HCC-ART score, a simple, highly sensitive and specific test for early diagnosis of hepatocellular carcinoma: a large-scale, multicentre study.

BACKGROUND: A simple scoring system is needed to discriminate HCC from patients with chronic liver diseases (CLD). The simplest score would be one that requires only variables that can be documented simply from routine laboratory tests without the need for sophisticated tests. METHODS: Data from the estimation group (1351 patients) and the validation group (2208 patients) were retrospectively analysed. Liver fibrosis-negative control and liver cirrhosis were compared with HCC. Area under ROC curve (AUC) were used to develop HCC-α-fetoprotein-routine test (HCC-ART). RESULTS: Hepatocellular carcinoma-AFP-routine test showed diagnostic accuracy for liver cirrhosis vs HCC with ROC curves of 0.99%, sensitivity of 97%, and specificity of 96% in the estimation, and 0.95%, 90%, and 83%, respectively, in the validation. Sensitivity (97%) and specificity (100%) were obtained to discriminate HCC from liver fibrosis. Area under curve for AFP at 400 U l(-1) was 0.70, sensitivity was 41%, and specificity was 99% in the estimation, and 0.77%, 54%, and 99%, respectively, in the validation. The AUC for HCC-ART in HCC with single tumour, absent vascular invasion, size <2 cm and CLIP score (0-1) were 0.95, 0.93, 0.86, 0.87, respectively, compared with 0.72, 0.71, 0.71, 0.50, respectively, for AFP. CONCLUSION: Hepatocellular carcinoma-AFP-routine test could increase the accuracy of HCC screening and surveillances and could be used worldwide without extra efforts.

Effect of host portal and peripheral sera fractions on cell proliferation of Schistosoma mansoni schistosomules

Schistosomules of Schistosoma mansoni were incubated in medium containing hamster (highly susceptible host) portal or peripheral venous serum, or rat (poorly susceptible host) portal or peripheral venous serum or their fractions in the presence of bromodeoxyuridine (BrdU) in order to determine effects of host sera on cell proliferation. BrdU labeling indices (BLIs) were significantly increased in the presence of portal (33.05±0.70, p0.05) of hamsters, compared to schistosomules cultured in presence of control medium (18.96±0.66). This stimulatory effect was substantially reproduced by fraction 4 (31.03±0.69, p>0.05) separated from hamster portal serum. In contrast, no significant differences were observed in the BLIs in rat portal or peripheral sera as well as their fractions when compared to control medium. Taken together, it was concluded that portal serum of hamster and its fraction which includes a low molecular weight protein (20 kDa) enhanced cell proliferation of S. mansoni schistosomules. This could explain the localization and preference of S. mansoni schistosomules and worms to portal-mesenteric venous system.

Effect of host portal and peripheral sera fractions on cell proliferation of Schistosoma mansoni schistosomules.

Schistosomules of Schistosoma mansoni were incubated in medium containing hamster (highly susceptible host) portal or peripheral venous serum, or rat (poorly susceptible host) portal or peripheral venous serum or their fractions in the presence of bromodeoxyuridine (BrdU) in order to determine effects of host sera on cell proliferation. BrdU labeling indices (BLIs) were significantly increased in the presence of portal (33.05±0.70, p<0.05), but not in peripheral serum (19.1±0.85, p>0.05) of hamsters, compared to schistosomules cultured in presence of control medium (18.96±0.66). This stimulatory effect was substantially reproduced by fraction 4 (31.03±0.69, p>0.05) separated from hamster portal serum. In contrast, no significant differences were observed in the BLIs in rat portal or peripheral sera as well as their fractions when compared to control medium. Taken together, it was concluded that portal serum of hamster and its fraction which includes a low molecular weight protein (20 kDa) enhanced cell proliferation of S. mansoni schistosomules. This could explain the localization and preference of S. mansoni schistosomules and worms to portal-mesenteric venous system.

Stereochemical control of reductions. 9. Haptophilicity studies with 1,1-disubstituted 2-methyleneacenaphthenes.

A series of 1-methyl-2-methyleneacenaphthenes has been synthesized, bearing an additional variable substituent (R) at the 1-position. These compounds have been hydrogenated in ethanol over a 5% Pd/C catalyst under standardized conditions in order to assess the haptophilicity of R, its ability to enforce addition of hydrogen from its own face of the molecule by coordination to the catalyst surface. The order of decreasing haptophilicity, assessed as the product epimer ratio, for the groups studied was R = CH(2)NH(2), CH(2)NMe(2), CH(2)OH, CHNOH, CH(2)OMe, CHO, CONH(2), CH(2)NHCOMe, COOK, COMe, CN, CONHOH, COOH, COOMe, COONa, COOLi. Because knowledge of group haptophilicities offers potential for stereochemical control in such reductions, comparisons are provided with haptophilic orders found in other molecular systems. It is shown that absolute haptophilicities can be manipulated by varying the dielectric constant of the solvent employed.

Expression of p21WAF1/CIP1 in bladder cancer: relation to schistosomiasis.

Cell cycle regulation is mediated in part through expression of the cyclin-dependent kinase inhibitor p21WAF1/CIP1. Loss of p21WAF1/CIP1 expression may, therefore, contribute partially to schistosomal carcinogenesis in the urinary bladder. We compared p21WAF1/CIP1 expression in schistosomal and nonschistosomal bladder cancer to explore possible differences in p21WAF1/CIP1 expression between the two subtypes and the possible association between schistosomiasis and loss of p21WAF1/CIP1 expression. Tumor specimens were obtained from 130 patients who underwent transurethral biopsy or cystectomy. p21WAF1/CIP1 was determined by immunodot blot, Western blot, and enzyme immunoassay (EIA). We validated a highly sensitive quantitative EIA assay for determination of p21WAF1/CIP1 in cell lysates. Precision, analytical recovery, and linearity were all excellent. Our results did not show any correlation between p21WAF1/CIP1 expression and most clinicopathologic variables. Lower expression of p21WAF1/CIP1 was evident in squamous cell carcinoma (SCC) and schistosomal subtype than in transitional cell carcinoma and nonschistosomal tumors. Our data suggest a potential role for p21WAF1/CIP1 alteration in schistosomal carcinogenesis.

Human portal serum stimulates cell proliferation in immature Schistosoma mansoni.

Schistosomula of Schistosoma mansoni were incubated in RPMI 1640 medium containing 10% fetal calf serum, 10% human portal venous or 10% human peripheral venous sera in the presence of bromodeoxyuridine (BrdU) in order to measure differences in cell proliferation. The rates of cell proliferation as expressed by BrdU labelling indices (BLI) were determined as a function of time of incubation by immunohistochemistry using monoclonal antibody to BrdU. Compared to schistosomula cultured in the presence of RPMI plus 10% fetal calf serum, BLIs were increased by 60% in the presence of human portal, but not in peripheral serum. This stimulatory effect was substantially reproduced by a fraction of portal serum with a molecular weight range between 1 and 50 kDa. However, in the presence of human peripheral venous serum, either whole or fractionated, schistosomula showed no significant difference compared to RPMI plus 10% fetal calf serum alone. Furthermore, human portal serum fractions of molecular weight greater than 50 kDa also revealed no significant difference relative to control. The results indicate that portal venous serum component(s) of a molecular weight range higher than most simple nutrients can greatly stimulate the rate of cell proliferation of Schistosoma mansoni schistosomula.

Immunochemical studies of serum, urine and calculus proteins in urolithiasis.

Total serum protein levels in 70 patients with urolithiasis were not significantly different from those in 20 control subjects, although certain variations were detected in individual protein patterns. In contrast, total urinary protein was significantly higher in patients with urolithiasis. 4-6 different components, i.e., albumin, alpha 1-acidic glycoprotein, alpha 1-antitrypsin, Gc-globulin, fibrinogen and immunoglobulin G, were found in the matrices of calculi and in urine, suggesting that proteinuria may play a role in the formation of stones in patients with urolithiasis.

Serum and urinary amino acid pattern in schistosomal infection among Egyptians.

The amino acid pattern in plasma and urine of Bilharzial Egyptian patients with different degrees of complications was investigated. The results obtained showed that in mansoniasis, accumulation of amino acids in the circulation is due to derangement in liver function which retards the utilization of amino acids in protein synthesis particularly in the advanced stage of the disease. This is also in part due to liver cell degeneration which parallel the severity of the infection. Aminoaciduria in haematobiasis is partly an overflow type, while in severe cases urinary tract tissue degeneration may be a participating factor. Aminoaciduria in haematobiasis is due to haematuria and urinary tract tissue degeneration.