Production of proangiogenic cytokines during thalidomide treatment of multiple myeloma

Recently a growing number of studies have suggested the efficacy of thalidomide (THAL) in the treatment of relapsed or resistant multiple myeloma. Some of these studies indicate that the thalidomide antimyeloma effect is associated with decreased vessel density. Here we first present our experience with THAL treatment and then focus on the determination of the role of proangiogenic cytokines during THAL therapy. Thirty relapsing or resistant multiple myeloma (MM) patients were treated with THAL at a median dose of 400 mg/daily. Eighteen responded to THAL therapy and 12 were resistant or intolerant to THAL. We determined the plasma level of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) as the main biological parameters associated with tumour angiogenesis. In addition I1-6 and TNFalpha levels were also assayed. Assessment of peripheral blood (PB) and bone marrow (BM) cytokine levels were done before and during THAL treatment at weeks 4 and 8 of therapy. In the responder group VEGF, bFGF I1-6 and TNFalpha concentrations were significantly decreased after four weeks of therapy both in PB and BM. In the non-responder group no significant changes in bFGF and VEGF levels were observed. However, a significant increase in IL-6 and TNF concentrations was evident. We conclude that the significant decrease of VEGF, bFGF, I1-6 and TNFalpha concentrations reflected response to THAL therapy. Also it seems that VEGF is a better marker of response to treatment than bFGF.     

Distribution and binding of positional isomers of 125I-hippuran, 125I-benzoate and 125I-phenylacetate in the blood components of mice

On examining the dependencies between the parameters characterizing the structure and distribution of substances of acid character in the blood of experimental mice in the in vitro conditions it was demonstrated that both plasma and erythrocyte binding are structurally dependent. With increasing lipophilicity, the values of the drug fraction bound to proteins in the separated plasma, the values of the fraction bound to plasma proteins in the samples of whole blood, and the distribution into the erythrocytes in a suspension of erythrocytes are increased. With increasing lipophilicity, the distribution into the erythrocytes in the samples of the whole blood and the fraction in the plasma blood fluid are decreased.