Undifferentiated cell populations may influence tumor growth in malignant glioma. We investigated potential disruptions in the retinoic acid (RA) differentiation pathway that could lead to a loss of differentiation capacity, influencing patient prognosis. Expression of key molecules belonging to the RA differentiation pathway was analyzed in 283 astrocytic gliomas and was correlated with tumor proliferation, tumor differentiation, and patient survival. In addition, in situ concentrations of retinoids were measured in tumors, and RA signaling events were studied in vitro. Unlike other tumors, in gliomas expression of most RA signaling molecules increased with malignancy and was associated with augmented intratumoral retinoid levels in high-grade gliomas. Aberrantly expressed RA signaling molecules included i) the retinol-binding protein CRBP1, which facilitates cellular retinoid uptake; ii) ALDH1A1, capable of activating RA precursors; iii) the RA-degrading enzyme CYP26B1; and iv) the RA-binding protein FABP5, which can inhibit RA-induced differentiation. In contrast, expression of the RA-binding protein CRABP2, which fosters differentiation, was decreased in high-grade tumors. Moreover, expression of CRBP1 correlated with tumor proliferation, and FABP5 expression correlated with an undifferentiated tumor phenotype. CRBP1 and ALDH1A1 were independent prognostic markers for adverse patient survival. Our data indicate a complex and clinically relevant deregulation of RA signaling, which seems to be a central event in glioma pathogenesis.

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Two simple, sensitive, and rapid spectrofluorimetric methods were developed and validated for the determination of albendazole. The first method (method I) was based on the quenching effect of albendazole on the native fluorescence of erythrosine B. The fluorescence intensity was measured at 554 nm after extraction at 527 nm. In the second method (method II) the drug was reacted with lanthanum(III) ions to form a metal complex, which was measured at 340 nm after excitation at 295 nm.The suitable pH was 3.4 (Teorell-Stenhagen buffer) and pH 5.5 (phosphate buffer solution), for method I and II, respectively. The influence of experimental factors on the fluorescence intensity of the reaction products was investigated and optimized. The linear concentration ranges were 0.2-3.5 and 0.06-0.90 mg mL À1, with detection limits of 0.049 and 0.019 mg mL À1 for method I and II, respectively. ICH guidelines were followed for validation of the developed procedures, and the results were acceptable.The Gibb's free energy change of the reactions was À24.6 and À27.5 kJ mol À1 for method I and II, respectively. These negative values indicated the high feasibility of these reactions at ambient temperature. The proposed procedures were applied successfully for the determination of albendazole in commercial dosage forms and spiked human plasma. The results showed high precision, accuracy and recovery of the reported methods without any significant interference from pharmaceutical excipients or plasma components.