Some of the divergences observed may be explained by the fact that various eveniences may influence the serum IGF-I levels: age and gender , inflammatory processes , other concomitant diseases [49, 50], endocrine diseases , nutrition , 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 , 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 BKM120 clinical trial 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
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