Multicentric evaluation of the MDR phenotype in leukemia

True

“…11,12,25 This is despite considerable disagreement about optimal detection methods and the way to define thresholds for overexpression. 17,26 The general notion that Pgp expression may have a detrimental effect on the outcome of chemotherapy treatment of AML has lead to current phase III clinical trials with the Pgp function blockers cyclosporin A and PSC833 in order to test the hypothesis that Pgp blockade may improve clinical outcome in this disease.…”

“…One problem relates to the correct measurement of P-glycoprotein or its pumping activity in patient cells, which despite considerable effort, including at least three multicenter studies has not been solved definitively. [15][16][17] A second problem is the lack of an established, validated cytotoxicity test which has proven to be predictive of clinical response in AML. Such a test would allow determination of the net effect of Pgp expression on drug resistance by measuring the cytotoxicity of a drug such as DNR with and without the presence of an agent that completely inhibits Pgpmediated DNR efflux.…”

True

“…Several laboratories from the United States and Europe have teamed up under the leadership of WT Beck (University of Illinois at Chicago, USA) and JP Marie (Hô pital d'Hotel-Dieu, Paris, France), respectively, in an effort to advise a suitable methodology for the detection of MDR in clinical routine laboratory diagnostics. 4,5 In contrast to cells with high levels of drug resistance, the balance of results presented from these workshops did rather not speak Correspondence: T …”

“…Several laboratories from the United States and Europe have teamed up under the leadership of WT Beck (University of Illinois at Chicago, USA) and JP Marie (Hô pital d'Hotel-Dieu, Paris, France), respectively, in an effort to advise a suitable methodology for the detection of MDR in clinical routine laboratory diagnostics. 4,5 In contrast to cells with high levels of drug resistance, the balance of results presented from these workshops did rather not speak Correspondence: T Efferth; Fax: +49-9131-8526493 Received 28 June 1999; accepted 7 July 1999 in favor of the detection of clinically relevant low-level resistance. To define consensus recommendations for the standardized of detection of resistance genes expressed in low amounts is therefore more difficult as initially estimated.…”

“…Immunohistochemistry, however, came under debate with respect to its reproducibility to detect low levels of P-glycoprotein expression in large multicentric evaluations. 4,5 Although immunohistochemistry is a morphological means with inherent limitations concerning quantitative evaluation, many semiquantitative immunohistochemical studies provided evidence for the prognostic value of P-gp for patients' survival or a disease-free interval and corroboration has come from investigations measuring mRNA expression. [7][8][9][10] This speaks of some validity of immunohistochemistry in general.…”