Biomedical subjects

A DeJesus

Publications and source records attributed to A DeJesus.

5 recordsLinked to original sources

PubMed1995

Sensitivity of camptothecin-resistant human leukemia cells and tumors to anticancer drugs with diverse mechanisms of action.

Human leukemia U-937 cell clones resistant to 9-nitrocamptothecin (9NC) appear after exposure to increase 9NC-concentrations. Drug resistance is irreversible, regardless of whether the 9NC-resistant (U-937/CR150) cells grow in media with or without 9NC. U-937/CR150 cells are more sensitive than wild type U-937 (U-937/wt) cells to topoisomerase II-directed drugs, amsacrine, daunorubicin, and etoposide. The mitotic inhibitor, vincristine, induces hyperdiploidy in U-937/wt, but not in U-937/CR150 cells, whereas the antimetabolites, cytarabine and methotrexate, and the nitrosourea, carmustine, elicit similar responses in both U-937/wt and U-937/CR150 cells. U-937/CR150-generated tumors in nude mice are sensitive to etoposide. The clinical implications of increased sensitivity of 9NC-resistant tumors to some anticancer drugs are discussed.

Animals↗

PubMed1994

Development of resistance to 9-nitro-camptothecin by human leukemia U-937 cells in vitro correlates with altered sensitivities to several anticancer drugs.

We have recently reported that exposure of human leukemia U-937 cells to progressively increasing concentrations of 9-nitro-camptothecin (9NC) resulted in cell sublines exhibiting various levels of resistance to 9NC. Here, we report responses of wild-type (U-937/wt) and 9NC-resistant (U-937/CR) cells to various anticancer drugs used extensively in cancer chemotherapy. U-937/CR cells were more sensitive than U-937/wt cells to several commonly used drugs of diverse origin including the topoisomerase II-directed drugs amsacrine, etoposide and daunorubicin; the vinca alkaloid vincristine; and the antimetabolite methotrexate. No responses were induced by carmustine in either cell type, whereas similar responses were induced by cytarabine. The sensitivity to the drugs was investigated by monitoring cell proliferation, by determining cell cycle perturbations assessed by flow cytometry analysis of DNA content and by microscopy of stained cells. The results in this report indicate that development of 9NC resistance by the U-937 cells is accompanied by increased sensitivities to other anticancer drugs in vitro and very likely in vivo.

Antineoplastic Agents↗

PubMed1994

Partial characterization of human leukemia U-937 cell sublines resistant to 9-nitrocamptothecin.

Human leukemia U-937 cell sublines exhibiting various levels of resistance to 9-nitrocamptothecin (9NC) were developed after exposure to progressively increased 9NC concentrations. Increases in 9NC resistance of the cells were accompanied by decreases in proliferation rate; appearance of morphological and functional features that correlate with granulocytic maturation; decreased synthesis of topoisomerase I; increased synthesis of topoisomerase II; and inability or decreased ability to induce tumors when xenografted in nude mice. 9NC-resistant cells, transferred and propagated in 9NC-free media for 6 months, continue to exhibit resistance and other features similar to cells propagated in continual presence of 9NC. Finally, 9NC-resistant U-937 cells respond to physiological and non-physiological agents of cell differentiation, indicating that alternative treatments can be successfully used to inhibit growth of 9NC-resistant U-937 cells and tumors.

Animals↗

PubMed1991

Human platelet aggregation and shape change are coupled to separate thromboxane A2-prostaglandin H2 receptors.

The relationships of human platelet thromboxane A2-prostaglandin H2 (TxA2/PGH2) receptor occupation as assessed by equilibrium binding of the TxA2/PGH2 agonist [125I]BOP to the functional responses of I-BOP-induced platelet shape change and aggregation were determined before and after specific, irreversible inactivation of platelet TxA2/PGH2 receptors with the photolyzable TxA2/PGH2 antagonist I-PTA-PON3. I-BOP stimulated platelet shape change and aggregation with concentrations producing a half-maximal response of 173 +/- 39 pM (n = 4) and 1.8 +/- 0.4 nM (n = 6), respectively (means +/- SE). Covalent inactivation of TxA2/PGH2 receptors with I-PTA-PON3 caused rightward shifts of I-BOP shape change and aggregation dose-response curves and resulted in pharmacological dissociation constants (Kd) of 134 pM and 1.95 nM, respectively. Isotherms of [125I] BOP binding to intact platelets (n = 6) were shallow with Hill coefficients of -0.68 +/- 0.03 and were best described by a two-site model with 222 +/- 58 sites/platelet of high affinity (Kd = 270 +/- 60 pM) and 818 +/- 90 sites/platelet of lower affinity (Kd = 3.9 +/- 1.2 nM). The relationship of I-BOP occupancy of high-affinity receptors to shape-change responses was linear (r = 0.97, P less than 0.001), but the occupancy-response relationship for the lower affinity receptor and platelet aggregation was hyperbolic with half-maximal aggregation occurring after occupation of 25% of the receptors. After covalent inactivation of a variable proportion of the receptors with I-PTA-PON3, the occupancy-response relationship for platelet aggregation resulted in a similar hyperbola indicating an excess of low-affinity receptors coupled to aggregation (spare receptors).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗

PubMed1982

Needle stimulation.

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Electromyography↗