Akiyama, S.-I., Cornwell, M. M., Kuwano, M., Pastan, I., and Gottesman, M. M., 1988, Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog, Mol. Pharmacol.33:144–147. PubMedCAS Google Scholar
Almquist, K. C., Loe, D. W., Hipfner, D. R., Mackie, J. E., Cole, S. P. C., and Deeley, R. G., 1995, Characterization of the Mr 190,000 multidrug resistance protein (MRP) in drug-selected and transfected human tumor cells, Cancer Res.55:102–110. PubMedCAS Google Scholar
Al-Shawi, M. K., and Senior, A. E., 1993, Characterization of the adenosine triphosphate activity of Chinese hamster P-glycoprotein, J. Biol. Chem.268:4197–4206. PubMedCAS Google Scholar
Al-Shawi, M. K., Urbatsch, I. L., and Senior, A. E., 1994, Covalent inhibitors of P-glycoprotein in ATPase activity, J. Biol. Chem.269:8986–8992. PubMedCAS Google Scholar
Ambudkar, S. V., LeLong, I. H., Zhang, J., Cardarelli, C. O., Gottesman, M. M., and Pastan, I., 1992, Partial purification and reconstitution of the human multidrug-resistance pump: Characterization of the drug-stimulatable ATP hydrolysis. Proc. Natl. Acad. Sci. USA89:8472–8476. PubMedCAS Google Scholar
Artursson. P., 1990, Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorbtive (Caco-2) cells, J. Pharmaceut. Sci.79:476–482. CAS Google Scholar
Artursson, P., and Karlsson, J., 1991, Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells, Biochem. Biophys. Res. Commun.175:880–885. ArticlePubMedCAS Google Scholar
Audus, K. L., Bartel, R. L., Hidalgo, I. J., and Borchardt, R. T., 1990, The use of cultured epithelial and endothelial cells for drug transport and metabolism studies, Pharmaceut. Res.7:435–451. ArticleCAS Google Scholar
Augustijns, P. F., Bradshaw, T. P., Gan, L.-S. L., Hendren, R. W., and Thakker, D. R., 1993, Evidence for a polarized efflux system in Caco-2 cells capable of modulating cyclosporin A transport, Biochem. Biophys. Res. Commun.197:360–365. ArticlePubMedCAS Google Scholar
Azzaria, M., Shurr, E., and Gros, P., 1989, Discrete mutations introduced in the predicted nucleotide-binding sites of the mdr1 gene abolish its ability to confer multidrug resistance, Mol. Cell. Biol.9:5289–5297. PubMedCAS Google Scholar
Beck, W. T., and Qian X-dong, 1992, Photoaffinity substrates for P-glycoprotein, Biochem. Pharmacol.43:89–93. ArticlePubMedCAS Google Scholar
Biedler, J. L., 1994, Drug resistance: Genotype versus phenotype, Cancer Res.54:666–678. PubMedCAS Google Scholar
Biedler, J. L., and Riehm, H., 1970, Cellular resistance to actinomycin D in Chinese hamster cells in vitro; cross resistance, radioautographic and cytogenetic studies, Cancer Res.30:1174–1184. PubMedCAS Google Scholar
Borchardt, R. T., Smith, P., and Wilson, G., 1996, General principles in the characterization and use of model systems for biopharmaceutical studies, in: Models for Assessing Drug Absorption and Metabolism (R. T. Borchardt, P. Smith, and G. Wilson, eds.), Plenum Press, New York, pp. 1–11. Google Scholar
Borst, P., Schinkel, A. H., Smit, J. J. M., Wagenaar, E., Van Deemter, L., Smith, A. J., Eijdems, W. H. M., Baas, F., and Zaman, G. J. R., 1993, Classical and novel forms of multidrug resistance and the physiological functions of P-glycoproteins in mammals, Pharmacol. Ther.60:289–299. ArticlePubMedCAS Google Scholar
Bremer, S., Hoof, T., Wilke, M., Busche, R., Scholte, B., Riordan, J. R., Maass, G., and Tümmler, B., 1992, Quantitative expression patterns of multidrug-resistance P-glycoprotein (MDR1) and differentially spliced cystic-fibrosis transmembrane-conductance regulator mRNA transcripts in human epithelia, Eur. J. Biochem.206:137–149. ArticlePubMedCAS Google Scholar
Brown, P. C., Thorgeirsson, S. S., and Silverman, J. A., 1993, Cloning and regulation of the rat mdr2 gene, Nucleic Acids Res.21:3885–3891. PubMedCAS Google Scholar
Buschman, E., and Gros, P., 1991, Functional analysis of chimeric genes obtained by exchanging homologous domains of the mouse mdr1 and mdr2 genes, Mol. Cell. Biol.11:595–603. PubMedCAS Google Scholar
Callaghan, R., and Riordan, J. R., 1993, Synthetic and natural opiates interact with P-glycoprotein in multidrug-resistant cells, J. Biol. Chem.268:16059–16064. PubMedCAS Google Scholar
Cavet, M. E., West, M., and Simmons, N. L., 1996, Transport and epithelial secretion of the cardiac glycoside, digoxin, by human intestinal epithelial (Caco-2) cells, Br. J. Pharmacol.118:1389–1396. PubMedCAS Google Scholar
Chaudhary, P. M., and Roninson, I. B., 1991, Expression and activity of P-glycoprotein, a multidrug efflux pump, in human and hematopoietic stem cells, Cell66:85–94. ArticlePubMedCAS Google Scholar
Chaudhary, P. M., Metchener, E. B., and Roninson, I. B., 1992, Expression and activity of the multidrug resistance P-glycoprotein in human peripheral blood lymphocytes, Blood80:2735–2739. PubMedCAS Google Scholar
Chin, J. E., Soffir, R., Noonan, K. E., Choi, K., and Roninson, I. B., 1989, Structure and expression of the human MDR (P-glycoprotein) gene family, Mol. Cell. Biol.9:3808–3820. PubMedCAS Google Scholar
Chin, K.-V., Tanaka, S., Darlington, G., Pastan, I., and Gottesman, M. M., 1990, Heat shock and arsenite increase expression of the multidrug resistance (MDR1) gene in human renal carcinoma cells, J. Biol. Chem.265:221–226. PubMedCAS Google Scholar
Choi, K., Frommel, T. H. O., Stern, R. K., Perez, C. F., Kriegler, M., Tsuruo, T., and Roninson, I. B., 1991, Multidrug resistance after retroviral transfer of the human MDR1 gene correlates with P-glycoprotein density in the plasma membrane and is not affected by cytotoxic selection, Proc. Natl. Acad. Sci. USA88:7386–7390. PubMedCAS Google Scholar
Cole, S. P. C., Bhardwaj, G., Gerlach, J. H., Mackie, J. E., Grant, C. E., Almquist, K. C., Stewart, A. J., Kurz, E. U., Duncan, A. M. V., and Deeley, R. G., 1992, Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line, Science258:1650–1654. PubMedCAS Google Scholar
Cordon-Cardo, C., O’Brien, J. P., Casals, D., Rittman-Grauer, L., Biedler, J. L., Melamed, M. R., and Bertino, J. R., 1989, Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites, Proc. Natl. Acad. Sci. USA86:695–698. PubMedCAS Google Scholar
Cornwell, M. M., Tsuruo, T., Gottesman, M. M., and Pastan, I., 1987, ATP-binding properties of P-glycoprotein from multidrug resistant KB cells, FASEB J.1:51–54. PubMedCAS Google Scholar
Dantzig, A. H., Shepard, R. L., Cao, J., Law, K. L., Ehlhardt, W. J., Baughman, T. M., Bumol, T. F., and Starling, J. J., 1996, Reversal of P-glycoprotein-mediated multidrug resistance by a potent cycloproyldibenzosuberane modulator, LY335979, Cancer Res.56:4171–4179. PubMedCAS Google Scholar
de Lannoy, I. A. M., and Silverman, M., 1992, The MDR1 product, P-glycoprotein, mediates the transport of the cardiac glycoside, digoxin, Biochem. Biophys. Res. Commun.189:551–557. PubMed Google Scholar
Deuchars, K. L., Duthie, M., and Ling, V., 1992, Identification of distinct P-glycoprotein gene sequences in rat, Biochim. Biophys. Acta1130:157–165. PubMedCAS Google Scholar
Devault, A., and Gros, P., 1990, Two members of the mouse mdr gene family confer multidrug resistance with overlapping but distinct drug specificities, Mol. Cell. Biol.10:1652–1663. PubMedCAS Google Scholar
Doige, C. A., and Sharom, F. J., 1992, Transport properties of P-glycoprotein in plasma membrane vesicles from multidrug-resistant Chinese hamster ovary cells, Biochim. Biophys. Acta1109:161–171. PubMedCAS Google Scholar
Doige, C. A., Yu, X., and Sharom, F. J., 1992, ATPase activity of partially purified P-glycoprotein from multidrug-resistant Chinese hamster ovary cells, Biochim. Biophys. Acta1109:149–160. PubMedCAS Google Scholar
Doige, C. A., Yu, X., and Sharom, F. J., 1993, The effects of lipids and detergents on ATPase-active P-glycoprotein, Biochim. Biophys. Acta1146:65–72. PubMedCAS Google Scholar
Drion, N., Lemaire, M., Lefauconnier, J.-M., and Scherrmann, J.-M., 1996, Role of P-glycoprotein in the blood-brain transport of colchicine and vinblastine, J. Neurochem.67:1688–1693. PubMedCAS Google Scholar
Endicott, J. A., and Ling, V., 1989, The biochemistry of P-glycoprotein mediated multidrug resistance, Annu. Rev. Biochem.58:137–171. ArticlePubMedCAS Google Scholar
Ferry, D. R., Traunecker, H., and Kerr, D. J., 1996, Clinical trials of P-glycoprotein reversal in solid tumours, Eur. J. Cancer32A:1070–1081. PubMedCAS Google Scholar
Fisher, G. A., Lum, B. L., Hausdorff, J., and Sikic, B. I., 1996, Pharmacological considerations in the modulation of multidrug resistance, Eur. J. Cancer32A:1082–1088. PubMedCAS Google Scholar
Flens, M. J., Zaman, G. J. R., van der Valk, P., Izquierdo, M. A., Schroeijers, A. B., Scheffer, G. L., van der Groep, P., de Haas, M., Meijer, C. J. L. M., and Scheper, R. J., 1996, Tissue distribution of the multidrug resistance protein, Am. J. Pathol.148:1237–1247. PubMedCAS Google Scholar
Fojo, A. T., Ueda, K., Slamon, D. J., Poplack, D. G., Gottesman, M. M., and Pastan, I., 1987, Expression of a multidrug-resistance gene in human tumors and tissues, Proc. Natl. Acad. Sci. USA84:265–269. PubMedCAS Google Scholar
Ford, J. M., 1996, Experimental reversal of P-glycoprotein-mediated multidrug resistance by pharmacological chemosensitizers, Eur. J. Cancer32A:991–1001. PubMedCAS Google Scholar
Ford, J. M., and Hait, W. N., 1990, Pharmacology of drugs that alter multidrug resistance in cancer, Pharmacol. Rev.42:155–199. PubMedCAS Google Scholar
Gan, L.-S. L., Moseley, A., Khosla, B., Augustijns, P. F., Bradshaw, T. P., Hendren, R. W., and Thakker, D. R., 1996, CYP3A-like cytochrome P450-mediated metabolism and polarized efflux of cyclosporin A in Caco-2 cells, Drug Metab. Dispos.24:344–349. PubMedCAS Google Scholar
Gant, T. W., Silverman, J. A., Bisgaard, H. C., Burt, R. K., Marino, P. A., and Thorgeirsson, S. S., 1991, Regulation of 2-acetylaminofluorene and 3-methylcholanthrene mediated induction of mdr and cytochrome P450IA gene family expression in primary hepatocyte cultures and rat liver, Mol. Carcin.4:499–509. CAS Google Scholar
Georges, E., Zhang, J.-T., and Ling, V., 1991, Modulation of ATP and drug binding by monoclonal antibodies against P-glycoprotein, J. Cell. Physiol.148:479–484. ArticlePubMedCAS Google Scholar
Georges, E., Tsuruo, T., and Ling, V., 1993, Topology of P-glycoprotein as determined by epitope mapping of MRK-16 monoclonal antibody, J. Biol. Chem.268:1792–1798. PubMedCAS Google Scholar
Germann, U. A., 1996, P-glycoprotein—A mediator of multidrug resistance in tumour cells, Eur. J. Cancer32A:927–944. PubMedCAS Google Scholar
Germann, U. A., Ford, P. J., Shlaykhter, D., Mason, V. S., and Harding, M. W., 1997a, Chemosensitization and drug accumulation effects of VX-710, verapamil, cyclosporin A, MS-209 and GF120918 in multidrug resistant HL60/ADR cells expressing the multidrug resistance-associated protein MRP, Anticancer Drugs8:141–155. PubMedCAS Google Scholar
Germann, U. A., Shlaykhter, D., Mason, V. S., Zelle, R. E., Duffy, J. P., Galullo, V., Armistead, D. M., Saunders, J. O., Boger, J., and Harding, M. W., 1997b, Cellular and biochemical characterization of VX-710 as an chemosensitizer: Reversal of P-glycoprotein mediated multidrug resistance in vitro, Anticancer Drugs8:125–140. PubMedCAS Google Scholar
Goldstein, L. J., 1996, MDR1 gene expression in solid tumors, Eur. J. Cancer32A:1039–1050. PubMedCAS Google Scholar
Goldstein, L. J., Galski, H., Fojo, A. T., Willingham, M., Lai, S.-L., Gazdar, A., Pirker, R., Green, A., Crist, W., Brodeur, G. M., Lieber, M., Cossman, J., Gottesman, M. M., and Pastan, I., 1989, Expression of a multidrug resistance gene in human cancers, J. Natl. Cancer Inst.81:116–124. PubMedCAS Google Scholar
Gottesman, M. M., and Pastan, I., 1993, Biochemistry of multidrug resistance mediated by the multidrug transporter, Annu. Rev. Biochem.62:385–427. ArticlePubMedCAS Google Scholar
Grant, C. E., Valdimarsson, G., Hipfner, D. R., Almquist, K. C., Cole, S. P. C., and Deeley, R. G., 1994, Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs, Cancer Res.54:357–361. PubMedCAS Google Scholar
Greenberger, L. M., 1993, Major photoaffinity drug labeling sites for iodaryl azidoprazosin in P-glycoprotein are within or immediately C-terminal to transmembrane domains 6 and 12, J. Biol. Chem.268:11417–11425. PubMedCAS Google Scholar
Griffiths, N. M., Hirst, B. H., and Simmons, N. L., 1994, Active intestinal secretion of the fluorquinolone antibacterials ciprofloxacin, norfloxacin and pefloxacin; a common secretory pathway? J. Pharmacol. Exp. Ther.269:496–502. PubMedCAS Google Scholar
Gros, P., Ben-Neriah, Y., Croop, J. M., and Housman, D. E., 1986a, Isolation and expression of a complementary DNA that confers multidrug resistance, Nature323:728–731. ArticlePubMedCAS Google Scholar
Gros, P., Croop, J., and Housman, D., 1986b, Mammalian multidrug resistance gene: Complete cDNA sequence indicates strong homology to bacterial transport proteins, Cell47:37l–380. Article Google Scholar
Gros, P., Croop, J., Roninson, I., Varshavsky, A., and Housman, D. E., 1986c, Isolation and characterization of DNA sequences amplified in multidrug-resistant hamster cells, Proc. Natl. Acad. Sci. USA83:337–341. PubMedCAS Google Scholar
Gros, P., Raymond, M., Bell, J., and Housman, D., 1988, Cloning and characterization of a second member of the mouse mdr gene family, Mol. Cell. Biol.8:2770–2778. PubMedCAS Google Scholar
Guild, B. C., Mulligan, R. C., Gros, P., and Housman, D. E., 1988, Retroviral transfer of a murine cDNA for multidrug resistance confers pleiotropic drug resistance to cells without prior drug selection, Proc. Natl. Acad. Sci. USA85:1595–1599. PubMedCAS Google Scholar
Hamada, H., and Tsuruo, T., 1988, Purification of the 170–180 kilodalton membrane glycoprotein associated with multidrug resistance, J. Biol. Chem.263:1454–1458. PubMedCAS Google Scholar
Hammond, J. R., Johnstone, R. M., and Gros, P., 1989, Enhanced efflux of 3-H-vinblastine from Chinese hamster ovary cells transfected with full length complementary DNA clone for the MDR1 gene, Cancer Res.49:3867–3871. PubMedCAS Google Scholar
Hidalgo, I. J., Raub, T. J., and Borchardt, R. T., 1989, Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability, Gastroenterology96:736–749. PubMedCAS Google Scholar
Higgins, C. F., 1992, ABC transporters: From microorganisms to man, Annu. Rev. Cell Biol.8:67–113. ArticlePubMedCAS Google Scholar
Hill, B. A., Brown, P. C., Preisegger, K.-H., and Silverman, J. A., 1996, Regulation of mdr1b gene expression in Fischer, Wistar and Sprague-Dawley rats in vivo and in vitro, Carcinogenesis.17:451–457. PubMedCAS Google Scholar
Horio, M., Pastan, I., Gottesman, M. M., and Handler, J. S., 1990, Transepithelial transport of vinblastine by kidney-derived cell lines. Application of a new kinetic model to estimate in situ K m of the pump, Biochim. Biophys. Acta1027:116–122. PubMedCAS Google Scholar
Hunter, J., Hirst, B. H., and Simmons, N. L., 1991, Epithelial secretion of vinblastine by human intestinal adenocarcinoma cell (HCT-8 and T84) layers expressing P-glycoprotein, Br. J. Cancer64:437–444. PubMedCAS Google Scholar
Hunter, J., Hirst, B. H., and Simmons, N. L., 1993, Drug absorption limited by P-glycoprotein-mediated secretory drug transport in human intestinal epithelial Caco-2 cell layers, Pharmaceut. Res.10:743–749. ArticleCAS Google Scholar
Huwyler, J., Drewe, J., Klusemann, C., and Fricker, G., 1996, Evidence for P-glycoprotein-modulated penetration of morphine-6-glucuronide into brain capillary endothelium, Br. J. Pharmacol.118:1879–1885. PubMedCAS Google Scholar
Hyafil, F., Vergely, C., Du Vignaud, P., and Grand-Perret, T., 1993, In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative, Cancer Res.53:4595–4602. PubMedCAS Google Scholar
Ito, K., Suzuki, H., Hirohashi, T., Kume, K., Shimizu, T., and Sugiyama, Y., 1997, Molecular cloning of canalicular multispecific organic anion transporter defective in EHBR, Am. J. Physiol.272:G16–G22. PubMedCAS Google Scholar
Izquierdo, M. A., Scheffer, G. L., Flens, M. J., Giaccone, G., Broxterman, H. J., Meijer, C. J. L. M., van der Valk, P., and Scheper, R. J., 1996a, Broad distribution of the multidrug resistance related vault lung resistance protein in normal human tissues and tumors, Am. J. Pathol.148:877–887. PubMedCAS Google Scholar
Izquierdo, M. A., Scheffer, G. L., Flens, M. J., Schroeijers, A. B., van der Valk, P., and Scheper, R. J., 1996b, Major vault protein LRP-related multidrug resistance, Eur. J. Cancer.32A:979–984. PubMedCAS Google Scholar
Jedlitschky, G., Leier, I., Buchholz, U., Center, M., and Keppler, D., 1994, ATP-dependent transport of glutathione S-conjugates by the multidrug resistance-associated protein, Cancer Res.54:4833–4836. PubMedCAS Google Scholar
Jetté, L., Murphy, G. F., Leclerc, J.-M., and Beliveau, R., 1995, Interaction of drugs with P-glycoprotein in brain capillaries, Biochem. Pharmacol.50:1701–1709. PubMed Google Scholar
Juliano, R. L., and Ling, V., 1976, A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants, Biochim. Biophys. Acta455:152–162. PubMedCAS Google Scholar
Juranka, P. F., Zastawny, R. L., and Ling, V., 1989, P-glycoprotein: Multidrug-resistance and a superfamily of membrane-associated transport proteins, FASEB J.3:2583–2592. PubMedCAS Google Scholar
Kanamaru, H., Kakehi, Y., Yoshida, O., Nakanishi, S., Pastan, I., and Gottesman, M. M., 1989, MDR1 RNA levels in human renal cell carcinomas: Correlation with grade and prediction of reversal of doxorubicin resistance by quinidine in tumor explants, J. Natl. Cancer Inst.81:844–849. PubMedCAS Google Scholar
Karlsson, J., Kuo, S.-M., Ziemniak, J., and Artursson, P., 1993, Transport of celiprolol across human intestinal epithelial (Caco-2) cells: Mediation of secretion by multiple transporters including P-glycoprotein, Br. J. Pharmacol.110:1009–1016. PubMedCAS Google Scholar
Kartner, N., Riordan, J. R., and Ling, V., 1983, Cell surface P-glycoprotein associated with multidrug resistance in mammalian cell lines, Science221:1285–1288. PubMedCAS Google Scholar
Kartner, N., Evernden-Porelle, D., Bradley, G., and Ling, V., 1985, Detection of P-glycoprotein in multidrug resistant cell lines by monoclonal antibodies, Nature316:820–823. ArticlePubMedCAS Google Scholar
Keller, R. P., Altermatt, H. J., Nooter, K., Poschmann, G., Laissue, J. A., Bollinger, P., and Hiestand, P. C., 1992, SDZ PSC833, a non-immunosuppressive cyclosporine: Its potency in overcoming P-glycoprotein-mediated multidrug resistance of murine leukemia, Int. J. Cancer50:593–597. PubMedCAS Google Scholar
Kelly, R., and Smith, T. W., 1996, Pharmacological treatment of heart failure, in: Goodman and Gilman’s The Pharmacological Basis of Therapeutics (J. G. Hardman, L. E. Limbird, P. B. Molinoff, R. W. Ruddon, and A. G. Gilman eds.), McGraw-Hill, New York, pp. 809–838. Google Scholar
Kohno, K., Sato, S.-., Takano, H., Matsuo, K.-i., and Kuwano, M., 1989, The direct activation of human multidrug resistance gene by anticancer agents, Biochem. Biophys. Res. Commun.164:1415–1421. Google Scholar
Kool, M., de Haas, M., Scheffer, G. L., Scheper, R. J., van Eijk, M. J. T., Juijn, J. A., Baas. F., and Borst, P., 1997, Analysis of expression of cMOAT (MRP2), MRP3, MRP4, MRP5 homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines, Cancer Res.57:3537–3547. PubMedCAS Google Scholar
Krishnamachary, N., and Center, M. S., 1993, The MRP gene associated with a non-P-glycoprotein multidrug resistance encodes a 190-kDa membrane bound glycoprotein, Cancer Res.53:3658–3661. PubMedCAS Google Scholar
Kruh, G. D., Chan, A., Myers, K., Gaughan, K., Miki, T., and Aaronson, S. A., 1994, Expression complementary DNA library transfer establishes mrp as a multidrug resistance gene, Cancer Res.54:1649–1652. PubMedCAS Google Scholar
Lai, S.-L., Goldstein, L. J., Gottesman, M. M., Pastan, I., Tsai, C.-M., Johnson, B. E., Muslshine, J. L., Ihde, D. C., Kayser, K., and Gazdar, A. F., 1989, MDR1 gene expression in lung cancer, J. Natl. Cancer Inst.81:1144–1150. PubMedCAS Google Scholar
Leu, B.-L., and Huang, J.-d., 1995, Inhibition of intestinal P-glycoprotein and effects on etoposide absorption, Cancer Chemother. Pharmacol.35:432–436. ArticlePubMedCAS Google Scholar
Loe, D. W., Almquist, K. C., Cole, S. P. C., and Deeley, R. G., 1996a, ATP-dependent 17□-estradiol 17-(□-d-glucuronide) transport by multidrug resistance protein (MRP), J. Biol. Chem.271:9683–9689. ArticlePubMedCAS Google Scholar
Loe, D. W., Deeley, R. G., and Cole, S. P. C., 1996b, Biology of the multidrug resistance-associated protein, MRP, Eur. J. Cancer32A:945–957. PubMedCAS Google Scholar
Loo, T. W., and Clarke, D. M., 1993, Functional consequences of phenylalanine mutations in the predicted transmembrane domain p-glycoprotein, J. Biol. Chem.268:19965–19972. PubMedCAS Google Scholar
Loo, T. W., and Clarke, D. M., 1995, Membrane topology of a cysteine-less mutant of human P-glycoprotein, J. Biol. Chem.270:843–848. ArticlePubMedCAS Google Scholar
Lum, B. L., Kaubisch, S., Yahanda, A. M., Adler, K. M., Jew, L., Ehsan, M. N., Brophy, N. A., Halsey, J., Gosland, M. P., and Sikic, B. I., 1992, Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase I trial to modulate multidrug resistance, J. Clin. Oncol.10:1635–1642. PubMedCAS Google Scholar
Lum, B. L., Gisher, G. A., Brophy, N. A., Yahanda, A. M., Adler, K. M., Kaubisch, S., Halsey, J., and Sikic, B. I., 1993, Clincal trials of modulation of multidrug resistance, Cancer (Suppl.) 72:3502–3514. PubMedCAS Google Scholar
Mauad, T. H., van Nieuwkerk, C. M. J., Dingemans, K. P., Smit, J. J. M., Schinkel, A. H., Notenboom, R. G. E., van den Bergh Weerman, M. A., Verkruisen, R. P., Groen, A. K., Oude Elferink, R. P. J., Borst, P., and Offerhaus, G. J. A., 1994, Mice with homozygous disruption of the mdr2 P-glycoprotein gene: A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis, Am. J. Pathol.145:1237–1245. PubMedCAS Google Scholar
Mayer, U., Wagenaar, E., Beijnen, J. H., Smit, J. W., Meijer, D. K. F., van Asperen, J., Borst, P., and Schinkel, A. H., 1996, Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr1a P-glycoprotein, Br. J. Pharmacol.119:1038–1044. PubMedCAS Google Scholar
Morrow, C. S., Nakagawa, M., Goldsmith, M. E., Madden, M. J., and Cowan, K. H., 1994, Reversible transcription activation of mdr1 by sodium butyrate treatment of human colon cancer cells, J. Biol. Chem.269:10739–10746. PubMedCAS Google Scholar
Müller, M., Meijer, C., Zaman, G. J. R., Borst, P., Scheper, R. J., Mulder, N. H., de Vries, E. G. E., and Jansen, P. L. M., 1994, Overexpression of the gene encoding the multidrug resistance-associated protein results in increased ATP-dependent glutathione S-conjugate transport, Proc. Natl. Acad. Sci. USA91:13033–13037. PubMed Google Scholar
Müller, M., de Vries, E. G. E., and Jansen, P. L. M., 1996a, Role of the multidrug resistance protein (MRP) in glutathione S-conjugate transport in mammalian cells, J. Hepatol.24:100–108. PubMed Google Scholar
Müller, M., Roelofsen, H., and Jansen, P. L. M., 1996b, Secretion of organic anions by hepatocytes: Involvement of homologues of the multidrug resistance protein, Sem. Liver Dis.16:211–220. Google Scholar
Nakatsukasa, H., Silverman, J. A., Gant, T. W., Evarts, R. P., and Thorgeirsson, S. S., 1993, Expression of multidrug resistance genes in rat liver during regeneration and after carbon tetrachloride intoxication, Hepatology18:1202–1207. ArticlePubMedCAS Google Scholar
Nerurkar, M. M., Burton, P. S., and Borchardt, R. T., 1996, The use of surfactants to enhance the permeability of peptides through Caco-2 cells by inhibition of an apically polarized efflux system, Pharmaceut. Res.13:528–534. ArticleCAS Google Scholar
Ng, W. F., Sarangi, F., Zastawny, R. L., Veniot-Drebot, L., and Ling, V., 1989, Identification of members of the P-glycoprotein multigene family, Mol. Cell. Biol.9:1224–1232. PubMedCAS Google Scholar
Nogae, I., Kohno, K., Kikuchi, J., Kuwano, M., Akiyama, S.-I., Kiue, A., Suzuki, K.-I., Yoshida, Y., Cornwell, M. M., Pastan, I., and Gottesman, M. M., 1989, Analysis of structural features of dihydropyridine analogs needed to reverse multidrug resistance and to inhibit photoaffinity labelling of P-glycoprotein, Biochem. Pharmacol.38:519–527. PubMedCAS Google Scholar
Oude Elferink, R. P. J., and Groen, A. K., 1995, The role of mdr2 P-glycoprotein in biliary lipid secretion. Cross-talk between cancer research and biliary physiology, J. Hepatol.23:617–625. ArticlePubMedCAS Google Scholar
Pastan, I., Gottesman, M. M., Ueda, K., Lovelace, E., Rutherford, A. V., and Willingham, M. C., 1988, A retrovirus carrying an MDR1 cDNA confers multidrug resistance and polarized expression of P-glycoprotein in MDCK cells, Proc. Natl. Acad. Sci. USA85:4486–4490. PubMedCAS Google Scholar
Paul, S., Breuninger, L. M., Tew, K. D., Shen, H., and Kruh, G. D., 1996, ATP-dependent uptake of natural product cytotoxic drugs by membrane vesicles establishes MRP as a broad specificity transporter, Proc. Natl. Acad. Sci. USA93:6929–6934. ArticlePubMedCAS Google Scholar
Paulusma, C. C., Bosma, P. J., Zaman, G. J. R., Bakker, C. T. M., Otter, M., Scheffer, G. L., Scheper, R. J., Borst, P., and Oude Elferink, R. P. J., 1996, Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene, Science271:1126–1128. PubMedCAS Google Scholar
Rabbaa, L., Dautrey, S., Colas-Linhart, N., Carbon, C., and Farinotti, R., 1996, Intestinal elimination of ofloxacin entantiomers in the rat: Evidence of a carrier-mediated process, Antimicrob. Agents Chemother.40:2126–2130. PubMedCAS Google Scholar
Relling, M. V., 1996, Are the major effects of P-glycoprotein modulators due to altered pharmacokinetics of anticancer drugs? Ther. Drug Monit.18:350–356. ArticlePubMedCAS Google Scholar
Riordan, J. R., Deuchars, K., Kartner, N., Alon, N., Trent, J., and Ling, V., 1985, Amplification of P-glycoprotein genes in multidrug-resistant cell mammalian cell lines, Nature316:817–819. ArticlePubMedCAS Google Scholar
Rome, L. H., Kedersha, N. L., and Chungai, D. C., 1991, Unlocking vaults: Organelles in search of a function, Trends Cell Biol.1:47–50. ArticlePubMedCAS Google Scholar
Roninson, I. B., Chin, J. E., Choi, K., Gros, P., Housman, D. E., Fojo, A., Shen, D.-W., Gottesman, M. M., and Pastan, I., 1986, Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells, Proc. Natl. Acad. Sci. USA83:4538–4542. PubMedCAS Google Scholar
Rosenberg, M. F., Callaghan, R., Ford, R. C., and Higgins, C. F., 1997, Structure of the multidrug resistance P-glycoprotein to 2.5 nm resolution determined by electron microscopy and image analysis, J. Biol. Chem.272:10685–10694. ArticlePubMedCAS Google Scholar
Ruetz, S., and Gros, P., 1994, Phosphotidylcholine translocase: A physiological role for the mdr2 gene, Cell77:1071–1081. ArticlePubMedCAS Google Scholar
Ruetz, S., and Gros, P., 1995, Enhancement of Mdr2-mediated phosphotidylcholine translocation by the bile salt taurocholate, J. Biol. Chem.270:25388–25395. PubMedCAS Google Scholar
Ruetz, S., Brault, M., Kast, C., Hemenway, C., Heitman, J., Grant, C. E., Cole, S. P. C., Deeley, R. G., and Gros, P., 1996, Functional expression of the multidrug resistance-associated protein in the yeast Saccharomyces cerevisiae, J. Biol. Chem.271:4154–4160. PubMedCAS Google Scholar
Saeki, T., Ueda, K., Tanigawara, Y., Hori, R., and Komano, T., 1993, Human P-glycoprotein transports cyclosporin A and FK506, J. Biol. Chem.268:6077–6080. PubMedCAS Google Scholar
Scheffer, G. L., Wijngaard, P. L. J., Flens, M. J., Izquierdo, M. A., Slovak, M. L., Pinedo, H. M., Meijer, C. J. L. M., Clevers, H. C., and Scheper, R. J., 1995, The drug resistance-related protein LRP is the human major vault protein, Nature Med.1:578–582. PubMedCAS Google Scholar
Scheper, R. J., Broxterman, H. J., Scheffer, G. L., Kaaijk, P., Dalton, W. S., van Heijningen, T. H. M., van Kalken, C. K., Slovak, M. L., de Vries, E. G. E., van der Valk, P., Meijer, C. J. L. M., and Pindeo, H. M., 1993, Overexpression of a Mr 110,000 vesicular protein in non-P-glycoprotein-mediated multidrug resistance, Cancer Res.53:1475–1479. PubMedCAS Google Scholar
Schinkel, A. H., Roelofs, M. E. M., and Borst, P., 1991, Characterization of the human MDR3 P-glycoprotein and its recognition by P-glycoprotein-specific monoclonal antibodies, Cancer Res.51:2628–2635. PubMedCAS Google Scholar
Schinkel, A. H., Smit, J. J. M., van Tellingen, O., Beijnen, J. H., Wagenaar, E., van Deemter, L., Mol, C. A. A. M., van der Valk, M. A., Robanus-Maandag, E. C., te Riele, H. P. J., Berns, A. J. M., and Borst, P., 1994, Disruption of the mouse mdrla P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs, Cell77:491–502. ArticlePubMedCAS Google Scholar
Schinkel, A. H., Wagenaar, E., van Deemter, L., Mol, C. A. A. M., and Borst, P., 1995, Absence of the mdr1a P-glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin and cyclosporine A, J. Clin. Invest.96:1698–1705. ArticlePubMedCAS Google Scholar
Schinkel, A. H., Wagenaar, E., Mol, C. A. A. M., and van Deemter, L., 1996, P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs, J. Clin. Invest.97:2517–2524. PubMedCAS Google Scholar
Schinkel, A. H., Mayer, U., Wagenaar, E., Mol, C. A. A. M., van Deemter, L., Smit, J. J. M., van der Valk, M. A., Voordouw, A. C., Spits, H., van Tellingen, O., Zijlmans, J. M. J. M., Fibbe, W. E., and Borst, P., 1997, Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug transporting) P-glycoproteins, Proc. Natl. Acad. Sci. USA94:4028–4033. ArticlePubMedCAS Google Scholar
Schrenk, D., Gant, T. W., Preisegger, K.-H., Silverman, J. A., Marino, P., and Thorgeirsson, S. S., 1993, Induction of multidrug resistance gene expression during cholestasis in rats and nonhuman primates, Hepatology17:854–860. ArticlePubMedCAS Google Scholar
Schuetz, E. G., Beck, W. T., and Schuetz, J. D., 1996a, Modulators and substrates of P-glycoprotein and cytochrome p4503A coordinately up-regulate these proteins in human colon carcinoma cells, Mol. Pharmacol.49:311–318. PubMedCAS Google Scholar
Schuetz, E. G., Schinkel, A. H., Relling, M. V., and Schuetz, J. D., 1996b, P-glycoprotein: A major determinant of rifampicin-inducible expression of cytochrome P4503A in mice and humans, Proc. Natl. Acad. Sci. USA93:4001–4005. ArticlePubMedCAS Google Scholar
Shapiro, A. B., and Ling, V., 1994, ATPase activity of purified and reconstituted P-glycoprotein from chinese hamster ovary cells, J. Biol. Chem.269:3745–3754. PubMedCAS Google Scholar
Sharom, F. J., Yu, X., and Doige, C. A., 1993, Functional reconstitution of drug transport and ATPase activity in proteoliposomes containing partially purified P-glycoprotein, J. Biol. Chem.268:24197–24202. PubMedCAS Google Scholar
Sharom, F. J., Yu, X., Chu, J. W. K., and Doige, C. A., 1995, Characterization of the ATPase activity of P-glycoprotein from multidrug-resistant Chinese hamster ovary cells, Biochem. J.308:38l–390. Google Scholar
Shen, D.-W., Cardarelli, C., Hwang, J., Cornwell, M. M., Richert, N., Ishi, S., Pastan, I., and Gottesman, M. M., 1986, Multiple drug resistant human KB carcinoma cells independantly selected for high-level resistance to colchicine, adriamycin or vinblastine show changes in expression of specific proteins, J. Biol. Chem.261:7762–7770. PubMedCAS Google Scholar
Silverman, J. A., and Schrenk, D., 1997, Expression of the multidrug resistance genes in the liver, FASEB J.11:308–313. PubMedCAS Google Scholar
Silverman, J. A., Raunio, H., Gant, T. W., and Thorgeirsson, S. S., 1991, Cloning and characterization of a member of the rat multidrug resistance (mdr) gene family, Gene106:229–236. ArticlePubMedCAS Google Scholar
Smit, J. J. M., Schinkel, A. H., Oude Elferink, R. P. J., Groen, A. K., Wagenaar, E., van Deemter, L., Mol, C. A. A. M., Ottenhoff, R., van der Lugt, N. M. T., van der Valk, M. A., van Roon, M. A., Offerhaus, G. J. A., Berns, A. J. M., and Borst, P., 1993, Homozygous disruption of the murine mdr2 p-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease, Cell75:451–462. ArticlePubMedCAS Google Scholar
Smit, J. J. M., Schinkel, A. H., Mol, C. A. A. M., Majoor, D., Mooi, W. J., Jongsma, A. P. M., Lincke, C. R., and Borst, P., 1994, Tissue distribution of the human MDR3 P-glycoprotein, Lab. Invest.71:638–649. PubMedCAS Google Scholar
Smith, A. J., Timmermans-Hereijgers, J. L. P. M., Roelofsen, B., Wirtz, K. W. A., van Blitterswijk, W. J., Smit, J. J. M., Schinkel, A. H., and Borst, P., 1994, The human MDR3 P-glycoprotein promotes translocation of phosphotidylcholine through the plasma membrane of fibroblasts from transgenic mice, FEBS Lett.354:263–266. ArticlePubMedCAS Google Scholar
Sparreboom, A., van Asperen, J., Mayer, U., Schinkel, A. H., Smit, J. W., Meijer, D. K. F., Borst, P., Nooijen, W. J., Beijnen, J. H., and van Tellingen, O., 1997, Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine, Proc. Natl. Acad. Sci. USA94:2031–2035. ArticlePubMedCAS Google Scholar
Stewart, A. J., Canitrot, Y., Baracchini, E., Dean, N. M., and Deely, R. G., 1996, Reduction of expression of the multidrug resistance protein, MRP, in human tumor cells by antisense phophorothioate oligonuclotides, Biochem. Pharmacol.51:461–469. ArticlePubMedCAS Google Scholar
Su, S.-F., and Huang, J.-D., 1996, Inhibition of the intestinal digoxin absorption and exsorption by quinidine, Drug Metab. Dispos.24:142–147. PubMedCAS Google Scholar
Tanaka, K., Hirai, M., Tanigawara, Y., Ueda, K., Takano, M., Hori, R., and Inui, K.-I., 1997, Relationship between expression level of P-glycoprotein and daunorubicin transport in LLC-PK1 cells transfected with human MDR1 gene, Biochem. Pharmacol.53:741–746. ArticlePubMedCAS Google Scholar
Tanigawara, Y., Okamura, N., Hirai, M., Yasuhara, M., Ueda, K., Kioka, N., Komano, T., and Hori, R., 1992, Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1), J. Pharmacol. Exp. Ther.263:840–845. PubMedCAS Google Scholar
Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M. M., Pastan, I., and Willingham, M. C., 1987, Cellular localization of the multidrug resistance gene product P-glycoprotein in normal human tissues, Proc. Natl. Acad. Sci. USA84:7735–7738. PubMedCAS Google Scholar
Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M. M., Pastan, I., and Willingham, M. C., 1989, Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: Evidence for localization in brain capillaries and crossreactivity on one antibody with a muscle protein, J. Histochem. Cytochem.37:159–164. PubMedCAS Google Scholar
Thorgeirsson, S. S., Huber, B. E., Sorrell, S., Fojo, A. T., Pastan, I., and Gottesman, M. M., 1987, Expression of the multidrug-resistance gene in hepatocarcinogenesis and regenerating rat liver, Science236:1120–1122. PubMedCAS Google Scholar
Tsuruo, T., Iida, H., Tsukagoshi, S., and Sakurai, Y., 1981, Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil, Cancer Res, 41:1967–1972. PubMedCAS Google Scholar
Twentyman, P. R., 1992, Cyclosporins as drug resistance modifiers, Biochem. Pharmacol.43:109–117. ArticlePubMedCAS Google Scholar
Twentyman, P. R., and Versantvoort, C. H. M., 1996, Experimental modulation of MRP (multidrug resistance-associated protein)-mediated resistance, Eur. J. Cancer32A: 1002–1009. PubMedCAS Google Scholar
Ueda, K., Cardarelli, C., Gottesman, M. M., and Pastan, I., 1987a, Expression of a full length cDNA for the human “MDR1” gene confers resistance to colchicine, doxorubicin and vinblastine, Proc. Natl. Acad. Sci. USA84:3004–3008. PubMedCAS Google Scholar
Ueda, K., Clark, D. P., Chen, C.-J., Roninson, I. B., Gottesman, M. M., and Pastan, I., 1987b, The human multidrug resistance (mdr1) gene: cDNA cloning and transcription initiation, J. Biol. Chem.262:505–508. PubMedCAS Google Scholar
van Asperen, J., Schinkel, A. H., Beijnen, J. H., Nooijen, W. J., Borst, P., and van Tellingen, O., 1996, Altered pharmacokinetics of vinblastine in mdr1a P-glycoprotein-deficient mice, J. Natl. Cancer Inst.88:994–999. PubMed Google Scholar
van Asperen, J., van Tellingen, O., Sparreboom. A., Schinkel, A. H., Borst, P., Nooijen, W. J., and Beijnen, J. H., 1997, Enhanced oral bioavailability of paclitaxel in mice treated with the P-glycoprotein blockers SDZ PSC 833 or cyclosporin A, Proc. Am. Assoc. Cancer Res.38:5. Google Scholar
van der Bliek, A. M., Baas, F., Ten Houte de Lange, T., Kooiman, P. M., van der Velde-Koerts, T., and Borst, P., 1987, The human mdr3 gene encodes a novel P-glycoprotein homologue and gives rise to alternatively spliced mRNAs in liver, EMBO J.6:3325–3331. PubMed Google Scholar
van der Bliek, A. M., Kooiman, P. M., Schneider, C., and Borst, P., 1988, Sequence of mdr3 cDNA encoding a human p-glycoprotein, Gene71:401–411. PubMed Google Scholar
van de Vrie, W., Gheuens, E. E., Durante, N. M., De Bruijn, E. A., Marquet, R. L., van Oosterom, A. T., and Eggermont, A. M., 1993, In vitro and in vivo chemosensitizing effect of cyclosporin A on an intrinsic multidrug-resistant rat colon tumour, J. Cancer Res. Clin. Oncol.119:609–614. ArticlePubMed Google Scholar
van de Vrie, W., Jonker, A. M., Marquet, R. L., and Eggermont, A. M. M., 1994, The chemosensitizer cyclosporin A enhances the toxic side-effects of doxorubicin in the rat, J. Cancer Res. Clin. Oncol.120:533–538. ArticlePubMed Google Scholar
van Kalken, C. K., Giaccone, G., van der Valk, P., Kuiper, C. M., Hadisaputro, M. M. N., Bosma, S. A. A., Scheper, R. J., Meijer, C. J. L. M., and Pinedo, H. M., 1992, Multidrug resistance gene (P-glycoprotein) expression in the human fetus, Am. J. Pathol.141:1063–1072. PubMed Google Scholar
Wacher, V. J., Wu, C.-Y., and Benet, L. Z., 1995, Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: Implications for drug delivery and activity in cancer chemotherapy, Mol. Carcin.13:129–134. CAS Google Scholar
Wacher, V. J., Salphati, L., and Benet, L. Z., 1996, Active secretion and enterocytic drug metabolism barriers to drug absorption, Adv. Drug Deliv. Rev.20:99–112. ArticleCAS Google Scholar
Yang, C.-P. H., Cohen, D., Greenberger, L. M., Hsu, S. I.-H., and Horwitz, S. B., 1990, Differential transport of two mdr gene products are distiguished by progesterone, J. Biol. Chem.265:10282–10288. PubMedCAS Google Scholar
Yoshimura, A., Kuwazuru, Y., Sumizawa, T., Ichikawa, M., Ikeda, S.-I., Uda, T., and Akiyama, S.-I., 1989, Cytoplasmic orientation and two-domain structure of the multidrug transporter, P-glycoprotein, demonstrated with sequence-specific antibodies, J. Biol. Chem.264:16282–16291. PubMedCAS Google Scholar
Zacherl, J., Hamilton, G., Thalhammer, T., Riegler, M., Cosentini, E. P., Ellinger, A., Bischof, G., Schweitzer, M., Teleky, B., Koperna, T., and Wenzl, E., 1994, Inhibition of P-glycoprotein-mediated vinblastine transport across HCT-8 intestinal carcinoma monolayers by verapamil, cyclosporine A and SDZ PSC 833 in dependence on extra cellular pH, Cancer Chemother. Pharmacol.34:125–132. ArticlePubMedCAS Google Scholar
Zaman, G. J. R., Versantvoort, C. H. M., Smit, J. J. M., Eijdems, E. W. H. M., de Haas, M., Smith, A. J., Broxterman, H. J., Mulder, N. H., de Vries, E. G. E., Baas, F., and Borst, P., 1993, Analysis of the expression of MRP, the gene for a new putative transmembrane drug transporter, in human multidrug resistant lung cancer cell lines, Cancer Res.53:1747–1750. PubMedCAS Google Scholar
Zaman, G. J. R., Flens, M. J., van Leusden, M. R., de Haas, M., Mülder, H. S., Lankelma, J., Pindeo, H. M., Scheper, R. J., Baas, F., Broxterman, H. J., and Borst, P., 1994, The human multidrug resistance-associated protein MRP is a plasma membrane drug-efflux pump, Proc. Natl. Acad. Sci. USA91:8822–8826. PubMedCAS Google Scholar
Zaman, G. J. R., Lankelma, J., van Tellingen, O., Beijnen, J., Dekker, H., Paulusma, C., Oude Elferink, R. P. J., Baas, F., and Borst, P., 1995, Role of glutathione in the export of compounds from cells by the multidrug-resistance-associated protein, Proc. Natl. Acad. Sci. USA92:7690–7694. PubMedCAS Google Scholar
Zhang, J.-T., and Ling, V., 1991, Study of membrane orientation and glycosylated extracellular loops of mouse P-glycoprotein by in vitro translation, J. Biol. Chem.266: 18224–18232. PubMedCAS Google Scholar
Zhou, D. C., Simonin, G., Faussat, A. M., Zittoun, R., and Marie, J. P., 1997, Effect of the multidrug inhibitor GG918 on drug sensitivity of human leukemic cells, Leukemia11:1516–1522. ArticlePubMedCAS Google Scholar