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Biomedical subjects

D Kessel

Publications and source records attributed to D Kessel.

At least 181 records · Page 10Linked to original sources
PubMed1985

Correlations between anthracycline resistance, drug accumulation and membrane glycoprotein patterns in solid tumors of mice.

Both impaired drug accumulation and appearance of a new membrane glycoprotein species (mol. wt. approx. 180,000) are often associated with high levels of drug-induced resistance to a group of natural products which includes adriamycin (ADR) and daunorubicin (DNR). In this study, we examined solid murine mammary, pancreatic and colon tumors varying in degrees of inherent or (in vivo) induced adriamycin resistance. Neither impaired drug accumulation nor alterations in membrane glycoprotein patterns were correlated with drug resistance in these tumors. These results suggest that permeability and glycoprotein alterations may only be associated with very high degrees of drug resistance.

Animals↗
PubMed1985

Anthracycline resistance in P388 murine leukemia and its circumvention by calcium antagonists.

Daunorubicin transport was compared in P388 murine leukemia and in P388/Adramycin (ADR), an anthracycline-resistant subline. We can demonstrate an energy-dependent outward transport system in P388/ADR which limits drug accumulation. Although no calcium requirement for the outward transport process could be shown, several calcium antagonists inhibited outward transport of daunorubicin in P388/ADR and modified the drug resistance pattern. But these agents failed to alter calcium fluxes in either cell line, suggesting that their mode of action in these studies was not related to interactions with calcium-dependent processes. Accumulation differences could not account for the level of daunorubicin resistance observed in the P388/ADR cell line, nor could resistance be wholly circumvented by calcium antagonists.

Animals↗
PubMed1985

Biological and biophysical properties of the tumor-localizing component of hematoporphyrin derivative.

Reverse-phase chromatography, aqueous gel exclusion, and nonaqueous gel exclusion were assessed as procedures for preparative fractionation of the tumor-localizing product hematoporphyrin derivative. Porphyrin accumulation, fluorescence, and photodynamic cytotoxicity were monitored using the murine Sarcoma 180 tumor. Aqueous gel exclusion chromatography can provide a hematoporphyrin derivative fraction enriched in the tumor-localizing component. A further enrichment occurs when this procedure is carried out at 55 degrees C, but nonlocalizing porphyrins could not be eliminated. While providing a better separation, reverse-phase chromatography cannot provide a tumor-localizing fraction free from contaminating protoporphyrin. However, this and other contaminants can be eliminated from the tumor-localizing fraction via nonaqueous gel exclusion chromatography. This latter separation provides two tumor-localizing products: a fast-eluting fraction enriched in the major photosensitizing component(s); and a more complex slowly eluting fraction enriched in fluorescence localizers.

Animals↗
PubMed1985

Promotion of daunorubicin uptake and toxicity by the calcium antagonist tiapamil and its analogs.

Studies were performed with the anthracycline-responsive P388 murine leukemia cell line, and with P388/ADR, a subline selected for doxorubicin resistance. In the P388/ADR cell line, the observed 100-fold daunorubicin resistance is associated with an outward drug transport system which can be inhibited by several calcium antagonists, eg, verapamil and nifedipine. An examination of compounds related to tiapamil, a verapamil analog, has identified a structure which is tenfold more effective than verapamil at potentiating anthracycline accumulation and responsiveness in P388/ADR cells. At no nontoxic level of any calcium antagonist examined was it possible to wholly reverse the degree of daunorubicin resistance found in the P388/ADR cell line.

Animals↗
PubMed1984

Effects of ruthenium red on accumulation and cytotoxicity of m-AMSA, vinblastine and daunorubicin in leukemia cells.

Effects of ruthenium red on accumulation and cytotoxicity of m-AMSA, vinblastine and daunorubicin were examined in the P388 murine leukemia cell line and in an adriamycin-resistant subline, P388/ADR, which is cross-resistant to all three agents. Ruthenium red increased m-AMSA accumulation by both P388 and P388/ADR cells; the extent of this effect was a function of the concentration of both agents. Uptake enhancement occurred within 5 min of exposure of cells to ruthenium red and was readily reversed when cells were suspended in fresh medium. A 24-hr exposure to ruthenium red was needed to affect vinblastine or daunorubicin accumulation, and the effect was substantially less than that observed with m-AMSA. Ruthenium red protected P388 cells from m-AMSA toxicity. These data, together with reports indicating a protective effect of ruthenium red against vinblastine and anthracycline toxicity, suggest that the dye promotes tight binding of m-AMSA and other agents to cellular loci on which toxic effects are not exerted.

Aminoacridines↗
PubMed1984

m-AMSA as a probe for transport phenomena associated with anthracycline resistance.

Kinetics of transport of the acridine derivative 4'-(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA) were examined in P388 murine leukemia cells and in P388/ADR, a subline selected for adriamycin resistance and cross-resistant to a variety of drugs including m-AMSA. Compared with the drug-responsive parent cell line, P388/ADR cells showed impaired accumulation of m-AMSA and an enhanced rate of drug exodus. Competition studies demonstrated structural specificity of the outward transport process. There was a low degree of intracellular m-AMSA binding, and steady-state drug levels were reached in less than 1 min. These results suggest that m-AMSA will be a useful probe for studying transport systems associated with anthracycline resistance.

Aminacrine↗
PubMed1984

Daunorubicin accumulation by human myeloblasts varying in anthracycline resistance.

Circulating myeloblasts were obtained from patients with acute myelogenous leukemias varying widely in anthracycline responsiveness. Studies were carried out in vitro to assess the capacity of such cells for daunorubicin accumulation. There was no correlation between drug responsiveness patterns in vivo vs. drug transport phenomena measured in vitro. A mode of enhanced anthracycline exodus demonstrable in certain drug-resistant murine leukemia cell lines could not be detected in the drug-resistant human myeloblasts.

Animals↗
PubMed1984

Interactions between calcium antagonists, calcium fluxes and anthracycline transport.

The calcium antagonists verapamil and nifedipine promote responsiveness to anthracyclines in certain drug-resistant cell lines. Their mode of action involves inhibition of anthracycline exodus, leading to promotion of intracellular drug retention. We examined the relationship between calcium fluxes and anthracycline responsiveness in the P388 murine leukemia, and in a drug-resistant sub-line, P388/ADR. Verapamil and nifedipine promoted daunorubicin accumulation by P388/ADR cells, but this occurred regardless of extracellular calcium concentration and did not involve perturbation of calcium transport. We conclude that these agents promote drug retention via mechanisms not related to calcium ion fluxes.

Animals↗
PubMed1984

Kinin effects on chloride secretion do not require eicosanoid synthesis.

The actions of bradykinin on colonic epithelia from essential fatty acid-deficient (EFAD) rats has been examined. Electrogenic chloride secretion as short circuit current (SCC) and release of immunoreactive prostaglandin E2 (iPGE2) and i 6-keto PGF1 alpha have been measured. Resting release of prostanoids was significantly less in EFAD than in control tissues. Bradykinin, in a maximally effective concentration, produced no increase in prostanoid release in EFAD tissues in contrast to controls, while the SCC response was 55% of that in controls. In EFAD tissues the SCC response to bradykinin was the same whether or not the cyclooxygenase inhibitor piroxicam was present. EFAD tissues were not more sensitive to prostaglandins than control tissues. We conclude that while prostaglandin release contributes to the totality of the response to bradykinin, the latter's effect on electrogenic chloride secretion does not require the obligatory production of arachidonic acid metabolites.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Role of sialyltransferase in hypercupraemia of non-Hodgkin's lymphoma.

Copper, ceruloplasmin and sialyltransferase activity were measured in serum of 25 patients with lymphoreticular malignancies, in an attempt to study the sialyltransferase activity and correlation if any with the activity of the disease and ceruloplasmin. All 3 parameters were elevated in active disease but no definite correlation between sialyltransferase activity and copper or ceruloplasmin could be found. We conclude that plasma sialyltransferase activity is increased in lymphomas.

Adult↗
PubMed1984

Sidedness of the reaction to beta-lactoglobulin in sensitised colonic epithelia.

The short circuit current reaction to beta-lactoglobulin shown by the epithelial lining of the colon from guinea-pigs fed with cows' milk is elicited only when the challenge is applied to the basolateral side of the tissue. However if the apical surface of the epithelium is subjected to controlled lesioning with ultraviolet irradiation then apical challenge with beta-lactoglobulin becomes effective. A similar situation ensues when preparations are aged in vitro at room temperature in oxygenated Krebs-Henseleit solution. Although irradiation causes insignificant changes in the electrical resistance of the tissue, the evidence suggests that it allows beta-lactoglobulin to penetrate the epithelium from the apical side. If the model is applicable to clinical conditions of food allergic disease then it appears that concomitant changes in epithelial permeability as well as the development of sensitivity are required.

Animals↗