- Licenciado in Biochemistry, Universidad Austral de Chile, 1997
- Biochemist, Universidad Austral de Chile, 1997
- Ph.D. in Molecular Biosciences, Universidad Andrés Bello, Chile, 2005
- Postdoctorate, Universidad Austral de Chile, 2006-2008
Our laboratory is interested in studying the phenomenon of multiple drug resistance (MDR), one of the main causes for cancer chemotherapy failure. This MDR phenotype is characterized by expression of one or various membrane transport proteins: P-glycoprotein (P-gp) and multiple drug resistant associated proteins (MRPs, BMDP/ABCG2). These proteins act as pumps, expelling harmful molecules towards the cell exterior, participating in this way to natural detoxification processes. Brain cells normally express low levels of some of the drug resistant transporters. However, in brain tumours, drug resistance is generally associated with a decrease in intracellular accumulation of the drug, a fact that is attributed to overexpression of these specific transporters in the cell membrane. Besides this, chemotherapy is seen to be less effective for brain tumours than for other cancer types, in part because arrival of molecules to the brain is finally regulated by the endothelial cells of the cerebral microvasculature that make up the hematoencephalic barrier (BHE).
With the aim of discovering new therapies for brain cancer, we propose a study of several drugs that may modulate drug resistance, such as immunosuppressors (tacrolymus and cyclosporin A) and natural drugs such as leptocarpin, in both hematoencephalic barrier cell lines as well as in primary culture of human gliomas. We speculate that local application of joint therapies, comprising modulator molecules, together with drug substrates of these transporters, will permit modification of the effective intracellular concentration of these drugs, thereby decreasing pharmacological resistance in tumour cells.
Cárcamo JG, Quezada CA, González-Oyarzún M. (2009) Membrane Transporters and Receptors in Disease. Multidrug resistance proteins. 2009: 153-170, ISBN: 978-81-308-0330-2 Editors: Luis Sobrevia and Paola Casanello.
Rauch MC, San Martín A, Ojeda D, Quezada C, Salas M, Cárcamo JG, Yañez AJ, Slebe JC, Claude (2009). Tacrolimus causes a blockage of protein secretion which reinforces its immunosuppressive activity and also explains some of its toxic side-effects. Transpl Immunol. 22(1-2):72-81.
Quezada C., Garrido W, González-Oyarzún M, Rauch M.C., Salas M, San Martín R., Claude A., Yañez A., Slebe J.C. and Cárcamo J.G. (2008) Effect of tacrolimus on activity and expression of Pgp and ABCA5 proteins in hematoencephalic barrier cells. Biological and Pharmaceutical Bulletin, 31(10) 1911-1916.
Valladares D, Quezada C, Montecinos P, Concha II, Yañez AJ, Sobrevia L, San Martín R. (2008) “Adenosine A(2B) receptor mediates an increase on VEGF-A production in rat kidney glomeruli”. Biochemistry Biophysical Research Communication, 366(1):180-185.
San Martín R, Hurtado W, Quezada C, Molina A, Álvarez M, Vera MI, Reyes A and Krauskopf M. (2007) “The prolactin receptor gene of carp fish: structure, promoter characterization and expression of short forms” Journal of Cell Biochemistry 100(4):970-980.
Quezada, C., Navarro, C., San Martín, R., Molina, A., Álvarez, M., Bachellerie, J.P., Ganot, P., Krauskopf, M., and Vera, M.I. (2006) “Genomic organization of nucleolin gene in a teleost fish”. Biological Research, 39 (2): 353-365. 4.2.