Transporters in the Gastrointestinal Tract

Anderle, Pascale; Nielsen, Carsten Uhd

doi:10.1002/9783527623860.ch10

Cited by 2 publications

(1 citation statement)

References 216 publications

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“…Yet, when performing PCA filtering on solute carriers, transporters mostly responsible for active uptake, differentiated Caco-2 cells emerged as most akin to small intestinal enterocytes (Figure 4 ). When the analysis was extended to include expression of drug transporters known to be involved in uptake and secretion in the small intestine (Trans_BC [ 41 ]), differentiated Caco-2 cells clustered with normal colonocytes as well as small intestinal enterocytes (Figure 5 ). However, when focusing only on transporters potentially relevant for uptake (i.e.…”

Section: Resultsmentioning

confidence: 99%

Defining new criteria for selection of cell-based intestinal models using publicly available databases

et al. 2012

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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.

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Section: Resultsmentioning

confidence: 99%

Defining new criteria for selection of cell-based intestinal models using publicly available databases

et al. 2012

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Organic Stereochemistry. Part 5

Testa¹,

Vistoli²,

Pedretti³

et al. 2013

Helvetica Chimica Acta

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This review continues a general presentation of the principles of stereochemistry with special reference to the medicinal sciences. Here, we discuss and illustrate molecular and clinical phenomena of stereoselectivity in pharmacological effects, namely activity differences between stereoisomers, principally enantiomers. The review begins with didactic models of chiral recognition, with a main focus on the early model of Easson and Stedman. There follows a Molecular Modeling (MM) and Molecular Dynamics (MD) depiction of the differential interaction of the enantiomers of hyoscyamine with cholinergic muscarinic receptors. The next section is devoted to various rationalizations in stereoselective pharmacological activity, e.g., the influence of optical purity on enantioselectivity, Pfeiffer's rule, and eudismic analysis. The review ends with selected examples taken from various fields of preclinical and clinical pharmacology, of differences between stereoisomers in terms of drug absorption, distribution, and excretion. The influence of conformational factor in molecular pharmacology will be discussed in Part 6, while stereoselective aspects of xenobiotic metabolism will be reviewed in Parts 7 and 8.

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Transporters in the Gastrointestinal Tract

Cited by 2 publications

References 216 publications

Defining new criteria for selection of cell-based intestinal models using publicly available databases

Defining new criteria for selection of cell-based intestinal models using publicly available databases

Organic Stereochemistry. Part 5

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