• TSP-1 secreted by bone marrow stromal cells contributes to retinal ganglion cell neurite outgrowth and survival.

      Yu, Keming; Ge, Jian; Summers, James Bradley; Li, Fan; Liu, Xuan; Ma, Ping; Kaminski, Joseph; Zhuang, Jing; Department of Radiology (2008-06-25)
      BACKGROUND: Bone marrow stromal cells (BMSCs) are pluripotent and thereby a potential candidate for cell replacement therapy for central nervous system degenerative disorders and traumatic injury. However, the mechanism of their differentiation and effect on neural tissues has not been fully elucidated. This study evaluates the effect of BMSCs on neural cell growth and survival in a retinal ganglion cell (RGCs) model by assessing the effect of changes in the expression of a BMSC-secreted protein, thrombospondin-1 (TSP-1), as a putative mechanistic agent acting on RGCs. METHODS AND FINDINGS: The effect of co-culturing BMSCs and RGCs in vitro was evaluated by measuring the following parameters: neurite outgrowth, RGC survival, BMSC neural-like differentiation, and the effect of TSP-1 on both cell lines under basal secretion conditions and when TSP-1 expression was inhibited. Our data show that BMSCs improved RGC survival and neurite outgrowth. Synaptophysin, MAP-2, and TGF-beta expression are up-regulated in RGCs co-cultured with BMSCs. Interestingly, the BMSCs progressively displayed neural-like morphology over the seven-day study period. Restriction display polymerase chain reaction (RD-PCR) was performed to screen for differentially expressed genes in BMSCs cultured alone or co-cultured with RGCs. TSP-1, a multifactorial extracellular matrix protein, is critically important in the formation of neural connections during development, so its function in our co-culture model was investigated by small interfering RNA (siRNA) transfection. When TSP-1 expression was decreased with siRNA silencing, BMSCs had no impact on RGC survival, but reduced neurite outgrowth and decreased expression of synaptophysin, MAP-2 and TGF-beta in RGCs. Furthermore, the number of BMSCs with neural-like characteristics was significantly decreased by more than two-fold using siRNA silencing. CONCLUSIONS: Our data suggest that the TSP-1 signaling pathway might have an important role in neural-like differentiation in BMSCs and neurite outgrowth in RGCs. This study provides new insights into the potential reparative mechanisms of neural cell repair.
    • Combined use of preoperative 18F FDG-PET imaging and intraoperative gamma probe detection for accurate assessment of tumor recurrence in patients with colorectal cancer.

      Sarikaya, Ismet; Povoski, Stephen P; Al-Saif, Osama H; Kocak, Ergun; Bloomston, Mark; Marsh, Steven; Cao, Zongjian; Murrey, Douglas A; Zhang, Jun; Hall, Nathan C; et al. (2007-08-09)
      BACKGROUND: The purpose of this study was to combine intraoperative gamma probe (GP) detection with preoperative fluorine 18-fluoro-2-deoxy-glucose positron emission tomography (18F FDG-PET) imaging in order to improve detection of tumor recurrence in colorectal cancer (CRC) patients. METHODS: Twenty-one patients (12 females, 9 males) with a mean age of 54 years (range 31-78) were enrolled. Patients were suspected to have recurrent CRC by elevated CEA (n = 11), suspicious CT findings (n = 1), and clinically suspicious findings (n = 9). Preoperative FDG-PET scan and intraoperative GP study were performed in all patients. Mean time interval between preoperative FDG-PET scan and surgery was 16 days (range 1-41 days) in 19 patients. For intraoperative GP studies, 19 patients were injected with a dose of 10-15 mCi 18F FDG at approximately 30 minutes before the planned surgery time. In two patients, the intraoperative GP study was performed immediately after preoperative FDG-PET scan. RESULTS: Preoperative FDG-PET and intraoperative GP detected 48 and 45 lesions, respectively. A total of 50 presumed site of recurrent disease from 20 patients were resected. Thirty-seven of 50 presumed sites of recurrent disease were histological-proven tumor positive and 13 of 50 presumed sites of recurrent disease were histological-proven tumor negative. When correlated with final histopathology, the number of true positive lesions and false positive lesions by preoperative FDG-PET and intraoperative GP were 31/9 and 35/8, respectively. Both preoperative FDG-PET and intraoperative GP were true positive in 29 lesions. Intraoperative GP detected additional small lesions in the omentum and pelvis which were not seen on preoperative FDG-PET scan. FDG-PET scan demonstrated additional liver metastases which were not detected by intraoperative GP. Preoperative FDG-PET detected distant metastasis in the lung in one patient. The estimated radiation dose received by a surgeon during a single 18F FDG GP surgery was below the occupational limit. CONCLUSION: The combined use of preoperative FDG-PET and intraoperative GP is potentially helpful to the surgeon as a roadmap for accurately locating and determining the extent of tumor recurrence in patients with CRC. While intraoperative GP appears to be more sensitive in detecting the extent of abdominal and pelvic recurrence, preoperative FDG-PET appears to be more sensitive in detecting liver metastases. FDG-PET is also a valuable method in detecting distant metastases.