Drug resistance mechanisms

Shaw T, Bartholomeusz A, Locamini S (2006) HBV drug resistance mechanisms, detection and interpretation. J Hepatol 44 593-606... 

Simonsen G.S., H. Haaheim, K.H. Dahl, H. Kruse, A. Lovseth, O. Olsvik, and A. Sundsfjord (1998). Transmisssion of vanA-type vancomycin-resistant enterococci and vanA resistance elements between chicken and humans at avoparcin-exposed farms. Microbial Drug Resistance—Mechanisms Epidemiology and Disease 4 313-318. 

Tikofsky, L.L., Barlow, J.W., Santisteban, C. and Schukken, Y.H. 2003. A comparison of antimicrobial susceptibility patterns for Staphylococcus aureus in organic and conventional dairy herds. Microbial Drug Resistance-Mechanisms Epidemiology and Disease 9 S39-S45. 

First Model In Silico Model for Deducing Drug Resistance Mechanisms... 

Following this line of work, we made the discoveries reported here. Before we indicate these, we note that the microarray datasets that we analyzed for tetracycline and chloroquine do not contain many differentially regulated reactions. The possibility remains that studying drug resistance mechanisms of the malaria parasites at the transcriptional level of their proteins is not reliable (Karine Le Roch, personal communication). 

With the first in silico model, we were able to use the biochemical network of P.falciparumto deduce its drug resistance mechanism(s) using two sets of gene expression data obtained from treatment of the parasite with chloroquine and tetracycline. Our work is the first to develop and apply computational means toward the elucidation of these mechanisms in P. falciparum. Our work suggests viable mechanisms for the resistance of the malaria parasite to chloroquine and tetracycline. When these results are experimentally tested they may provide useful weapons to efficiently cleanse malaria parasites from the blood stream. 

Either the catalytic subunit or both subunits are overexpressed in several drug-resistant human cancer cells such as cisplatin-resistant ovarian cancer cells and melphalan-resistant prostate cancer cells, suggesting that elevated production of glutathione may induce drug-resistance mechanisms in these cancer cells (Figure... 

It is concluded that the sensitivities of the MDR- and MRP-mediated drug resistance mechanisms by the inhibitory flavonoids and isoflavonoids might differ because of selective activity based on their chemical structures this is in good agreement with other studies. 

Martin TW, Dauter Z, Devedjiev Y, Sheffield P, Jelen F, He M, Sherman DH, Otlewski J, Derewenda ZS, Derewenda U. Molecular basis of mitomycin C resistance in streptomyces structure and function of the MRD protein. Structure 2002 10(7) 933—942. Sheldon PJ, Johnson DA, August PR, Liu HW, Sherman DH. Characterization of a mitomycin-binding drug resistance mechanism from the producing organism, Streptomyces lavendulae. J. Bacteriol. 1997 179(5) 1796-1804. 

The responses of these three cancer types were found to differ during clinical trials of MDR-1 inhibitors (123). For the first class, MDR-1 inhibition has had little effect on the efficacy of the cancer therapy. It appears that too many other transporters and drug resistance mechanisms are present in front-line defense organs such as kidney, liver, and intestine. For the second class, at least transiently improved responses to anticancer drugs have been seen with MDR-1 inhibitor cotherapy. However, a second relapse is seen as other transport... 

From Methods in Molecular Medicine, Vol. 28 Cytotoxic Drug Resistance Mechanisms Edited by R. Brown and U. Boger-Brown Humana Press Inc., Totowa, NJ... 

Resistance to anticancer drugs is viewed as one of the most significant barriers to the effective treatment of malignant tumors. It is therefore not surprising that despite the difficulties previously mentioned, many studies have been and continue to be performed to determine the clinical significance of specific drug-resistance mechanisms. 

As can be seen from the evidence previously presented, the significance that specific drug-resistance mechanisms play in the clinical response of tumors to cytotoxic agents is unclear. In the majority of tumors, for every study that has shown a correlation between a marker of resistance and poor outcome, another study has shown no such association. Does different evidence exist that might help in determining the clinical importance of specific mechanisms of drug resistance ... 

A different approach to improving the clinical data on the significance of drug-resistance mechanisms might be to study the development of resistance in sequential biopsy samples from the same individual(s). Although this seems attractive in principle, the reality is that, for most patients, tissue samples are not easy to obtain. With hematological tumors, repeat samples of bone marrow or lymph node biopsies obtained pre- and post-chemotherapy are a possibility. However, with solid tumors it is often unfeasible, or unethical, to attempt to obtain tissue samples after chemotherapy or at relapse. 

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