Multidrug resistant tumours

Bennis, S. Chapey, C. Couvreur, P. Robert, J. Enhanced cytotoxicity of doxorubicin encapsulated in polyiso-hexylcyanoacrylate nanospheres against multidrug-resistant tumour cells in culture. Eur. J. Cancer 1994, 1, 89-93. 

An established and clinically important interaction. Ciclosporin alters the pharmacokinetics of the anthracyclines resulting in increased serum levels. This pharmacokinetic interaction has complicated study into the value of using ciclosporin to modulate multidrug resistance in tumours and thereby improve the response to chemotherapy. In the case of anthracyclines and etoposide , (p.630), any benefit could just be attributed to dose intensification. Consequently, some have suggested reducing the dose of the anthracycline. The use of high-dose ciclosporin for multidrug resistant tumour modulation remains experimental and should only be used in clinical studies. Concurrent use should be very well monitored. More study is needed to find out the possible effects of low-dose ciclosporin. 

Except for its narrow specificity, the ATRI gene product shares a number of properties with the higher eukaryotic MDR proteins responsible for multidrug resistance in tumour cells. The MDR gene products are also transmembrane proteins which seem to function as ATP-dependent drug-efflux pumps pumping out a variety of structurally unrelated compounds (see [25,26]). 

Merrit JE, Sullivan JA, Drew L, Khan A, Wilson K, Mulqueen M, Harris W, Bradshaw D, Hill CH, Rumsby M, Warr R (1999) The bisindolylmaleimide protein kinase C inhibitor, Ro 32-2241, reverses multidrug resistance in KB tumour cells. Cancer Chemother Pharmacol 43 371-378... 

Germann UA. P-glycoprotein-a mediator of multidrug resistance in tumour cells. Eur J Cancer 1996 32A(6) 927-944. 

Kaye SB. Multidrug resistance clinical relevance in solid tumours and strategies for circumvention. Curr Opin Oncol 1998 10(suppl 1) S15-S19. 

Wishart GC, Plumb JA, Morrison JG, et al. Adequate tumour quinidine levels for multidrug resistance modulation can be achieved in vivo. Eur J Cancer 1992 28 (1) 28—31. 

Broxterman, H. J., Lankelma, J., and Pinedo, H. M. (1996) How to probe clinical tumour samples for P-glycoprotein and multidrug resistance-associated protein. Eur. J. Cancer 32A, 1024-1033. 

Laurand, A. Laroche-Clary, A. Larrue, A. Huet, S. Soma, E. Bonnet, J. Robert, J. Quantification of the expression of multidrug resistance-related genes in human tumour ceU lines grown with free doxorubicin or doxorubicin encapsulated in polyisohexylcyanoacrylate nanospheres. Anticancer Res. 2004, 24, 3781-3788. 

Le, L.H., Moore, M.J., Siu, L.L., Oza, A.M., MacLean, M., Fisher, B. etal. (2005) Phase I study of the multidrug resistance inhibitor zosuquidar administered in combination with vinorelbine in patients with advanced solid tumours. Cancer Chemotherapy and Pharmacology, 56 (2), 154—160. 

P-glycoprotein expression may occur in tumour types derived from tissues that normally express the protein, like renal cell cancer, but its overexpression may also be induced by the treatment with anticancer drugs. All Vinca alkaloids used in cancer therapy can induce the expression of P-glycoprotein and the associated multidrug resistance phenotype, due to the capacity of P-glycoprotein to pump out of the cell a... 

Cleary I, Doherty G, Moran E, Clynes M. The multidrug-resistant human lung tumour cell line, DLKP-AlO, expresses novel drug accumulation and sequestration systems. Biochem Pharmacol 1997 53 1493-1502. 

Barbarics E, Kronauge IF, Cohen D, Davison A, Jones AG and Croop JM. Characterization of P-glycoprotein transport and inhibition in vivo. Cancer Res 1998 58 276-282. Balhnger JR, Muzzammil T and Moore MJ. Technetium-99m-furifosmin as an agent for functional imaging of multidrug resistance in tumours. J Nucl Med 1997 38 1915-1919. 

Soma, C.E. Dubernet, C. Barratt, G. Nemati, R Appel, M. Benita, S. Couvreur, P. Ability of doxorubicin-loaded nanoparticles to overcome multidrug resistance of tumour cells after their capture by macrophages. Pharm. Res. 1999, 16 (11), 1710-1716. 

Robinson LJ, Roberts WK, Ling TT, Lamming D, Sternberg SS, Roepe PD (1997) Human MDRl protein overexpression delays the apoptotic cascade in Chinese hamster ovary fibroblasts. Biochemistry 36 11169-11178 Roepe PD (2001) pH and multidrug resistance. In Goode JA, Chadwick DJ (eds) The tumour microenvironment Causes and consequences of hypoxia and acidity. Novartis Foundation Symposium 240. John Wiley Sons, Ltd, Chichester, New York, pp 232-250... 

Applications of Hyaluronic Acid Nanoparticles in Reversing Tumour Multidrug Resistance... 

---