Uptake Assays to Monitor Anthracyclines Entry into Mammalian Cells.

Anthracyclines, such as doxorubicin and daunorubicin, are DNA damaging agents that autofluoresce and can be readily detected in cells. Herein, we developed suitable assays to quantify and localize daunorubicin in mammalian cells. These assays can be exploited to identify components that are involved in the uptake of anthracyclines.

VEGF Requires the Receptor NRP-1 To Inhibit Lipopolysaccharide-Dependent Dendritic Cell Maturation.

To stimulate a productive T cell response, dendritic cells (DC) must undergo maturation characterized by heightened cell surface expression of MHC and costimulatory molecules as well as cytokine production. Conversely, the inhibition of DC maturation is a central mechanism of immune tolerance. The control of the DC maturation process relies on the integration of several cellular stimulatory or inhibitory signals.

The human organic cation transporter OCT1 mediates high affinity uptake of the anticancer drug daunorubicin.

Anthracyclines such as daunorubicin are anticancer agents that are transported into cells, and exert cytotoxicity by blocking DNA metabolism. Although there is evidence for active uptake of anthracyclines into cells, the specific transporter involved in this process has not been identified. Using the high-grade serous ovarian cancer cell line TOV2223G, we show that OCT1 mediated the high affinity (Km ~ 5 μM) uptake of daunorubicin into the cells, and that micromolar amounts of choline completely abolished the drug entry.

Complementation of the Yeast Model System Reveals that Caenorhabditis elegans OCT-1 Is a Functional Transporter of Anthracyclines.

The yeast plasma membrane protein Agp2 belongs to the family of amino acid transporters. It acts as a regulator that controls the expression of several uptake transporter genes such as DUR3 and SAM3 encoding two high-affinity polyamine permeases. agp2Δ mutants display extreme resistance to several cationic compounds including polyamines, the anticancer agent bleomycin, and cationic antifungal peptides.

A functional autophagy pathway is required for rapamycin-induced degradation of the Sgs1 helicase in Saccharomyces cerevisiae.

In yeast Saccharomyces cerevisiae, the immunosuppressant rapamycin mimics starvation by inhibiting the kinase Tor1. We recently documented that this treatment triggers a rapid degradation of Sgs1, a helicase involved in several biological processes such as the prevention of genomic instability. Herein, we show that yeast strains deleted for genes ATG2, ATG9, and PEP4, encoding components of the autophagy pathway, prevent rapamycin-induced degradation of Sgs1.

Clinical significance of antinuclear antibodies, anti-neutrophil cytoplasmic antibodies and anticardiolipin antibodies in heroin abusers.

Background: Different autoantibodies and immunologic abnormalities have been described in heroin abusers positive for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus, as well as in addicts with negative viral markers.

Objectives: To investigate the prevalence of different autoantibodies in heroin addicts.

Methods: We studied 10 heroin addicts (8 males and 2 females aged 18-30 years) with a mean duration of heroin abuse of 46.