The blood-brain barrier and oncology: new insights into function and modulation

J Bart, HJM Groen, NH Hendrikse, WTA van der Graaf, W Vaalburg, EGE de Vries*

*Bijbehorende auteur voor dit werk

Onderzoeksoutputpeer review

155 Citaten (Scopus)

Samenvatting

The efficacy of chemotherapy for malignant primary or metastatic brain tumours is still poor. This is at least partly due to the presence of the blood-brain barrier (BBB). The functionality of the BBB can be explained by physicochemical features and efflux pump mechanisms. An overview of the literature is presented with emphasis on oncology.

The BBB consists of capillary endothelial cells that lack fenestrations and are connected together with continuous tight junctions, with a high electrical resistance. Permeability of tight junctions can be increased in vitro by contraction of the cytoskeleton, caused by bradykinin agonists. Different efflux pumps are present in the BBB. Examples are P-glycoprotein (P-gp), organic anion transporters, (OAT) and multidrug-resistance-associated proteins (MRP)(1 and 3). These pumps act as a multi-specific efflux pump for various chemotherapeutic drugs. Experiments have shown that P-gp can be inhibited by different non-chemotherapeutic substrates such as cyclosporin A. The functionality in vivo of P-gp can be measured with positron emission tomography and [C-11]-verapamil or with single photon emission computer tomography and Tc-99m-sestamibi,

MRP1 and MRP3 act as organic anion transporters that in vitro act as efflux pumps for substances that are conjugated or co-transported with glutathione and glucuronide, respectively. Methotrexate has been recently demonstrated to be transported by MRP1 and MRP3.

Results of studies which demonstrate the clinical relevance and applicability of BBB modulators are eagerly awaited. (C) 2000 Harcourt Publishers Ltd.

Originele taal-2English
Pagina's (van-tot)449-462
Aantal pagina's14
TijdschriftCANCER TREATMENT REVIEWS
Volume26
Nummer van het tijdschrift6
StatusPublished - dec-2000

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