Inclusion/exclusion criteria.

<p>Inclusion/exclusion criteria.</p

Placental ABC efflux transporter expression in pregnancies complicated by insulin-managed diabetes.

<p><b>A</b>, MDR1 (ABCB1). <b>B</b>, MRP2 (ABCC2). <b>C</b>, BCRP (ABCG2). Boxes represent quartiles enclosing 50% of the data and the whiskers at either end extend to the 25^th and 75^th quartiles. The median is marked by a line, the mean is marked by an “+” and outliers are marked by a “•” outside the 25^th and 75^th quartiles. The “Combined” group presents data from all patients (n = 33) and was not included in statistical analyses. <b>D</b>, Spearman correlation analysis of the relationship between HbA1c levels (%) and BCRP protein expression in diabetic pregnancies (p<0.05).</p

Localization of MDR1, MRP2, and BCRP in placenta.

<p>The syncytiotrophoblast (S) layer of the placenta is comprised of multinucleated (N) cells that contain a number of apically-localized transport proteins that contribute to the function of the placental barrier, including MDR1, MRP2, and BCRP.</p

Placental ABC efflux transporter expression in pregnancies complicated by insulin-managed diabetes.

<p><b>A</b>, MDR1 (ABCB1). <b>B</b>, MRP2 (ABCC2). <b>C</b>, BCRP (ABCG2). Boxes represent quartiles enclosing 50% of the data and the whiskers at either end extend to the 25^th and 75^th quartiles. The median is marked by a line, the mean is marked by an “+” and outliers are marked by a “•” outside the 25^th and 75^th quartiles. The “Combined” group presents data from all patients (n = 33) and was not included in statistical analyses. <b>D</b>, Spearman correlation analysis of the relationship between HbA1c levels (%) and BCRP mRNA expression in diabetic pregnancies (p<0.01).</p

Ratio-Dependent Synergism of a Doxorubicin and Olaparib Combination in 2D and Spheroid Models of Ovarian Cancer

Ovarian cancer is the fourth leading cause of death in women in developed countries. Even though patients with the most lethal form of the disease (HGSOC; high grade serous ovarian cancer) respond well to initial treatment, they often relapse with progressively resistant disease. Inhibitors of the poly­(ADP-ribose) polymerase (PARP) enzymes are a relatively new class of molecularly targeted small molecule drugs that show promise in overcoming resistance. The present study explores the combination of a DNA damaging agent, doxorubicin (DOX), with the PARP inhibitor, olaparib (OLP), in order to achieve optimal synergy of both drugs in serous ovarian cancer. This drug combination was evaluated and optimized in 2D monolayers and 3D multicellular tumor spheroids (MCTS) using a genetically and histologically characterized panel of nine OC cell lines with or without BRCA1 or BRCA2 mutations. Combination index (CI) values of DOX and OLP were determined using the Chou and Talalay method. The potency of this drug combination was found to rely heavily on the molar ratios at which the two drugs are combined. In general, MCTS growth inhibition was reflective of the patterns predicted by the CI values obtained in monolayers. Promising combination ratios identified in this study warrant further preclinical and clinical investigation