PubMed Health⌕ Search

Biomedical subjects

E Altschuler

Publications and source records attributed to E Altschuler.

23 records · Page 2Linked to original sources
PubMed1991

Effect of bryostatin 1 on drug-induced, topoisomerase II-mediated DNA cleavage and topoisomerase II gene expression in human leukemia cells.

Unlike PMA, bryostatin 1 has been found to have a minimal effect on drug-induced topoisomerase II-mediated DNA cleavage and no effect on topoisomerase II mRNA levels. Furthermore, bryostatin 1 overcame the down-regulatory effects of PMA treatment on (1) drug-induced, topoisomerase II-mediated DNA cleavage, (2) drug-induced cytotoxicity, and (3) topoisomerase II gene expression. Thus, it is unlikely that the effects of phorbol ester treatment on topoisomerase II-mediated events are a direct consequence of protein kinase C activation per se. Rather, the results with bryostatin 1 suggest that the phorbol ester effects are related to more distal effects of phorbol ester treatment that may be related to monocytoid differentiation.

Bryostatins↗
PubMed1991

The effect of staurosporine on drug-induced, topoisomerase II-mediated DNA cleavage in human leukemia cells.

Phorbol-12-myristate 13-acetate (PMA), a stimulator of protein kinase C, dramatically decreased topoisomerase II-reactive drug-induced DNA cleavage in HL-60 human leukemia cells. The effect of staurosporine, an inhibitor of protein kinase C, on drug-induced, topoisomerase II-mediated DNA cleavage was quantified in the same cells. Staurosporine decreased the magnitude of 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA)- and etoposide-induced DNA cleavage in a dose- and time-dependent fashion. Measurement of several parameters of cell proliferation revealed no clear and uniform correlation between staurosporine's inhibition of these parameters and its effects on drug-induced DNA cleavage. A direct comparison with PMA's effects on drug-induced DNA cleavage showed that whereas PMA's inhibition of etoposide-induced cleavage was much greater than its inhibition of m-AMSA-induced cleavage, the magnitude of staurosporine's effect on the cleavage produced by the two topoisomerase II-reactive drugs was similar. Thus, although PMA stimulates protein kinase C and staurosporine inhibits this enzyme, it is unlikely that the actions of either on topoisomerase II-reactive, drug-induced DNA cleavage are mediated directly via protein kinase C. Furthermore, it is likely that the mechanisms by which PMA and staurosporine inhibit topoisomerase II-reactive drug-induced cleavage are different.

Alkaloids↗
PubMed1990

Phorbol ester effects on topoisomerase II activity and gene expression in HL-60 human leukemia cells with different proclivities toward monocytoid differentiation.

We examined the effects of phorbol ester treatment on topoisomerase II-mediated events in two human leukemia cell lines with different proclivities toward phorbol ester-induced monocytoid differentiation. HL-60 is the parent line that will terminally differentiate; 1E3 is a derived line that will not terminally differentiate. Within 24 h of phorbol ester treatment, etoposide-induced, topoisomerase II-mediated DNA cleavage declined 10-fold, whereas 4'-(9-acridinylamino)-methanesulfon-m-anisidide- induced DNA cleavage declined 3-fold in HL-60. In phorbol-treated 1E3, etoposide-induced DNA cleavage declined only 2-fold, whereas 4'-(9-acridinylamino)methanesulfon-m-anisidide-induced cleavage was barely affected. There was a 2- to 3-fold decline in topoisomerase II activity within the nuclear extracts from phorbol-treated HL-60 cells but not from phorbol-treated 1E3 cells. Immunoblotting experiments with anti-topoisomerase II antibodies indicated that phorbol treatment produced a structural change in the immunoreactive topiosomerase II in HL-60 nuclear extracts but produced no change in 1E3 topoisomerase II. Phorbol ester treatment also produced a decline in the level of topoisomerase II gene expression in HL-60 but not in 1E3 cells. By contrast, the cytotoxicity of etoposide in both lines was decreased following phorbol treatment. Thus, phorbols may uncouple the mechanisms linking drug-induced, topoisomerase II-DNA cleavable complex stabilization with drug-induced cytotoxicity, particularly in 1E3.

Amsacrine↗
PubMed1990

The risk and efficacy of anticoagulant therapy in the treatment of thromboembolic complications in patients with primary malignant brain tumors.

Twenty-three patients with malignant glial neoplasms were treated with anticoagulant therapy for thromboembolic complications. Fifteen patients had deep vein thrombosis alone, and 8 patients had both deep vein thrombosis and pulmonary embolism. Serum prothrombin times were maintained at 1.25 times control for an average of 5.8 months per patient, for a total patient exposure to warfarin therapy of 132 patient-months (11 patient-years). Only 1 patient suffered a recurrent pulmonary embolism, and this occurred during an episode of gastrointestinal bleeding, when anticoagulant therapy had to be discontinued prematurely. All patients were followed with serial computed tomographic or magnetic resonance imaging scans, and no patient showed radiographic evidence of intratumoral hemorrhage either during or after warfarin therapy. One patient, who died from a large recurrent glioblastoma, was found at autopsy to have scattered foci of intratumoral hemorrhage. This series, together with a review of the available literature, suggests that oral anticoagulant therapy is both a safe and effective means of treating thromboembolic complications in patients with residual malignant glial tumors.

Adult↗