Endothelial cells (EC) were extracted through a lectin-based method from bone marrow of 57 patients with active multiple myeloma (MM) and compared with their healthy quiescent counterpart, human umbilical vein EC (HUVEC). MMECs exhibit specific antigens that indicate ongoing angiogenesis and embryo vasculogenesis; solid intercellular connections, hence stability of MM neovessels; and frequent interactions with plasma cells, hence tumor dissemination. They show heterogeneous antigen expression, hence existence of subsets. Their main genetic markers are indicative of a vascular phase. They show intrinsic angiogenic ability, because they rapidly form a capillary network in vitro, and extrinsic ability, because they generate numerous new vessels in vivo. They vividly secrete growth and invasive factors for plasma cells. They signal through kinases mandatory for development of neovascularization. Ultrastructurally, they are abnormal and show metabolic activation, like tumor ECs. Thalidomide heavily interferes with their functions. Vasculogenesis and angiogenesis might contribute to the MM vascular tree and progression, in the form of growth, invasion, and dissemination. In view of the heterogeneity of the antigenic phenotype of MMECs, a mixture (or a sequence) of antiangiogenic agents coupled with thalidomide would seem plausible for the biologic management of MM.

NAMI-A is a ruthenium-based compound with selective anti-metastasis activity in experimental models of solid tumours. We studied whether this activity was dependent on anti-angiogenic ability of NAMI-A. We thus investigated its in vitro effects on endothelial cell functions necessary for angiogenesis to develop, as well as its in vivo effects in the chick embryo chorioallantoic membrane model. Endothelial cell proliferation, chemotaxis, and secretion of the matrix-degrading enzyme metalloproteinase-2 were inhibited by NAMI-A in a dose-dependent manner, and without morphologic signs of cell apoptosis or necrosis. Lastly, NAMI-A displayed a dose-dependent in vivo anti-angiogenic activity in the chorioallantoic membrane model. These data suggest that the anti-angiogenic activity of NAMI-A can contribute to its anti-metastatic efficacy in mice bearing malignant solid tumours.

The reaction of platinum(II) [Pt(II)] or palladium(II) [Pd(II)] with 2-acetyl pyridine 4N-ethyl thiosemicarbazone, HAc4Et (1) results in the complexes [Pt(Ac4Et)2] (2) and [Pd(Ac4Et)2] (3). In a panel of human tumor cell lines of different origins (breast, colon, and ovary cancers), and containing also cisplatin-refractory/resistant cell lines, the in vitro growth inhibitory effect of 1–3 was compared to that of cisplatin by using the sulforodamine B assay. After a 96-hour continuous treatment, both the thiosemicarbazone HAc4Et and the metal compounds [Pt(Ac4Et)2] and [Pd(Ac4Et)2] exhibit very remarkable growth inhibitory activities with mean IC50 values of 0.9 nM (0.22–2.47 nM), 0.7 nM (0.15–2 nM) and 0.5 nM (0.17–1.02 nM), respectively. In contrast, cisplatin shows a markedly lower growth inhibitory potency, the mean IC50 in the panel being 2.8 µM (0.2–8 µM). In addition to their major cell growth inhibitory potency, complexes 1–3 are characterized by a growth inhibitory profile different from that of cisplatin, being active towards cisplatin-refractory tumor cell lines. These findings, along with the ability of completely overcoming acquired cisplatin resistance from either multifocal or reduced uptake origin, confirm the antitumor potential of HAc4Et and support the hypothesis that both [Pt(Ac4Et)2] and [Pd(Ac4Et)2] complexes can be characterized by cellular pharmacological properties distinctly different from those of cisplatin.