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Biomedical subjects

Qun Wang

Publications and source records attributed to Qun Wang.

At least 19 recordsLinked to original sources
PubMed2007

Frequent loss of PDCD4 expression in human glioma: possible role in the tumorigenesis of glioma.

Programmed cell death 4 (PDCD4) was recently identified as a novel tumor suppressor gene. The loss of PDCD4 expression was found in several types of human cancer cell lines. To date, however, the status of PDCD4 expression in human glioma tissue is not known. In the present study, the expression of PDCD4 in 30 glioma samples was determined at both mRNA and protein levels by means of RT-PCR, Western blotting, and immunohistochemistry. Herein, we demonstrate, for the first time, that 47% (14/30) of glioma samples lost the expression of PDCD4 mRNA, and 77% (23/30) of glioma samples lacked the PDCD4 protein expression, whereas adjacent normal glial tissues expressed high levels of PDCD4 mRNA and protein. Furthermore, the loss of PDCD4 expression does not significantly correlate with the pathological and clinical features of the glioma. Our new data suggest that the loss of PDCD4 expression is a frequent event in human glioma and may partially contribute to the development of the tumor.

Adult↗
PubMed2006

A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2.

Commensalism is critical to a healthy Th1/Th2 cell balance. Polysaccharide A (PSA), which is produced by the intestinal commensal Bacteroides fragilis, activates CD4+ T cells, resulting in a Th1 response correcting the Th2 cell skew of germ-free mice. We identify Toll-like receptors as crucial to the convergence of innate and adaptive responses stimulated by PSA. Optimization of the Th1 cytokine interferon-gamma in PSA-stimulated dendritic cell-CD4+ T cell co-cultures depends on both Toll-like receptor (TLR) 2 and antigen presentation. Synergy between the innate and adaptive responses was also shown when TLR2-/- mice exhibited impaired intraabdominal abscess formation in response to B. fragilis. Commensal bacteria, using molecules like PSA, potentially modulate the Th1/Th2 cell balance and the response to infection by coordinating both the innate and adaptive pathways.

Animals↗
PubMed2006

Chitosan/starch fibers and their properties for drug controlled release.

Fibers of chitosan and starch, with salicylic acid (SA) as model drug incorporated in different concentrations, were obtained by spinning their solution through a viscose-type spinneret into a coagulating bath containing aqueous tripolyphosphate (TPP) and ethanol. Chemical, morphological and mechanical properties characterization was carried out, as well as the studies of the factors that influence the drug releasing from chitosan/starch fibers. These factors included the component ratio of chitosan and starch, the loaded amount of SA, the pH and the ionic strength of the release solution and others. The diameter of the fibers is around 15+/-3 microm. The best values of the tensile strength at 12.21 cN/tex and breaking elongation at 25.13% of blend fibers were obtained when the starch content was 30 wt%; the water-retention value (WRV) of blend fibers increased as the composition of starch was raised. The results of controlled release tests showed that the amount of SA released increased with an increase in the proportion of starch present in the fiber. Moreover, the release rate of drug decreased as the amount of drug loaded in the fiber increased, but the cumulative release amount is increasing. The chitosan/starch fibers were also sensitive to pH and ionic strength. The release rate was being accelerated by a lower pH and a higher ionic strength, respectively. All the results indicated that the chitosan/starch fiber was potentially useful in drug delivery systems.

Chitosan↗
PubMed2006

Spiral turbulence developed through the formation of superimposed target waves in an oscillatory reaction-diffusion medium.

An approach leading to the development of spiral turbulence is reported here in an oscillatory reaction-diffusion medium, which is through the spontaneous formation of targetlike waves near the core of a spiral wave. The newly formed target wave emerges with its own characteristic frequency and propagates on top of the original spiral wave, which eventually leads to the breakup of the spiral at a location far from the spiral center. The radius of the surviving spiral segment decreases rapidly with the bifurcation control parameter. Calculation of power spectra suggests that the meandering of the spiral tip is responsible for the onset of the superimposed target and the phase desynchronization of the superimposed target waves.

Journal Article↗
PubMed2006

The H+-linked monocarboxylate transporter (MCT1/SLC16A1): a potential therapeutic target for high-risk neuroblastoma.

Neuroblastomas produce high amounts of lactic acid and upregulate the H(+)-linked monocarboxylate transporter isoform 1 (MCT1/SLC16A1). We found elevated MCT1 mRNA levels in fresh neuroblastoma biopsy samples that correlated positively with risk of fatal disease and amplification of the "proto-oncogenic" transcription factor MYCN. We further investigated MCT as a potential therapeutic target in vitro. The neuroblastoma cell lines evaluated were Sk-N-SH, CHP134, IMR32, and NGP. All lines exhibited decreased intracellular pH at low tumor-like extracellular pH. Lonidamine or exogenous lactate further lowered intracellular pH. Immediate early lowering of intracellular pH with lonidamine or lactate at extracellular pH 6.5 correlated positively with diminished cell viability within 48 h. These findings indicate that MCT1 is a potential therapeutic target and that neuroblastoma therapy may be enhanced by therapeutic strategies to inhibit or overwhelm MCT. Additional experiments indicated that the mechanism of cell death by lonidamine or exogenous lactate is similar to that obtained using alpha-cyano-4-OH-cinnamate, a well established MCT inhibitor. Because lactate production is also high in melanoma and many other tumor types, MCT inhibitors may have broad application in cancer treatment. Such treatment would have selectivity by virtue of the acidic milieu surrounding tumors, because MCT is increasingly active as extracellular pH decreases below 7.0 and lactic acid production increases.

Antineoplastic Agents↗
PubMed2006

Simple and complex spatiotemporal structures in a glycolytic allosteric enzyme model.

Pattern formation in glycolysis is studied with a classical reaction-diffusion allosteric enzyme model. It is found that, similar to recent experimental reports in the yeast extracts, a small magnitude local perturbation can induce transient target waves in a two dimensional oscillatory medium. An above threshold stimulation generates target waves which eventually evolve into spatiotemporal chaos upon collisions with the boundary or other wave activities. Detailed simulation studies show that the studied simple glycolytic reaction-diffusion model can support three types of spatiotemporal behaviors which are independent of the boundary conditions: (1) a spatially uniform stable steady state, (2) periodic global oscillations and (3) spatiotemporal chaos.

Adenosine Diphosphate↗
PubMed2006

Integrative genomics identifies distinct molecular classes of neuroblastoma and shows that multiple genes are targeted by regional alterations in DNA copy number.

Neuroblastoma is remarkable for its clinical heterogeneity and is characterized by genomic alterations that are strongly correlated with tumor behavior. The specific genes that influence neuroblastoma biology and are targeted by genomic alterations remain largely unknown. We quantified mRNA expression in a highly annotated series of 101 prospectively collected diagnostic neuroblastoma primary tumors using an oligonucleotide-based microarray. Genomic copy number status at the prognostically relevant loci 1p36, 2p24 (MYCN), 11q23, and 17q23 was determined by PCR and was aberrant in 26, 20, 40, and 38 cases, respectively. In addition, 72 diagnostic neuroblastoma primary tumors assayed in a different laboratory were used as an independent validation set. Unsupervised hierarchical clustering showed that gene expression was highly correlated with genomic alterations and clinical markers of tumor behavior. The vast majority of samples with MYCN amplification and 1p36 loss of heterozygosity (LOH) clustered together on a terminal node of the sample dendrogram, whereas the majority of samples with 11q deletion clustered separately and both of these were largely distinct from the copy number neutral group of tumors. Genes involved in neurodevelopment were broadly overrepresented in the more benign tumors, whereas genes involved in RNA processing and cellular proliferation were highly represented in the most malignant cases. By combining transcriptomic and genomic data, we showed that LOH at 1p and 11q was associated with significantly decreased expression of 122 (61%) and 88 (27%) of the genes mapping to 1p35-36 and all of 11q, respectively, suggesting that multiple genes may be targeted by LOH events. A total of 71 of the 1p35-36 genes were also differentially expressed in the independent validation data set, providing a prioritized list of candidate neuroblastoma suppressor genes. Taken together, these data are consistent with the hypotheses that the neuroblastoma transcriptome is a sensitive marker of underlying tumor biology and that chromosomal deletion events in this cancer likely target multiple genes through alteration in mRNA dosage. Lead positional candidates for neuroblastoma suppressor genes can be inferred from these data, but the potential multiplicity of transcripts involved has significant implications for ongoing gene discovery strategies.

Chromosome Aberrations↗
PubMed2006

Effects of endogenous beta-amyloid overproduction on tau phosphorylation in cell culture.

Alzheimer's disease is characterized by beta-amyloid (Abeta) overproduction and tau hyperphosphorylation. Recent studies have shown that synthetic Abeta promotes tau phosphorylation in vitro. However, whether endogenously overproduced Abeta promotes tau phosphorylation and the underlying mechanisms remain unknown. Here, we used mouse neuroblastoma N2a stably expressing wild-type amyloid precursor protein (APPwt) or the Swedish mutant APP (APPswe) to determine the alterations of phosphorylated tau and the related protein kinases. We found that phosphorylation of tau at paired helical filament (PHF)-1, pSer396 and pThr231 epitopes was significantly increased in cells transfected with APPwt and APPswe, which produced higher levels of Abeta than cells transfected with vector or amyloid precursor-like protein 1. The activity of glycogen synthase kinase-3 (GSK-3) was up-regulated with a concomitant reduction in the inhibitory phosphorylation of GSK-3 at its N-terminal Ser9 residue. In contrast, the activity of cyclin-dependent kinase-5 (CDK-5) and protein kinase C (PKC) was down-regulated. Inhibition of GSK-3 by LiCl, but not inhibition of CDK-5 by roscovitine, arrested Abeta secretion and tau phosphorylation. Inhibition of PKC by GF-109203X activated GSK-3, whereas activation of PKC by phorbol-12,13-dibutyrate inhibited GSK-3. These results suggest that endogenously overproduced Abeta induces increased tau phosphorylation through activation of GSK-3, and that inactivation of PKC is at least one of the mechanisms involved in GSK-3 activation.

Amyloid beta-Protein Precursor↗
PubMed2006

Ischemia-induced increase in RGS7 mRNA expression in gerbil hippocampus.

The present study investigated the changes in the expression of regulators of G-protein-coupled signaling proteins RGS2, 7 and 8 in gerbil hippocampus to better understand alterations of G-protein-coupled receptors signaling after cerebral ischemia. In situ hybridization revealed a transient, robust early increase in RGS7 mRNA levels in the dentate gyrus after ischemia. RGS8 mRNA expression started to increase at a later time point in the CA3 region but no changes were found for RGS2. Our results show a subtype-, time-, and subregion-specific regulation in mRNA expression of RGS proteins after cerebral ischemia in gerbil hippocampus.

Animals↗
PubMed2006

Apocynin protects against global cerebral ischemia-reperfusion-induced oxidative stress and injury in the gerbil hippocampus.

Increased production of reactive oxygen species (ROS) following cerebral ischemia-reperfusion (I/R) is an important underlying cause for neuronal injury leading to delayed neuronal death (DND). In this study, apocynin, a specific inhibitor for NADPH oxidase, was used to test whether suppression of ROS by the NADPH oxidase inhibitor can protect against ischemia-induced ROS generation and decrease DND. Global cerebral ischemia was induced in gerbils by a 5-min occlusion of bilateral common carotid arteries (CCA). Using measurement of 4-hydroxy-2-nonenal (HNE) as a marker for lipid peroxidation, apocynin (5 mg/kg body weight) injected i.p. 30 min prior to ischemia significantly attenuated the early increase in HNE in hippocampus measured at 3 h after I/R. Apocynin also protected against I/R-induced neuronal degeneration and DND, oxidative DNA damage, and glial cell activation. Taken together, the neuroprotective effects of apocynin against ROS production during early phase of I/R and subsequent I/R-induced neuronal damage provide strong evidence that inhibition of NADPH oxidase could be a promising therapeutic mechanism to protect against stroke damage in the brain.

Acetophenones↗
PubMed2006

Peroxynitrite induces Alzheimer-like tau modifications and accumulation in rat brain and its underlying mechanisms.

To investigate the upstream effector that led to tau hyperphosphorylation, nitration, and accumulation as seen in Alzheimer's disease brain, and the underlying mechanisms, we bilaterally injected SIN-1, a recognized peroxynitrite donor, into the hippocampus of rat brain. We observed that the level of nitrated and hyperphosphorylated tau was markedly increased in rat hippocampus 24 h after drug administration, and these alterations were prevented by preinjection of uric acid, a natural scavenger of peroxynitrite. Concomitantly, we detected a significant activation in glycogen synthase kinase-3beta (GSK-3beta) and p38 MAPKs, including p38alpha, p38beta, and p38delta, but no obvious change was measured in the activity of p38gamma, ERK, and c-Jun amino-terminal kinase (JNK). Both nitrated tau and hyperphosphorylated tau were aggregated in the hippocampus, in which the activity of 20S proteasome was significantly arrested in SIN-1-injected rats. Further studies demonstrated that the hyperphosphorylated tau was degraded as efficiently as normal tau by 20S proteasome, but the nitrated tau with an unorderly secondary structure became more resistant to the proteolysis. These results provide the first in vivo evidence showing that peroxynitrite simultaneously induces tau hyperphosphorylation, nitration, and accumulation, and that activation of GSK-3beta, p38alpha, p38beta, p38delta isoforms and the inhibition of proteasome activity are respectively responsible for the peroxynitrite-induced tau hyperphosphorylation and accumulation. Our findings reveal a common upstream stimulator and a potential therapeutic target for Alzheimer-like neurodegeneration.

Alzheimer Disease↗
PubMed2006

[Mechanism of tau hyperphosphorylation in brain cortex of diabetic rats and effect of LiCl].

OBJECTIVE: To explore the mechanism of tau hyperphosphorylation and the effect of LiCl on tau phosphorylation and the memory retention deficits in streptozotocin-induced diabetes mellitus (DM) rats. METHODS: The rats were randomly divided into control, DM, DM + NaCl, and DM + LiCl groups and diabetes was induced by streptozotocin. The activity of glycogen synthase kinase-3 (GSK-3) was measured by 32P-labelling. The level of tau phosphorylated and changes of memory retention were examined by Western blotting and step down test, respectively. RESULTS: Compared with control group, the activity of GSK-3 and tau phosphorylation was increased, and the memory retention was impaired in DM group. When the rats were treated with LiCl, the activity of GSK-3 and hyperphosphorylation of tau were significantly arrested (P < 0.05, P < 0.01), and the memory retention deficit was significantly improved (P < 0.05). CONCLUSION: The hyperphosphorylation of tau can be induced by activation of GSK-3 in diabetic rats. Lithium protects tau from hyperphosphorylation and may rescue memory retention in the rats by inhibiting GSK-3 activity.

Animals↗
PubMed2006

[Impact of catalytic ozonation with ferric hydroxide on HAAs formation potential of a filtered surface water].

Formation potential of five haloacetic acids (HAA5FP) of a filtered surface water was studied after ozonation alone and catalytic ozonation with a ferric hydroxide (FeOOH). Factors studied were oxidation time, bromide, pH, bicarbonate alkalinity, and ozone dosages. The haloacetic acids detected were dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), and dibromoacetic acid (DBAA) when bromide existed. The catalytic ozonation caused a reduction of HAA5FP of the non-bromide containing water for 9.5% - 18.3% compared to that of ozonation in 5-20 minutes. Incremental addition of bromide led to a much lower HAA5FP after catalytic ozonation than that after ozonation. HAA5FP of the water at neutral pH was higher than that at acidic and basic conditions. Catalytic ozonation showed a most advantageous potential in controlling HAA5FP over ozonation at neutral pH. The HAA5FP decreased as bicarbonate concentration increased, and the disparity between ozonation and catalytic ozonation was also reduced. The HAA5FP after catalytic ozonation was 11.2% to 28.0% lower than that after ozonation while the ratio of O3/TOC ranging from 0.45 to 1.43. The effect of catalytic ozonation on HAA5FP of the water is closely related to its enhanced generation of hydroxyl radicals in catalytic process.

Acetates↗
PubMed2005

Chromosome 1p and 11q deletions and outcome in neuroblastoma.

BACKGROUND: Neuroblastoma is a childhood cancer with considerable morbidity and mortality. Tumor-derived biomarkers may improve risk stratification. METHODS: We screened 915 samples of neuroblastoma for loss of heterozygosity (LOH) at chromosome bands 1p36 and 11q23. Additional analyses identified a subgroup of cases of 11q23 LOH with unbalanced 11q LOH (unb11q LOH; defined as loss of 11q with retention of 11p). The associations of LOH with relapse and survival were determined. RESULTS: LOH at 1p36 was identified in 209 of 898 tumors (23 percent) and LOH at 11q23 in 307 of 913 (34 percent). Unb11q LOH was found in 151 of 307 tumors with 11q23 LOH (17 percent of the total cohort). There was a strong association of 1p36 LOH, 11q23 LOH, and unb11q LOH with most high-risk disease features (P<0.001). LOH at 1p36 was associated with amplification of the MYCN oncogene (P<0.001), but 11q23 LOH and unb11q LOH were not (P<0.001 and P=0.002, respectively). Cases with unb11q LOH were associated with three-year event-free and overall survival rates (+/-SE) of 50+/-5 percent and 66+/-5 percent, respectively, as compared with 74+/-2 percent and 83+/-2 percent among cases without unb11q LOH (P<0.001 for both comparisons). In a multivariate model, unb11q LOH was independently associated with decreased event-free survival (P=0.009) in the entire cohort, and both 1p36 LOH and unb11q LOH were independently associated with decreased progression-free survival in the subgroup of patients with features of low-risk and intermediate-risk disease (P=0.002 and P=0.02, respectively). CONCLUSIONS: Unb11q LOH and 1p36 LOH are independently associated with a worse outcome in patients with neuroblastoma.

Analysis of Variance↗
PubMed2005

Genomic organization, gene duplication, and expression analysis of interleukin-1beta in channel catfish (Ictalurus punctatus).

Interleukin-1beta (IL-1beta) is one of the pivotal early response pro-inflammatory cytokines that enables organisms to respond to infection and induces a cascade of reactions leading to inflammation. In spite of its importance and two decades of studies in the mammalian species, genes encoding IL-1beta were not identified from non-mammalian species until recently. Recent research, particularly with genomic approaches, has led to sequencing of IL-1beta from many species. Clinical studies also suggested IL-1beta as an immunoregulatory molecule potentially useful for enhancing vaccination. However, no IL-1beta genes have been identified from channel catfish, the primary aquaculture species from the United States. In this study, we identified two distinct cDNAs encoding catfish IL-1beta. Their encoding genes were identified, sequenced, and characterized. The catfish IL-1beta genes were assigned to bacterial artificial chromosome (BAC) clones. Genomic studies indicated that the IL-1beta genes were tandemly duplicated on the same chromosome. Phylogenetic analysis of various IL-1beta genes indicated the possibility of recent species-specific gene duplications in channel catfish, and perhaps also in swine and carp. Expression analysis indicated that both IL-1beta genes were expressed, but exhibited distinct expression profiles in various catfish tissues, and after bacterial infection with Edwardsiella ictaluri.

Amino Acid Sequence↗
PubMed2005

NK-lysin of channel catfish: gene triplication, sequence variation, and expression analysis.

Antimicrobial peptides (AMPs) are important components of the host innate immune response against microbial invasion. In addition to the previously known four classes of antimicrobial peptides, a fifth class of antimicrobial peptides has been recently identified to include NK-lysins that have a globular three-dimensional structure and are larger with 74-78 amino acid residues. NK-lysin has been shown to harbor antimicrobial activities against a wide spectrum of microorganisms including bacteria, fungi, protozoa, and parasites. To date, NK-lysin genes have been reported from only a limited number of organisms. We previously identified a NK-lysin cDNA in channel catfish. Here we report the identification of two novel types of NK-lysin transcripts in channel catfish. Altogether, three distinct NK-lysin transcripts exist in channel catfish. In this work, their encoding genes were identified, sequenced, and characterized. We provide strong evidence that the catfish NK-lysin gene is tripled in the same genomic neighborhood. All three catfish NK-lysin genes are present in the same genomic region and are tightly linked on the same chromosome, as the same BAC clones harbor all three copies of the NK-lysin genes. All three NK-lysin genes are expressed, but exhibit distinct expression profiles in various tissues. In spite of the existence of a single copy of NK-lysin gene in the human genome, and only a single hit from the pufferfish genome, there are two tripled clusters of NK-lysin genes on chromosome 17 of zebrafish in addition to one more copy on its chromosome 5. The similarity in the genomic arrangement of the tripled NK-lysin genes in channel catfish and zebrafish suggest similar evolution of NK-lysin genes.

Amino Acid Sequence↗
PubMed2005

Proliferation of human neuroblastomas mediated by the epidermal growth factor receptor.

Neuroblastoma is a common solid tumor of childhood that is derived from the neural crest. Expression of epidermal growth factor (EGF) receptors (EGFRs) has been associated with enhanced cell growth and aggressive behavior in other tumors. Here, we examined the expression profile of EGFRs in neuroblastoma cell lines and primary tumors. We found that all 13 neuroblastoma cell lines examined expressed EGFR1 (HER1), most at readily detectable levels. Low levels of other human EGFR family receptors were also detected in almost all cell lines. All primary tumors examined expressed readily detectable levels of HER1 and HER3 and lower levels of HER2 and HER4. EGF had a significant effect on the proliferation of neuroblastoma cell lines in vitro. EGF treatment (100 ng/mL) of the cell lines SY5Y and NLF significantly increased cell number (P < 0.01). EGF stimulated more cells to enter S and G2-M phase, as suggested by flow cytometry, indicating that EGF increases cell number by increasing proliferation, with no appreciable change in apoptosis. EGF exposure resulted in receptor autophosphorylation and activation of both the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT pathways. Exposure to 0.5 micromol/L ZD1839, a HER1-specific inhibitor, caused a 40% to 50% reduction in the number of SY5Y and NLF cells grown in medium containing 10% fetal bovine serum (P < 0.01). Even at 0.01 micromol/L, ZD1839 inhibited autophosphorylation of HER1 by EGF. At 0.1 micromol/L, it also blocked phosphorylation of AKT, but not MAPK, in NLF cells. Additional studies showed that the PI3K/AKT-specific inhibitor LY294002 had a more profound effect than the MAPK-specific inhibitor U0126 in blocking EGF-induced cell proliferation. This suggests that the PI3K/AKT pathway is the main signaling pathway responsible for the proliferation effects of EGF in neuroblastomas. Our results also indicate that ZD1839 is a potent inhibitor of neuroblastoma cell proliferation; therefore, it may be a useful, biologically based therapeutic agent for these tumors.

Cell Growth Processes↗