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A Aszalos

Publications and source records attributed to A Aszalos.

71 records · Page 4Linked to original sources
PubMed1975

Differential potentiation by nystatin of the effect of antibiotics on yeast and mammalian cells.

The effect of the polyene antibiotic nystatin, used in combination with several other antibiotics, on the membranes of Candida albicans SC#8169 (yeast) cells and of Chinese hamster ovary and 3T3 (mammalian) cells was investigated. It was concluded from determinations of the viability of the yeast cells and from measurements of deoxyribonucleic acid synthesis by the mammalian cells that nystatin acts synergistically with several antibiotics on yeast cells, but not on CHO and 3T3 cells. This selective action of nystatin may prove useful in chemotherapy.

Animals↗
PubMedDate not supplied

Effect of cyclosporin A on the anti-CD3 antibody- and concanavalin A-induced activation and membrane potential of human T lymphocytes.

The immunosuppressive effect of cyclosporin A (CsA) was studied on the anti-CD3 antibody (anti-CD3)- and concanavalin A (Con A)-induced activation of human T lymphocytes. A similar suppressive effect was observed in the Con A- and anti-CD3-induced proliferation as measured by the amount of [3H]thymidine incorporated on the third day of culture. When the cells were washed 30 min after activation with anti-CD3, the response was diminished and the CsA sensitivity was increased. In contrast, addition of interleukin-2 (IL-2) resulted in a significantly increased response and a decreased sensitivity. In cultures activated with anti-CD3, CsA treatment resulted in suppression of proliferation after 3 days and an enhancement after 5 days. This latter phenomenon was not seen in cultures treated with Con A. Removal of macrophages (MPH) abolished the proliferative response to anti-CD3. The addition of 10% MPH restored the response, while pretreatment of MPH with CsA diminished this ability. There were differences in the activation kinetics elicited by these two agents as reflected by the changes in membrane potential and the rate of IL-2 receptor (Tac) expression. The changes in the membrane potential (in the absence of CsA) seemed to be parallel with Tac expression and thymidine incorporation. CsA caused a hyperpolarization of the cell membrane. Both Con A and anti-CD3 brought about a strong depolarization which was blocked by the presence of CsA.

Antibodies↗
PubMedDate not supplied

Combinations of P-glycoprotein blockers, verapamil, PSC833, and cremophor act differently on the multidrug resistance associated protein (MRP) and on P-glycoprotein (Pgp).

Clinical studies are currently in progress to evaluate functional modifiers of P-glycoprotein (Pgp), an efflux pump associated with resistance to cancer chemotherapy. However, the effects of these modifiers on a more recently discovered efflux pump, the multidrug resistance associated protein (MRP), have not yet been fully characterized. MRP is expressed in most human tissues and is overexpressed in several tumor types. For these reasons, we have investigated the effects of three prototype Pgp modifiers, which act by different modes on the function of Pgp, on the function of MRP in two MRP-overexpressing cell lines: UMCC/VP lung and MCF-7/VP breast cancer cells. Clinically optimal plasma levels of verapamil, cremophor, and PSC833 have been shown to completely block the function of Pgp in Pgp-over expressing cells. However, in the two MRP-over expressing cell lines, these modifiers only partially blocked the function of MRP and combinations of these optimal concentrations acted antagonistically. Similar antagonistic effects were seen with combinations of suboptimal concentration levels of these blockers, while these combinations resulted in synergistic effects in Pgp overexpressing cells. For two biophysical parameters measured at the plasma membrane, membrane fluidity and membrane potential, the effects of these modifiers were essentially similar in Pgp and MRP expressing cells. We suggest that the 170 kD Pgp and the 190 kD MRP glycoproteins, imbedded in the plasma membranes, respond differently to simultaneous effects of the investigated prototype resistance modifiers. These results also suggest that the identification of the specific mechanism of drug resistance is important for the selection of chemotherapeutic strategies to block the efflux pump on the cancer cell.

3T3 Cells↗
PubMedDate not supplied

Influence of beta-adrenergic antagonists, H1-receptor blockers, analgesics, diuretics, and quinolone antibiotics on the cellular accumulation of the anticancer drug, daunorubicin: P-glycoprotein modulation.

BACKGROUND: Treatment of patients with several drugs simultaneously may result in modulation of the naturally expressed P-glycoprotein (Pgp) at different tissues. With this possibility in mind, we have assessed the ability of different classes of drugs to modulate Pgp function in vitro. Modulation of the Pgp function was studied at in vitro drug concentrations comparable to therapeutic blood levels of the drugs. MATERIALS AND METHODS: Human blood brain barrier endothelial cells and human colon adenocarcinoma cells were transduced or transfected with the multidrug resistance gene (MDR1) to express Pgp. The uptake of fluorescent substrates of Pgp, Rhodamine 123 and daunorubicin, into these cells and NIH3T3/MDR1 and MDCK/MDR1 cells was measured by flow cytometry and in monolayers in the presence and absence of the different drugs. RESULTS: From the tested six H1-receptor blockers, seven beta-adrenergic antagonists, four analgesics, ten diuretics and five quinolons, five drugs inhibited Pgp at therapeutic blood levels and two at somewhat higher concentrations. Significant synergism for blocking Pgp could be demonstrated for several drugs. CONCLUSION: We conclude that administration of several drugs which modulate the function of Pgp to patients may adversely affect the natural function of this efflux pump and may cause drug-drug interactions induced side effects.

3T3 Cells↗
PubMedDate not supplied

Biochemical and clinical aspects of efflux pump related resistance to anti-cancer drugs.

This review paper will focus on the molecular biological, biochemical and biophysical aspects of the following three efflux pumps: P-glycoprotein (Pgp), Multidrug Resistance Protein (MRP) and Lung cancer Resistance-related Protein. Since suppression of the function of these pumps has clinical implications, novel approaches developed in our laboratory for blocking the function of Pgp and MRP are also discussed. The second part of this review will summarize the clinical significance and the results of clinical trials designed to suppress the effects of these efflux pumps.

ATP Binding Cassette Transporter, Subfamily B, Mem↗