کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2755038 1149805 2013 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Combination of Pim Kinase Inhibitor SGI-1776 and Bendamustine in B-Cell Lymphoma
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیهوشی و پزشکی درد
پیش نمایش صفحه اول مقاله
Combination of Pim Kinase Inhibitor SGI-1776 and Bendamustine in B-Cell Lymphoma
چکیده انگلیسی

BackgroundSGI-1776 is a small-molecule Pim kinase inhibitor that primarily targets c-MYC–driven transcription and cap-dependent translation in mantle cell lymphoma (MCL) cells. Bendamustine is an alkylating chemotherapeutic agent approved for use in B-cell lymphoma that is known to induce DNA damage and initiate response to repair.Materials and MethodsOur studies were conducted in MCL cell lines JeKo-1 and Mino, as well as primary B-cell lymphoma samples of MCL and splenic marginal zone lymphoma (SMZL), where we treated cells with SGI-1776 and bendamustine. We measured levels of cellular apoptosis, macromolecule synthesis inhibition, and DNA damage induced by drug treatments.ResultsBoth SGI-1776 and bendamustine effectively induced apoptosis as single agents, and when used in combination, an additive effect in cell killing was observed in MCL cell lines JeKo-1 and Mino, as well as in MCL and SMZL primary cells. As expected, SGI-1776 was effective in inducing a decrease of global RNA and protein synthesis, and bendamustine significantly inhibited DNA synthesis and generated a DNA damage response. When used in combination, the effects were intensified in DNA, RNA, and protein synthesis inhibition compared with single-agent treatments.ConclusionThese data provide a foundation and suggest the feasibility of using Pim kinase inhibitors in combination with chemotherapeutic agents such as bendamustine in B-cell lymphoma.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinical Lymphoma Myeloma and Leukemia - Volume 13, Supplement 2, September 2013, Pages S355–S362
نویسندگان
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