The blood-brain barrier and oncology:New insights into function and modulation
| Autor: | E.G.E. de Vries, W.T.A. van der Graaf, NH Hendrikse, Joost Bart, W Vaalburg, Harry J.M. Groen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
Oncology
medicine.medical_specialty Organic anion transporter 1 Antineoplastic Agents Ion Pumps Blood–brain barrier Capillary Permeability In vivo Internal medicine medicine Humans Radiology Nuclear Medicine and imaging ATP Binding Cassette Transporter Subfamily B Member 1 P-glycoprotein biology Tight junction business.industry Brain Neoplasms General Medicine Membrane transport Drug Resistance Multiple medicine.anatomical_structure Blood-Brain Barrier biology.protein ATP-Binding Cassette Transporters Efflux Multidrug Resistance-Associated Proteins business |
| Zdroj: | Bart, J, Groen, H J M, Hendrikse, N H, Van der Graaf, W T A, Vaalburg, W & De Vries, E G E 2000, ' The blood-brain barrier and oncology : New insights into function and modulation ', Cancer Treatment Reviews, vol. 26, no. 6, pp. 449-462 . https://doi.org/10.1053/ctrv.2000.0194 |
| DOI: | 10.1053/ctrv.2000.0194 |
| Popis: | 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 [11C]-verapamil or with single photon emission computer tomography and 99mTc-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. |
| Databáze: | OpenAIRE |
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