tretinoin and oblimersen

For the majority of patients with advance malignancies, current therapies are noncurative. Developing therapeutic agents that enhance the apoptotic effects and hence antitumor potential of currently available chemotherapy agents represents a rationale investigative strategy. Several chemotherapeutic agents including antimicrotubule agents and all-trans-retinoic acid utilize these pathways to mediate tumor cell killing. With specific agents such as oblimersan sodium in randomized "pivotal" studies, and agents targeting the TRAIL receptor-family recently entering early clinical study, cautious optimism is warranted.

Topics: Antineoplastic Agents; Apoptosis; Apoptosis Regulatory Proteins; Clinical Trials as Topic; Drug Design; Genes, bcl-2; Humans; Membrane Glycoproteins; Models, Biological; Neoplasm Proteins; Neoplasms; Oligodeoxyribonucleotides, Antisense; Proto-Oncogene Proteins c-bcl-2; Recombinant Proteins; Thionucleotides; TNF-Related Apoptosis-Inducing Ligand; Tretinoin; Tumor Necrosis Factor-alpha

To explore whether the oligonucleotide uptake in hematological tumor cells is related to cellular species and proliferation.. Intracellular mean fluorescence intensity was measured by flow cytometry.. After treatment with FITC-labeled G3139 at the concentration of 0.60 mumol.L-1 for 4 h, the G3139 uptake into peripheral blood mononuclear cell and bone marrow mononuclear cell in hematological tumor patients was significantly higher than that in normal control. There was different uptake of G3139 among the malignant hematological tumor cell strains, and the uptake in cells derived from monocyte, B lymphocyte and myeloid cell was much higher than that in cells derived from T lymphocyte. After treatment with all-trans retinoic acid (ATRA), HL60 cell proliferation was markedly inhibited and the uptake of G3139 decreased significantly.. Hematological tumor cells were capable of taking up oligonucleotide, and the oligonucleotide uptake in hematological tumor cells is related to its cellular species and its activation.

Topics: Biological Transport; Cell Division; Genes, bcl-2; HL-60 Cells; Humans; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Promyelocytic, Acute; Leukocytes, Mononuclear; Lymphoma, Non-Hodgkin; Oligonucleotides, Antisense; Thionucleotides; Tretinoin; Tumor Cells, Cultured