Axon extension during development is guided by many factors, but the signaling mechanisms responsible for its regulation remain largely unknown. We have now investigated the role of the transmembrane protein CD47 in this process in N1E-115 neuroblastoma cells. Forced expression of CD47 induced the formation of neurites and filopodia. Furthermore, an Fc fusion protein containing the extracellular region of the CD47 ligand SHPS-1 induced filopodium formation, and this effect was enhanced by CD47 overexpression. SHPS-1-Fc also promoted neurite and filopodium formation triggered by serum deprivation. Inhibition of Rac or Cdc42 preferentially blocked CD47-induced formation of neurites and filopodia, respectively. Overexpression of CD47 resulted in the activation of both Rac and Cdc42. The extracellular region of CD47 was sufficient for the induction of neurite formation by forced expression, but the entire structure of CD47 was required for enhancement of filopodium formation by SHPS-1-Fc. Neurite formation induced by CD47 was also inhibited by a mAb to the integrin ␤3 subunit. These results indicate that the interaction of SHPS-1 with CD47 promotes neurite and filopodium formation through the activation of Rac and Cdc42, and that integrins containing the ␤3 subunit participate in the effect of CD47 on neurite formation. INTRODUCTIONThe extension of axons from neurons to their target cells during development of the nervous system is guided by a variety of environmental cues, which include diffusible chemoattractants and chemorepellents, extracellular matrix proteins, and cell adhesion molecules (Tessier-Lavigne and Goodman, 1996;Dickson, 2002). In response to these guidance cues, the growth cone of the axon produces and retracts filopodia and lamellipodia, processes that require the temporal and spatial regulation of the actin cytoskeleton. Members of the Rho family of small G proteins, including Rho, Rac, and Cdc42, are implicated as key mediators that link guidance signals to rearrangement of the actin cytoskeleton (Ridley et al., 1992;Nobes and Hall, 1995;Kozma et al., 1997;Luo et al., 1997;Hirose et al., 1998;Takai et al., 2001;Arakawa et al., 2003). Although Rac and Cdc42 promote neurite extension, Rho inhibits it or induces growth cone collapse. These proteins are also implicated in dendritic development (Threadgill et al., 1997). Although certain guidance factors, including slit, semaphorin, and ephrin, have been shown to regulate Rho family proteins (Wahl et al., 2000;Whitford and Ghosh, 2001;Wong et al., 2001), it remains unclear how other extracellular cues control neurite extension through these small G proteins.CD47, also known as integrin-associated protein (IAP), was originally identified in association with the integrin ␣v␤3 (Brown et al., 1990). It is a member of the immunoglobulin (Ig) superfamily, possessing an Ig-V-like extracellular region, five putative transmembrane domains, and a short cytoplasmic tail (Brown and Frazier, 2001). CD47 is implicated in the regulation of multiple cellular processe...

18F‐Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is usually used to screen malignancy in patients with dermatomyositis (DM). Additionally, it is well known that FDG‐PET/CT provides valuable information for evaluating the activity of several inflammatory diseases, such as sarcoidosis, atherosclerosis, inflammatory bowel disease and rheumatoid arthritis. Therefore, the objective of this study was to evaluate the clinical usefulness of FDG‐PET/CT for the detection of inflammatory lesions and disease activity of both myopathy and interstitial lung disease (ILD) in DM patients. We measured the maximum standardized uptake value (SUVmax) in the muscles and lungs in 22 DM patients, and compared with magnetic resonance imaging (MRI) and high‐resolution computed tomography (HRCT) findings in the same muscle and lung regions as well as with clinical findings. We found that the location of increased FDG uptake was nearly consistent with the region of ILD and myositis detected by HRCT or MRI, respectively. There was a significant positive correlation between lung HRCT score and SUVmax in each lung. Serum Krebs von den Lungen‐6 levels also revealed significant positive correlation with total SUVmax of right and left lungs. Regarding FDG‐PET/CT and myopathy, total SUVmax in the muscles was significantly correlated with serum cytokeratin levels. Our results suggest that FDG uptake (SUVmax) might be useful for not only the detection of malignant tumors, but also the evaluation of the location and activity of ILD and myositis in DM patients.

Objective Detectable serum thyroglobulin (Tg) in patients with differentiated thyroid carcinoma (DTC) after total thyroidectomy indicates progression of the disease. Thyroglobulin doubling-time (TgDT) is a powerful prognostic predictor in patients with DTC. We aimed to evaluate the value of the dynamic TgDT for early detection of progressive disease (PD) in the patients of metastatic DTC with 131I radioactive iodine (RAI) therapy. Methods We retrospectively evaluated 21 patients undergoing RAI therapy with metastatic DTC. Patients were defined as PD or non-PD according to Response Evaluation Criteria in Solid Tumors 1.1. TgDT was calculated by Excel-based software using Tg values measured during routine follow-up. Whole data (WDT), initial four data (IDT) and recent four data (RDT) of TgDT after total thyroidectomy were calculated and compared. Results Among the 21 patients (10 men; median age, 62 years old; range, 33–80), 11 patients were classified into PD and 10 were into non-PD. The initial Tg after total thyroidectomy showed a significant difference between PD and non-PD patients (P = 0.013). Short WDT, IDT and RDT (less than one year) showed a high correlation with PD (P < 0.05). RDT showed the highest predictive value for PD (P < 0.001). All the 11 PD patients showed RDT less than one year before PD (median follow-up, 157 days; range, 88–252). Conclusions RDT is a powerful PD predictor in patients with metastatic DTC. Dynamic monitoring of RDT should be applied for the early detection of PD in clinic.

No abstract

Objectives The aim of this study was to identify whether diffusion-weighted magnetic resonance imaging (DW-MRI) can predict the malignant behavior of preoperative well-differentiated pancreatic neuroendocrine tumors (PanNETs). Method Forty patients with PanNETs who underwent pancreatectomy were enrolled in this study. The apparent diffusion coefficient (ADC) values were measured. Clinicopathological factors were compared in patients with high ADC and low ADC values and in patients with and without lymph node metastasis (LNM). Result The low ADC group was significantly associated with higher Ki-67 index, higher mitotic count, larger tumor size, higher rate of LNM, and venous invasion. In patients with low ADC values, the incidence of LNMs was 33.3%. In patients with high ADC values, there were no patients with LNM being 0%. A significant negative correlation was found between the mean ADC values and the Ki-67 index and between the mean ADC values and the mitotic count. In multivariate analysis, neural invasion and mean ADC values B 1458 were independent predictors of LNM. Conclusion ADC values obtained using DW-MRI in the preoperative assessment of patients with PanNETs might be a useful predictor of malignant potential, especially LNM.