MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 663-aa member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.
Tiara[5]arenes (T[5]s), a new class of five‐fold symmetric oligophenolic macrocycles that are not accessible from the addition of formaldehyde to phenol, were synthesized for the first time. These pillar[5]arene‐derived structures display both unique conformational freedom, differing from that of pillararenes, with a rich blend of solid‐state conformations and excellent host–guest interactions in solution. Finally we show how this novel macrocyclic scaffold can be functionalized in a variety of ways and used as functional crystalline materials to distinguish uniquely between benzene and cyclohexane.
DNA modifications vary in form and function but generally do not alter Watson-Crick base pairing. Diaminopurine (Z) is an exception because it completely replaces adenine and forms three hydrogen bonds with thymine in cyanophage S-2L genomic DNA. However, the biosynthesis, prevalence, and importance of Z genomes remain unexplored. Here, we report a multienzyme system that supports Z-genome synthesis. We identified dozens of globally widespread phages harboring such enzymes, and we further verified the Z genome in one of these phages, Acinetobacter phage SH-Ab 15497, by using liquid chromatography with ultraviolet and mass spectrometry. The Z genome endows phages with evolutionary advantages for evading the attack of host restriction enzymes, and the characterization of its biosynthetic pathway enables Z-DNA production on a large scale for a diverse range of applications.
Summarv We have characterised an etoposide-resistant subline of the small-cell lung cancer cell line.UMCC-1. derinved at our centre. Subline UMCC-1 VP was developed bY culturing the parent hne in increasing concentrations of etoposide over 16 months. UMCC-1 VP is 20-fold resistant to etoposide by MTT assays. relative to the parent line. and is cross-resistant to doxorubicin. vincristine and actinomycin D. but not to taxol. cisplatin. melphalan. thiotepa or idarubicin. Topoisomerase II immunoblotting demonstrates a 500o reduction of the protein in the resistant subline. The UMCC-1 VP subline demonstrates a marked decrease in the accumulation of [3HIetoposide relative to the parent line. as well as a modest reduction in the accumulation of daunorubicin. Reverse transcription-polymerase chain reaction assays demonstrate no detectable mdrl expression but marked expression of the multidrug resistance-associated protein (MRP) that MRP may contribute to clinical drug resistance in human cancer (Schneider et al.. 1995).Etoposide is one of the most clinically important drugs in the frontline treatment of SCLC tumours (Cavalli et al.. 1978). The activity of etoposide results from a specific interaction of the drug with the nuclear enzyme topoisomerase II (Yang et al.. 1985). This enzyme has the ability to alter the topological state of DNA and has a critical role in DNA replication. chromosomal segregation and RNA transcription (Liu. 1989: Osheroff et al.. 1991 Chemosensitzivit!u testing MTT (3-(4.5-dimethy lthiazol-2-yl)X-1.5-dipeny ltetrazolium bromide) assays A-ere performed with minor modifications of the method of Mosmann (1983
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