التفاصيل البيبلوغرافية
| العنوان: |
The PARP inhibitor olaparib enhances the cytotoxicity of combined gemcitabine, busulfan and melphalan in lymphoma cells. |
| المؤلفون: |
Valdez, Benigno C.1 (AUTHOR) bvaldez@mdanderson.org, Li, Yang1 (AUTHOR), Murray, David2 (AUTHOR), Liu, Yan1 (AUTHOR), Nieto, Yago1 (AUTHOR), Champlin, Richard E.1 (AUTHOR), Andersson, Borje S.1 (AUTHOR) |
| المصدر: |
Leukemia & Lymphoma. 2017, Vol. 58 Issue 11, p2705-2716. 12p. 5 Black and White Photographs, 1 Chart, 2 Graphs. |
| مصطلحات موضوعية: |
*LYMPHOMA treatment, *BUSULFAN, *MELPHALAN, *ANTINEOPLASTIC agents, *POLY(ADP-ribose) polymerase, *COMBINATION drug therapy, *STEM cell transplantation, *JANUS kinases, *THERAPEUTICS |
| مستخلص: |
The combination of gemcitabine (Gem), busulfan (Bu), and melphalan (Mel) is a promising regimen for autologous stem-cell transplantation (SCT) for lymphomas. To further improve the efficacy of [Gem + Bu + Mel], we added poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (Ola). We hypothesized that Ola would inhibit the repair of damaged DNA caused by [Gem + Bu + Mel]. Exposure of J45.01 and Toledo cell lines to IC10–20 of individual drug inhibited proliferation by 6–16%; [Gem + Bu + Mel] by 20–27%; and [Gem + Bu + Mel + Ola] by 61–67%. The synergistic cytotoxicity of the four-drug combination may be attributed to activation of the DNA-damage response, inhibition of PARP activity and DNA repair, decreased mitochondrial membrane potential, increased production of reactive oxygen species, and activation of the SAPK/JNK stress signaling pathway, all of which may enhance apoptosis. Similar observations were obtained using mononuclear cells isolated from patients with T-cell lymphocytic leukemia. Our results provide a rationale for undertaking clinical trials of this drug combination for lymphoma patients undergoing SCT. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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