期刊
ONCOTARGET
卷 8, 期 7, 页码 11219-11227出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.14494
关键词
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资金
- Department of Defense/Air Force Office of Scientific Research [FA95501310192]
- National Institutes of Health/National Cancer Institute [U54CA151880, R01CA167041]
- T32 Carcinogenesis training grant [T32CA09560]
- Northwestern University Flow Cytometry Facility
- Cancer Center Support [NCI CA060553]
- Special Program Molecular Clinical Oncology-5 per Mille [9965]
- Italian Association of Cancer Research (AIRC) [17006]
- [15189]
Chronic lymphocytic leukemia (CLL) remains incurable despite the introduction of new drugs. Therapies targeting receptors and pathways active specifically in malignant B cells might provide better treatment options. For instance, in B cell lymphoma, our group has previously shown that scavenger receptor type B-1 (SR-B1), the high-affinity receptor for cholesterol-rich high-density lipoproteins (HDL), is a therapeutic target. As evidence suggests that targeting cholesterol metabolism in CLL cells may have therapeutic benefit, we examined SR-B1 expression in primary CLL cells from patients. Unlike normal B cells that do not express SR-B1, CLL cells express the receptor. As a result, we evaluated cholesterol-poor synthetic HDL nanoparticles (HDL NP), known for targeting SR-B1, as a therapy for CLL. HDL NPs potently and selectively induce apoptotic cell death in primary CLL cells. HDL NPs had no effect on normal peripheral blood mononuclear cells from healthy individuals or patients with CLL. These data implicate SR-B1 as a target in CLL and HDL NPs as targeted monotherapy for CLL.
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