ABSTRACT
Vinorelbine (VNR) is a semi-synthetic Vinca rosea alkaloid that has been employed both as a single agent and in combination, and has shown significant antitumor activity. As little is known about VNR activity on human leukemia, we studied its in vitro cytotoxic effect on human leukemia cell lines (FLG 29.1, HL60, K562, Balm 4, CEM and Daudi) and on fresh leukemia cells from 28 patients: 2 acute myeloid leukemia (AML); 3 chronic myeloid leukemia in blastic phase (CML-BP); 5 acute lymphoblastic leukemia (ALL); 18 B-chronic lymphatic leukemia (B-CLL), employing the colorimetric INT assay and determining the IC50. We observed that VNR exerts its cytotoxic activity on leukemic cell lines in a dose-dependent fashion. The lymphoid cell lines appear more sensitive than the myeloid ones to the VNR-dependent growth inhibition. A similar pattern was noticed for leukemia cells in primary cultures. VNR is not effective on CML-BP cells, shows variable activity on the AML and ALL cells and is very effective against B-CLL cells. VNR inhibited the growth of fresh B-CLL cells from 15 of 18 patients, the IC50 doses ranging from 4 ng/ml to 83 microg/ml (doses coinciding with the plasma levels obtained in clinics). These observations strongly suggest that VNR could be useful in clinics for the treatment of B-CLL.
Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , B-Lymphocytes/drug effects , B-Lymphocytes/pathology , Leukemia, Lymphoid/drug therapy , Leukemia, Lymphoid/pathology , Leukemia, Myeloid/drug therapy , Leukemia, Myeloid/pathology , Vinblastine/analogs & derivatives , Vinblastine/therapeutic use , Acute Disease , Adult , Aged , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/toxicity , Colorimetry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Filaggrin Proteins , Humans , In Vitro Techniques , Male , Middle Aged , Tumor Cells, Cultured/drug effects , Vinblastine/administration & dosage , Vinblastine/toxicity , VinorelbineABSTRACT
The A. have studied 28 pairs of rats; 17 pairs received 1,1 g of soya oil; 7 pairs were starved. The partners were kept; one at the environmental temperature of 6 degrees C, the other at 30 degrees C. After a night, all rats were tested for xylose absorption. Xylose intestinal absorption in the rats kept at the environmental temperature of 30 degrees C after soya oil decreased of 42,88 +/- 8,14 of the value found at 6 degrees C; it decreased of 15,59 +/- 3,20% after a night of fast. Both decreases were significant (P less 0.01).
