Biomedical subjects

S Xiong

Publications and source records attributed to S Xiong.

At least 19 recordsLinked to original sources

PubMed2006

Gene amplification and associated loss of 5' regulatory sequences of CoAA in human cancers.

CoAA is an RRM-containing transcriptional coactivator that stimulates transcriptional activation and regulates alternative splicing. We show that the CoAA gene is amplified at the chromosome 11q13 locus in a subset of primary human cancers including non-small cell lung carcinoma, squamous cell skin carcinoma and lymphoma. Analysis of 42 primary tumors suggests that CoAA amplifies independently from the CCND1 locus. Detailed mapping of three CoAA amplicons reveals that the amplified CoAA gene is consistently located at the 5' boundaries of the amplicons. The CoAA coding and basal promoter sequences are retained within the amplicons but upstream silencing sequences are lost. CoAA protein is overexpressed in tumors containing the amplified CoAA gene. RNA dot blot analysis of 100 cases of primary tumors suggests elevated CoAA mRNA expression. CoAA positively regulates its own basal promoter in transfection assays. Thus, gene amplification, loss of silencing sequence and positive feedback regulation may lead to drastic upregulation of CoAA protein. CoAA has transforming activities when tested in soft agar assays, and CoAA is homologous to oncoproteins EWS and TLS, which regulate alternative splicing. These data imply that CoAA may share a similar oncogenic mechanism with oncogene EWS and that CoAA deregulation may alter the alternative splicing of target genes.

Animals↗

PubMed2006

Altered expression of zinc transporters-4 and -6 in mild cognitive impairment, early and late Alzheimer's disease brain.

Accumulating evidence suggests that a disruption of zinc (Zn) homeostasis may play a role in the pathogenesis of Alzheimer's disease. Although several Zn transporter proteins responsible for the regulation of Zn balance are present in the brain, there has been little study of these proteins in Alzheimer's disease. To determine if alterations of Zn transporter proteins exist, levels of Zn transporter-4, which functions to remove Zn from the cytoplasm to endosomal/lysosomal compartments, and Zn transporter-6, which allocates cytoplasmic Zn to the trans-Golgi network, were measured in the hippocampus/parahippocampal gyrus, superior and middle temporal gyrus, and cerebellum of subjects with mild cognitive impairment, early Alzheimer's disease, late stage Alzheimer's disease, and age-matched controls using Western blot analysis and protein specific antibodies. Our results show that Zn transporter-4 and Zn transporter-6 are significantly (P<0.05) increased in hippocampus/parahippocampal gyrus of early Alzheimer's disease and Alzheimer's disease subjects. Zn transporter-6 is also increased (P<0.1) in the superior and middle temporal gyrus of Alzheimer's disease brain.

Aged↗

PubMed2006

Th2-dominated antitumor immunity induced by DNA immunization with the genes coding for a basal core peptide PDTRP and GM-CSF.

Our previous study showed that DNA vaccination with a plasmid vector encoding a core peptide of mucin1 (PDTRP) provided modest protection against challenge with tumor cells that expressed mucin1 protein. We report here that a DNA vaccine comprising a modified PDTRP plasmid and GM-CSF coding sequence at the C-terminus induced better protection against tumor challenge. The increased protection was directly correlated with a stronger PDTRP-specific immune response induced by the GM-CSF fusion plasmid. The plasmid encoding GM-CSF and the target PDTRP antigen induced a greater PDTRP-specific Th proliferation, antibodies, and cytotoxicity. Interestingly, the modified plasmid vaccine predominantly enhanced the type 2 immune responses manifested by an increased IgG1 to IgG2a antibody ratio and a greater induction of GATA-3 and IL-4 mRNA than that of T-bet and IFN-gamma mRNA in spleen cells from vaccinated mice. In addition, protection against tumor challenge in vaccinated mice showed that there was no significant change in mice survival after in vivo CD8+CTL depletion, indicating that antitumor immunity augmented by plasmid encoding GM-CSF and target PDTRP gene vaccine was dominated by Th2 immune response.

Animals↗

PubMed2005

4-Hydroxynonenal disrupts zinc export in primary rat cortical cells.

Accumulating evidence implicates oxidative stress in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD). Increased lipid peroxidation, decreased levels of polyunsaturated fatty acids, and increased levels of 4-hydroxynonenal (HNE) have been demonstrated in AD brain. Proteins responsible for zinc export are localized on the plasma membrane and may be vulnerable to damage from lipid peroxidation. To test this hypothesis, cultured primary rat cortical neurons were incubated with (65)Zn for 1h and then treated with HNE (0-35 microM) for 4 h. Levels of (65)Zn in aliquots of medium were measured at 1, 2, 4h following treatment with HNE and intracellular (65)Zn measured after 4h using liquid scintillation counting. The amount of (65)Zn in medium did not differ significantly. However, a statistically significant (p<0.05) increase of (65)Zn was observed inside cortical neurons after treatment with 20 microM HNE for 4 hours. These data suggest that HNE may impair a protein essential for zinc export leading to increased levels of intracellular zinc.

Aldehydes↗

PubMed2005

Alterations in zinc transporter protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and late-stage Alzheimer's disease.

Several studies show increased levels of zinc (Zn) in the Alzheimer's disease (AD) brain. More recently, alterations in synaptic Zn and Zn transporter proteins (ZnT) have been implicated in the accumulation of amyloid plaques in an animal model of AD. To determine if alterations in ZnT proteins are present in AD brain, we measured levels of ZnT-1, the protein responsible for export of Zn to the extracellular space in the amygdala (AMY), hippocampus/parahippocampal gyrus (HPG), superior and middle temporal gyrus (SMTG), inferior parietal lobule (IPL), and cerebellum (CER) of 19 AD and 14 age-matched control subjects. To determine if alterations of ZnT-1 occur early in the progression of AD, we analyzed protein levels in the HPG, SMTG and CER of 5 subjects with mild cognitive impairment (MCI), 5 subjects with early AD (EAD) and 4 appropriately age-matched controls. Western blot and dot-blot analysis showed statistically significant (p 0.05) elevations of ZnT-1 in AD AMY, HPG, and IPL and significantly depleted ZnT-1 in AD SMTG compared to age-matched control subjects. We also observed statistically significant elevations of ZnT-1 in the HPG of EAD subjects compared with controls. In contrast to late-stage AD subjects, ZnT-1 levels were significantly decreased in HPG of subjects with MCI and were significantly elevated in the SMTG of both MCI and EAD subjects compared with age-matched controls. Correlation analysis of ZnT-1 levels and senile plaque (SP) and neurofibrillary tangle (NFT) counts in the AMY and CA1 and subiculum of AD HPG showed a significant (p 0.05) positive correlation with SP counts and a trend towards a significant (p = 0.12) positive correlation with NFT counts in AMY. Overall, our results show alterations in one of the key proteins responsible for maintenance of Zn homeostasis early in the progression of AD suggesting that alterations in Zn balance could be involved in the pathogenesis of neuron degeneration and amyloid deposition in AD.

Aged↗

PubMed2005

Activity of adefovir dipivoxil against all patterns of lamivudine-resistant hepatitis B viruses in patients.

One hundred and thirty-one post-liver transplantation patients with chronic hepatitis B and failing lamivudine therapy with detectable serum hepatitis B virus (HBV) deoxyribonucleic acid by hybridization assays or > or =1 x 10(6) copies/mL by polymerase chain reaction, and elevated alanine transaminase levels despite continuous lamivudine, were enrolled in an open-label study of adefovir dipivoxil. The B and C domains of HBV polymerase were sequenced for baseline samples to determine the presence of lamivudine resistance mutations. The results showed that 98% of the samples had tyrosine-methionine-aspartate-aspartate (YMDD) mutations, indicating a strong correlation between the above clinical definition of lamivudine treatment failure and the presence of YMDD mutations. In addition to the rtM204V/I and the rtL180M mutations, the mutation rtV173L was identified in 19% of patients. Four major patterns of lamivudine-resistant HBV were identified: rtL180M + rtM204V (60%), rtV173L + rtL180M + rtM204V (19%), rtM204I (9%) and rtL180M + rtM204I (9%). Treatment with adefovir dipivoxil showed similar antiviral efficacy in patients with lamivudine-resistant virus from all four patterns.

Adenine↗

PubMed2005

Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer's disease.

Increasing evidence suggests that oxidative stress is associated with normal aging and several neurodegenerative diseases, including Alzheimer's disease (AD). Here we quantified multiple oxidized bases in nuclear and mitochondrial DNA of frontal, parietal, and temporal lobes and cerebellum from short postmortem interval AD brain and age-matched control subjects using gas chromatography/mass spectrometry with selective ion monitoring (GC/MS-SIM) and stable labeled internal standards. Nuclear and mitochondrial DNA were extracted from eight AD and eight age-matched control subjects. We found that levels of multiple oxidized bases in AD brain specimens were significantly (p < 0.05) higher in frontal, parietal, and temporal lobes compared to control subjects and that mitochondrial DNA had approximately 10-fold higher levels of oxidized bases than nuclear DNA. These data are consistent with higher levels of oxidative stress in mitochondria. Eight-hydroxyguanine, a widely studied biomarker of DNA damage, was approximately 10-fold higher than other oxidized base adducts in both AD and control subjects. DNA from temporal lobe showed the most oxidative damage, whereas cerebellum was only slightly affected in AD brains. These results suggest that oxidative damage to mitochondrial DNA may contribute to the neurodegeneration of AD.

Aged↗

PubMed2004

Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B.

BACKGROUND AND AIMS: Adefovir dipivoxil possesses potent in vitro and in vivo antiviral activity in wild-type hepatitis B. This study assessed the safety and efficacy of adefovir dipivoxil alone and in combination with lamivudine compared with ongoing lamivudine therapy in patients with chronic hepatitis B with compensated liver disease and lamivudine-resistant hepatitis B virus (HBV). METHODS: Fifty-nine hepatitis B e antigen (HBeAg)-positive patients with genotypic evidence of lamivudine-resistant HBV, serum alanine aminotransferase (ALT) level > or =1.2 times the upper limit of normal, and serum HBV DNA level > or =6 log(10) copies/mL despite ongoing treatment with lamivudine were randomized to adefovir dipivoxil 10 mg, lamivudine 100 mg, or addition of adefovir dipivoxil to ongoing lamivudine daily. The primary end point was the time-weighted average change from baseline in serum HBV DNA level (DAVG) up to week 16. RESULTS: Rapid reductions in serum HBV DNA level were seen by 4 weeks in all recipients of adefovir dipivoxil; DAVG(16) was -0.07 in the lamivudine group compared with -2.45 and -2.46 log(10) copies/mL in the adefovir dipivoxil/lamivudine and adefovir dipivoxil monotherapy groups, respectively (P < 0.001). Median change from baseline in serum HBV DNA level at week 48 was 0.0, -3.59, and -4.04 log(10) copies/mL in the lamivudine, adefovir dipivoxil/lamivudine, and adefovir dipivoxil groups, respectively. ALT level normalized in 10 of 19 (53%) and 9 of 18 (47%) recipients of adefovir dipivoxil/lamivudine and adefovir dipivoxil, respectively, compared with 1 of 19 (5%) recipients of lamivudine. Three patients receiving adefovir dipivoxil or adefovir dipivoxil/lamivudine and none receiving lamivudine monotherapy were HBeAg negative at week 48 and one became hepatitis B surface antigen negative. CONCLUSIONS: These data, limited to patients with compensated liver disease, indicate that adefovir dipivoxil alone or in combination with ongoing lamivudine therapy provides effective antiviral therapy in patients with lamivudine-resistant HBV.

Adenine↗

PubMed2004

Allogenic donor splenocytes pretreated with antisense peptide against B7 prolong cardiac allograft survival.

The interaction of T cell CD28/CTLA-4 receptors with B7 on antigen-presenting cells (APCs) represents an important co-stimulatory pathway in T cell activation or anergy. Our previous study indicated that recipients immunized with allogenic donor immature dendritic cells (DCs) or resting B cells could induce specific immune tolerance and prolong allograft survival. A possible mechanism for this observation is that the expression of B7 molecules is either at a low level or lacking on these cells. The present study investigates whether blockade of B7 molecules on donor splenocytes with a B7 antisense peptide (B7AP), i.e. a peptide analogue of the CD28-binding region, could induce specific immune tolerance and prolong allograft survival in the recipients. Both the lymphocyte proliferation reaction and the mice pinna cardiac allograft experiment were performed to evaluate the role of B7AP in inducing specific immune tolerance in recipients in vitro and in vivo. The results showed that 56.65% and 20.52% of C57BL/6 splenocytes expressed B7.1 and B7.2 molecules, respectively, on their cell surface. There were no significant changes of the B7 expression on such splenocytes after being treated by the B7AP (53.28% and 19.06%, respectively). B7AP inhibited the mixed lymphocyte reaction by up to 38.4% and a dose-response correlation was observed for inhibition. The recipients (BALB/c) immunized with B7AP-pretreated C57BL/6 splenocytes induced a specific immune hypo-response (43%versus control) and notably prolonged survival of the C57BL/6 cardiac allograft by up to 20.3 days. In contrast to the normal saline group (average: 8.6 days) and FTD(10) control peptide group (<4 days), the cardiac allograft survival of the test group was extended for an additional 11.7 days. These results strongly support the notion that immunization with donor splenocytes, which had been pretreated with B7AP, induced specific immune tolerance and prolonged allograft survival in the recipients.

Animals↗

PubMed2001

Multiple signaling pathways involved in activation of matrix metalloproteinase-9 (MMP-9) by heregulin-beta1 in human breast cancer cells.

Matrix metalloproteinase-9 (MMP-9) plays important roles in tumor invasion and angiogenesis. Secretion of MMP-9 has been reported in various cancer types including lung cancer, colon cancer, and breast cancer. In our investigation of MMP-9 regulation by growth factors, MMP-9 was activated by heregulin-beta1 as shown by zymography in both SKBr3 and MCF-7 breast cancer cell lines. Increase in MMP-9 activity was due to increased MMP-9 protein and mRNA levels, which mainly results from transcriptional upregulation of MMP-9 by heregulin-beta1. Heregulin-beta1 activates multiple signaling pathways in breast cancer cells, including Erk, p38 kinase, PKC, and PI3-K pathways. We examined the pathways involved in heregulin-beta1-mediated MMP-9 activation using chemical inhibitors that specifically inhibit each of these heregulin-beta1-activated pathways. The PKC inhibitor RO318220 and p38 kinase inhibitor SB203580 completely blocked heregulin-beta1-mediated activation of MMP-9. MEK-1 inhibitor PD098059 partially blocked MMP-9 activation, whereas PI3-K inhibitor wortmannin had no effect on heregulin-beta1-mediated MMP-9 activation. Therefore, at least three signaling pathways are involved in the activation of MMP-9 by heregulin-beta1. Since MMP-9 is tightly associated with invasion/metastasis and angiogenesis, our studies suggest that blocking heregulin-beta1-mediated activation of MMP-9 by inhibiting the related signaling pathways may provide new strategies for inhibition of cancer metastasis and angiogenesis.

Breast Neoplasms↗

PubMed2001

Expression of glutathione-S-transferase isozyme in the SY5Y neuroblastoma cell line increases resistance to oxidative stress.

Glutathione-S-transferases (GSTs) are a superfamily of enzymes that function to catalyze the nucleophilic attack of glutathione on electrophilic groups of a second substrate. GSTs are present in many organs and have been implicated in the detoxification of endogenous alpha, beta unsaturated aldehydes, including 4-hydroxynonenal (HNE). Exogenous GST protects hippocampal neurons against HNE in culture. To test the hypothesis that overexpression of GST in cells would increase resistance to exogenous or endogenous HNE induced by oxidative stress, stable transfectants of SY5Y neuroblastoma cells with GST were established. Stable GST transfectants demonstrated enzyme activities 13.7 times (Clone 1) and 30 times (Clone 2) higher than cells transfected with vector alone. GST transfectants (both Clones 1 and 2) demonstrated significantly (p <.05) increased resistance to ferrous sulfate/hydrogen peroxide (20.9% for Clone 1; 46.5% for Clone 2), amyloid beta-peptide (12.2% for Clone 1; 27.5.% for Clone 2), and peroxynitrite (24.3% for Clone 1; 43.9% for Clone 2), but not to exogenous application of HNE in culture medium. GST transfectants treated with 1,1,4-tris (acetyloxy)nonane, a nontoxic derivative of HNE that is degraded to HNE intracellularly, demonstrated a statistically significant (p <.05) increase in viability in a dose-dependent manner compared with SY5Y cells transfected with vector alone. These results suggest that overexpression of GST increases resistance to endogenous HNE induced by oxidative stress or released in the degradation of 1,1,4-tris (acetyloxy)nonane, but not to exogenous application of HNE.

Aldehydes↗

PubMed2001

Study on the degeneracy of antisense peptides using affinity chromatography.

The degeneracy of antisense peptides was studied by high-performance affinity chromatography. A model sense peptide (AAAA) and its antisense peptides (CGGG, GGGG, RGGG, SGGG) were designed and synthesized according to the degeneracy of genetic codes. An affinity column with AAAA as the ligand was prepared. The affinity chromatographic behaviors of antisense peptides on the column were evaluated. The results indicated that model antisense peptides have clear retention on the immobilized AAAA affinity column. RGGG showed the strongest affinity interaction. Similar result was obtained from another experiment that Arg-substituted antisense peptide of fusion peptide (1-11) of influenza virus A was also shown the highest affinity binding to immobilized fusion peptide.

Amino Acid Sequence↗

PubMed2001

New method for high-performance liquid chromatographic separation and fluorescence detection of ginsenosides.

A novel pre-column derivatization method for the quantitative determination of ginsenosides by HPLC with fluorescence detection was established. The double bond at the C24-C25 position of ginsenoside was converted into an aldehyde group by means of ozonolysis. Then the aldehyde group reacts with FMOC-hydrazine forming the ginsenoside FMOC-hydrazone. The derivatized products were separated by RP-HPLC with gradient elution. The detection limits of ginsenosides Rg1 and Rb1 were 2.0 ng (about 2.5 pmol) and 1.0 ng (about 0.9 pmol), respectively. This method can be used for all ginsenosides having the C24-C25 double bond.

Chromatography, High Pressure Liquid↗

PubMed2001

Up-regulation of vascular endothelial growth factor in breast cancer cells by the heregulin-beta1-activated p38 signaling pathway enhances endothelial cell migration.

Heregulin (HRG) belongs to a family of polypeptide growth factors that bind to receptor tyrosine kinases ErbB3 and ErbB4. HRG binding induces ErbB3 and ErbB4 heterodimerization with ErbB2, activating downstream signal transduction. Vascular endothelial growth factor (VEGF) is a primary regulator of physiological angiogenesis and is a major mediator of pathological angiogenesis, such as tumor-associated neovascularization. In this study, we demonstrate that HRG-beta1 increased secretion of VEGF from breast cancer cells in a time- and dosage-dependent manner and that this increase resulted from up-regulation of VEGF mRNA expression via transcriptional activation of the VEGF promoter. Deletion and mutational analysis revealed that a CA-rich upstream HRG response element located between nucleotide-2249 and -2242 in the VEGF promoter mediated HRG-induced transcriptional up-regulation of VEGF. While investigating the downstream signaling pathways involved in HRG-mediated up-regulation of VEGF, we found that HRG activated extracellular signal-regulated protein kinases, Akt kinase, and p38 mitogen-activated protein kinase (MAPK). However, only the specific inhibitor of p38 MAPK (SB203580), not extracellular signal-regulated kinase inhibitor PD98059 nor the inhibitor of phosphatidylinositol 3-kinase-Akt pathway (Wortmannin), blocked the up-regulation of VEGF by HRG. The HRG-stimulated secretion of VEGF from breast cancer cells resulted in increased migration of murine lung endothelial cells, an activity that was inhibited by either VEGF-neutralizing antibody or SB203580. These results show that HRG can activate p38 MAPK to enhance VEGF transcription via an upstream HRG response element, leading to increased VEGF secretion and angiogenic response in breast cancer cells.

Breast Neoplasms↗

PubMed2001

Three novel high performance affinity chromatographic media for the separation of antithrombin III from human plasma.

Novel monodisperse, non-porous, cross-linked poly (glycidyl methacrylate) beads (PGMA) were employed as the support for high performance affinity chromatography. Heparin was covalently attached to PGMA beads by three different coupling methods. Heparin-PGMA-I was prepared by directly coupling amino-groups of heparin with PGMA. Heparin-PGMA-II and III were prepared by the coupling of heparin to amino-PGMA, which was obtained by amination of PGMA. Heparin-PGMA-II was prepared by coupling the carboxyl groups of heparin to amino-PGMA by using water-soluble carbodiimide as coupling reagent, and heparin-PGMA-III was prepared by the reductive amination of heparin and amino-PGMA with sodium cyanoborohydride. The heparin contents of heparin-PGMA-I, II and III were 1.6, 10.2 and 1.0 mg/g beads, respectively. Their affinity capacities for antithrombin III were investigated. Their binding activity to antithrombin III was not proportional to the content of heparin immobilized, and heparin-PGMA-I was the most efficient affinity medium for antithrombin III. The resultant affinity media presented minimal non-specific interaction with other proteins and can be used in a wide pH range. All the three heparin-PGMA beads were exploited for the separation of antithrombin III from human plasma. The purity of antithrombin III obtained was higher than 90%, which was confirmed by high performance size exclusion chromatography.

Antithrombin III↗

PubMed2001

Capillary electrophoresis of catecholamines with laser-induced fluorescence intensified charge-coupled device detection.

A capillary electrophoresis-laser-induced fluorescence-intensified charge-coupled device system was used for the separation and determination of catecholamines. Optimization of derivatization and separation conditions was investigated in order to reach a high separation efficiency and sensitivity. All fluorecein isothiocyanate derivatives of catecholamines were satisfactorily separated within 12 min. The detection limits were in attomole ranges. This method allows determination of catecholamines with high separation efficiencies and sensitivity.

Benzoates↗

PubMed2001

Characterization of tetrathiofulvalene compounds using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Tetrathiofulvalene compounds are important components of charge-transfer complexes, which may be applied in various fields of scientific research and practical applications. Some of these compounds cannot be characterized by mass spectrometry. Here, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was used for the characterization of tetrathiofulvalenes. The samples could be easily desorbed and ionized to form singly charged ions, and mass spectra with isotopic resolution readily obtained. The mass spectrometric results for 26 compounds have shown that MALDI-TOF is more effective and convenient than other mass spectrometry methods, and resolves the problem of mass spectrometric characterization of tetrathiofulvalene compounds.

Journal Article↗

PubMed2001

Novel rhodopsin mutation in a Chinese family with autosomal dominant retinitis pigmentosa.

PURPOSE: To identify mutations in the rhodopsin (RHO) gene in Chinese patients with autosomal dominant retinitis pigmentosa (ADRP) and to measure the prevalence rate of RHO mutations in Chinese ADRP cases. METHODS: Thirteen Chinese families with ADRP were clinically characterized. The complete coding region and intron splice sites of RHO were analyzed for mutations with single-strand conformation polymorphism (SSCP) analysis and direct genomic sequencing. RESULTS: One of the 13 Chinese families with ADRP was found to have a new, previously unidentified RHO mutation, a change from GAG to TAG at codon 341. The mutation (E341X) results in an in-frame stop codon, leading to the truncation of the rhodopsin protein. Mutation E341X was not detected in 100 normal control individuals. Patients carrying mutation E341X reported night blindness and showed optic atrophy, vessel attenuation, and a few bone spicule-like pigments in peripheral retina at the age of 23-25 years. At the age of 30 years, visual acuity was severely impaired, peripheral visual field was greatly constricted, rod and cone ERG was not detectable, and only a slight left cone response remained. CONCLUSIONS: We have identified a novel rhodopsin mutation (E341X) in a Chinese family with ADRP. The location and character of the mutation expand the spectrum of RHO mutations causing RP. Identification of a RHO mutation in one of the 13 ADRP families studied suggests that only 7.7% of the ADRP cases in a Chinese population were caused by RHO mutations, a ratio significantly lower than that from North America or Europe.

Adult↗