Angiogenesis plays an important role in multiple myeloma (MM) progression. Various mitogens such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) have been implicated in the angiogenic process of various malignancies. Interleukin-6 (IL-6) is a growth factor of myeloma cells and its signaling is mediated via a cell surface receptor complex (IL-6r). IL-6 and tumor necrosis factor-alpha (TNF-a) are involved in the secretion of VEGF by IL-6r expressing myeloma cells. In this study, serum FGF-2, VEGF, IL-6r, and TNF-a were measured in 46 untreated MM patients and were studied in relation to disease stage (by Salmon-Durie criteria) and severity [assessed by serum b 2microglobulin (b 2 M), C-reactive protein (CRP), a 1 -antitrypsin (a 1 AT), and lactic dehydrogenase (LDH) levels]. The results showed that FGF-2, VEGF, IL-6r, and TNF-a were significantly elevated in MM patients in comparison to controls (p<0.008) and were significantly higher in stage III disease in comparison to stages I and II (p<0.03). The mean concentrations of IL-6r were 877€374, 1220€308, 1431€878, and 453€180 pg/ml for stages I, II, and III and controls, respectively. Levels of b 2 M, a 1 AT, CRP, and LDH were all significantly higher in MM patients than controls and increased with advancing stage of disease. There were positive correlations of both VEGF and FGF-2 with IL-6r, TNF-a, b 2 M, a 1 AT, CRP, and LDH. We conclude that IL-6r and TNF-a increase in parallel to VEGF and FGF-2 with increasing stage of MM disease. These molecules correlate with biochemical markers of disease activity and may play a role in the progression of multiple myeloma.
Technetium 99m-2-methoxyisobutylisonitrile (Tc-99m MIBI) is a lipophilic agent that accumulates preferentially within living malignant cells due to the higher transmembrane electrical potential as a consequence of the higher metabolic rate than in the surrounding normal cells. It has been effectively used to detect malignant tumors at diagnosis and follow-up and has been reported to be useful in detecting disease lesions in multiple myeloma. We studied 28 consecutive patients with multiple myeloma at diagnosis to determine the value of Tc-99m MIBI in comparison with Tc-99m methylene diphosphonate (MDP), conventional X-rays, computed tomography (CT) scan, and magnetic resonance imaging (MRI). We found 26 patients with obvious osteolytic lesions in X-rays, 22 patients with positive Tc-99m MIBI scans, and 15 patients with positive Tc-99m MDP scans. There was no coincidence of the positive lesions in the two scans, while in two patients the osteolytic areas were positive in the Tc-99m MDP scans, and in one case the osteolytic area was positive in the Tc-99m MIBI scan. The intensity of Tc-99m MIBI scans correlated with disease activity as determined by lactate dehydrogenase (LDH) (p<0.05), C-reactive protein (CRP) (p<0.01), beta2-microglobulin (p<0.05), and serum ferritin (p<0.01). We believe that Tc-99m MIBI scintigraphy can detect bone marrow lesions in myeloma patients that cannot be detected by other imaging methods and that it can be useful especially in solitary myeloma to exclude other involved sites. In addition, it could be a prognostic factor related to disease activity and multidrug resistance. We believe that a multicenter study is needed to evaluate the usefulness of this agent.
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