Hepatocellular carcinoma HepG2 cells (G cells) were subjected to selection first with gamma-radiation and then doxorubicin (Dox). The radiation treatment consisted of 2 Gy for 10 days (G2) or 10 Gy for 2 days (G10) and the Dox treatment was continuous exposure for up to 10 microM. Compared with respective parental G, G2, G10 cells, the Dox-selected cells showed mdr1 amplification/P-glycoprotein...

Labor analgesia using continuous epidural infusions of low-dose bupivacaine and fentanyl may be maintained for many hours. We examined the potential for drug accumulation in both mother and neonate after these long-term infusions. Pregnant women receiving a 10-mL/h continuous infusion of labor analgesia with 0.125% bupivacaine and 2 micrograms/mL of fentanyl were evaluated. Maternal venous and ...

Mechanisms contributing to reduced cytotoxic drug accumulation were studied in two multidrug-resistant (MDR) human lung cancer cell lines without P-glycoprotein expression. In these (non-small cell) SW-1573/2R120 and (small cell) GLC4/ADR MDR cells, the steady-state accumulation of [14C]daunorubicin was 30 and 12%, respectively, of that in the parent cells. When cells, at steady state, were per...

The human ovarian cancer cell lines A2780 and A2780/CP70 were studied to investigate the cellular basis for their relative sensitivities to tetrachloro(DL-trans)-l,2-diamminecyclohexaneplatinum(IV) (ormaplatin). Cells were exposed to ormaplatin for 1 h in all experiments. As assessed by colony formation assays, the A2780/CP70 cell line [50% inhibitory dose (ICso) = 3.6 pM] was 9.5-fold more res...

The human ovarian cancer cell lines A2780 and A2780/CP70 were studied to investigate the cellular basis for their relative sensitivities to tetrachloro(DL-trans)-l,2-diamminecyclohexaneplatinum(IV) (ormaplatin). Cells were exposed to ormaplatin for 1 h in all experiments. As assessed by colony formation assays, the A2780/CP70 cell line [50% inhibitory dose (ICso) = 3.6 pM] was 9.5-fold more res...

Specific delivery of therapeutic agents to solid tumors and their bioavailability at the target site are the most clinically important and challenging goals in cancer therapy. Liposomes are promising nanocarriers and have been well investigated for cancer therapy. In spite of preferred accumulation in tumors via the enhanced permeability and retention (EPR) effect, inefficient drug release at t...

Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-po...

The human ovarian cancer cell lines A2780 and A2780/CP70 were studied to investigate the cellular basis for their relative sensitivities to tetrachloro(DL-trans)-1,2-diamminecyclohexaneplatinum(IV) (ormaplatin). Cells were exposed to ormaplatin for 1 h in all experiments. As assessed by colony formation assays, the A2780/CP70 cell line [50% inhibitory dose (IC50) = 3.6 microM] was 9.5-fold more...

The effects of human immunodeficiency virus (HIV) protease inhibitors (PI) on the accumulation of the fluorescent bile salt analogue cholyl-glycylamido-fluorescein (CGamF) were determined in organic anion transporting polypeptide (OATP)-1B1 and -1B3-expressing Chinese hamster ovary (CHO) cells. In addition, interaction studies in Caco-2 monolayers, known only to express the OATP2B1 isoform, wer...

Yeast is a powerful model system for studying the action of small-molecule therapeutics. An important limitation has been low efficacy of many small molecules in yeast due to limited intracellular accumulation. We used the DNA binding domain of the pleiotropic drug resistance regulator pleiotropic drug resistance 1 (Pdr1) fused in-frame to transcription repressors to repress Pdr1-regulated gene...