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Li B.,Zhejiang University | Xu H.,No. 202 Hospital of Peoples Liberation Army | Li Z.,Zhejiang University | Yao M.,Zhejiang University | And 5 more authors.
International Journal of Nanomedicine | Year: 2012

Background: Multidrug resistance (MDR) mediated by the overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), remains one of the major obstacles to effective cancer chemotherapy. In this study, lipid/ particle assemblies named LipoParticles (LNPs), consisting of a dimethyldidodecylammonium bromide (DMAB)-modifed poly(lactic-co-glycolic acid) (PLGA) nanoparticle core surrounded by a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) shell, were specially designed for anticancer drugs to bypass MDR in human breast cancer cells that overexpress P-gp. Methods: Doxorubicin (DOX), a chemotherapy drug that is a P-gp substrate, was conjugated to PLGA and encapsulated in the self-assembled LNP structure. Physiochemical properties of the DOX-loaded LNPs were characterized in vitro. Cellular uptake, intracellular accumulation, and cytotoxicity were compared in parental Michigan Cancer Foundation (MCF)-7 cells and P-gp-overexpressing, resistant MCF-7/adriamycin (MCF-7/ADR) cells. Results: This study found that the DOX formulated in LNPs showed a signifcantly increased accumulation in the nuclei of drug-resistant cells relative to the free drug, indicating that LNPs could alter intracellular traffc and bypass drug effux. The cytotoxicity of DOX loaded-LNPs had a 30-fold lower half maximal inhibitory concentration (IC 50) value than free DOX in MCF-7/ADR, measured by the colorimetric cell viability (MTT) assay, correlated with the strong nuclear retention of the drug. Conclusion: The results show that this core-shell lipid/particle structure could be a promising strategy to bypass MDR. © 2012 Li et al. Source


Jiang H.,General Hospital of Shenyang Military Command | Bai X.,Southern Medical University | Meng F.,No. 202 Hospital of Peoples Liberation Army | Zhang C.,General Hospital of Shenyang Military Command | Zhang X.,General Hospital of Shenyang Military Command
Oncology Letters | Year: 2014

Human epidermal growth factor receptor 2 (HER2) amplification and overexpression are associated with poor prognosis and resistance to cytotoxic drugs in patients with breast cancer. Increases in the number of HER2 gene copies have been shown to be associated with chromosome 17 polysomy. The use of whole, intact nuclei for fluorescence in situ hybridization (FISH) assay improves the accuracy of the results. FISH analysis of whole nuclei (WNFISH) and immunohistochemistry (IHC) were used to analyze HER2 gene amplification and HER2 protein expression in 109 breast cancer specimens. Chromosome 17 polysomy and its correlations with HER2 gene amplification, HER2 protein expression and the clinicopathological outcomes of the patients were also investigated. Among the 109 cases, WNFISH detected HER2 amplification in 30 cases, equivocal amplification in 19 cases and no amplification in 60 cases. WNFISH detected chromosome 17 centromere (CEP17) polysomy in 37 cases and no polysomy in 72 cases. Among the 109 cases assessed by tissue microarray and IHC, 31 cases were HER2-negative, 14 cases were scored 1+, 23 cases were scored 2+ and 41 cases were scored 3+. The results demonstrated that in the cases with chromosome 17 polysomy, the HER2 gene was amplified, HER2 protein expression was increased and the incidences of nuclear atypia and lymph node metastases were higher compared with those in the cases without chromosome 17 polysomy. Chromosome 17 polysomy may correlate with increased malignant potential and metastatic spread in breast cancer. Source


Wang W.,No. 455 Hospital of Peoples Liberation Army | Cheng M.-H.,Shanghai University | Wang X.-H.,No. 202 Hospital of Peoples Liberation Army
Molecules | Year: 2013

Phytochemical investigation of the 70% EtOH extract of the leaves of Alstonia scholaris afforded seven new monoterpenoid indole alkaloids: scholarisins I-VII (1-7), and three known compounds: (3R,5S,7R,15R,16R,19E)- scholarisine F (8), 3-epi-dihydrocorymine (9), and (E)-16-formyl-5α- methoxystrictamine (10). Structural elucidation of all the compounds was accomplished by spectral methods such as 1D- and 2D-NMR, IR, UV, and HRESIMS. The isolated compounds were tested in vitro for cytotoxicity against seven tumor cell lines, anti-inflammatory activities against Cox-1 and Cox-2, and antifungal potential against five species of fungi. Compounds 1, 6, and 10 exhibited significant cytotoxicities against all the tested tumor cell lines with IC50 values of less than 30 μM and selective inhibition of Cox-2 comparable with the standard drug NS-398 (>90%). Additionally, 1, 2, 3 and 8 showed antifungal activity against two fungal strains (G. pulicaris and C. nicotianae). © 2013 by the authors. Source


Liu C.-Y.,No. 202 Hospital of Peoples Liberation Army | Zhang Z.-H.,Southwest Hospital | Yang H.-F.,General Hospital of Shenyang Military Command | Xu H.,No. 202 Hospital of Peoples Liberation Army | And 2 more authors.
Asian Pacific Journal of Tropical Medicine | Year: 2016

Objective: To investigate the phenotypic characteristics and functional capability differences of mouse bone marrow-derived dendritic cells after stimulation with Mycobacterium tuberculosis in the presence or absence of vitamin D3. Methods: Mouse bone marrow-derived cells were cultured with GM-CSF (20 ng/mL). Then, one was added with 100 nmol/L of 25(OH)D3, while the other did not. On day 6, 5 μg/mL of BCG was added to stimulate the cells for 24 h. On day 7, suspension cells were harvested for phenotypic and functional analyses. Results: The percentages of CD86 dendritic cells (DCs) in the control group and 25(OH)D3 group were 66.97% ± 8.29% and 52.18% ± 8.52%, respectively; the mean fluorescence intensities of MHC-II in the control group and 25(OH)D3 group were 1 102.16 ± 371.02 and 681.62 ± 292.71. The expression levels of MHC- II and CD86 on the surface of the DCs in 25(OH)D3 group were significantly lower than those of the control group. The ability of the DCs to stimulate proliferation of T-lymphocytes was also significantly lower than that of the control group. Conclusions: These findings suggest that 25(OH)D3 modulates the immune response by affecting the maturation and function of DCs in Mycobacterium tuberculosis period. © 2016 Hainan Medical College. Source


Cao D.-H.,Liaoning Medical University | Ren M.-H.,Peoples Hospital of Beijing University | Liu X.-L.,Liaoning Medical University | Jin C.-L.,Liaoning Medical University | Meng Z.-Y.,No. 202 Hospital of Peoples Liberation Army
Chinese Journal of Medical Genetics | Year: 2010

Objective: To identify the type of a pedigree with spinocerebellar ataxia, and carry out asymptomatic carrier detection and prenatal diagnosis. Methods: The blood samples of two patients in the spinocerebellar ataxia pedigree were collected. Based on the clinical characteristics of the pedigree and the disease incidence in China, the regions containing the CAG repeat of the SCA1, SCA2 and SCA3/MJD genes were amplified by polymerase chain reaction (PCR). The numbers of CAG repeats in the normal and abnormal allele fragments were identified by using agarose gel electrophoresis and DNA sequencing. We further carried out tests on the children of the patients and fetus to identify the presence of the abnormal allele. Results: The numbers of CAG repeat in the SCA1 and SCA2 genes were in the normal range. The CAG repeat number in one allele of SCA3/MJD gene was in the normal range, while that in the other allele was in the abnormal range. One of the children of the patients and the fetus carried the abnormal allele. Conclusion: It was confirmed that the pedigree was SCA3/MJD by gene diagnosis. One of the children of the patients was asymptomatic carrier and the fetus also carried the abnormal allele. Source

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