Showing papers by "Malcolm J. Moore published in 1999"
TL;DR: In stage I nonseminoma patients, surveillance history, physical examination, tumor markers and abdominopelvic CT are necessary components of the followup protocol and should be followed beyond 5 years and likely for life in addition to regular patient self-examination.
69 citations
TL;DR: Results show that sestamibi imaging can detect inhibition of Pgp function and suggest that this approach could be used clinically to document effective delivery of chemosensitizers.
Abstract: Sestamibi is known to be a substrate for P-glycoprotein, the membrane transporter which confers multidrug resistance by pumping certain chemotherapeutic agents out of tumour cells. In this study, the utility of sestamibi imaging for detecting inhibition of P-glycoprotein (Pgp) function by two potent, second-generation chemosensitizers, PSC833 and GG918, was assessed in a mouse xenograft model of multidrug-resistant human breast cancer, MCF7-AdrR. Preliminary in vitro studies confirmed that MCF7-AdrR cells accumulate only low levels of sestamibi and that both sensitizers inhibit transporter function to a similar extent, resulting in 20-fold higher accumulation of sestamibi. MCF7-AdrR cells were grown as a xenograft in SCID mice and sestamibi kinetics in the tumour were analysed by dynamic imaging (30 frames at a rate of one frame per minute). Administration of either chemosensitizer produced a dose-dependent slowing of the efflux rate of sestamibi compared to untreated tumours. The same effect was evident in two additional parameters: percent activity remaining at 30 min determined by imaging and sestamibi levels measured in excised tissues. These results show that sestamibi imaging can detect inhibition of Pgp function and suggest that this approach could be used clinically to document effective delivery of chemosensitizers.
28 citations