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Biomedical subjects

Hai Yan

Publications and source records attributed to Hai Yan.

At least 19 recordsLinked to original sources
PubMed2006

Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers.

Tyrosine kinases are major regulators of signal transduction cascades involved in cellular proliferation and have important roles in tumorigenesis. We have recently analyzed the tyrosine kinase gene family for alterations in human colorectal cancers and identified somatic mutations in seven members of this gene family. In this study we have used high-throughput sequencing approaches to further evaluate this subset of genes for genetic alterations in other human tumors. We identified somatic mutations in GUCY2F, EPHA3, and NTRK3 in breast, lung, and pancreatic cancers. Our results implicate these tyrosine kinase genes in the pathogenesis of other tumor types and suggest that they may be useful targets for diagnostic and therapeutic intervention in selected patients.

Adenocarcinoma↗
PubMed2006

Adsorption of microcystins by carbon nanotubes.

The production of cyanobacterial toxins microcystins (MCs) by cyanobacterial bloom which may promote the growth of tumor in human liver is a growing environmental problem worldwide. In this paper, the adsorption of MC-RR and LR, which were extracted from cyanobacterial cells in Dianchi Lake in China, by carbon nanotubes (CNTs), wood-based activated carbon (ACs) and clays were investigated. Compared with ACs and clay materials of sepiolite, kaolinite and talc tested, CNTs were found to have a strong ability in the adsorption of MCs. At the concentrations of 21.5 mg l(-1) MC-RR and 9.6 mg l(-1) MC-LR in 50 mmol phosphate buffer solution (pH 7.0), the adsorption amounts of MCs by CNTs with the range of outside diameter from 2 to 10nm were 14.8 and 5.9 mg g(-1), which were about four times higher than those by other adsorbents tested. It was shown that with the decrease of CNTs outside diameters from 60 to 2 nm, the adsorption amount of MCs was apparently increased, however the size of CNTs particles formed in solution declined. This result implies that the size of CNTs tube pore that is fit for the molecular dimension of MCs plays a dominant role. Furthermore the specific surface area of CNTs was also found to be a factor in the adsorption of MCs. The results suggested that the selection of suitable size of CNTs as a kind of adsorbent is very important in the efficient eliminating MCs from drinking water in future.

Adsorption↗
PubMed2006

[Characterization of enzymatic degradation of microcystins by a new isolated bacterium].

A strain of bacterium capable of biodegrading microcystin (MC) RR and MC-LR was isolated from the sediments of Dianchi Lake. It was demonstrated that the enzymes in cell-free extract of this bacterium were responsible for the degradation of MC-RR and MC-LR, and the dead-end products of MC-RR and MC-LR catalyzed by these enzymes were observed on HPLC chromatograms. Results show that the optimum pH for the activities of these enzymes was in the range from 6.0 to 8.0, however the metal ions of Cu2+, Mn2+ and Zn2+ had no apparent effects on the enzymatic degradation of MC-RR and MC-LR.

Bacteria↗
PubMed2005

Removal of cyanobacterial blooms in Taihu Lake using local soils. I. Equilibrium and kinetic screening on the flocculation of Microcystis aeruginosa using commercially available clays and minerals.

Algal removal abilities of 26 clays/minerals were classified into three categories according to the 8-h equilibrium removal efficiency (Q8h) and removal rate at a clay loading of 0.7 g/L. Type I clays (sepiolite, talc, ferric oxide, and kaolinite) had a Q8h > 90%, a t50 (time needed to remove 50% of the algae) < 15 min, and a t80 < 2.5 h. Type II clays (6 clays) had a Q8h 50-90%, a t50 < 2.5 h, and a t80 > 2.5 h. Type III clays (14 clays) with Q8h < 50%, t50 > 8 h and t80 > 14 h had no practical value in removal of algal blooms. When the clay loading was reduced to 0.2 g/L, Q8h for all the 25 materials decreased to below 60%, except for sepiolite whose Q8h remained about 97%. The high efficiency for sepiolite to flocculate M. aeruginosa cells in freshwaters was due to the mechanism of netting and bridging effect.

Aluminum Silicates↗
PubMed2005

Identification of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid.

Through digital karyotyping of permanent medulloblastoma cell lines, we found that the homeobox gene OTX2 was amplified more than 10-fold in three cell lines. Gene expression analyses showed that OTX2 transcripts were present at high levels in 14 of 15 (93%) medulloblastomas with anaplastic histopathologic features. Knockdown of OTX2 expression by siRNAs inhibited medulloblastoma cell growth in vitro, whereas pharmacologic doses of all-trans retinoic acid repressed OTX2 expression and induced apoptosis only in medulloblastoma cell lines that expressed OTX2. These observations suggest that OTX2 is essential for the pathogenesis of anaplastic medulloblastomas and that these tumors may be amenable to therapy with all-trans-retinoic acid.

Antineoplastic Agents↗
PubMed2005

Snapshot of the allele-specific variation in human gene expression.

The analysis of gene differential expression is complicated by the potentially subtle differences associated with alterations in a single allele as well as by variations between individuals that arise from environmental or physiological factors. To circumvent these analytic problems, a method, named allele-specific differential expression analysis, was developed to compare the relative expression levels of two alleles of the same gene within the same cellular sample. The studies of allele-specific expression revealed that differential expression is relatively common in the human population.

Alleles↗
PubMed2005

Digital karyotyping technology: exploring the cancer genome.

Identifying gene-specific alterations in cancer genomes has revealed molecules that are causal effectors of carcinogenesis and specific targets for cancer molecular diagnosis and molecular-based cancer therapies. Whole-genome analyses of many cancer genomes at the resolution of single genes is thus a desirable yet incompletely realized goal that could expedite progress in cancer diagnosis and treatment. Although methods for routine whole-genome sequencing or high-resolution epigenetic measurements are currently under development, high-resolution measurements of gene copy number, or 'gene dosage', are now underway in several laboratories. Digital karyotyping, array comparative genomic hybridization, and single nucleotide polymorphism arrays are techniques that have the potential to detect gene amplification, homozygous deletion and loss of heterozygosity at or below the average length of single genes. Recently, digital karyotyping of a small number (<20) of colon and brain cancer genomes has revealed tumor cases with significant genetic dosage alterations affecting few and, in some cases, only one complete gene. These experiments suggest that gene-specific gene dosage alterations may be sufficiently frequent to enable the identification of promising tumor gene candidates in small-scale experiments. The purpose of this review is to describe our understanding of cancer as a genetic disease, review the basic principles, methodologies and interpretational issues of traditional and high-resolution whole-genome screens, and describe the potential of our first detailed look at whole cancer genomes for progress in the understanding and treatment of cancer.

Genome, Human↗
PubMed2004

Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas.

The phosphatidylinositol 3'-kinase pathway is activated in multiple advanced cancers, including glioblastomas, through inactivation of the PTEN tumor suppressor gene. Recently, mutations in PIK3CA, a member of the family of phosphatidylinositol 3'-kinase catalytic subunits, were identified in a significant fraction (25-30%) of colorectal cancers, gastric cancers, and glioblastomas and in a smaller fraction of breast and lung cancers. These mutations were found to cluster into two major "hot spots" located in the helical and catalytic domains. To determine whether PIK3CA is genetically altered in brain tumors, we performed a large-scale mutational analysis of the helical and catalytic domains. A total of 13 mutations of PIK3CA within these specific domains were identified in anaplastic oligodendrogliomas, anaplastic astrocytomas, glioblastoma multiforme, and medulloblastomas, whereas no mutations were identified in ependymomas or low-grade astrocytomas. These observations implicate PIK3CA as an oncogene in a wider spectrum of adult and pediatric brain tumors and suggest that PIK3CA may be a useful diagnostic marker or a therapeutic target in these cancers.

Astrocytoma↗
PubMed2004

Mutational analysis of the tyrosine phosphatome in colorectal cancers.

Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice-site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRT) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.

Catalytic Domain↗
PubMed2004

Detection of allelic variations of human gene expression by polymerase colonies.

BACKGROUND: Quantification of variations of human gene expression is complicated by the small differences between different alleles. Recent work has shown that variations do exist in the relative allelic expression levels in certain genes of heterozygous individuals. Herein, we describe the application of an immobilized polymerase chain reaction technique as an alternative approach to measure relative allelic differential expression. RESULTS: Herein, we report a novel assay, based on immobilized polymerase colonies, that accurately quantifies the relative expression levels of two alleles in a given sample. Mechanistically, this was accomplished by PCR amplifying a gene in a cDNA library in a thin polyacrylamide gel. By immobilizing the PCR, it is ensured that each transcript gives rise to only a single immobilized PCR colony, or "polony". Once polony amplified, the two alleles of the gene were differentially labeled by performing in situ sequencing with fluorescently labeled nucleotides. For these sets of experiments, silent single nucleotide polymorphisms (SNPs) were used to discriminate the two alleles. Finally, a simple count was then performed on the differentially labeled polonies in order to determine the relative expression levels of the two alleles. To validate this technique, the relative expression levels of PKD2 in a family of heterozygous patients bearing the 4208G/A SNP were examined and compared to the literature. CONCLUSIONS: We were able to reproduce the results of allelic variation in gene expression using an accurate technology known as polymerase colonies. Therefore, we have demonstrated the utility of this method in human gene expression analysis.

Alleles↗
PubMed2004

Increase in biodegradation of dimethyl phthalate by Closterium lunula using inorganic carbon.

The effect and mechanism of inorganic carbon (IC) on the biodegradation of dimethyl phthalate (DMP) by a green microalga Closterium lunula was investigated. The growth of this microalga and the biodegradation of DMP were significantly enhanced when the initial IC was increased. An intermediate product of DMP biodegradation was identified as phthalic acid (PA) that was accumulated and caused a sharp decrease in pH of microalgal culture medium, which inhibited both the growth of microalga and the biodegradation of DMP. A suggested second-order kinetic equation of organic pollutant biodegradation by microalgae (-dC/dt = kNr) fitted well with the experimental data. The increase of IC caused a decline in biodegradation rate constant for organic carbon (k) and an increase in growth (N) by supplying a favorite carbon source and mitigating the decrease of pH. As the net effect, the overall biodegradation rate of DMP was promoted as IC increased, which was dominated by the increase of microalgal growth.

Biodegradation, Environmental↗
PubMed2004

Allelic variations in gene expression.

PURPOSE OF REVIEW: Genetic variants determine phenotypic variability. Many genetic studies suggest that protein structural variations predispose the population to more than 1000 different hereditary diseases. Unfortunately, despite the study of genetic polymorphisms for many decades, the milder phenotypic variations believed to account for most human physical and behavioral differences and underlying the most common human genetic diseases (including cancers) cannot be accounted for easily by these variations in the protein coding sequences. Thus, it has been hypothesized that the study of natural differential expression presenting within and among populations may enhance understanding of human phenotypic variation. RECENT FINDINGS: During the last year, reports identifying variations in gene expression in different organisms and finding subtle changes of gene expression associated with common genetic disease have pointed to variations in gene expression as playing a central role in molecular evolution and human disease. Advances in the functional analysis of gene regulatory networks-in particular, new methods for distinguishing cis-acting components from trans-acting factors-have provided the impetus for these discoveries. SUMMARY: This review represents current knowledge about allelic variation in gene expression and its increasingly important role in understanding the genotype-phenotype relation. Characterization of these allelic variations may open largely uncharted territory in genomics for biomedical researchers and may eventually lead to the discovery of the causative genes of common hereditary diseases and their mechanism of action.

Alleles↗
PubMed2004

A method to extract algae toxin of microcystin-LR.

A simple and low-cost method to obtain cyanobacterial toxin microcystin-LR (MC-LR) was developed. A new strain of Microcystis aeruginosa, named DC-1, producing microcystin-LR but not microcystin-RR, was separated from the field blooming algae samples of Dianchi Lake, in southwest of China. Following three times' freeze and thaw treatment, the cultivated DC-1 cells were extracted with 40% methanol in water. The extract was centrifuged and the supernatant applied to a Hydrophilic-Lipophilic Balance (HLB) SPE cartridge. Eluted impurities with a certain gradient from 30% to 50% methanol in water, MC-LR was finally eluted from the HLB cartridge with 60% methanol in water, and samples containing 3.85% to 14.8% of MC-LR were obtained. These MC-LR samples may be used in adsorption and biodegradation experiments instead of using expensive standard reagents.

Bacterial Toxins↗
PubMed2004

Effects of nitrogen forms on the production of cyanobacterial toxin microcystin-IR by an isolated Microcystis aeruginosa.

A cyanobacterial strain, which produced high content of microcystin-LR (MC-LR) but no microcystin-RR (MC-RR), was isolated from the hypertrophic Dianchi Lake in China and identified as Microcystis aeruginosa DC-1. Effects of nitrogen containing chemicals and trace elements on the growth and the production of MC-LR by this strain were studied. In the presence of bicine, compared with urea and ammonium, nitrate greatly promoted the growth and the production of MC-LR. However, leucine and arginine, which were the constitutional components in the molecular structure of MC-LR or RR, inhibited the production of MC-LR. Iron and silicon up to 10 mg/L had little effects on the growth of M. aeruginosa DC-1, but the production of MC-LR was apparently enhanced. Under all conditions studied here, only MC-LR but no RR was detected within the cells of M. aeruginosa DC-1. Thus, chemical forms of nitrogen, rather than the usually concerned the total nitrogen, and trace elements played important roles in the production of MC toxins during cyanobacterial blooms.

Amino Acids↗
PubMed2004

[Isolation and activity of bacteria for the biodegradation of microcystins].

The abilities of bacterial communities, which collected from the sediment and surface water of Dianchi Lake, for the biodegradation of microcystins (MCs) were firstly investigated. It was shown that the biodegradation rates of both MC-RR and LR by bacteria in sediment were apparently higher than those by bacteria on surface water. Five strains of bacteria, which have the abilities in the biodegradation of MCs, from the sediment were isolated using the liquid and solid medium containing MC-RR and LR as the carbon and nitrogen sources, which was extracted and purified from the cells of cyanobacterial bloom. Among the bacteria isolated, bacterium D was found to have a strong ability in the biodegradation of MCs. Initial MC-RR and LR of 60.1 mg x L(-1) and 38.7 mg x L(-1) were completely removed in 3 days and the average biodegradation rates per day for MC-RR and LR were 20.0 mg x L(-1) and 12.9 mg x L(-1), respectively.

Bacteria↗
PubMed2003

Transforming single DNA molecules into fluorescent magnetic particles for detection and enumeration of genetic variations.

Many areas of biomedical research depend on the analysis of uncommon variations in individual genes or transcripts. Here we describe a method that can quantify such variation at a scale and ease heretofore unattainable. Each DNA molecule in a collection of such molecules is converted into a single magnetic particle to which thousands of copies of DNA identical in sequence to the original are bound. This population of beads then corresponds to a one-to-one representation of the starting DNA molecules. Variation within the original population of DNA molecules can then be simply assessed by counting fluorescently labeled particles via flow cytometry. This approach is called BEAMing on the basis of four of its principal components (beads, emulsion, amplification, and magnetics). Millions of individual DNA molecules can be assessed in this fashion with standard laboratory equipment. Moreover, specific variants can be isolated by flow sorting and used for further experimentation. BEAMing can be used for the identification and quantification of rare mutations as well as to study variations in gene sequences or transcripts in specific populations or tissues.

Base Sequence↗