PubMed Health⌕ Search

Biomedical subjects

M Beksac

Publications and source records attributed to M Beksac.

24 records · Page 2Linked to original sources

A rapid drug sensitivity assay for neoplasmatic cells.

A vital dye exclusion method following a 4 day tumor sensitivity assay was used to predict clinical response to chemotherapeutics in 16 patients with acute nonlymphoblastic leukemia (n = 12), acute lymphoblastic leukemia (n = 2), diffuse poorly differentiated lymphoma (n = 1) and oat cell carcinoma (n = 1). After 4 days of incubation, controls and drug-supplied cells were stained with fast green and hematoxylin-eosin. A tumor cell survival of 30% was used to distinguish in vitro resistance and in vitro sensitivity. Eight patients responded and five did not respond to the chemotherapy protocol. This agreed with the in vitro results. Two patients who were sensitive in vitro responded only partially in vivo but two additional patients sensitive in vitro did not respond. These results indicate that this short-term method may give a simple estimation of drug resistance.

Adult↗

Effects of retinoids on in vitro differentiation of bone marrow cells in the myelodysplastic syndrome.

The effect of retinoids on cell differentiation in the myelodysplastic syndrome was studied in short-term liquid cultures of bone marrow from 13 patients. After incubation with 13-cis-retinoic acid there was a significant decrease in the percentages of promyelocytes and in Leu-M3-binding cells. Lue-M3 is mainly a monocyte marker, and retinoids thus seem to induce a shift from monocytoid to myeloid differentiation. Patients with refractory anemia with an excess of blasts responded the most, and did also show a significant decrease in OKIa1-binding cells. Etretinate, on the other hand, did not show any differentiation-inducing activity. The results support earlier reports that retinoic acid might be useful in the treatment of the myelodysplastic syndrome. Whether this in vitro technique offers a possibility to predict the clinical outcome remains to be shown.

Aged↗

Cytotoxicity of monoclonal antibodies against individually immunophenotyped human leukemic cells.

Peripheral blood and bone marrow mononuclear cells from 12 patients with acute myeloid leukemia (AML), 2 patients with acute lymphatic leukemia, and 1 patient with chronic myeloid leukemia in blastic crisis were taken at diagnosis or in relapse. Cells were immunophenotyped with a panel of monoclonal antibodies (Moab) (OKIa, Leu M1, Leu M2, Leu M3, Leu M4, B1, Okt 11, J5) and the same antibodies were used in an in vitro cytotoxicity test. Of the 14 patients, 10 had antibody-binding cells, and the percentage of lysed cells was almost equal to that of blasts. The other 4 patients had few binding cells and little lysis. Acute leukemia with and without preceding myelodysplastic features did not differ in immunophenotype. Mean spontaneous release of 51Cr was 12.7% and complement alone caused an additional average release of 11.8%. Four single antibodies together with complement showed a mean 51Cr release of 0.7-32.4% above that found with complement alone. Combinations of Moabs resulted in 51Cr release at least 10% above the single most efficient Moab in 8 out of 12 patients. Not all blast cells showed antibody binding, nor were all antibody-binding cells susceptible to cytotoxicity. Normal bone marrow growth in vitro seemed to be stimulated by factors in complement and in the Moab. When this stimulation was compensated for by adding fetal calf serum, cytotoxicity tests prior to CFUc assays resulted in a mean decrease of 46% of colonies and 25% of clusters in normal bone marrow. CFUc are thus sensitive to the cytotoxicity, although CFU may also be resistant.

Antibodies, Monoclonal↗

Decreased retention of vinca alkaloids in chronic lymphatic leukemia cells from refractory patients.

Uptake and retention of vincristine (VCR), vinblastine (VB), and vindesine (VD) in isolated mononuclear cells from six healthy donors and in leukemic cells from 12 patients with chronic lymphatic leukemia (CLL) were studied: Three patients responded to VCR-containing regimens, whereas 4 patients were or became refractory and five patients did not receive VCR. Incubation of leukemic or normal cells with 1 microgram/ml vinca alkaloid for 1-24 h showed a steady state level after 1-2 h. Normal cells both took up and retained significantly more drug than those from patients, both responding and refractory. Cells from VCR-refractory patients had a significantly (P less than 0.01) lower drug retention than those from patients responding to or not receiving VCR. In contrast, the difference in uptake was not statistically significant.

Aged↗

Leukemic myeloblasts expressing lymphoid markers.

Out of 60 patients with acute myeloid leukemia not preceded by chronic myelocytic leukemia or any preleukemic phase, 7 had both lymphoid and myeloid markers. All patients expressed common acute lymphatic leukemia antigen (CALLA) in 20% or more of their leukemic cells, which also showed positive peroxidase reaction. In addition, 4 patients had Auer rods. Two additional patients had morphologically clear acute monocytic leukemia (FAB M5b) and cells expressing CALLA. In 4 of the 7 patients the sum of the percentages of peroxidase or Leu M1 + and CALLA-positive blast cells exceeded 100%, suggesting that at least some of the cells had both myeloid and lymphoid markers. Moreover, out of 3 patients where double staining with the CALLA antibody J5 and the myeloid marker Leu M1 was performed, 2 had both markers on the same cells.

Adult↗

Alternating combination chemotherapy does not delay development of refractoriness in myeloma.

Sixty-seven patients with stage II and III myeloma were subjected to 3 consecutive prospective phase II studies. Nineteen patients had received melphalan - prednisolone (melphalan group), 17 cyclophosphamide - vincristine - prednisolone (cyclophosphamide group) and 22 alternating combinations of 7 cytostatics and prednisolone (alternating group). Nine patients were unevaluable. The median time until response was achieved was 5, 5 and 3 months respectively. The purpose of the study was to see if combination or alternating combination chemotherapy can delay the appearance of refractoriness. Patients were regarded as refractory after progression, which was defined as advance from stage II to stage III, and, in stage III as an increase of the monoclonal serum protein of more than 25% and/or the monoclonal urine protein of more than 100% despite continued treatment. Refractoriness was not delayed by alternating combination treatment. Thirty per cent of the patients became refractory after 10 months of response in the melphalan group and after 11 months in the cyclophosphamide and the alternating chemotherapy groups. The results remained after stratification for stage.

Antineoplastic Combined Chemotherapy Protocols↗