BackgroundThe criteria for choosing relevant cell lines among a vast panel of available intestinal-derived lines exhibiting a wide range of functional properties are still ill-defined. The objective of this study was, therefore, to establish objective criteria for choosing relevant cell lines to assess their appropriateness as tumor models as well as for drug absorption studies.ResultsWe made use of publicly available expression signatures and cell based functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium. We have compared a panel of intestinal cell lines with patient-derived normal and tumor epithelium and classified them according to traits relating to oncogenic pathway activity, epithelial-mesenchymal transition (EMT) and stemness, migratory properties, proliferative activity, transporter expression profiles and chemosensitivity. For example, SW480 represent an EMT-high, migratory phenotype and scored highest in terms of signatures associated to worse overall survival and higher risk of recurrence based on patient derived databases. On the other hand, differentiated HT29 and T84 cells showed gene expression patterns closest to tumor bulk derived cells. Regarding drug absorption, we confirmed that differentiated Caco-2 cells are the model of choice for active uptake studies in the small intestine. Regarding chemosensitivity we were unable to confirm a recently proposed association of chemo-resistance with EMT traits. However, a novel signature was identified through mining of NCI60 GI50 values that allowed to rank the panel of intestinal cell lines according to their drug responsiveness to commonly used chemotherapeutics.ConclusionsThis study presents a straightforward strategy to exploit publicly available gene expression data to guide the choice of cell-based models. While this approach does not overcome the major limitations of such models, introducing a rank order of selected features may allow selecting model cell lines that are more adapted and pertinent to the addressed biological question.

Background The risks associated with over-the-counter medication are often underestimated by consumers. The incorrect use of certain medications can lead to significant patient harm. Inappropriate use can be prevented by pharmaceutical counselling. Objective To determine the number and nature of drug-related problems in over-the-counter medication with a special emphasis on high-risk over-the-counter medications. Setting Fifty-two community pharmacies in Finland. Method This observational study was conducted as a questionnaire survey. The pharmacists working in participating pharmacies documented the observed drug-related problems and pharmacy interventions in over-the-counter medication during 1 week using an electronic study form based on the Westerlund drug-related problem classification system. Main outcome measure The prevalence of drugrelated problems and problem types in different medication categories. Results The 52 community pharmacies documented 339 drug-related problems in 0.6% of over-the-counter customers, the most common problem being "Uncertainty about the indication for the drug" (39.2%). A significant proportion of the documented problems (26.3%) concerned high-risk over-thecounter medications, and the majority of these cases were associated with non-steroidal anti-inflammatory drugs (21.8%). In total, pharmacies made 641 interventions to resolve the drug-related problems. For majority of drug-related problems (87%), pharmacist's intervention involved counselling. In more than half of the problem cases, the pharmacy intervention was precautionary. Conclusion Pharmacists intervene in and prevent problems related to over-the-counter medications, including high-risk medications like analgesics, in which inappropriate use due to consumers' lack of knowledge can lead to severe consequences. As the selection and use of over-the-counter medications is continuously increasing, pharmaceutical counselling should be readily available and actively provided for consumers to achieve safer self-medication.

ABSTRACT:The human colon carcinoma cell line Caco-2 is often used as a model for intestinal drug absorption. To better understand xenobiotic glucuronidation in Caco-2 cells, we have examined the expression levels of different UDP-glucuronosyltransferases (UGTs) in them. The effects of two main factors were investigated, namely, passage number and cell differentiation. Hence, the mRNA levels of 15 human UGTs of subfamilies 1A and 2B were assessed in both undifferentiated and fully differentiated cells at four passage levels: P31, P37, P43, and P49. Quantitative reverse transcriptasepolymerase chain reaction was used to determine the mRNA levels of individual UGTs, and the values were normalized using ␤-actin as a reference gene. The results indicate that although passage number in the tested range exerts a mild effect on the expression level of several UGTs, the contribution of cell differentiation is much larger. The expression of nearly all the UGTs that were examined in this study was significantly, sometimes greatly, increased during cell differentiation. UGT1A6 was a distinct exception to this rule, however, because it was already highly expressed in the undifferentiated cells. The mRNA findings were confirmed at the enzyme activity level by measuring the glucuronidation of 1-naphthol, a very good substrate for UGT1A6, as well as estradiol that is not glucuronidated by this enzyme. The results revealed that 1-naphthol glucuronidation activity was high in both the differentiated and undifferentiated cells, whereas estradiol glucuronidation was only detected in the differentiated cells. Thus, Caco-2 cell differentiation plays a major role in UGT expression and ensuing metabolic reactions.

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