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Tu Y.,The Forth Military Medical University | Lu J.,The Forth Military Medical University | Fu J.,Shanxi Medical University | Cao Y.,The Forth Military Medical University | And 4 more authors.
Japanese Journal of Clinical Oncology | Year: 2010

Objective: Neuroepithelial-transforming protein 1 is a member of the guanine nucleotide exchange factor family, a group of proteins which are known to activate and thereby regulate Rho family members. Deregulation of neuroepithelial-transforming protein 1 expression has been found in certain types of human tumors. To investigate its prognostic value in human gliomas, which is currently unknown, we examined the correlation between neuroepithelialtransforming protein 1 expression and prognosis in patients with gliomas. Methods: Immunohistochemical staining was performed to detect neuroepithelial-transforming protein 1 expression patterns in the biopsies from 96 patients with primary gliomas. Kaplan-Meier survival and Cox's regression analyses were performed to evaluate the prognosis of patients. Results: Immunohistochemical analysis with anti-neuroepithelial-transforming protein 1 antibody revealed that neuroepithelial-transforming protein 1 was significantly associated with the Karnofsky performance scale score and World Health Organization grades of patients with gliomas. Especially, the positive expression rates of neuroepithelial-transforming protein 1 were significantly higher in patients with higher grade (P = 0.001) and lower Karnofsky's performance scale score (P = 0.005). The median survival of patients with high neuroepithelialtransforming protein 1 expression was significantly shorter than that with low expression and without expression (316, 892 and 1180 days, respectively). Cox's multifactor analysis showed that the Karnofsky performance scale (P = 0.01), World Health Organization grade (P = 0.008) and neuroepithelial-transforming protein 1 (P = 0.006) were independent prognosis factors for human glioma. Conclusions: Taken together, our study indicates for the first time that neuroepithelial-transforming protein 1 status may be a highly sensitive marker for glioma prognosis and suggest that the expression patterns of neuroepithelial-transforming protein 1 might be a potent tool for predicting the clinical prognosis of glioma patients. © The Author (2010). Published by Oxford University Press. All rights reserved.


Lui N.-P.,Hong Kong Baptist University | Chen L.-W.,The Forth Military Medical University | Yung W.-H.,Chinese University of Hong Kong | Chan Y.-S.,University of Hong Kong | Yung K.K.-L.,Hong Kong Baptist University
PLoS ONE | Year: 2012

Here we report a previously unknown self repair mechanism during extremely early stages of rat Parkinsonism. Two important cell survival signaling cascades, Phosphatidylinositol-3 kinases (PI3K)/Akt pathway and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway, could be responsible for this potential endogenous rescue system. In the 6-hydroxydopamine-lesioned rat, the phosphorylated p44/42 MAPK and its downstream target, the phosphorylated Bad at Ser 112, were up-regulated at post-lesion day 3 and lasted for a couple of weeks. Although the change in the phosphorylated Akt kinase was negligible throughout the studied period, its downstream target, the phosphorylated Bad at 136, was increased from post-lesion day 3 to post-lesion day 14. In the mean time, nestin-positive reactive astrocytes with low levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) appeared at post-lesion day 3 in 6-hydroxydopamine-lesioned rat. BDNF was expressed in both striatum and substantia nigra whereas GDNF was displayed in striatum only. At post-lesion day 14, nestin, BDNF and GDNF expressions were diminished. These neurotrophic factors were believed to initiate the above anti-apoptotic signal transduction cascades as we could see that their expression patterns were similar. The data strongly suggest that there is an endogenous repair effort by evoking the cell survival signaling and possibly via the releases of BDNF and GDNF from nestin-immunoreactive reactive astrocytes. ERK/MAPK pathway was proposed to be the key endogenous neuroprotective mechanisms, particularly in early stages of rat Parkinsonism. However, the self repair effort is only functional within an extremely short time window immediately after onset. © 2012 Lui et al.


PubMed | Xi'an Jiaotong University, Oncology Research Laboratory, The Forth Military Medical University and University of Texas Southwestern Medical Center
Type: | Journal: Oncotarget | Year: 2016

Bladder cancer is the most common malignancy of the urinary tract for which the accurate measurement of minimal residual disease is critical to treatment and determining prognosis. Although cystoscope examination and voided urine cytology remain the current standard of care for detecting residual disease, these approaches are limited by mechanical trauma and lack sensitivity. To develop a new accurate noninvasive method, we developed a novel contrast agent where the surface of superparamagnetic iron oxide (SPIO) nanoparticles is functionalized with a bladder cancer-specific fluorescein isothiocyanate (FITC) labeled cell penetrating peptide (CPP)-polyarginine peptides (R11) for active targeting and imaging. The stable nanoparticles have an average hydrodynamic diameter of 51 nm, surface charge of -21 mV and MRI r2 relaxivity 135 mM-1s-1. In vitro cell studies demonstrated that the R11-conjugated SPIO (SPIO-R11) nanoparticles were taken up by bladder cancer cells (T24) in a dose-dependent manner, which was higher than unconjugated SPIO. TEM showed that SPIO-R11 was mainly concentrated on cell vesicle and lysosome, not in cell nucleus, and no obvious damage was seen on cell ultrastructure. Moreover, uptake of the nanoparticles showed significantly more SPIO-R11 accumulation in bladder cancer cells than in immortalized bladder epithelial cells unlike control SPIO. Further, SPIO-R11 was compatible with immortalized bladder epithelial cells at all tested concentrations up to 200 g/mL after 72 h incubation. Moreover, SPIO-R11 decreased the magnetic resonance T2 relaxation time by 73% in tumors cells in vitro compared to 12% with SPIO. These results indicate great potential of SPIO-R11 as contrast agent to target bladder cancer for diagnostic and therapeutic applications.


PubMed | Northwest University, China, Xi'an Jiaotong University and The Forth Military Medical University
Type: Journal Article | Journal: Artificial cells, nanomedicine, and biotechnology | Year: 2016

Polymerized porcine hemoglobin (pPolyHb), which was synthesized from chemically modified porcine hemoglobin, can carry and deliver oxygen to tissues in addition to restoring intravascular volume. Assessment of the inflammatory response generated in the host is a part of the overall safety evaluation of pPolyHb. In this study, we measured the levels of IL-1, IL-10, and CD11b/CD18 in response to pPolyHb stimulation, both in vivo (in rats) and in vitro. Our results suggest that the levels of these indicators are not statistically changed by pPolyHb, indicating that pPolyHb is not immunotoxic to cells and animals in this respect.

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