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He H.,Capital Medical University | Zhao Z.-H.,Pudong New Area District Zhoupu Hospital | Han F.-S.,Capital Medical University | Wang X.-F.,Capital Medical University | Zeng Y.-J.,Capital Medical University
International Journal of Clinical and Experimental Medicine | Year: 2015

Objects: to probe into the effects of PKCε on migration and paracrine functions of stem cells and potential molecular mechanisms. Methods: Bone Marrow mesenchymal stem cells (BMMSCs) were obtained from rat femur and passaged. mRNA and protein levels of capital proteins in PKCε signaling, SDF-1/CXCR4 axis and PI3K/AKT pathway in the MSCs in different conditions treating with PKC agonist, specific PKCε inhibitor, CXCR4 antagonist or PI3K inhibitor for 24 hours were analyzed by real-time PCR and western blot, and migration abilities were observed by migration assay in vitro and the changes of paracrine factors in different treatments were analyzed by protein clips assay. Results: the levels of p-JNK, p-P38MAPK, SDF-1, CXCR4, PI3K and p-AKT increased significantly after treating with PKC agonist (P < 0.05) and decreased obviously after treating with specific PKCε inhibitor. Migration ability and paracrine function of MSCs were enhanced in PMA group and attenuated in PKCε inhibitor group, and inhibiting activity of CXCR4 or PI3K attenuated the effects of PKCε, but not abolished completely. Conclusion: There was cross-talking between PKCε signaling and SDF-1/CXCR4 axis and PI3K/AKT pathway in signal transduction of MSCs. Activating PKCε could improve migration ability and paracrine function of MSCs partly at least independent of SDF-1/CXCR4 axis and PI3K/AKT pathway. © 2015, E-Century Publishing Corporation. All Rights Reserved. Source


Zhu W.,Fudan University | Zhan D.,Fudan University | Wang L.,Fudan University | Ma D.,Fudan University | And 5 more authors.
Oncology Reports | Year: 2016

TRAIL is a tumor-selective apoptosis-inducing cytokine playing a vital role in the surveillance and elimination of some tumor cells. However, some tumors are resistant to TRAIL treatment. Proteasome inhibitor MG132 exhibits antiproliferative and pro-apoptotic properties in many tumors. In this study, we demonstrated that proteasome inhibitor MG132 in vitro and in vivo potentiates TRAIL-induced apoptosis in gallbladder carcinoma GBC-SD cells. MG132 was able to inhibit the proliferation of GBC-SD cells and induce apoptosis in a dose-dependent manner. The induction of apoptosis by proteasome inhibitor MG132 was mainly through the extrinsic apoptotic pathways of caspase activation such as caspase-8, caspase-3 and PARP cleavage. In addition, this process was also dependent on the upregulation of death receptor 5 (DR5), which promoted TRAIL-induced apoptosis in GBC-SD cells. Taken together, these findings indicate that MG132 possesses anti-gallbladder cancer potential that correlate with regulation of DR5-dependent pathway, and suggest that MG132 may be a promising agent for sensitizing GBC-SD cells to TRAILinduced apoptosis. Source


Cheng M.,Pudong New Area District Zhoupu Hospital | Zhi K.,Shanghai University | Gao X.,Pudong New Area District Zhoupu Hospital | He B.,Fudan University | And 4 more authors.
Molecular Cancer | Year: 2013

Background: Cancer is both a systemic and a genetic disease. The pathogenesis of cancer might be related to dampened immunity. Host immunity recognizes nascent malignant cells - a process referred to as immune surveillance. Augmenting immune surveillance and suppressing immune escape are crucial in tumor immunotherapy. Methods: A recombinant plasmid capable of co-expressing granulocyte-macrophage colony- stimulating factor (GM-SCF), interleukin-21 (IL-21), and retinoic acid early transcription factor-1 (Rae-1) was constructed, and its effects determined in a mouse model of subcutaneous liver cancer. Serum specimens were assayed for IL-2 and INF-γ by ELISA. Liver cancer specimens were isolated for Rae-1 expression by RT-PCR and Western blot, and splenocytes were analyzed by flow cytometry. Results: The recombinant plasmid inhibited the growth of liver cancer and prolonged survival of tumor-loaded mice. Activation of host immunity might have contributed to this effect by promoting increased numbers and cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL) following expression of GM-SCF, IL-21, and Rae-1. By contrast, the frequency of regulatory T cells was decreased, Consequently, activated CTL and NK cells enhanced their secretion of INF-γ, which promoted cytotoxicity of NK cells and CTL. Moreover, active CTL showed dramatic secretion of IL-2, which stimulates CTL. The recombinant expression plasmid also augmented Rae-1 expression by liver cancer cells. Rae-1 receptor expressing CTL and NK cells removed liver cancer. Conclusions: The recombinant expression plasmid inhibited liver cancer by a mechanism that involved activation of cell-mediated immunity and Rae-1 in liver cancer. © 2013 Cheng et al.; licensee BioMed Central Ltd. Source


Cheng M.,Pudong New Area District Zhoupu Hospital | Gao X.,Pudong New Area District Zhoupu Hospital | Wang Y.,Wuhan University of Technology | Chen H.,Zhejiang Huafon Spandex Co. | And 4 more authors.
International Journal of Nanomedicine | Year: 2013

Nanoparticle drug delivery systems using polymers hold promise for clinical applications. We synthesized dual-ligand modified chitosan (GCGA) nanoparticles using lactic acid, glycyrrhetinic acid, and chitosan to target the liver in our previous studies. We then synthesized the GCGA/5-FU nanoparticles by conjugating 5-fluorouracil (5-FU) onto the GCGA nanomaterial, which had a mean particle size of 239.9 nm, a polydispersity index of 0.040, a zeta potential of +21.2 mV, and a drug loading of 3.90%. GCGA/5-FU nanoparticles had good slow release properties, and the release process could be divided into five phases: small burst release, gentle release, second burst release, steady release, and slow release. Inhibitory effects of GCGA/5-FU on tumor cells targeted the liver, and were time and dose dependent. GCGA nanoparticles significantly prolonged the efficacy of 5-FU on tumor cells, and alleviated the resistance of tumor cells to 5-FU. GCGA/5-FU nanoparticles were mostly concentrated in the liver, indicating that the GCGA nanoparticles were liver targeting. GCGA/5-FU nanoparticles significantly suppressed tumor growth in orthotopic liver transplantation mouse model, and improved mouse survival. © 2013 Cheng et al. Source


Lu Y.,Pudong New Area District Zhoupu Hospital | Wang L.,Shanghai JiaoTong University | Hao Y.,Shanghai JiaoTong University | Wang Z.,Pudong New Area District Zhoupu Hospital | And 2 more authors.
BMC Musculoskeletal Disorders | Year: 2013

Background: Multi-detector computed tomography (MDCT) was used in order to assess the trabecular distribution of proximal femur and its relationship with hip fragility fractures. Methods. A total of 99 elderly women were scanned by MDCT including: 27 trochanteric hip fractures (group A), 40 femoral neck fractures (group B), and 32 non-fractures (group C). A mid-coronal MPR image of the proximal femur was reconstructed for every patient by e-Film95 software. Four regions of interest (ROI) were chosen in the images including compressive trabecula (ComT), tensile trabecula (TenT), trochanteric trabecula (TroT) and Ward's triangle (WT) region. The mean CT values were measured by the software. Results: The mean age was 81.44, 74.10 and 69.25 years for groups A, B and C, respectively. There was significant inter-group differences based on one-way ANOVA (P<0.05). The CT values in the four ROIs had significant differences in the groups except for TenT between group A and B (P>0.05). After the age adjustment with ANCOVA, the mean CT values of TroT and WT were significantly lower in group A as compared to that of the group B (P<0.05). However, there were no significant differences for ComT and TenT between groups A and B (P>0.05). Conclusions: The occurrence of femoral neck fracture was closely related to the degeneration of ComT and TenT. Trochanteric hip fractures were associated with a more severe degeneration in TroT as well as an enlargement of WT region besides the ComT and TenT degeneration. We concluded that the hip fragility fractures might be predicted by the measurement of the mean CT values in ComT, TenT, TroT and WT region. © 2013 Lu et al.; licensee BioMed Central Ltd. Source

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