Showing papers by "Yi Chen published in 2001"

Gene-Expression Profiles in Hereditary Breast Cancer

Abstract: Background Many cases of hereditary breast cancer are due to mutations in either the BRCA1 or the BRCA2 gene. The histopathological changes in these cancers are often characteristic of the mutant gene. We hypothesized that the genes expressed by these two types of tumors are also distinctive, perhaps allowing us to identify cases of hereditary breast cancer on the basis of gene-expression profiles. Methods RNA from samples of primary tumors from seven carriers of the BRCA1 mutation, seven carriers of the BRCA2 mutation, and seven patients with sporadic cases of breast cancer was compared with a microarray of 6512 complementary DNA clones of 5361 genes. Statistical analyses were used to identify a set of genes that could distinguish the BRCA1 genotype from the BRCA2 genotype. Results Permutation analysis of multivariate classification functions established that the gene-expression profiles of tumors with BRCA1 mutations, tumors with BRCA2 mutations, and sporadic tumors differed significantly from each othe...

Estrogen Receptor Status in Breast Cancer Is Associated with Remarkably Distinct Gene Expression Patterns

Abstract: To investigate the phenotype associated with estrogen receptor alpha (ER) expression in breast carcinoma, gene expression profiles of 58 node-negative breast carcinomas discordant for ER status were determined using DNA microarray technology. Using artificial neural networks as well as standard hierarchical clustering techniques, the tumors could be classified according to ER status, and a list of genes which discriminate tumors according to ER status was generated. The artificial neural networks could accurately predict ER status even when excluding top discriminator genes, including ER itself. By reference to the serial analysis of gene expression database, we found that only a small proportion of the 100 most important ER discriminator genes were also regulated by estradiol in MCF-7 cells. The results provide evidence that ER+ and ER- tumors display remarkably different gene-expression phenotypes not solely explained by differences in estrogen responsiveness.

Human Prostate Cancer and Benign Prostatic Hyperplasia Molecular Dissection by Gene Expression Profiling

Abstract: Critical aspects of the biology and molecular basis for prostate malignancy remain poorly understood. To reveal fundamental differences between benign and malignant growth of prostate cells, we performed gene expression profiling of primary human prostate cancer and benign prostatic hyperplasia (BPH) using cDNA microarrays consisting of 6500 human genes. Frozen prostate specimens were processed to facilitate extraction of RNA from regions of tissue enriched in either benign or malignant epithelial cell growth within a given specimen. Gene expression in each of the 16 prostate cancer and nine BPH specimens was compared with a common reference to generate normalized measures for each gene across all of the samples. Using an analysis of complete pairwise comparisons of expression profiles among all of the samples, we observed clearly discernable patterns of overall gene expression that differentiated prostate cancer from BPH. Further analysis of the data identified 210 genes with statistically significant differences in expression between prostate cancer and BPH. These genes include many not recognized previously as differentially expressed in prostate cancer and BPH, including hepsin, which codes for a transmembrane serine protease. This study reveals for the first time that significant and widespread differences in gene expression patterns exist between benign and malignant growth of the prostate gland. Gene expression analysis of prostate tissues should help to disclose the molecular mechanisms underlying prostate malignant growth and identify molecular markers for diagnostic, prognostic, and therapeutic use.

Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease

Abstract: Little is known about the genetic regulation of medulloblastoma dissemination, but metastatic medulloblastoma is highly associated with poor outcome. We obtained expression profiles of 23 primary medulloblastomas clinically designated as either metastatic (M+) or non-metastatic (M0) and identified 85 genes whose expression differed significantly between classes. Using a class prediction algorithm based on these genes and a leave-one-out approach, we assigned sample class to these tumors (M+ or M0) with 72% accuracy and to four additional independent tumors with 100% accuracy. We also assigned the metastatic medulloblastoma cell line Daoy to the metastatic class. Notably, platelet-derived growth factor receptor alpha (PDGFRA) and members of the downstream RAS/mitogen-activated protein kinase (MAPK) signal transduction pathway are upregulated in M+ tumors. Immunohistochemical validation on an independent set of tumors shows significant overexpression of PDGFRA in M+ tumors compared to M0 tumors. Using in vitro assays, we show that platelet-derived growth factor alpha (PDGFA) enhances medulloblastoma migration and increases downstream MAP2K1 (MEK1), MAP2K2 (MEK2), MAPK1 (p42 MAPK) and MAPK3 (p44 MAPK) phosphorylation in a dose-dependent manner. Neutralizing antibodies to PDGFRA blocks MAP2K1, MAP2K2 and MAPK1/3 phosphorylation, whereas U0126, a highly specific inhibitor of MAP2K1 and MAP2K2, also blocks MAPK1/3. Both inhibit migration and prevent PDGFA-stimulated migration. These results provide the first insight into the genetic regulation of medulloblastoma metastasis and are the first to suggest a role for PDGFRA and the RAS/MAPK signaling pathway in medulloblastoma metastasis. Inhibitors of PDGFRA and RAS proteins should therefore be considered for investigation as possible novel therapeutic strategies against medulloblastoma.

Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer

Abstract: The biological significance of DNA amplification in cancer is thought to be due to the selection of increased expression of a single or few important genes. However, systematic surveys of the copy number and expression of all genes within an amplified region of the genome have not been performed. Here we have used a combination of molecular, genomic, and microarray technologies to identify target genes for 17q23, a common region of amplification in breast cancers with poor prognosis. Construction of a 4-Mb genomic contig made it possible to define two common regions of amplification in breast cancer cell lines. Analysis of 184 primary breast tumors by fluorescence in situ hybridization on tissue microarrays validated these results with the highest amplification frequency (12.5%) observed for the distal region. Based on GeneMap'99 information, 17 known genes and 26 expressed sequence tags were localized to the contig. Analysis of genomic sequence identified 77 additional transcripts. A comprehensive analysis of expression levels of these transcripts in six breast cancer cell lines was carried out by using complementary DNA microarrays. The expression patterns varied from one cell line to another, and several overexpressed genes were identified. Of these, RPS6KB1, MUL, APPBP2, and TRAP240 as well as one uncharacterized expressed sequence tag were located in the two common amplified regions. In summary, comprehensive analysis of the 17q23 amplicon revealed a limited number of highly expressed genes that may contribute to the more aggressive clinical course observed in breast cancer patients with 17q23-amplified tumors.

Quantum noise in second generation, signal recycled laser interferometric gravitational wave detectors

Abstract: It has long been thought that the sensitivity of laser interferometric gravitational-wave detectors is limited by the free-mass standard quantum limit, unless radical redesigns of the interferometers or modifications of their input or output optics are introduced. Within a fully quantum-mechanical approach we show that in a second-generation interferometer composed of arm cavities and a signal recycling cavity, e.g., the LIGO-II configuration, (i) quantum shot noise and quantum radiation-pressure-fluctuation noise are dynamically correlated, (ii) the noise curve exhibits two resonant dips, (iii) the standard quantum limit can be beaten by a factor of 2, over a frequency range Δf/f∼1, but at the price of increasing noise at lower frequencies.

Transcription program of human herpesvirus 8 (kaposi's sarcoma-associated herpesvirus).

Abstract: Human herpesvirus 8 (HHV-8), a gammaherpesvirus implicated in Kaposi's sarcoma, primary effusion lymphoma, and Castleman's disease, encodes several pathogenically important cellular homologs. To define the HHV-8 transcription program, RNA obtained from latently infected body cavity-based lymphoma 1 cells induced to undergo lytic replication was used to query a custom HHV-8 DNA microarray containing nearly every known viral open reading frame. The patterns of viral gene expression offer insights into the replication and pathogenic strategies of HHV-8.

Gastrointestinal stromal tumors with KIT mutations exhibit a remarkably homogeneous gene expression profile

Abstract: Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the digestive tract, are believed to arise from the interstitial cells of Cajal. GISTs are characterized by mutations in the proto-oncogene KIT that lead to constitutive activation of its tyrosine kinase activity. The tyrosine kinase inhibitor STI571, active against the BCR-ABL fusion protein in chronic myeloid leukemia, was recently shown to be highly effective in GISTs. We used 13,826-element cDNA microarrays to define the expression patterns of 13 KIT mutation-positive GISTs and compared them with the expression profiles of a group of spindle cell tumors from locations outside the gastrointestinal tract. Our results showed a remarkably distinct and uniform expression profile for all of the GISTs. In particular, hierarchical clustering of a subset of 113 cDNAs placed all of the GIST samples into one branch, with a Pearson correlation >0.91. This homogeneity suggests that the molecular pathogenesis of a GIST results from expansion of a clone that has acquired an activating mutation in KIT without the extreme genetic instability found in the common epithelial cancers. The results provide insight into the histogenesis of GIST and the clinical behavior of this therapeutically responsive tumor.

Failure of hormone therapy in prostate cancer involves systematic restoration of androgen responsive genes and activation of rapamycin sensitive signaling

Abstract: Androgen deprivation therapy for advanced prostate cancer is often effective, but not curative. Molecular pathways mediating the therapeutic response and those contributing to the subsequent hormone-refractory cell growth remain poorly understood. Here, cDNA microarray analysis of human CWR22 prostate cancer xenografts during the course of androgen deprivation therapy revealed distinct global gene expression profiles in primary, regressing and recurrent tumors. Elucidation of the genes involved in the transition between these states implicated specific molecular mechanisms in therapy failure and tumor progression. First, we identified a set of androgen-responsive genes whose expression decreased during the therapy response, but was then systematically restored in the recurrent tumors. In addition, altered expression of genes that encode known targets of rapamycin or that converge on the PI3K/AKT/FRAP pathway was observed in the recurrent tumors. Further suggestion for the involvement of these genes in hormone-refractory prostate cancer came from the observation that cells established from the recurrent xenografts were strongly inhibited in vitro by rapamycin. The results of this functional genomic analysis suggest that the combined effect of re-expression of androgen-responsive genes as well as the activation of rapamycin-sensitive signaling may drive prostate cancer progression, and contribute to the failure of androgen-deprivation therapy.

Influence of supports on the activities of copper oxide species in the low-temperature NO+CO reaction

Abstract: Activity measurements were made of the NO+CO reaction over a series of CuO/CeO2 and CuO/γ-Al2O3 catalysts with various loading amounts of CuO at low-temperatures, XRD, TPR, UV–DRS and XPS were also used for the characterization of the catalysts. The results show that NO conversions have an intimate relation with the loading amount of CuO and the supports used at temperature lower than 200°C, and the activities decreased in the order: CuO/CeO2>CuO/γ-Al2O3>crystalline CuO. Under these reaction conditions, the activities of the catalysts strongly depended on the surface dispersed copper oxide species. When the temperature was increased to 300°C, NO completely conversed to N2 over the catalysts, which meant that the temperature had strongly influenced the reaction. The influence of the support on the activities of the supported copper oxide species was tentatively discussed in the view of the strong interactions between active components and the supports which significantly promoted the reduction of the surface dispersed copper oxide species.

Genome-wide expression changes induced by HTLV-1 Tax: evidence for MLK-3 mixed lineage kinase involvement in Tax-mediated NF-κB activation

Abstract: The Tax protein of human T-lymphotropic virus type 1 (HTLV-1), an oncoprotein that transactivates viral and cellular genes, plays a key role in HTLV-1 replication and pathogenesis. We used cDNA microarrays to examine Tax-mediated transcriptional changes in the human Jurkat T-cell lines JPX-9 and JPX-M which express Tax and Tax-mutant protein, respectively, under the control of an inducible promoter. Approximately 300 of the over 2000 genes examined were differentially expressed in the presence of Tax. These genes were grouped according to their function and are discussed in the context of existing findings in the literature. There was strong agreement between our results and genes previously reported as being Tax-responsive. Genes that were differentially expressed in the presence of Tax included those related to apoptosis, the cell cycle and DNA repair, signaling factors, immune modulators, cytokines and growth factors, and adhesion molecules. Functionally, we provide evidence that one of these genes, the mixed-lineage kinase MLK-3, is involved in Tax-mediated NF-κB signaling. Our current results provide additional insights into Tax-mediated signaling.

Cation distribution and infrared properties of NixMn1-xFe2O4 ferrites

Abstract: The spinel ferrite system Ni x Mn1 − x Fe2O4, with x = 0, 0.1, 0.25, 0.5, 0.75 and 1, is prepared by the standard double sintering ceramic method. X-ray diffraction and IR spectroscopy are used to analyze the relationship between infrared properties and content of the nickel ions. With nickel ion substitution addition, the lattice parameter, X-ray density, cation distribution, inversion parameter and radius of octahedral and tetrahedral sites are calculated. The IR spectra obtained at room temperature in the frequency range 350–1000 cm−1, show four absorption bands. The high frequency band (ν1) and low frequency band (ν2) are assigned to the tetrahedral and octahedral complexes, respectively. The relationship between bands and nickel content was also investigated and found that the absorption bands linearly increase with the increasing content of nickel ions, which is correlated to the cation distribution calculated by Bertaut method.

Optical noise correlations and beating the standard quantum limit in advanced gravitational-wave detectors

Abstract: The uncertainty principle, applied naively to the test masses of a laser-interferometer gravitational-wave detector, produces a standard quantum limit (SQL) on the interferometer's sensitivity. It has long been thought that beating this SQL would require a radical redesign of interferometers. However, we show that LIGO-II interferometers, currently planned for 2006, can beat the SQL by as much as a factor two over a bandwidth Deltaf similar to f, if their thermal noise can be pushed low enough. This is due to dynamical correlations between photon shot noise and radiation-pressure noise, produced by the LIGO-II signal-recycling mirror.

Microkinetic analysis of isopropanol dehydrogenation over Cu/SiO2 catalyst

Abstract: The reaction of isopropanol dehydrogenation to acetone over the Cu/SiO2 catalyst was studied using the method of microkinetic analysis. This analysis provided a picture about the coverage of different surface species and their influences on the reaction rate. Specifically, the analysis reinforced the previously proposed mechanism and added some new findings for the reaction. It was found that under the normal reaction conditions, the catalyst surface is mostly covered by the isopropoxyl groups and the overall reaction rate is controlled by the elimination of α-H of the isopropoxyl groups. In addition, the elimination of the α-H is significantly affected by the availability of surface Cu sites. At the low hydrogen partial pressure, the number of bare surface Cu sites increases with the increasing of hydrogen partial pressure, leading to the increased overall reaction rate and thus the positive reaction order with respect to hydrogen. Thus, hydrogen can enhance the rate of this reaction via some kinetic factors under the specific coverage regime, although it is thermodynamically unfavorable for the reaction.

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

Abstract: 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. Copyright © 2001 John Wiley & Sons, Ltd. Abbreviations used: CBQCA 3-(4-carboxybenzoyl)-2-quinoline carboxaldehyde CCD charge-coupled device DA dopamine, E, epinephrine FITC fluorescein isothiocyanate S-HT serotoni Lif, laser-induced fluorescence NE noreginephrine.

Preparation, Characterization, and Ferroelectric Properties of the Alkylamine-Intercalated Layered Perovskite-Type Oxides (CnH2n+1NH3-Sr2Nb3O10, n ) 1-6)

Abstract: A series of alkylamine-intercalated layered perovskite-type oxides, CnH2n+1NH3−Sr2Nb3O10 (n = 1−6), were prepared through a stepwise exchange process. X-ray powder diffraction (XRD) patterns of the...

Field-induced three- and two-dimensional freezing in a quantum spin liquid.

Abstract: Field-induced commensurate transverse magnetic ordering is observed in the Haldane-gap compound Ni(C{sub 5}D{sub 14} N{sub 2}){sub 2}N{sub 3} (PF{sub 6} ) by means of neutron diffraction. Depending on the direction of applied field, the high-field phase is shown to be either a three-dimensional ordered Neel state or a short-range ordered state with dominant two-dimensional spin correlations. The structure of the high-field phase is determined, and properties of the observed quantum phase transition are discussed.

Positron annihilation lifetime in mesoporous silica MCM-41 at different vacuum levels

Abstract: Positron annihilation lifetime spectra of MCM-41 and zeolite Y were measured at different vacuum levels. When the experiments were carried out in air, a very long lifetime component (τ4 = 35-45 ns, I4 = 15-20%) was observed for MCM-41, while the longest lifetime for zeolite Y was only 2-4 ns with an intensity of 15-25%. However, when the experiments were carried out in vacuum, the very long lifetime components could be observed for both samples, although with different intensities, ~30% for MCM-41 and ~10% for zeolite Y. For MCM-41 in air, the longest lifetime (τ4) is ~42 ns, corresponding to the ortho-positronium (o-Ps) annihilation lifetime in MCM-41 cavities. This value is slightly longer but very close to the value of 39 ns, which was estimated by using a bouncing quantum particle model. These peculiar positron annihilation characteristics were explained by air quenching mechanism of o-Ps annihilation in MCM-41. It was suggested that because of the existence of the very long lifetime component even in air, positron lifetime spectroscopy could be a very useful tool for nondestructive measurement of the cavity size of mesoporous solids such as MCM-41.

A Study on VPO Specimen Supported on Aluminum-Containing MCM-41 for Partial Oxidation of n-Butane to MA

Abstract: Dispersed vanadium–phosphorus oxide species supported on Al-MCM-41 with different vanadium loadings have been synthesized for the first time for partial oxidation of butane to MA. It was found that the VPO species was dispersed over the Al-MCM-41 support material, both in the internal channel and on the external surface. With increasing vanadium loading, n-butane conversion increased but MA selectivity decreased considerably under the same reaction conditions. At lower conversions (<30%), rather high MA selectivity (ca. 70%) can be achieved on the low loading sample. Compared with the amorphous structure of large pore SiO2 support, the unique structure of the MCM-41 and the incorporated Al3+ in the framework do have an impact on the reaction behavior of the supported VPO specimen. The chemical nature of the supported VPO species and the interaction between the applied VPO species and the support was found to vary notably with the content of vanadium in the sample and likewise affected the related physico-chemical characteristics and their reaction behaviors.

Analysis of expression patterns: the scope of the problem, the problem of scope.

Abstract: Studies of the expression patterns of many genes simultaneously lead to the observation that even in closely related pathologies, there are numerous genes that are differentially expressed in consistent patterns correlated to each sample type. The early uses of the enabling technology, microarrays, was focused on gathering mechanistic biological insights. The early findings now pose another clear challenge, finding ways to effectively use this kind of information to develop diagnostics.

Ordinary-temp hydrolysis process for synthesizing nm-class rutile-type TiO2 with high specific surface area from TiCl4

Abstract: An ordinary-temp hydrolysis process for synthesizing nm-class rutile-type TiO2 with large specific surface area includes such steps as hydrolyzing TiCl4 as raw material to obtain precursor, and direct preparing said TiO2 by using beta-cyclodextrin (beta-CD), SiO2, Al2O3, or TiO2 of different crystal type as crystal seed. Its advantages are high productivity, low cost, large specific surface area and uniform sizes.

Preparation of tetragonal zirconia containingtitanium nitride powder by in-situ selective nitridation

Abstract: A novel in-situ preparation technique has been developed for selective reaction in solid solution. A thermodynamic approach was employed to analyze the selective nitridation conditions of the (Zr,Ti)O2 solid solution system and to define the temperature range of the selective nitridation. Tetragonal zirconia containing titanium nitride powder was synthesized by carbothermal reduction under a nitrogen atmosphere in the selected temperature range. The influence of reaction temperature on selective nitridation was evaluated by X-ray diffraction. Elemental quantitative analysis showed that the ratio of selective nitridation of titanium oxide reached about 93%. The morphology of the resultant powder was observed by scanning electron microscopy. The average particle size of the powders obtained was found to be in the range 300–400 nm.