- Major in Biochemistry. Universidad Austral de Chile. 1989
- Biochemist. Universidad Austral de Chile. 1990.
- Research Fellow. Memorial Sloan-Kettering Cancer Center, New York USA. 1994.
- Ph.D., Universidad Austral de Chile. 1999.
- Postdoctorate, Universidad de Concepción. 2000-2002. Fondecyt.
Our laboratory focuses mainly on the study of the biochemical and molecular mechanisms of the pharmacology against cancer as well as the phenomenon of multiple drug resistance (MDR). We aim to identify and characterize new antitumour drugs of both natural and synthetic origin, to search for new modulators for drug resistance, as well as to characterize their pharmacological interaction with other antitumour and immunosuppressor drugs.
Drug resistance is a phenomenon associated mainly with a decrease in intracellular drug accumulation, which is itself attributed to transporter expression, mainly of the ABC type, in the cell membrane. Once a drug has entered the lipid phase of the plasma membrane, or reached the cytoplasm, it is transported back out again towards the extracellular space. Some members of the ABC superfamily have been recognized for their important physiological role in different processes, such as transport of organic anions, cholesterol, surfactant secretion and biliar salts. They have also been associated with certain pathologies, such as the Dubin-Johnson syndrome and cystic fibrosis. And at least ten of these transporters, mainly Pgp, MRPs (MRP-1, -2, -3, -4, -5, -8), BCRP (ABCG2), have been clearly implicated in conferring resistance to antitumour drugs, while the role of other transporters, particularly those of the ABCA family, is still uncertain. Two proteins, RLIP76 and MVP (LRP) that do not belong to the ABC protein family have also been recognized in conferring multiple drug resistance in different tumour types. In general, the poor effectiveness and specificity of chemotherapy, plus the fact that multiple drug resistance occurs, suggests that current antitumour agents have reached their most effective level. With this in mind, our laboratory is studying the pharmacological potential of several natural and synthetic drugs. These include leptocarpin, a sesquiterpene lactone isolated from a plant native to southern Chile and several synthetic isoxazole and pyrazole derivatives. Likewise, different biochemical and molecular studies, as well as characterization of antitumour activity and drug resistance modulation of all molecules under study, is being carried out in cell lines from various tumours of human origin, as well as from hematoencephalic barrier cell models, and in primary tissue cultures from human cerebral tumours in collaboration with the Barros Luco-Trudeau Hospital in Santiago. We also use ex-vivo cell cultures from different leukaemia cancers in collaboration with the Instituto de Hematología, of the Hospital Regional de Valdivia. We hope that the proposed studies will help to forward a clear and decisive scientific view of the mechanisms involved in modulation of the multiple drug resistance phenotype at the level of cerebral barriers, cerebral tumours and leukaemias. We are also hopeful that they may provide new pharmacological and therapeutic approaches, for more effective treatment with good clinical tolerance against cancer or other medication.
- Rauch MC, San Martín A, Ojeda D, Quezada C, Salas M, Cárcamo JG, Yañez AJ, Slebe JC, Claude A. (2009) Tacrolimus causes a blockage of protein secretion which reinforces its immunosuppressive activity and also explains some of its toxic side-effects. Transpl. Immunol. 2009 Jul 21.
- Pérez A, Ojeda P, Valenzuela X, Ortega M, Sánchez C, Ojeda L, Castro M, Cárcamo JG, Rauch MC, Concha II, Rivas CI, Vera JC, Reyes AM. (2009) Endofacial competitive inhibition of the glucose transporter 1 activity by gossypol. Am. J. Physiol. Cell. Physiol. 2009 Jul;297(1):C86-93.
- Cárcamo J.G., Quezada C.A., González-Oyarzún M. (2009) Multidrug Resistance Proteins in Membrane Transporters and Receptors in Disease. Chapter 7: 153-170. ISBN: 978-81-308-0330-2. Editors: L. Sobrevia & P. Casanello. Research Signpost 37/661 (2), Fort P.O., Trivandrum-695 023, Kerala, India.
- Quezada C., Garrido W., San Martín R., Rauch C., Claude A., Salas M., Yañez A., Slebe J. C., & Cárcamo J.G. (2008) Modulation of the activity and expression of protein of multiple resistances to drugs by cyclosporin-A and tacrolimus in cells of hematoencephalic barrier. Biol. Pharm. Bull. 31(10): 1911-1916.
- Montecinos V, Guzman P, Barra V, Villagran M, Munoz-Montesino C, Sotomayor K, Escobar E, Godoy A, Mardones L, Sotomayor P, Guzman C, Vasquez O, Gallardo V, van Zundert B, Bono MR, Onate SA, Bustamante M, Carcamo JG, Rivas CI, Vera JC. (2007) Vitamin C is an essential antioxidant that enhances survival of oxidatively stressed human vascular endothelial cells in the presence of a vast molar excess of glutathione. J Biol Chem. 282(21):15506-15.
- Godoy A., Ormazabal V., Moraga-Cid G., Zúñiga F.A., Sotomayor P., Barra, V., Vasquez, O., Montecinos V., Mardones L., Guzmán C., Villagrán M., Aguayo L., Oñate S., Reyes A.M., Cárcamo J.G., Rivas C.I., & Vera J.C. (2007) Mechanistic insights and functional determinants of the transport cycle of the ascorbic acid transporter svct2: Activation by sodium and absolute dependence on bivalent cations. J. Biol. Chem. 282(1):615-24.
- Martínez R.,, Kesternich V., Carrasco H., Álvarez-Contreras C., Montenegro C., Ugarte R., Gutiérrez E., Moreno J., García C., Werner E. & Cárcamo J.G. (2006) Synthesis and conformational analysis of leptocarpin derivatives. Influence of modification of the oxirane ring on leptocarpin’s cytotoxic activity. J. Chil. Chem. Soc., 51(3):982-986.
- Yáñez, A.J., Bertinat, R., Spichiger, C., Cárcamo, J.G., García, M.A., Concha, I.I., Nualart, F., and Slebe, J.C. (2005) Novel expression of liver FBPase in alpha and beta cells of human and rat pancreas. J. Cell. Physiol. 205(1):19-24.
- Maulen, N.P., Henríquez, E., Kempe, S., Cárcamo, J.G., Schmid-Kotsas, A., Bachem, M., Grünert, A., Bustamante, M., Nualart, F., & Vera, J.C. (2003). Upregulation and polarized expression of the sodium-ascorbic acid transporter SVCT1 in post-confluent differentiated Caco-2 cells. J. Biol. Chem. 278: 9035-9041.
- Van Zundert, B., Alvarez, F.J., Yevenes, G.E., Cárcamo J.G., Vera, J.C., Aguayo, L.G. (2002). Glycine receptors involved in synaptic transmission are selectively regulated by cytoskeleton in mouse spinal neurons. J. Neurophysiol. 87: 640-644.