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Abstract: Recent advances in cancer biology have subsequently led to the development of new molecularly targeted anti-cancer agents that can effectively hit cancer-related proteins and pathways. Despite better insight into genomic aberrations and diversity of cancer phenotypes, it is apparent that proteomics too deserves attention in cancer research. Currently, a wide range of proteomic technologies are being used in quest for new cancer biomarkers with effective use. These, together with newer technologies such as multiplex assays could significantly contribute to the discovery and development of selective and specific cancer biomarkers with diagnostic or prognostic values for monitoring the disease state. This review attempts to illustrate recent advances in the field of cancer biomarkers and multifaceted approaches undertaken in combating cancer. [Copyright &y& Elsevier]

Background and Aim: The present study was aimed to evaluate the hepatic zonation of multidrug resistance-associated protein 2 (mrp2), an important drug transporter, and its potential changes during the induction of its expression by known inducer, dexamethasone (DEX). Methods: The hepatic expression of mrp2 was studied by immunohistochemistry with consequent quantification by measurement of integral optical densities of mrp2 staining in the periportal and perivenous areas of the liver acinus in control and DEX-pretreated rats (1 mg/kg daily per os for 4 days). Overall changes in mrp2 expression and function produced by DEX were monitored using Western blotting and an in vivo clearance study of endogenous-conjugated bilirubin, a mrp2 substrate. Results: In the control animals, a quantitative image analysis revealed the primary periportal localization of mrp2 within the liver acinus with the expression of mrp2 being 16.7-fold of that in the perivenous area. After DEX pretreatment, the expression of mrp2 increased, especially in the perivenous hepatocytes. The overall expression of mrp2 increased 3.2-fold in comparison with the control group. This observation was confirmed by Western blotting, which showed a 1.3-fold increase in the mrp2 protein after DEX pretreatment. The functional consequences of the induced mrp2 protein in the livers of the DEX-pretreated rats were demonstrated by the increased biliary excretion of conjugated bilirubin. Conclusion: In conclusion, these results indicate the zonation of mrp2 protein expression primarily to periportal hepatocytes. The induction by DEX produced spatially disproportional changes with an increase in the mrp2 protein being most prominent in the perivenous hepatocytes. [ABSTRACT FROM AUTHOR]

1. The effect of dexamethasone on hepatic and renal P-glycoprotein (P-gp) expression, localization and activity was investigated in rats after 4 days oral administration of two dose regimens (1 or 25 mg/kg per day). Simultaneous increases in liver weight were evaluated by quantitative histological examination. 2. In the liver, dexamethasone pretreatment produced hepatomegaly as a consequence of extensive periportal fat accumulation, which was quantified by densitometry of oil red O-stained liver sections. Quantitative immunohistochemical analysis revealed preferential periportal zonation of P-gp in control animals. Dexamethasone pretreatment resulted in spatially disproportional induction of P-gp protein expression within the liver acinus characterized by preferential increase in pericentral areas, with consequent uniform panlobular distribution. Western blot analysis confirmed these results, showing increases in P-gp protein. Quantitative reverse transcription–polymerase chain reaction analysis revealed no statistically significant change in liver mdr1b mRNA expression after either dexamethasone treatment regimen. The expression of mdr1a mRNA was significantly decreased by 85–87%. 3. In the kidney, dexamethasone reduced mdr1a mRNA expression by 69–89%, whereas mdr1b mRNA expression was increased in a dose-dependent manner. However, despite tendencies, no significant increases in P-gp expression were observed at the protein level. 4. The in vivo function of P-gp was evaluated by measuring renal and biliary secretion of rhodamine-123 (Rho123) under a steady state plasma concentration. The biliary, renal and tubular secretory clearance of Rho123 was significantly increased only after high-dose dexamethasone. 5. In conclusion, the present study suggests that drug interactions observed during corticosteroid therapy may be mediated, at least in part, through increased biliary, and also renal, excretion of P-gp substrates. Expression of P-gp in the liver showed primary periportal zonation with differential changes during induction. Accompanying hepatomegaly may be explained by severe microvesicular steatosis selectively localized to the periportal areas. [ABSTRACT FROM AUTHOR]

Discusses the effective systemic treatment for severe psoriasis. Evaluation of the relationships between methotrexate pharmacokinetics and its therapeutic effect/toxicity; Determination of the pharmacokinetics of methotrexate; Response of patients treated with methotrexate.

Discusses the use of human hepatocytes cultured in vitro in the study of hepatocytic properties. Comparison of the hepatocytes in situ and in vitro; Analysis of the expression levels and distribution patterns of MRP2 and MDR1; Difference in the expression of hepatocytes.

Presents a study evaluating the effect of dexamethasone on the intestinal, biliary and renal handling of rhodamine 123, a P-glycoprotein substrate, in rats in vivo. Increase in the P-glycoprotein level with dexamethasone; Demonstration of the simultaneous induction of P-glycoprotein expression; Examination of the dose-dependency of dexamethasone pretreatment on hepatic P-glycoprotein expression in rats.