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Bone morphogenetic protein-2 (BMP-2), a member of transforming growth factor-β superfamily, plays a crucial role in migration and metastasis of human cancer cells. Integrins are the major adhesive molecules in mammalian cells. Here we found that BMP-2 directed the migration and increased cell surface and mRNA expression of β1 integrin in human chondrosarcoma cancer cells (JJ012). Pretreated of JJ012 cells with phosphatidylinositol 3-kinase inhibitor (PI3K; Ly294002) or Akt inhibitor inhibited the BMP-2-mediated migration and integrin expression. BMP-2 increased the phosphorylation of p85 subunit of PI3K and serine 473 of Akt. In addition, NF-κB inhibitor (PDTC) or IκB protease inhibitor (TPCK) also inhibited BMP-2-mediated cells migration and integrin upregulation. Stimulation of JJ012 cells with BMP-2 induced IκB kinase (IKKα/β) phosphorylation, IκB phosphorylation, p65 Ser536 phosphorylation, and κB-luciferase activity. Furthermore, the BMP-2-mediated increasing of IKKα/β phosphorylation, IκB phosphorylation, and p65 Ser536 phosphorylation were inhibited by Ly294002 and Akt inhibitor. Co-transfection with p85 and Akt mutants also reduced the BMP-2-induced κB-luciferase activity. Taken together, these results suggest that the BMP-2 acts through PI3K/Akt, which in turn activates IKKα/β and NF-κB, resulting in the activations of β1 integrin and contributing the migration of human chondrosarcoma cells. J. Cell. Physiol. 217: 846–855, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: Laboratory measurements such as leucocyte count, neutrophil percentage and C-reactive protein (CRP) concentration are commonly used as diagnostic aids in patients with suspected acute appendicitis. The present study aimed to clarify the role of these laboratory tests in diagnosing acute appendicitis. Methods: The medical records of 897 patients who underwent appendicectomy for suspected acute appendicitis during a 30-month period were retrospectively reviewed. The laboratory findings were correlated with the histopathology of the excised appendices. Data were analysed to calculate the sensitivity and specificity of the individual tests, as well as the test combinations. Results: Histologically verified appendicitis was found in 740 of the 897 patients (82.5%). The rise in leucocyte count and neutrophil percentage correlated with the degree of appendiceal inflammation. The median CRP level was much higher in the patients with ruptured appendicitis compared with that in patients with a normal appendix (96.8 vs 39.6 mg/L, P < 0.001). However, patients with uncomplicated appendicitis had a lower median CRP concentration than those with a normal appendix, although the difference was not statistically significant (24.1 vs 39.6 mg/L, P = 0.079). The sensitivity of leucocyte count, neutrophil percentage and CRP in diagnosing acute appendicitis was 85.8, 87.2 and 76.5%, respectively, whereas the specificity was 31.9, 33.1 and 26.1%, respectively. Of the 740 patients with acute appendicitis, only six had all three tests simultaneously within the reference interval. Conclusions: Abnormal laboratory findings cannot reliably deliver a diagnosis of acute appendicitis. However, acute appendicitis is very unlikely when leucocyte count, neutrophil percentage and CRP level are simultaneously normal. [ABSTRACT FROM AUTHOR]