. Other antivirals are under development.
 ...
PMID:Chronic hepatitis B: a wider range of therapeutic options. 1772 44

2,4,6-Trinitrotoluene (TNT) is an important occupational and environmental pollutant. In TNT-exposed humans, notable toxic manifestations have included aplastic anaemia, toxic hepatitis, cataracts, hepatomegaly and liver cancer. Therefore, it is important to develop protection measures and to monitor workers involved in the clean-up of ammunition sites. Haemoglobin (Hb) adducts of TNT, 4-amino-2,6-dinitrotoluene (4ADNT) and 2-amino-4,6-dinitrotoluene (2ADNT), and the urine metabolites of TNT, 4ADNT and 2ADNT were found in 22-50% of the exposed workers, but not in the control group. The exposed workers were wearing protective equipment. The levels of erythrocytes, haemoglobin, creatinine, serum glutamic pyruvic transaminase and lymphocyte levels were significantly lower in the exposed workers than in the non-exposed workers. The levels of blood urea and reticulocytes were significantly higher in the exposed workers than in the non-exposed workers. Headache (26%), mucous membrane irritation (16%), sick leave (18%), lassitude (8%), anxiety (6%), shortness of breath (3%), nausea (5%) and allergic reactions (8%) were reported by the exposed workers. In a further analysis the U-4ADNT levels and the Hb-adduct levels were compared to the blood parameter and the health effects. The blood parameters were not significantly different between the U-4ADNT positive and U-4ADNT-negative group. Headache, mucous membrane irritation, sick leave, lassitude, anxiety, shortness of breath and allergic reactions were statistically not different between the two groups. Also in the workers with Hb-4ADNT adducts no significant negative changes were seen in regards to the changes of the blood parameters or the health effects. According to the results of the present study, it appears that the blood parameter changes and the health effects are more influenced by other factors than by the internal exposure to TNT.
 ...
PMID:Biomonitoring of workers cleaning up ammunition waste sites. 1785 74

Increasing numbers of patients with non-alcoholic steatohepatitis (NASH) are referred for liver transplant (LT). Our objective was to characterize patients with NASH among referred LT candidates (from 1998 to 2008), and we compared demographics, etiology of liver disease, diabetes, hypertension, smoking, obesity, cardiac disease, cancer, laboratory data, model for end-stage liver disease (MELD), and outcomes between NASH and non-NASH patients. Patients with NASH (n = 71) were compared to other chronic liver disease (n = 472). Patients with NASH were older (58.7 vs. 52.5 yr, p < 0.0001), Asian (53.5% vs. 34.7%, p = 0.03) and women (50.7% vs. 32.1%, p = 0.003). Patients with NASH had more diabetes, hypertension, obesity, cardiac disease, and smoking history (p < 0.05). Patients with NASH were equally likely to have liver cancer, but more likely to have non-liver cancers (20.8% vs. 4.4%, p = 0.008). There was no difference in MELD, but patients with NASH had lower protime/international normalized ratio (1.14 vs. 1.27, p = 0.04) and higher creatinine (1.26 vs. 0.98 mg/dL, p = 0.0018). Patients with NASH were equally likely to undergo evaluation, listing, and transplantation compared to non-NASH patients. While all patients with chronic liver disease can have renal dysfunction because of hepatorenal syndrome, patients with NASH have more renal dysfunction, perhaps related to diabetes, hypertension, and cardiovascular disease. Transplant centers should consider this carefully in selection of candidates for LT.
 ...
PMID:Implications of worse renal dysfunction and medical comorbidities in patients with NASH undergoing liver transplant evaluation: impact on MELD and more. 2195 82

Hepatocellular carcinoma (HCC) accounts for most liver cancer cases worldwide. Contraction of the hepatitis C virus (HCV) is considered a major risk factor for liver cancer. In order to identify the risk of cancer, metabolic profiling of serum samples from patients with HCC (n=40) and HCV (n=22) was performed by 1H nuclear magnetic resonance spectroscopy. Multivariate statistical analysis showed a distinct separation of the two patient cohorts, indicating a distinct metabolic difference between HCC and HCV patient groups based on signals from lipids and other individual metabolites. Univariate analysis showed that three metabolites (choline, valine and creatinine) were significantly altered in HCC. A PLS-DA model based on these three metabolites showed a sensitivity of 80%, specificity of 71% and an area under the receiver operating curve of 0.83, outperforming the clinical marker alpha-fetoprotein (AFP). The robustness of the model was tested using Monte-Carlo cross validation (MCCV). This study showed that metabolite profiling could provide an alternative approach for HCC screening in HCV patients, many of whom have high risk for developing liver cancer.
...
PMID:Differentiating hepatocellular carcinoma from hepatitis C using metabolite profiling. 2495 58


1 2 Next >>