Liposomal Nanoparticles of a Spleen Tyrosine Kinase P-Site Inhibitor Amplify the Potency of Low Dose Total Body Irradiation Against Aggressive B-Precursor Leukemia and Yield Superior Survival Outcomes in Mice
| Autor: | Sanjive Qazi, Jianjun Cheng, Dorothea E. Myers, Fatih M. Uckun |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Bone marrow transplantation
Radiation resistance medicine.medical_treatment lcsh:Medicine Nod General Biochemistry Genetics and Molecular Biology Total body irradiation Medicine Potency Cancer lcsh:R5-920 Leukemia business.industry Precision medicine lcsh:R General Medicine medicine.disease Personalized medicine 3. Good health Radiation therapy Apoptosis Low Dose Radiation Therapy Cancer research business lcsh:Medicine (General) |
| Zdroj: | EBioMedicine, Vol 2, Iss 6, Pp 554-562 (2015) |
| ISSN: | 2352-3964 |
| Popis: | This study was designed to improve the efficacy of radiation therapy against radiation-resistant leukemia. We report that the potency of low dose radiation therapy against B-precursor acute lymphoblastic leukemia (BPL) can be markedly enhanced by combining radiation with a liposomal nanoparticle (LNP) formulation of the SYK-P-site inhibitor C61 ("C61-LNP"). C61-LNP plus low dose total body irradiation (TBI) was substantially more effective than TBI alone or C61-LNP alone in improving the event-free survival outcome NOD/SCID mice challenged with an otherwise invariably fatal dose of human ALL xenograft cells derived from relapsed BPL patients. C61-LNP plus low dose TBI also yielded progression-free survival, tumor-free survival and overall survival outcomes in CD22ΔE12×BCR–ABL double transgenic mice with advanced stage, radiation-resistant BPL with lymphomatous features that were significantly superior to those of mice treated with TBI alone or C61-LNP alone. |
| Databáze: | OpenAIRE |
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