MM patients were classified as stage I or II when analysed at the onset of the disease and were treated with conventional therapeutic regimens MAPK inhibitor including melphalan (0.25 mg/Kg body weight/day) and prednisone (2 mg/Kg body weight) for 4 consecutive days. The course was repeated at every 6th week until tumour progression). The response was defined https://www.selleckchem.com/products/BI6727-Volasertib.html as minor response

when the serum M-protein had decreased by > 25% but < 50% or the urinary BJ had decreased by >50% but not to < 0.2 g in 24 h. The non response group was defined by serum M-protein levels that had decreased to < 25% or by urine BJ protein levels that had decreased to < 50% of initial levels. Intermediate situations were CBL-0137 solubility dmso categorized as a no change disease. Table 1 Main characteristics of MGUS, MM patients and healthy controls Group (n) MGUS (71) MM (77) Control (55) Gender       Male 38 49 28 Female 33 28 27 Age (y)         65.9 ± 10.5 66.7 ± 10.7 59.6 ± 14.5 Isotype (H)       IgG 62 48 — IgA

3 28 — IgM 6 — – IgD — 1 — Isotype (L)       K 38 54 — λ 33 23 — s-M Protein (g/L)         9.42 ± 4.61 25.8 ± 10.7 — Bence Jones       Yes 41 63 — No 30 14 — Clinical stage (*)         — I – II — Age is given as mean ± SD. MGUS vs MM: p = 0.11; MGUS vs CTR: p = 0.005; MM vs CTR: p = 0.0001; Gender: MGUS vs MM: p = 0.30; MGUS vs CTR: p = 0.91; MM vs CTR: p = 0.21. s-M Protein concentration is expressed as mean ± SD. MGUS vs MM: p = 0.0001 (*) according to the Durie & Salmon criteria [26]. Some of the myeloma patients, selected for having at least 6 subsequent determinations and from whom venous samples had been drawn at regular intervals starting from diagnosis, were included for a detailed analysis of the IGF-I changes during the clinical course of the disease (about 2.5 years). Two representative examples are shown in Figure 1 Figure 1 Serial measurements of IGF-1 and serum M-Protein (s-MP) from diagnosis (0) to last follow-up before death in two MM patients. Serum MP concentrations were derived from medical

records. The first Cyclooxygenase (COX) arrow indicates when MP treatment started, according to the protocol described in “”Methods; the others two arrows indicate the repetition of new cycles of therapy due to disease progression. [symbols: cube = IGF-I; diamond = s-M protein]. Cytokine measurements The detection of serum cytokines was performed on peripheral blood samples processed within 1 h after venipuncture by centrifugation (1500 gfor 10 min) Serum samples were collected from MGUS and MM patients as well as from 55 healthy blood donors and were stored at -70°C until testing. The angiogenic factors (VEGF and bFGF) were measured with a quantitative ELISA (Quantikine™ and Quantikine®; R&D Systems, Minneapolis, MN, USA), according to the manufacturer’s instructions and expressed as pg/ml.