The anti-tumour effects of thalidomide have been associated with its anti-angiogenic properties. Second generation thalidomide analogues are distinct compounds with enhanced therapeutic potential. Although these compounds are beginning to enter trials for the treatment of cancer there is very little information regarding the anti-angiogenic activity of these clinically relevant compounds. Furthermore, it is not known how the various immunomodulatory activities of these compounds relate to anti-angiogenic activity. In this study we assessed the anti-angiogenic activity of compounds from both IMiD TM and SelCID TM classes of analogues using a novel in vitro multicellular human assay system and the established rat aorta assay. Our results show that both the IMiDs and SelCIDs tested are significantly more potent than thalidomide. The anti-angiogenic potency of the analogues was not related to inhibition of endothelial cell proliferation, nor their TNF-a/PDE type 4 inhibitory properties. However, anti-migratory effects in vitro and inhibition of tumour growth in vivo was observed with the analogue IMiD-1 (clinically known as REVIMID TM ). Our results show that anti-angiogenic activity spans both currently defined classes of thalidomide analogue and is not related to their previously described immunomodulatory properties. Identification of the differential effects of these compounds will enable targeting of such compounds into the appropriate clinical setting.

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Objectives-Immunological abnormalities in idiopathic dilated cardiomyopathy (DCM) include an increase in soluble interleukin(IL)-2 receptor, disease specific cardiac autoantibodies, an HLA-DR4 association, and familial aggregation of disease; however, cytokine profiles have not been defined. Serum concentrations of IL-2, IL-4, IL-10, and IL-12 were measured in patients with DCM (WHO criteria), relatives with asymptomatic left ventricular enlargement (LVE), patients with ischaemic heart failure (IHD), and healthy controls. Design-Serum from 20 individuals from each of the four groups was assayed for cytokine concentrations by a commercial enzyme linked immunosorbent assay. Results-IL-2 concentrations were abnormally increased in DCM patients and relatives with LVE. Concentrations of IL-10 were increased in DCM patients. Concentrations of IL-4 and IL-12 were not increased in any of the groups. Conclusion-These abnormalities may reflect defective/inappropriate T cell function in patients with DCM and in their relatives with LVE.