Biomedical subjects

Xiaojuan Sun

Publications and source records attributed to Xiaojuan Sun.

9 recordsLinked to original sources

PubMed2006

Selenite induces apoptosis in sarcomatoid malignant mesothelioma cells through oxidative stress.

Malignant mesothelioma cells differentiate into sarcomatoid or epithelioid phenotypes. The sarcomatoid cell type is more resistant to chemotherapy and gives a worse prognosis. We have investigated whether selenite alone and in combination with doxorubicin induced apoptosis in variously differentiated mesothelioma cells. Selenite in concentrations that could potentially be administered to patients strongly inhibited the growth of the sarcomatoid mesothelioma cells (IC50 = 7.5 microM), whereas epithelioid cells were more sensitive to doxorubicin. Benign mesothelial cells remained largely unaffected. Selenite potentiated doxorubicin treatment. Apoptosis was the dominating mode of cell death. The toxicity of selenite was mediated by oxidative stress. Furthermore the activity of the thioredoxin system was directly dependent on the concentration of selenite. This offers a possible mechanism of action of selenite treatment. Our findings suggest that selenite is a promising new drug for the treatment of malignant mesothelioma.

Adenocarcinoma↗

PubMed2006

Proteasome inhibitor PSI induces apoptosis in human mesothelioma cells.

Malignant mesothelioma is an increasingly common tumor with an almost 100% mortality rate. It is refractory to conventional treatment. We have previously shown with SSH and microarray that the mRNA expression level of proteasome is higher in epithelioid mesothelioma cell lines than in sarcomatoid ones. This study evaluates the differential apoptotic effect of proteasome inhibitors on both of these mesothelioma sub-lines. Proteasome inhibitors show substantial anti-tumor activity in some tumor cells in vitro and in vivo, but the effects on mesothelioma cells has not been studied. The viability of mesothelioma cells was reduced in a dose- and time-dependent manner by the proteasome inhibitors tested; PSI was effective with a low dose, but higher concentrations were needed for calpain inhibitor I. The epithelioid mesothelioma cells are more sensitive to the inhibitors than the sarcomatoid ones, their IC50 after 24 h of treatment with PSI being 4 and 16 microm, respectively. Other mesothelioma cell lines show similar sensitivity. PSI seemed to decrease mesothelioma viability by inducing apoptosis, as verified by cell morphology, Western blotting analysis of caspase 3 cleavage, and flow-cytometric analysis. In conclusion, PSI, a representative agent that reduces viability and induces apoptosis of mesothelioma cells, might be useful in the treatment of patients with mesothelioma, especially of epithelioid phenotype.

Apoptosis↗

PubMed2006

Chondrocyte death induced by pathological concentration of chemokine stromal cell-derived factor-1.

OBJECTIVE: It had been found that the concentration of chemokine stromal cell-derived factor-1 (SDF-1) was significantly higher in synovial fluid (SF) of patients with osteoarthritis (OA; > or = 200 ng/ml) and rheumatoid arthritis (RA; > or = 700 ng/ml) compared to controls (< or = 100 ng/ml). Our aim was to determine whether the pathological concentration of SDF-1 induces chondrocyte death and to investigate mechanisms underlying such death. METHODS: Human OA chondrocytes were treated with different doses of SDF-1, or in combination with SF from patients with arthritis. Apoptotic and necrotic cells were labeled by annexin V and propidium iodide, respectively, and quantified by FACS analysis. Caspase-3 activity was quantified by a plate absorbance assay, and matrix metalloproteinase 13 mRNA levels were determined by RT-PCR. The release of high mobility group box chromatin protein 1, a specific marker of cell necrosis, and the activities of chondrocyte mitogen-activated protein kinases (MAPK) including ERK, JNK, and p38 in response to SDF-1 treatment were quantified by Western blot analysis. RESULTS: Pathological concentrations of SDF-1 (> or = 200 ng/ml) in SF or in recombinant form induced death of human chondrocytes in a necrosis-dependent manner. Chondrocyte death was inhibited by the treatment of cells with anti-CXCR4, an antibody blocking the interaction between SDF-1 and its receptor CXCR4. However, the rate of chondrocyte apoptosis and the level of caspase-3, a key apoptotic enzyme, were not affected by the treatment with anti-CXCR4. SDF-1 stimulated p38 MAPK activity in a dose- and time-dependent manner. The presence of the p38 MAPK inhibitor SB203580 during SDF-1 treatment abolished the induction of chondrocyte death by SDF-1. CONCLUSION: Our findings suggest a novel pathological mechanism by which high concentrations of SDF-1 in SF induce chondrocyte death during OA and RA.

Apoptosis↗

PubMed2006

[Changes in muscle satellite cells in denervated and innervated muscles].

OBJECTIVE: To explore the rule of changes in the myoblast stem cells (satellite cells) in the denervated and innervated muscles and to find out the cellular mechanism of the changes in the muscle morphology and function. METHODS: The denervated muscle-atrophy models were established from 27 Wistar rats aged 1 month. One to six months after operation, examinations of the histology, histochemistry, and morphology were performed on the specimens from the bilateral triceps muscle of the calves of 3 rats in each month. Meanwhile, examination of the cell biology was performed on the specimens from the bilateral triceps muscle of the calves of 1 rat 1, 2 and 3 weeks after operation, and monthly for 1-6 months after operation. The innervation models were established from 35 Wistar rats aged 1 month. Immediately after the denervation, and monthly for 1-6 months after operation, 5 denervated rats underwent the nerve implantation. The changes in the electrophysiological index were observed dynamically until 8 weeks after the nerve implantation. RESULTS: After the denervation, the muscle wet weight and the muscle cell area decreased rapidly, but the content of the collagen fibers increased gradually. The number of the nucleus in the period of proliferation was the greatest 3-4 months after the denervation, and then decreased rapidly. The muscle satellite cells began to increase obviously 3 weeks after the denervation, but 2 months later they decreased rapidly and 4 months later the number of the cells was the smallest. Four to five weeks after innervation, the muscle action potential could be induced, and the best innervation effect could be achieved in the implanted nerve after the 2-3 months on denervation, and at this time the differentiation ability of the satellite cells was the strongest. CONCLUSION: Four months after the denervation of the skeletal muscle, an extremely small number of the satellite cells can make the muscle enter the irreversible atrophy. However, when the innervation is performed 2-3 months after the denervation, the actively-growing satellite cells can promote a better functional recovery of the atrophic muscle.

Animals↗

PubMed2005

Molecular characterization of tumour heterogeneity and malignant mesothelioma cell differentiation by gene profiling.

Malignant mesothelioma is an aggressive tumour, characterized by a variable differentiation pattern and poor prognosis. At present, the clinical outcome in patients with malignant mesothelioma is mainly predicted by the morphological phenotype of the tumour. However, this conventional clinicopathological parameter is of limited value, partly because of the biological heterogeneity of this tumour and poor understanding of the regulatory mechanisms underlying the various patterns of growth. To elucidate the intrinsic molecular programmes that determine tumour differentiation, oligonucleotide arrays were used in an in vitro model of mesothelioma differentiation. The analysis of 2059 genes detected 102 genes that were significantly deregulated. Clustering of these genes into functional categories showed distinctive patterns for the two phenotypes, namely epithelioid and sarcomatoid. The molecular fingerprint of the sarcomatoid tumour component indicates overrepresentation of growth factor receptors and growth factor binding proteins, whereas epithelioid mesothelioma cells express other tumour-promoting factors involved in differentiation, metabolism, and regulation of apoptosis. These differences in the molecular phenotype may give a better basis for diagnosis and for designing novel therapies.

Blotting, Western↗

PubMed2004

Interaction of palladium(II) and platinum(II) complexes with microperoxidase-11 studied by electrospray mass spectrometry and MS/MS analysis.

Interactions of cis-[Pd(en)(H(2)O)(2)](2+) (en, ethylenediamine) and cis-[Pt(NH(3))(2)(H(2)O)(2)](2+) with microperoxidase-11 (MP-11) in a molar ratio of 1:1 or 2:1 at pH 1.4 were investigated via electrospray mass spectrometry and MS/MS analysis at room temperature and at 40 degrees C with an incubation time of 2 or 3 days. The composition of the Pd(II)- and Pt(II)-anchored MP-11 was confirmed on the basis of the precise molecular mass and the simulated isotope distribution pattern. MS/MS analysis revealed that the Pd(II) center anchored to the side chain of Cys7 as Pd(II) and MP-11 were mixed in an equimolar ratio and to side chains of Cys7 and Cys4 as Pd(II) and MP-11 mixed in a 2:1 molar ratio. When Pt(II) and MP-11 were mixed in a 2:1 molar ratio, Pt(II) first anchored to the side chain of Cys7, and then to the side chain of Cys4 with time. The initial coordination of Pd(II) and Pt(II) to the side chain of Cys7 is the essential step for the Pd(II)- and Pt(II)-promoted cleavage of the His8-Thr9 bond in MP-11. These results support the hypothesis that the Pd(II)-mediated cleavage of the His18-Thr19 bond in cytochorome c is due to the identical binding mode.

Amino Acid Sequence↗

PubMed2003

Mesothelial differentiation as reflected by differential gene expression.

Human mesothelial cells obtained from benign effusions retain their proliferative capacity and grow uniformly either with a fibroblastic or epithelioid morphology in vitro. These cultures therefore provide a model for the process of mesothelial differentiation in vivo. To study this differentiation, we isolated differentially expressed genes obtained by suppression subtractive hybridization. Of the nine genes found to be overexpressed in fibroblastic mesothelial cells, three are matrix-associated (integrin alpha5, collagen binding protein 2, human cartilage glycoprotein 39), whereas the others are associated with a proliferative cell type (14-3-3 epsilon, plexin B2, N33, and three genes encoding ribosomal elements). Seven of the eight genes upregulated in the epithelioid phenotype are related rather to specialized functions, such as metabolism (aldose reductase, lecithin:cholesterol acyltransferase, ATPase 6), cytoskeletal composition (cytokeratins 7 and 8), and regulation of differentiation (granulin, annexin II). Immunohistochemistry with available antibodies to six of the differentially expressed gene products confirmed the differences also in pleural tissues, where submesothelial cells displayed the fibroblastic markers, whereas surface cells displayed the epithelioid markers. In summary, this approach revealed a pattern of genes coordinately regulated during mesothelial differentiation and suggests that mesothelium may regenerate also by recruiting cells from the submesothelial layer. Some of the gene products may also be useful markers for differentiation and activation in serosal tissues.

14-3-3 Proteins↗

PubMed2003

Regioselective cleavage of myoglobin with copper(II) compounds at neutral pH.

Selective hydrolytic cleavage of myoglobin was studied with CuCl2, Cu(ClO4)2, Cu(AC)2, and binuclear Cu(II) complexes of 3,6,9,16,19,22-hexaaza-6,19-bis (2-hydroxyethyl)-tricyclo- [22,2,2,2(11,14)]-triaconta-1,11,13,24,27,29-hexaene (1) and 3,6,9,16,19,22-hexaaza-tricyclo-[22,2,2,2(11,14)]-triaconta- 1,11,13,24,27,29-hexaene (2). The sites of cleavage were precisely determined by LC-ESIMS and further confirmed by an MS/MS method through fragmentation from both the N-terminal and C-terminal. The peptide bonds of Gln91-Ser92 and Ala94-Thr95 were remarkably cleaved by Cu(II) anchored to the side chain of the His93 residue. The data presented in this study show that Cu(II)-mediated cleavage of myoglobin is able to proceed at neutral pH, more selectively than Pd(II)-mediated cleavage, and buffer solution of phosphate and NH4HCO3 accelerates the cleavage reaction.

Amino Acid Sequence↗

PubMed2003

Theoretical studies on vibrational spectra of mixed cyanide-halide complexes of platinum(IV) and palladium(IV).

The vibrational spectra of mixed cyanide-halide complexes, M(CN)4X 2 2- and M(CN)5X2- (M=Pt and Pd; X=F, Cl, Br and I), have been systematically investigated by ab initio RHF, B3LYP and MP2 methods with LanL2DZ and SDD basis sets. The calculated vibrational frequencies of platinum complexes are evaluated via comparison with the experimental values. In the infrared frequency region, the C--N stretching vibrational frequencies calculated at B3LYP level with two basis sets are in good agreement with the observed values with deviations, -16-4 cm(-1) for Pt(CN)4X 2 2- and -18 to -2 cm(-1) for Pt(CN)5X2-. However, in far-infrared region, the results obtained at RHF level are better than those calculated at B3LYP and MP2 levels. For RHF/SDD method, the deviations for Ptz.sbnd;X and Ptz.sbnd;C stretching vibrational frequencies are -14-1 and -12 to -2 cm(-1) in the complex Pt(CN)4X2 2-, -19 to -11 and -15-14 cm(-1) in the Pt(CN)5X2- complex, respectively. The vibrational frequencies of palladium(IV) and some platinum(IV) complexes that have not been experimentally reported are predicted.

Cyanides↗