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| Item Type: | Article |
|---|---|
| Title: | The thalidomide analogue, CC-4047, induces apoptosis signaling and growth arrest in childhood acute lymphoblastic leukemia cells in vitro and in vivo |
| Creators Name: | Shalapour, S., Zelmer, A., Pfau, M., Moderegger, E., Costa-Blechschmidt, C., van Landeghem, F.K., Taube, T., Fichtner, I., Buehrer, C., Henze, G., Seeger, K. and Wellmann, S. |
| Abstract: | PURPOSE: Thalidomide and its analogues have shown promise in the treatment of multiple myeloma but their therapeutic potential has not been evaluated in models of acute lymphoblastic leukemia (ALL). EXPERIMENTAL DESIGN: We assessed the effects of the thalidomide analogue, CC-4047, on the growth and apoptosis signaling of human B cell precursor (BCP) ALL cell lines and freshly obtained childhood BCP-ALL cells grown with or without stromal cells. In addition, we studied the effects of CC-4047 on the progression and dissemination of xenotransplanted human BCP-ALL cells in nonobese diabetic/severe combined immunodeficiency mice. RESULTS: CC-4047 reduced the proliferation of human BCP-ALL cell lines in vitro. In contrast with the antileukemic effect of cytarabin, this was more pronounced when cell lines or freshly obtained childhood BCP-ALL cells were cocultured with stromal cells. CC-4047 induced the cleavage of caspase-3, caspase-9, and poly(ADP-ribose) polymerase in stroma-cocultured BCP-ALL cells. The inhibition of tumor growth, caspase-3 cleavage, and reduced microvessel density was observed in nonobese diabetic/severe combined immunodeficiency mice inoculated s.c. with childhood BCP-ALL cells upon CC-4047 treatment. After i.v. BCP-ALL xenotransplantation, CC-4047 reduced splenic dissemination. CONCLUSIONS: The thalidomide analogue, CC-4047, displays profound cytostatic effects on stroma-supported human ALL cells both in vitro and in vivo. |
| Keywords: | Apoptosis, Blood Vessels, Caspase 3, Cell Proliferation, Cultured Tumor Cells, Inbred NOD Mice, Neoplasm Transplantation, SCID Mice, Pathologic Neovascularization, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Stromal Cells, Thalidomide, Xenograft Model Antitumor Assays, Animals, Mice |
| Source: | Clinical Cancer Research |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Volume: | 12 |
| Number: | 18 |
| Page Range: | 5526-5532 |
| Date: | 15 September 2006 |
| Official Publication: | https://doi.org/10.1158/1078-0432.CCR-06-0719 |
| PubMed: | View item in PubMed |
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