Some of the divergences observed may be explained by the fact that various eveniences may influence the serum IGF-I levels: age and gender [47], inflammatory processes [48], other concomitant diseases [49, 50], endocrine diseases [47], nutrition [47], drug administration and liver toxicity. Furthermore, melphalan therapy, which is hepatotoxic and therefore

should reduce IGF-I synthesis, has been reported to increase IGF-I molecules after the 4th course [40], possibly when it was effective in restoring the peripheral blood IGF-I amounts. It is also possible to speculate that the cytotoxic effect of therapy should release a great amount of endocellular molecules from necrotic cells with induction of inflammatory processes and IGF-I drop. In conclusion, as previously reported for other neoplastic diseases [42, 51], serum IGF-I selleck chemicals concentrations are clearly reduced in case of open disease. Therefore, a clinical use of serum determinations of this molecule should be made very carefully since this substance does not show a clear specificity for MM. A possible role of IGF-I as putative monitoring marker of malignant disease seems to emerge by our study, even though specific clinical trials need to be planned and the possible interference of other factors in serum

determinations should be considered. References 1. Berenson JR, Ed: Biology and management of multiple myeloma. Humana Press New Jersey, USA 2004. 2. Zhong H, Bowen JP: Antiangiogenesis drug www.selleck.co.jp/products/Fludarabine(Fludara).html design: multiple pathways targeting tumour vasculature. Curr Med Chem 2006, 13: 849–862.CrossRefPubMed 3. Shih T, Lindley C: Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies. Clin Torin 1 Ther 2006, 28: 1779–1802.CrossRefPubMed 4. Rosinol L, Cibeira MT, Segarra M, Cid MC, Filella X, Aymerich M, Rozman M, Arenillas L, Esteve J, Blade J, Montserrat E: Response to Thalidomide in multiple myeloma: impact of angiogenic factors. Cytokine 2004, 26: 145–148.CrossRefPubMed 5. Ribatti D, Nico B, Vacca A: Importance of the bone marrow microenvironment in inducine the angiogenic response in multiple myeloma. Oncogene 2006, 25: 4257–4266.CrossRefPubMed 6. Vacca A, Ribatti D: Bone marrow angiogenesis in multiple

myeloma. Leukemia 2006, 20: 193–199.CrossRefPubMed 7. Kumar S, Witzig TE, Timm M, Haug J, Wellik L, Kimlinger TK, Greipp PR, Rajkumar SV: Bone marrow angiogenic ability and expression of angiogenic cytokines in myeloma: evidence favoring loss of marrow angiogenesis inhibitory activity with disease progression. Blood 2004, 104: 1159–1165.CrossRefPubMed 8. Urba Ska-Rys H, Wierzbowska A, Robak T: Circulating angiogenic cytokines in multiple myeloma and related disorders. Eur Cytokine Netw 2003, 14: 40–51.PubMed 9. Ribas C, Colleoni GW, Silva MR, Carregoza MJ, Bordin JO: Prognostic significance of vascular endothelial growth factor immunoexpression in the context of adverse standard prognostic factors in multiple myeloma. Eur J Haematol 2004, 73: 311–317.CrossRefPubMed 10.