Clinical drug resistance

Miller TP, Grogan TM, Dalton WS, et al P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil. J Clin Oncol 9 17-24, 1991... 

Nitrofurantoin is bacteriostatic and bactericidal for many gram-positive and gram-negative bacteria. P aeruginosa and many strains of proteus are resistant, but in nitrofurantoin-susceptible populations resistant mutants are rare. Clinical drug resistance emerges slowly. There is no cross-resistance between nitrofurantoin and other antimicrobial agents. 

Molecular Imaging of MDR1 Pgp in Clinical Drug Resistance. 172... 

Far fewer studies to date have looked at the role of LRP in clinical drug resistance. LRP has been shown to have prognostic significance in AML and epithelial ovarian cancer (23). In the latter study, LRP was an independent determinant of response to treatment and overall survival, whereas Pgp and MRP were not. LRP levels were also shown to be increased post-chemotherapy in osteosarcoma and this was a poor prognostic sign (27). LRP levels prior to chemotherapy did not show prognostic significance. 

The problems inherent in many of the MDR reversal studies published to date mean that they do not, as yet, provide strong evidence for the importance of Pgp in the development of clinical drug resistance. Improvements in trial design and the development of more specific antagonists of Pgp may result in more significant results in the not-too-distant future. 

In addition to the ABC transporters, the MFS family transporters play an important role in clinical drug resistance [161]. The most prominent ones are Mdrl ]162, 163] and Flul ]164]. CaMDRl, formerly known as BEN confers resistance to a variety of different compounds. Cells lacking CaMDRl are susceptible to 4-nitro-quinoline-N-oxide, methotrexate, and cycloheximide ]165, 166]. The closest yeast homologue of CaMDRl is PLRl. As mentioned above, Flrl is known to be involved in drug transport and it mediates resistance to the same spectrum of drugs as CaMDRl. 

In cultured tumor cells, resistance to taxanes is associated in some lines with increased expression of the mdr-1 gene and its product, the P-glycoprotein other resistant cells have P-tubulin mutations, and these latter cells may display heightened sensitivity to vinca alkaloids. Other cell lines display an increase in survivin, an antiapoptotic factor or aurora kinase, an enzyme that promotes completion of mitosis. The basis of clinical drug resistance is not known. Cell death occurs by apoptosis, but the effectiveness of paclitaxel against experimental tumors does not depend on an intact p53 gene product. 

The basis of clinical drug resistance is not known. Resistance to taxanes in some tumor cells is due to increased expression of the P-glycoprotein other resistant cells have /3-tubulin mutations and may display heightened sensitivity to vinca alkaloids. Cell death occurs by apoptosis. 

Clinical drug resistance emerges very slowly when nitrofurantoin is used as a urinary antiseptic. There is no cross-resistance between the drug and other drugs used in the treatment of bacterial infections of the urinary tract. The answer is (B). 

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