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Nie J.,Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection | Nie J.,The Interdisciplinary Center | Nie J.,Soochow University of China | Ge X.,Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection | And 13 more authors.
Oncology Reports | Year: 2015

Esophageal squamous cell carcinoma (ESCC), one of the most common gastrointestinal tumors, is known for its high mortality rate. microRNAs (miRNAs) have been reported to play important regulatory roles in cancer metastasis and progression. miR-34a has been demonstrated to be associated with the development of and metastasis in certain types of cancer via various target genes, but its function and targets in ESCC are unknown. The aim of this study was to examine whether the expression of miR-34a was significantly decreased in ESCC tissues, compared with normal esophageal tissues using RT-PCR and western blot analysis. The results showed that miR-34a overexpression increased apoptosis and decreased clonogenic formation, but inhibited invasion and migration in ESCC cells by suppressing MMP-2 and -9 expression. Yin Yang-1 (YY1), a widely distributed transcription factor that belongs to the GLI-Kruppel class of zinc finger proteins, was found to be a direct target of miR-34a in ESCC cell lines. Rescue experiments indicated that the suppressive effect of miR-34a on invasion and migration was mediated by activating YY1 expression. Results of the present study showed that miR-34a is associated with ESCC migration and provides a potential therapeutic and diagnostic target for ESCC. © 2015, Spandidos Publications. All rights reserved. Source


Sihver L.,Soochow University of China | Sihver L.,Chalmers University of Technology | Ni J.,Soochow University of China | Sun L.,Soochow University of China | And 5 more authors.
Radiation and Environmental Biophysics | Year: 2014

Accurate dosimetric calculations at cellular and sub-cellular levels are crucial to obtain an increased understanding of the interactions of ionizing radiation with a cell and its nucleus and cytoplasm. Ion microbeams provide a superior opportunity to irradiate small biological samples, e.g., DNA, cells, and to compare their response to computer simulations. However, the phantoms used to simulate small biological samples at cellular levels are often simplified as simple volumes filled with water. As a first step to improve the situation in comparing measurements of cell response to ionizing radiation with model calculations, a realistic voxel model of a KB cell was constructed and used together with an already constructed geometry and tracking 4 (GEANT4) model of the horizontal microbeam line of the Centre d’Etudes Nucle´aires de Bordeaux-Gradignan (CENBG) 3.5 MV Van de Graaf accelerator at the CENBG, France. The microbeam model was then implemented into GEANT4 for simulations of the average number of particles hitting an irradiated cell when a specified number of particles are produced in the beam line. The result shows that when irradiating the developed voxel model of a KB cell with 200 α particles, with a nominal energy of 3 MeV in the beam line and 2.34 MeV at the cell entrance, 100 particles hit the cell on average. The mean specific energy is 0.209 ± 0.019 Gy in the nucleus and 0.044 ± 0.001 Gy in the cytoplasm. These results are in agreement with previously published data, which indicates that this model could act as a reference model for dosimetric calculations of radiobiological experiments, and that the proposed method could be applied to build a cell model database. © Springer-Verlag Berlin Heidelberg 2014. Source


Ding X.-Y.,Soochow University of China | Wang W.-J.,Soochow University of China | Gu Z.-L.,Soochow University of China | Hong C.-J.,Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection | Zhang X.-N.,Soochow University of China
Chinese Journal of New Drugs | Year: 2012

Objective: To establish an HPLC-MS/MS method for the determination of norcantharidin (NCTD), and to study the bioavailability and pharmaceutical characteristics of PVP-coated NCTD-Chitosan nanoparticles (PVP-NCTD-NP) in SD rats. Methods: Negative electrospray ionization (ESI -) with selected multi reaction monitoring (MRM) mode was used. Perchloric acid was adopted as protein precipitation agent. NCTD concentrations in rat plasma were determined after intravenous injection of PVP-NCTD-NP and NCTD solution. Pharmacokinetic parameters were calculated by 3P97 program. Results: The linear range was 0.1025~10.25 μg·mL -1(r=0.9992), and the detection limit was 50 ng·mL -1. The concentration-time data was fitted to a two-compartment model, while the relative bioavailability of PVP-NCTD-NP to NCTD was 325.5%. Conclusion: The method is sensitive, accurate, highly selective, and applicable to the pharmacokinetic study of NCTD. PVP-NCTD-NP formulation can promote the absorption of NCTD, and its bioavailability is significantly improved. Source


Liu H.,Soochow University of China | Liu H.,Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection | Xu Y.,Soochow University of China | Chen Y.,Fudan University | And 4 more authors.
Oncology Letters | Year: 2011

Malignant glioma is a highly invasive brain tumor resistant to conventional therapies. Secreted protein acidic and rich in cysteine (SPARC) has been shown to facilitate glioma invasion. However, the effects of SPARC on cell growth have yet to be adequately elucidated. In this study, we constructed a plasmid expressing shRNA against SPARC, evaluated the effect of SPARCshRNA on SPARC expression and then assessed its effect on cell growth in U-87MG cells. Using plasmid-delivered shRNA, we effectively suppressed SPARC expression in U-87MG cells. Cell growth curves and colony formation assay suggested that the introduction of SPARCshRNA resulted in an increase of cell growth and colony formation. We also showed that knockdown of SPARC expression was capable of promoting the cell cycle progression from the G1 to S phase. However, no difference was found in the level of apoptosis. A molecular analysis of signal mediators indicated that the inhibition of p-c-Raf (Ser259) and accumulation of p-GSK-3β (Ser9) and p-AKT (Ser473) may be connected with the growth promotion by SPARC shRNA. Our study may provide an insight into the biological function of SPARC in glioma. Source


Sihver L.,Soochow University of China | Sihver L.,Chalmers University of Technology | Ni J.,Soochow University of China | Sun L.,Soochow University of China | And 4 more authors.
Radiation and Environmental Biophysics | Year: 2014

Accurate dosimetric calculations at cellular and sub-cellular levels are crucial to obtain an increased understanding of the interactions of ionizing radiation with a cell and its nucleus and cytoplasm. Ion microbeams provide a superior opportunity to irradiate small biological samples, e.g., DNA, cells, and to compare their response to computer simulations. However, the phantoms used to simulate small biological samples at cellular levels are often simplified as simple volumes filled with water. As a first step to improve the situation in comparing measurements of cell response to ionizing radiation with model calculations, a realistic voxel model of a KB cell was constructed and used together with an already constructed geometry and tracking 4 (GEANT4) model of the horizontal microbeam line of the Centre d'Etudes Nucléaires de Bordeaux-Gradignan (CENBG) 3.5 MV Van de Graaf accelerator at the CENBG, France. The microbeam model was then implemented into GEANT4 for simulations of the average number of particles hitting an irradiated cell when a specified number of particles are produced in the beam line. The result shows that when irradiating the developed voxel model of a KB cell with 200 α particles, with a nominal energy of 3 MeV in the beam line and 2.34 MeV at the cell entrance, 100 particles hit the cell on average. The mean specific energy is 0.209 ± 0.019 Gy in the nucleus and 0.044 ± 0.001 Gy in the cytoplasm. These results are in agreement with previously published data, which indicates that this model could act as a reference model for dosimetric calculations of radiobiological experiments, and that the proposed method could be applied to build a cell model database. © 2014 Springer-Verlag Berlin Heidelberg. Source

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