Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro.
نویسندگان
چکیده
Thalidomide and its analog, Lenalidomide, are in current use clinically for treatment of multiple myeloma, complications of leprosy and cancers. An additional analog, Pomalidomide, has recently been licensed for treatment of multiple myeloma, and is purported to be clinically more potent than either Thalidomide or Lenalidomide. Using a combination of zebrafish and chicken embryos together with in vitro assays we have determined the relative anti-inflammatory activity of each compound. We demonstrate that in vivo embryonic assays Pomalidomide is a significantly more potent anti-inflammatory agent than either Thalidomide or Lenalidomide. We tested the effect of Pomalidomide and Lenalidomide on angiogenesis, teratogenesis, and neurite outgrowth, known detrimental effects of Thalidomide. We found that Pomalidomide, displays a high degree of cell specificity, and has no detectable teratogenic, antiangiogenic or neurotoxic effects at potent anti-inflammatory concentrations. This is in marked contrast to Thalidomide and Lenalidomide, which had detrimental effects on blood vessels, nerves, and embryonic development at anti-inflammatory concentrations. This work has implications for Pomalidomide as a treatment for conditions Thalidomide and Lenalidomide treat currently.
منابع مشابه
Reply to D’Amato et al. and Zeldis et al.: Screening of thalidomide derivatives in chicken and zebrafish embryos.
We thank D’Amato et al. (1) and Zeldis et al. (2) for their interest and comments on our article in PNAS (3). We carried out a screen of lenalidomide and pomalidomide primarily in chicken and zebrafish embryos, but also in several in vitro assays. Our goal was to determine any differential actions or responses and to visualize effects live and in vivo (3). Identifying such differences, we reaso...
متن کاملIn vitro Effect of Pomalidomide on Bone Marrow Mononuclear Cells from Multiple Myeloma Patients
Background: Many features of anticancer drugs, including cytotoxicity and/or cytokine induction, are studied using cell lines orhuman blood leukocytes. However, in a disease such as multiple myeloma, most cancerous cells are resided within bone marrowmononuclear cells. In the present study, we investigated the effect of pomalidomide on apoptosis and IL-2 production of bonemarrow mononuclear cel...
متن کاملInvestigation of Toxicological Effects of di-2-ethylhexyl with Fish Embryo Test (FET) in Zebrafish (Danio rerio)
Di(2-ethylhexyl)phthalate (DEHP) is a plasticizer in a variety of consumer products. Given the adverse toxicity effects of DEHP on living organisms, its high consumption and dispersal has been caused a serious concern. . Nowedays, the Fish Embryo Test (FET) method is widely used among the conventional methods of toxicology .The aim of the this study was to determine the acute toxicity of Di(2-e...
متن کاملEstablishment and the importance of chicken pluripotent stem cells and their role in vaccine production: review article
Chick embryos are a great historical research model in basic and applied sciences. Along with other animal models, avian and specifically chicken embryo has been attended, as well. Avian fertilized eggs as a natural bioreactor are an efficient tool for producing recombinant proteins and vaccines manufacturing. Due to the limitations of birds' eggs for viral replication, avian stem cells culture...
متن کاملThe Tween 80 Toxicity in Chicken Embryos and Effect on the Kinetics of Newcastle Disease Virus Replication
Background: Non-ionic surfactant, Tween-80 (TW80) is commonly used for drug delivery due to its effect on the cell membrane permeation. The change in permeability can also increase viral infectivity in cells. This study was undertaken to improve upon Newcastle disease virus (NDV) titer cultivated with embryonic chicken eggs. Methods: The toxicity of TW80 was investigated against chicken embryo...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 110 31 شماره
صفحات -
تاریخ انتشار 2013