Pentoxifylline reduces fibrin deposition and prolongs survival in neonatal hyperoxic lung injury.

Bronchopulmonary dysplasia is a leading cause of mortality and morbidity in preterm infants despite improved treatment modalities. Pentoxifylline, a phosphodiesterase inhibitor, inhibits multiple processes that lead to neonatal hyperoxic lung injury, including inflammation, coagulation, and edema. Using a preterm rat model, we investigated the effects of pentoxifylline on hyperoxia-induced lung injury and survival.

Gene expression profile and histopathology of experimental bronchopulmonary dysplasia induced by prolonged oxidative stress.

Oxidative stress is an important factor in the pathogenesis of bronchopulmonary dysplasia (BPD), a chronic lung disease of premature infants characterized by arrested alveolar and vascular development of the immature lung. We investigated differential gene expression with DNA microarray analysis in premature rat lungs exposed to prolonged hyperoxia during the saccular stage of development, which closely resembles the development of the lungs of premature infants receiving neonatal intensive care. Expression profiles were largely confirmed by real-time RT-PCR (27 genes) and in line with histopathology and fibrin deposition studied by Western blotting.

Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918.

This study was aimed at characterizing the role of BCRP/MXR/ABCP (BCRP) in resistance of the human ovarian tumor cell lines T8 and MX3 to camptothecins more extensively and investigating whether resistance can be reversed by inhibiting BCRP by GF120918. Camptothecins studied were topotecan, CPT-11, and its active metabolite SN-38, 9-aminocamptothecin, and the novel experimental camptothecins NX211, DX8951f, and BNP1350. Notably, DX8951f and BNP1350 appeared to be very poor substrates for BCRP, with much lower resistance factors observed both in T8 and MX3 cells than observed for the other camptothecins tested.

Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues.

High expression of the Breast Cancer Resistance Protein (BCRP) gene has been shown to be involved in resistance to chemotherapeutic drugs. Knowledge of the localization of BCRP protein in normal tissues may help unravel the normal function of this protein. Therefore, we characterized the tissue distribution and cellular localization of BCRP in frozen sections of normal human tissues.

Breast cancer resistance protein is localized at the plasma membrane in mitoxantrone- and topotecan-resistant cell lines.

Tumor cells may display a multidrug resistant phenotype by overexpression of ATP-binding cassette transporters such as multidrug resistance (MDRI) P-glycoprotein, multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP). The presence of BCRP has thus far been reported solely using mRNA data. In this study, we describe a BCRP-specific monoclonal antibody, BXP-34, obtained from mice, immunized with mitoxantrone-resistant, BCRP mRNA-positive MCF-7 MR human breast cancer cells.