Taurolidine: preclinical evaluation of a novel, highly selective, agent for bone marrow purging
| Autor: | Frederick A. Goulette, Ribizzi I, Paul Calabresi, Akhtar Ms, Devasis Chatterjee, James W. Darnowski |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Pathology
medicine.medical_specialty Taurine Drug Evaluation Preclinical Drug Resistance Antineoplastic Agents HL-60 Cells Transplantation Autologous chemistry.chemical_compound Mice medicine Tumor Cells Cultured Cytotoxic T cell Animals Humans Tumor Stem Cell Assay Bone Marrow Transplantation Transplantation Thiadiazines business.industry Chimera Bone Marrow Purging Hematology Transfection Taurolidine medicine.disease Bone marrow purging Mice Inbred C57BL Leukemia medicine.anatomical_structure chemistry Cancer cell Cancer research Female Bone marrow Stem cell Gentamicins business |
| Zdroj: | Bone marrow transplantation. 29(4) |
| ISSN: | 0268-3369 |
| Popis: | Taurolidine has been shown to have remarkable cytotoxic activity against selected human tumor cells at concentrations that spare normal cells. In this study we have extended this observation and assessed the ability of Taurolidine to purge tumor cells from chimeric mixtures of bone marrow (BM) and neoplastic cells. Normal murine BM and human leukemic (HL-60) or ovarian (PA-1) tumor cell lines were used as models. Exposure of tumor cells to 2.5 mM Taurolidine for 1 h resulted in the complete elimination of viable cells. In contrast, exposure of BM to 5 mMTaurolidine for 1 h reduced CFU-GM, BFU-E and CFU-GEEM colony formation by only 23.0%, 19.6% and 25.2%, respectively. Inhibition of long-term BM culture (LTBMC) growth following a 1 h exposure to 5 mM Taurolidine also was ∼20% compared to untreated LTBMC. Finally, chimeric cultures were generated from BM and HL-60GR or PA-1GR cells (tumor cells transfected with the geneticin resistance gene). Exposure of these chimeric cultures to 5 mM Taurolidine for 1 h totally eliminated viable cancer cells while minimally reducing viable BM cells. This finding was confirmed by subsequent positive selection for surviving tumor cells with geneticin. These findings reveal that Taurolidine holds promise for use in BM purging. Bone Marrow Transplantation (2002) 29, 313–319. doi:10.1038/sj.bmt.1703359 |
| Databáze: | OpenAIRE |
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