Publications (11)38.23 Total impact
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Article: Gammaretroviral vector integration occurs overwhelmingly within and near DNase hypersensitive sites.
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ABSTRACT: Concerns surrounding the oncogenic potential of recombinant gammaretroviral vectors has spurred a great deal of interest in vector integration site (VIS) preferences. Although gammaretroviral vectors exhibit a modest preference for integration near transcription start sites (TSS) of active genes, such associations only account for about a third of all VIS. Previous studies suggested a correlation between gammaretroviral VIS and DNase hypersensitive sites (DHS), which mark chromatin regions associated with cis-regulatory elements. In order to study this issue directly, we assessed the correlation between 167 validated gammaretroviral VIS and a deep genome-wide map of DHS, both determined in the same cell line (the human fibrosarcoma HT1080). The DHS map was developed by sequencing individual DNase I cleavage sites using massively parallel sequencing technologies. These studies revealed an overwhelming preference for integrations associated with DHS, with a median distance of only 238 bp between individual VIS and the nearest DHS for the experimental dataset, compared to 3 kb for a random dataset and 577 to 1457 bp for two unrelated cell lines (p<0.001). Indeed, nearly 84% of all VIS were found to be located within 1 kb of a DHS (p=10(-43)). Further, this correlation was statistically independent from the association with TSS. The preference for DHS far exceeds that seen for other hallmarks of gammaretroviral VIS, including TSS, and may help explain several aspects of gammaretroviral vector biology, including the mechanism of VIS selection, as well as the relative frequency and underlying biology of gammaretroviral vector-mediated genotoxicity.Human gene therapy 02/2012; 23(2):231-7. · 4.20 Impact Factor -
Article: [Effects of H-FABP gene polymorphisms and nutritional factors on pork quality].
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ABSTRACT: Pork quality is affected by both genetic and nutritional factors. However, few researches focused simultaneously on the effects of these two kinds of factors. In order to study the co-effects of these two kinds of factors simultaneously, we implemented this experiment, 136 PIC hybrid pigs with about 65 kg body weight were randomly divided into 4 groups; each group was fed with a different kind of rations. After 35 days of feeding, the pigs were slaughtered at about 95 kg body weight and the pork quality was evaluated. Then the polymorphism of H-FABP gene was analyzed and an association analysis was conducted. The results are as follows: (1) feed ingredient has very significant effect on meat color (MC), pH24, intramuscular fat (IMF, %), and intramuscular protein (IMP, %); (2) H-FABP gene polymorphism has very significant effect on IMF (%) and IMP (%); (3) the interaction between gene and feed ingredient has significant effect on pH and IMF (%), and pH and IMF (%) were the highest for AA genotype in group 0 and group 1, respectively. These results suggest that both genetic and nutritional factors should be concerned in the improvement of pork quality.Hereditas (Beijing) 08/2009; 31(7):713-8. -
Article: Genomic and functional assays demonstrate reduced gammaretroviral vector genotoxicity associated with use of the cHS4 chromatin insulator.
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ABSTRACT: Interest in the use of recombinant retroviral vectors for clinical gene therapy has been tempered by evidence of vector-mediated genotoxicity involving the activation of cellular oncogenes flanking sites of vector integration. We report here that the rate of gammaretroviral vector genotoxicity can be significantly reduced by addition of the cHS4 chromatin insulator, based on two complementary approaches for assessing vector-mediated genotoxicity. One approach involves the direct, genomewide assessment of cellular gene dysregulation using panels of transduced cell clones and genomic microarrays, whereas the other involves the functional assessment of malignant transformation using a factor-dependent cell line. Both assays are robust and quantitative, and indicate the cHS4 chromatin insulator can reduce vector-mediated genotoxicity approximately sixfold (ranged three to eight fold). These approaches also provide a means for assessing various aspects of vector-mediated genotoxicity, including the overall rate of cellular gene dysregulation, the potential influence of vector provirus over large genomic distances, and the involvement of oncogenic pathways in vector-mediated malignant transformation.Molecular Therapy 03/2009; 17(4):716-24. · 6.87 Impact Factor -
Article: Effect of constituents from Fructus Aurantii Immaturus and Radix Paeoniae Alba on gastrointestinal movement.
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ABSTRACT: Fructus Aurantii Immaturus and Radix Paeoniae Alba Powder (FPP) is a popular Chinese herbal prescription. The combination of Fructus Aurantii Immaturus and Radix Paeoniae Alba has been used to treat gastrointestinal disorders for hundreds of years. To our interest, this combination shows a bilateral effect on gastrointestinal peristalsis. Our present study was focused on the bilateral role of this combination on the gastrointestinal tract. The effective constituents and mechanisms were explored. Six monomer constituents from Radix Paeoniae Alba and Fructus Aurantii Immaturus were screened by intestinal transit assay. The bilateral roles of three effective constituents were authenticated by gastric emptying assay, and the combination of three constituents showed a bilateral effect. Then, the mediating receptors and the role of NO and NF- kappaB p65 were examined to determine the mechanism involved. The overall results suggest that the major effective constituents of this combination are synephrine, hesperidin and paeoniflorin. Synephrine inhibits the gastrointestinal movement, while hesperidin stimulates it. Paeoniflorin shows different effects on intestinal and gastric activity. The effect of synephrine relies on the alpha-adrenergic receptor, and the effect of hesperidin is mediated via the H1 histamine receptor. The regulation of hesperidin and synephrine on NF- kappaB p65 translocation and NO production through the alpha-receptor and the H1 receptor, respectively, is involved in the bilateral effect of the Fructus Aurantii Immaturus-Radix Paeoniae Alba combination.Planta Medica 12/2008; 75(1):24-31. · 2.15 Impact Factor -
Article: A flavonoid glycoside isolated from Smilax china L. rhizome in vitro anticancer effects on human cancer cell lines.
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ABSTRACT: The anticancer activity of eight crude extracts of Smilax china L. rhizome (SCR) against HeLa cells was assessed by MTT assay and clonogenic assay, the fraction rich in flavonoids had show good activity against HeLa cells. A bioassay-guided separation on this extract lead to the detection of kaempferol-7-O-beta-D-glucoside (KG), which belongs to flavonoid glycoside, displayed marked anticancer activity. We evaluated its in vitro cytotoxicity and antiproliferative effect in a panel of established cancer cell lines by MTT assay and clonogenic assay. KG induces A375 and HL60 cells apoptosis, which was demonstrated by morphological changes, DNA fragmentation and flow cytometric analysis. Fluorescent staining with Hoechst 33258 showed fragmentation and condensation of chromatin in the A375 and HL60 cells. Flow cytometric analysis shown that A375 and HL60 cells treated with KG resulted in the appearance of a hypodiploid peak (A0 region), probably due to the presence of apoptosing cells and/or apoptotic bodies with DNA content less than 2n. Quantitation of the hypodiploid cells shows a dose-dependent response to KG, and this result is in good accordance with that of the DNA fragmentation assay by agarose gel electrophoresis. Our results suggested that cell cycle arrest at G(1) phase and induce apoptosis as a mechanism by which KG exerts an antiproliferative effect.Journal of Ethnopharmacology 09/2007; 113(1):115-24. · 3.01 Impact Factor -
Article: Nuclear addressing provides a clue for the transforming activity of amino-truncated CCN3 proteins.
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ABSTRACT: CCN3 is a founding member of the CCN (Cyr61, Ctgf, Nov) family of cell growth and differentiation regulators. These secreted proteins are key regulators in embryonic development, and are associated with severe pathologies including fibrotic diseases and cancers. CCN3 was discovered as a MAV integration site in an avian nephroblastoma. Previous work established that the amino-truncated protein expressed in this tumor was inducing morphological transformation of chicken embryo fibroblasts, whereas the full-length secreted CCN3 protein was inhibiting cell growth. Amino-truncated variants were identified in cancer cell lines. Since the lack of signal peptide was expected to alter the fate of the truncated proteins, we hypothesized that modifications of CCN3 subcellular addressing could be responsible for the oncogenic activities of CCN3. The CCN proteins are composed of four structural modules (IGFBP, TSP1, VWC, and CT). We report that amino-truncated variants of CCN3 are addressed to the nucleus and that the carboxyterminal (CT) module of CCN3 is responsible for the nuclear addressing. Furthermore, our data identify nuclear CCN3 variants as potential transcriptional regulators. In this context, the CT module confers on nuclear CCN3 proteins a negative regulatory effect on transcription. We propose that the nuclear localization of amino-truncated CCN3 proteins be correlated to oncogenicity.Journal of Cellular Biochemistry 10/2006; 99(1):105-16. · 2.87 Impact Factor -
Article: [Distributions of polymorphism of ADD1, MC4R, H-FABP gene, associated with IMF and BF in 3 populations in pig].
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ABSTRACT: Different breeds of pigs varied in traits of meat quality, especially between local abroad varieties. Intramuscular fat content (IMF) and back fat thickness (BF) have extra difference between Chinese breeds and foreign breeds. We have known that polymorphism of H-FABP, MC4R and ADD1 gene associated relation with IMF or BF in recent research. The Meishan, Sutai and Duroc x Landrace x Yorkshair become experimental animal in this research. Result show three breeds have different IMF and BF because different distributions of polymorphism three genes. Meishan has particular genetic background, so it should be protected. The results of associated analysis show that the polymorphism of three genes was associated traits of IMF and BF, polymorphism of MC4R gene was not associated traits BF. The molecular marker can apply to pig breeding by molecular marker-assisted selection (MAS).Hereditas (Beijing) 03/2006; 28(2):159-64. -
Article: Integration of Myeloblastosis Associated Virus proviral sequences occurs in the vicinity of genes encoding signaling proteins and regulators of cell proliferation.
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ABSTRACT: Myeloblastosis Associated Virus type 1 (N) [MAV 1(N)] induces specifically nephroblastomas in 8-10 weeks when injected to newborn chicken. The MAV-induced nephroblastomas constitute a unique animal model of the pediatric Wilms' tumor. We have made use of three independent nephroblastomas that represent increasing tumor grades, to identify the host DNA regions in which MAV proviral sequences were integrated. Cellular sequences localized next to MAV-integration sites in the tumor DNAs were used to screen a Bacterial Artificial Chromosomes (BACs) library and isolate BACs containing about 150 kilobases of normal DNA corresponding to MAV integration regions (MIRs). These BACs were mapped on the chicken chromosomes by Fluorescent In Situ Hybridization (FISH) and used for molecular studies. The different MAV integration sites that were conserved after tumor cell selection identify genes involved in the control of cell signaling and proliferation. Syntenic fragments in human DNA contain genes whose products have been involved in normal and pathological kidney development, and several oncogenes responsible for tumorigenesis in human. The identification of putative target genes for MAV provides important clues for the understanding of the MAV pathogenic potential. These studies identified ADAMTS1 as a gene upregulated in MAV-induced nephroblastoma and established that ccn3/nov is not a preferential site of integration for MAV as previously thought. The present results support our hypothesis that the highly efficient and specific MAV-induced tumorigenesis results from the alteration of multiple target genes in differentiating blastemal cells, some of which are required for the progression to highly aggressive stages. This study reinforces our previous conclusions that the MAV-induced nephroblastoma constitutes an excellent model in which to characterize new potential oncogenes and tumor suppressors involved in the establishment and maintenance of tumors.Cell Communication and Signaling 02/2006; 4:1. · 5.50 Impact Factor -
Article: Deletions within the U3 long terminal repeat alter the tumorigenic potential of myeloblastosis associated virus type 1(N).
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ABSTRACT: The molecularly cloned myeloblastosis-associated virus type-1(N) (MAV-1(N)) strain induces specifically nephroblastomas in chicken. MAV-induced nephroblastoma constitutes a unique animal model of the human Wilms' tumor. We have previously shown that the MAV-1(N) long terminal repeats (LTR) were necessary and sufficient for nephroblastoma induction. Since major determinants for oncogenesis have been mapped in the U3 region of several other retroviruses, we have analyzed the tumorigenic potential of five recombinant viruses partially deleted in their U3 region. The results obtained indicated that deletions of the LTRs resulted in a modification of the pathogenic spectrum of MAV-1(N) and a decreased efficiency for nephroblastoma induction.Virology 12/2003; 316(1):84-9. · 3.35 Impact Factor -
Article: CCN3 and calcium signaling.
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ABSTRACT: The CCN family of genes consists presently of six members in human (CCN1-6) also known as Cyr61 (Cystein rich 61), CTGF (Connective Tissue Growth Factor), NOV (Nephroblastoma Overexpressed gene), WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins). Results obtained over the past decade have indicated that CCN proteins are matricellular proteins, which are involved in the regulation of various cellular functions, such as proliferation, differentiation, survival, adhesion and migration. The CCN proteins have recently emerged as regulatory factors involved in both internal and external cell signaling. CCN3 was reported to physically interact with fibulin-1C, integrins, Notch and S100A4. Considering that, the conformation and biological activity of these proteins are dependent upon calcium binding, we hypothesized that CCN3 might be involved in signaling pathways mediated by calcium ions.In this article, we review the data showing that CCN3 regulates the levels of intracellular calcium and discuss potential models that may account for the biological effects of CCN3.Cell Communication and Signaling 09/2003; 1(1):1. · 5.50 Impact Factor -
Article: The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway.
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ABSTRACT: We demonstrate a novel interaction of the nephroblastoma overexpressed gene (NOV), a member of the CCN gene family, with the Notch signaling pathway. NOV associates with the epidermal growth factor-like repeats of Notch1 by the CT (C-terminal cysteine knot) domain. The promoters of HES1 and HES5, which are the downstream transducers of Notch signaling, were activated by NOV. Expressions of NOV and Notch1 were concomitant in the presomitic mesoderm and later in the myocytes and chondrocytes, suggesting their synergistic effects in mesenchymal cell differentiation. In C2/4 myogenic cells, elevated expression of NOV led to down-regulation of MyoD and myogenin, resulting in inhibition of myotube formation. These results indicate that NOV-Notch1 association exerts a positive effect on Notch signaling and consequently suppresses myogenesis.Journal of Biological Chemistry 09/2002; 277(33):29399-405. · 4.77 Impact Factor
Top co-authors
Top Journals
Institutions
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2009
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University of Washington Seattle
- Division of Medical Genetics
Seattle, WA, USA
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2006–2009
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Shanghai University
Shanghai, Shanghai Shi, China
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2003–2006
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Université Paris Diderot - Paris 7
Paris, Ile-de-France, France
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