Showing papers by "Yi Chen published in 2007"

MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells.

Abstract: Neuroblastoma (NB) is one of the most common forms of cancer in children, accounting for 15% of pediatric cancer deaths. The clinical course of these tumors is highly variable and is dependent on such factors as age at presentation, stage, ploidy and genomic abnormalities. Hemizygous deletion of chromosome 1p occurs in approximately 30% of advanced stage tumors, is associated with a poor prognosis, and likely leads to the loss of one or more tumor suppressor genes. We show here that microRNA (miRNA)-34a (1p36.23) is generally expressed at lower levels in unfavorable primary NB tumors and cell lines relative to normal adrenal tissue and that reintroduction of this miRNA into three different NB cell lines causes a dramatic reduction in cell proliferation through the induction of a caspase-dependent apoptotic pathway. As a potential mechanistic explanation for this observation, we demonstrate that miR-34a directly targets the messenger ribonucleic acid (mRNA) encoding E2F3 and significantly reduces the levels of E2F3 protein, a potent transcriptional inducer of cell-cycle progression. Furthermore, miR-34a expression increases during retinoic acid-induced differentiation of the SK-N-BE cell line, whereas E2F3 protein levels decrease. Thus, adding to the increasing role of miRNAs in cancer, miR-34a may act as a suppressor of NB tumorgenesis.

IL-25 regulates Th17 function in autoimmune inflammation

Abstract: Interleukin (IL)-25 is a member of the IL-17 family of cytokines. However, unlike the other members of this family, IL-25 promotes T helper (Th) 2 responses. We now show that IL-25 also regulates the development of autoimmune inflammation mediated by IL-17–producing T cells. We have generated IL-25–deficient (il25−/−) mice and found that they are highly susceptible to experimental autoimmune encephalomyelitis (EAE). The accelerated disease in the il25−/− mice is associated with an increase of IL-23 in the periphery and a subsequent increase in the number of inflammatory IL-17–, IFNγ-, and TNF-producing T cells that invade the central nervous system. Neutralization of IL-17 but not IFNγ in il25−/− mice prevented EAE, suggesting that IL-17 is a major disease-promoting factor. IL-25 treatment at several time points during a relapse-remitting model or chronic model of EAE completely suppressed disease. IL-25 treatment induced elevated production of IL-13, which is required for suppression of Th17 responses by direct inhibition of IL-23, IL-1β, and IL-6 expression in activated dendritic cells. Thus, IL-25 and IL-17, being members of the same cytokine family, play opposing roles in the pathogenesis of organ-specific autoimmunity.

Methotrexate Conjugated to Gold Nanoparticles Inhibits Tumor Growth in a Syngeneic Lung Tumor Model

Abstract: Methotrexate (MTX), a stoichiometric inhibitor of dihydrofolate reductase, is a chemotherapeutic agent for treating a variety of neoplasms Impairment of drug import into cells and increase in drug export from cells may render cells resistant to MTX MTX, when locally administered in a soluble form, is rapidly absorbed through capillaries into the circulatory system, which may also account for therapeutic failure in patients To retain MTX within tumor cells for longer duration and alter its pharmacokinetic behavior, we proposed a new formulation of MTX bound to the gold nanoparticle (AuNP) that serves as drug carriers In this study, we developed the MTX-AuNP conjugate and examined its cytotoxic effect in vitro and antitumor effect in vivo Spectroscopic examinations revealed that MTX can be directly bound onto AuNP via the carboxyl group (-COOH) to form the MTX-AuNP complex and kinetically released from the nanoparticles The accumulation of MTX is faster and higher in tumor cells treated with MTX-AuNP than that treated with free MTX Notably, MTX-AuNP shows higher cytotoxic effects on several tumor cell lines compared with an equal dose of free MTX This can be attributed to the "concentrated effect" of MTX-AuNP Administration of MTX-AuNP suppresses tumor growth in a mouse ascites model of Lewis lung carcinoma (LL2), whereas an equal dose of free MTX had no antitumor effect In conclusion, these results suggest that by combining nanomaterials with anticancer drugs MTX-AuNP may be more effective than free MTX for cancer treatment

An All-Optical Trap for a Gram-Scale Mirror

Abstract: We report on a stable optical trap suitable for a macroscopic mirror, wherein the dynamics of the mirror are fully dominated by radiation pressure. The technique employs two frequency-offset laser fields to simultaneously create a stiff optical restoring force and a viscous optical damping force. We show how these forces may be used to optically trap a free mass without introducing thermal noise, and we demonstrate the technique experimentally with a 1 g mirror. The observed optical spring has an inferred Young's modulus of 1.2 TPa, 20% stiffer than diamond. The trap is intrinsically cold and reaches an effective temperature of 0.8 K, limited by technical noise in our apparatus.

Giant optical gyrotropy due to electromagnetic coupling

Abstract: The authors demonstrate a chiral photonic metamaterial with chirality provided by electromagnetic coupling between mutually twisted unconnected layers. In the visible and near-IR spectral ranges, the material exhibits polarization rotatory power of up to 2500°/mm and shows relatively low losses and negligible circular dichroism, making it a promising candidate for the development of chiral negative index media.

A phenomenological template family for black-hole coalescence waveforms

Abstract: Recent progress in numerical relativity has enabled us to model the non-perturbative merger phase of the binary black-hole coalescence problem. Based on these results, we propose a phenomenological family of waveforms which can model the inspiral, merger and ring-down stages of black-hole coalescence. We also construct a template bank using this family of waveforms and discuss its implementation in the search for signatures of gravitational waves produced by black-hole coalescences in the data of ground-based interferometers. This template bank might enable us to extend the present inspiral searches to higher-mass binary black-hole systems, i.e., systems with total mass greater than about 80 solar masses, thereby increasing the reach of the current generation of ground-based detectors.

Gene Expression Profiling Reveals Potential Biomarkers of Human Hepatocellular Carcinoma

Abstract: Purpose: Hepatocellular carcinoma (HCC), a common cancer worldwide, has a dismal outcome partly due to the poor identification of early-stage HCC. Currently, one third of HCC patients present with low serum α-fetoprotein (AFP) levels, the only clinically available diagnostic marker for HCC. The aim of this study was to identify new diagnostic molecular markers for HCC, especially for individuals with low serum AFP. Experimental Design: We used the microarray technique to determine the expression profiles of 218 HCC specimens from patients with either high or low serum AFP. From the microarray study, we selected five candidate genes (i.e., GPC3, PEG10, MDK, SERPINI1 , and QP-C ), which were overexpressed in HCCs. Using quantitative real-time PCR analyses, we validated the expression of these five genes in 50 AFP-normal and 8 AFP-positive HCC specimens and 36 cirrhotic noncancerous hepatic specimens, which include 52 independent specimens not used in microarray analysis. Results: A significant increase in the expression of the five candidate genes could be detected in most of the HCC samples, including those with normal serum AFP and small tumors. GPC3, MDK , and SERPINI1 encode known serum proteins. Consistently, a significant increase in serum midkine, encoded by MDK , was associated with HCC patients, including those with normal serum AFP. Using prediction analysis of microarray, we showed that a combined score of these five genes can accurately classify noncancerous hepatic tissues (100%) and HCC (71%). Conclusions: We suggest that a diagnostic signature approach using a combined score of these five biomarkers rather than a single marker may improve the prediction accuracy of HCC patients, including those with normal serum AFP and smaller-sized tumors.

Phenomenological template family for black-hole coalescence waveforms

Abstract: Recent progress in numerical relativity has enabled us to model the non-perturbative merger phase of the binary black-hole coalescence problem. Based on these results, we propose a phenomenological family of waveforms which can model the inspiral, merger, and ring-down stages of black hole coalescence. We also construct a template bank using this family of waveforms and discuss its implementation in the search for signatures of gravitational waves produced by black-hole coalescences in the data of ground-based interferometers. This template bank might enable us to extend the present inspiral searches to higher-mass binary black-hole systems, i.e., systems with total mass greater than about 80 solar masses, thereby increasing the reach of the current generation of ground-based detectors.

Amelioration of collagen-induced arthritis in rats by Nanogold

Abstract: Objective Angiogenesis plays a part in the pathogenesis of rheumatoid arthritis (RA), and nanogold inhibits the activity of an angiogenic factor, vascular endothelial growth factor (VEGF). We therefore investigated whether intraarticular delivery of nanogold ameliorates collagen-induced arthritis (CIA) in rats. Methods Binding of 13-nm nanogold to VEGF in human RA synovial fluid (SF) and its effects on RA SF–induced endothelial cell proliferation and migration were assessed. Nanogold was administered intraarticularly to rats with CIA before the onset of arthritis. Progression of CIA was monitored by measures of clinical, radiologic, and histologic changes. In addition, the microvessel density and extent of infiltrating macrophages as well as levels of tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) in the ankle joints were determined. Results Nanogold bound to VEGF in RA SF, resulting in inhibition of RA SF–induced endothelial cell proliferation and migration. Significant reductions in ankle circumference, articular index scores, and radiographic scores were observed in the nanogold-treated rats with CIA compared with their control counterparts. In addition, the histologic score (of synovial hyperplasia, cartilage erosion, and leukocyte infiltration), microvessel density, macrophage infiltration, and levels of TNFα and IL-1β were also significantly reduced in the ankle joints of nanogold-treated rats. Conclusion Our results are the first to demonstrate that intraarticular administration of nanogold ameliorates the clinical course of CIA in rats. Nanogold exerted antiangiogenic activities and subsequently reduced macrophage infiltration and inflammation, which resulted in attenuation of arthritis. These results demonstrate proof of principle for the use of nanogold as a novel therapeutic agent for the treatment of RA.

Upper limits on gravitational wave emission from 78 radio pulsars

Abstract: We present upper limits on the gravitational wave emission from 78 radio pulsars based on data from the third and fourth science runs of the LIGO and GEO 600 gravitational wave detectors The data from both runs have been combined coherently to maximize sensitivity For the first time, pulsars within binary (or multiple) systems have been included in the search by taking into account the signal modulation due to their orbits Our upper limits are therefore the first measured for 56 of these pulsars For the remaining 22, our results improve on previous upper limits by up to a factor of 10 For example, our tightest upper limit on the gravitational strain is 26×10-25 for PSR J1603-7202, and the equatorial ellipticity of PSR J2124–3358 is less than 10-6 Furthermore, our strain upper limit for the Crab pulsar is only 22 times greater than the fiducial spin-down limit

Searches for periodic gravitational waves from unknown isolated sources and Scorpius X-1: Results from the second LIGO science run

Abstract: We carry out two searches for periodic gravitational waves using the most sensitive few hours of data from the second LIGO science run. Both searches exploit fully coherent matched filtering and cover wide areas of parameter space, an innovation over previous analyses which requires considerable algorithm development and computational power. The first search is targeted at isolated, previously unknown neutron stars, covers the entire sky in the frequency band 160–728.8 Hz, and assumes a frequency derivative of less than 4×10^(−10) Hz/s. The second search targets the accreting neutron star in the low-mass x-ray binary Scorpius X-1 and covers the frequency bands 464–484 Hz and 604–624 Hz as well as the two relevant binary orbit parameters. Because of the high computational cost of these searches we limit the analyses to the most sensitive 10 hours and 6 hours of data, respectively. Given the limited sensitivity and duration of the analyzed data set, we do not attempt deep follow-up studies. Rather we concentrate on demonstrating the data analysis method on a real data set and present our results as upper limits over large volumes of the parameter space. In order to achieve this, we look for coincidences in parameter space between the Livingston and Hanford 4-km interferometers. For isolated neutron stars our 95% confidence level upper limits on the gravitational wave strain amplitude range from 6.6×10^(−23) to 1×10^(−21) across the frequency band; for Scorpius X-1 they range from 1.7×10^(−22) to 1.3×10^(−21) across the two 20-Hz frequency bands. The upper limits presented in this paper are the first broadband wide parameter space upper limits on periodic gravitational waves from coherent search techniques. The methods developed here lay the foundations for upcoming hierarchical searches of more sensitive data which may detect astrophysical signals.

Searching for a stochastic background of gravitational waves with the laser interferometer gravitational-wave observatory

Abstract: The Laser Interferometer Gravitational-Wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new Bayesian 90% upper limit is ΩGW × [H0/(72 km s−1 Mpc−1)]2 < 6.5 × 10-5. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss the complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.

Measurement of the inclusive jet cross section using the kT algorithm in pp̄ collisions at s=1.96TeV with the CDF II detector

Abstract: The authors report on measurements of the inclusive jet production cross section as a function of the jet transverse momentum in p{bar p} collisions at {radical}s = 1.96 TeV, using the k{sub T} algorithm and a data sample corresponding to 1.0 fb{sup -1} collected with the Collider Detector at Fermilab in Run II. The measurements are carried out in five different jet rapidity regions with |y{sup jet}| < 2.1 and transverse momentum in the range 54 < p{sub T}{sup jet} < 700 GeV/c. Next-to-leading order perturbative QCD predictions are in good agreement with the measured cross sections.

Search for gravitational-wave bursts in LIGO data from the fourth science run

Abstract: The fourth science run of the LIGO and GEO 600 gravitational-wave detectors, carried out in early 2005, collected data with significantly lower noise than previous science runs. We report on a search for short-duration gravitational-wave bursts with arbitrary waveform in the 64–1600 Hz frequency range appearing in all three LIGO interferometers. Signal consistency tests, data quality cuts and auxiliary-channel vetoes are applied to reduce the rate of spurious triggers. No gravitational-wave signals are detected in 15.5 days of live observation time; we set a frequentist upper limit of 0.15 day−1 (at 90% confidence level) on the rate of bursts with large enough amplitudes to be detected reliably. The amplitude sensitivity of the search, characterized using Monte Carlo simulations, is several times better than that of previous searches. We also provide rough estimates of the distances at which representative supernova and binary black hole merger signals could be detected with 50% efficiency by this analysis.

Upper Limit map of a background of gravitational waves

Abstract: We searched for an anisotropic background of gravitational waves using data from the LIGO S4 science run and a method that is optimized for point sources. This is appropriate if, for example, the gravitational wave background is dominated by a small number of distinct astrophysical sources. No signal was seen. Upper limit maps were produced assuming two different power laws for the source strain power spectrum. For an f^(−3) power law and using the50 Hz to 1.8 kHz band the upper limits on the source strain power spectrum vary between 1.2×10^(−48) Hz^(−1) (100 Hz/f)^3 and 1.2×10^(−47) Hz^(−1) (100 Hz/f)^3, depending on the position in the sky. Similarly, in the case of constant strain power spectrum, the upper limits vary between 8.5×10−49 Hz−1 and 6.1×10^(−48) Hz^(−1). As a side product a limit on an isotropic background of gravitational waves was also obtained. All limits are at the 90% confidence level. Finally, as an application, we focused on the direction of Sco-X1, the brightest low-mass x-ray binary. We compare the upper limit on strain amplitude obtained by this method to expectations based on the x-ray flux from Sco-X1.

Chimmitecan, a novel 9-substituted camptothecin, with improved anticancer pharmacologic profiles in vitro and in vivo.

Abstract: Purpose: This study aimed to evaluate antitumor activities and pharmacologic profiles of chimmitecan, a novel 9-small-alkyl–substituted lipophilic camptothecin, in comparison with irinotecan (CPT-11) and topotecan. Experimental Design: The in vitro cytotoxities of chimmitecan in human tumor cell lines and multidrug resistance (MDR) cells were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and sulforhodamin B assays. DNA relaxation, cleavage assays, and cellular band depletion assay were combined to delineate its effects on topoisomerase I. DNA damage, cell cycle arrest, and apoptosis were assessed using comet assay, flow cytometry, and DNA ladder analysis, respectively. The in vivo antitumor activities were measured in nude mice bearing human tumor xenografts. Results: Chimmitecan displayed more potent cytotoxicity than SN38 and topotecan. Neither a cross-resistance to chimmitecan in MDR cells nor an influence of human serum albumin in its cytotoxity was observed. Chimmitecan exhibited comparable effects on topoisomerase I compared with the reference drugs, including inhibiting topoisomerase I catalytic activity and trapping and stabilizing covalent topoisomerase I-DNA complexes. Furthermore, nanomolar levels of chimmitecan caused impressive DNA damage, G2-M phase arrest, and apoptosis in human leukemia HL60 cells. I.v. administration of chimmitecan inhibited the growth of HCT-116, MDA-MB-435, BEL-7402, and A549 human carcinoma xenografts in nude mice, with greater potency than CPT-11 against the latter two tumors models. Chimmitecan presented potent efficacy in A549 tumor model when given orally. Conclusions: Chimmitecan is a potent inhibitor of topoisomerase I and displays outstanding activity in vitro and in vivo . The substitution at the 9-position benefits chimmitecan a salient anti-MDR activity, stability in human serum albumin, improved solubility, and oral availability, which might favorably promise its therapeutic potential in clinical settings.

FLJ10540-elicited cell transformation is through the activation of PI3-kinase/AKT pathway.

Abstract: A significant challenge in the post-genomic era is how to prioritize differentially expressed and uncharacterized novel genes found in hepatocellular carcinoma (HCC) microarray profiling. One such category is cell cycle regulated genes that have only evolved in higher organisms but not in lower eukaryotic cells. Characterization of these genes may reveal some novel human cancer-specific abnormalities. A novel transcript, FLJ10540 was identified. FLJ10540 is overexpressed in HCC as examined by quantitative reverse transcription–polymerase chain reaction and immunohistochemistry. The patients with higher FLJ10540 expression had a poor survival than those with lower FLJ10540 expression. Functional characterization indicates that FLJ10540 displays a number of characteristics associated with an oncogene, including anchorage-independent growth, enhanced cell growth at low serum levels and induction of tumorigenesis in nude mice. FLJ10540-elicited cell transformation is mediated by activation of the phosphatidylinositol 3′-kinase (PI3K)/AKT pathway. Moreover, FLJ10540 forms a complex with PI3K and can activate PI3K activity, which provides a mechanistic basis for FLJ10540-mediated oncogenesis. Together, using a combination of bioinformatics searches and empirical data, we have identified a novel oncogene, FLJ10540, which is conserved only in higher organisms. The finding raises the possibility that FLJ10540 is a potential new therapeutic target for HCC treatment. These findings may contribute to the development of new therapeutic strategies that are able to block the PI3K/AKT pathway in cancer cells.

R16, a novel amonafide analogue, induces apoptosis and G2-M arrest via poisoning topoisomerase II.

Abstract: Amonafide, a naphthalimide derivative, although selected for exploratory clinical trials for its potent anticancer activity, has long been challenged by its unpredictable side effects. In the present study, a novel amonafide analogue, 2-(2-dimethylamino)-6-thia-2-aza-benzo-[def]-chrysene-1,3-diones (R16) was synthesized by substituting 5'-NH(2) of the naphthyl with a heterocyclic group to amonafide, with additional introduction of a thiol group. In a panel of various human tumor cell lines, R16 was more cytotoxic than its parent compound amonafide. It was also effective against multidrug-resistant cells. Importantly, the i.p. administration of R16 inhibited tumor growth in mice implanted with S-180 sarcoma and H(22) hepatoma. The molecular and cellular machinery studies showed that the R16 functions as a topoisomerase II (topo II) poison via binding to the ATPase domain of human topo IIalpha. The superior cytotoxicity of R16 to amonafide was ascribed to its potent effects on trapping topo II-DNA cleavage complexes. Moreover, using a topo II catalytic inhibitor aclarubicin, ataxia-telangiectasia-mutated (ATM)/ATM- and Rad3-related (ATR) kinase inhibitor caffeine and topo II-deficient HL-60/MX2 cells, we further showed that R16-triggered DNA double-strand breaks, tumor cell cycle arrest, and apoptosis were in a topo II-dependent manner. Taken together, R16 stood out by its improved anticancer activity, appreciable anti-multidrug resistance activities, and well-defined topo II poisoning mechanisms, as comparable with the parent compound amonafide. All these collectively promise the potential value of R16 as an anticancer drug candidate, which deserves further development.

Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) has potential tumour-suppressive activity in human lung cancer

Abstract: The expression of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is decreased in various tumours, but the role of IGFBP-rP1 in lung cancer is not yet clear. In this study, IGFBP-rP1 expression in lung cancer cell lines was evaluated and reduced expression of IGFBP-rP1 was found. In tissue microarrays containing 138 primary tumours and 20 normal lung tissues analysed by immunohistochemistry, 58 tumours (42%) exhibited no expression of IGFBP-rP1, while all 20 normal lung tissues showed high expression. In squamous cell lung cancer, low expression of IGFBP-rP1 was significantly linked to high-grade tumours. Treatment with 5-aza-2'-deoxycytidine restored the expression of IGFBP-rP1 in three of four lung cancer cell lines. Sequencing of PCR products of sodium bisulphite-treated genomic DNA from the three lung cancer cell lines revealed a heterogeneous methylation pattern in the region of exon 1 and intron 1. Stable transfection of IGFBP-rP1 full-length cDNA into the H2170 lung cancer cell line led to increased expression of IGFBP-rP1 protein. IGFBP-rP1-positive transfectants exhibited remarkably reduced colony-forming ability in soft agar, suppression of tumour growth rate in nude mice, and increased apoptotic cell number as well as activated caspase-3 expression level. The data suggest that IGFBP-rP1 is a tumour suppressor inactivated by DNA methylation in human lung cancer.

Hyperspectral imaging of plasmonic nanostructures with nanoscale resolution.

Abstract: We report on the first realization of a hyperspectral imaging technique for surface plasmon polaritons on metallic nanostructures. The technique uses a scanning electron beam and allows for simple visualization of light emission from decoupled plasmons, providing information on decay lengths and feature sizes with nanometer resolution.

Search for gravitational wave radiation associated with the pulsating tail of the SGR 1806-20 hyperflare of 27 December 2004 using LIGO

Abstract: We have searched for gravitational waves (GWs) associated with the SGR 1806−20 hyperflare of 27 December 2004. This event, originating from a Galactic neutron star, displayed exceptional energetics. Recent investigations of the x-ray light curve’s pulsating tail revealed the presence of quasiperiodic oscillations (QPOs) in the 30–2000 Hz frequency range, most of which coincides with the bandwidth of the LIGO detectors. These QPOs, with well-characterized frequencies, can plausibly be attributed to seismic modes of the neutron star which could emit GWs. Our search targeted potential quasimonochromatic GWs lasting for tens of seconds and emitted at the QPO frequencies. We have observed no candidate signals above a predetermined threshold, and our lowest upper limit was set by the 92.5 Hz QPO observed in the interval from 150 s to 260 s after the start of the flare. This bound corresponds to a (90% confidence) root-sum-squared amplitude h^(90%)_(rss-det) =4.5×10^(−22) strain Hz^(−1/2) on the GW waveform strength in the detectable polarization state reaching our Hanford (WA) 4 km detector. We illustrate the astrophysical significance of the result via an estimated characteristic energy in GW emission that we would expect to be able to detect. The above result corresponds to 7.7×10^(46) erg (=4.3×10^(−8) M_⊙c^2), which is of the same order as the total (isotropic) energy emitted in the electromagnetic spectrum. This result provides a means to probe the energy reservoir of the source with the best upper limit on the GW waveform strength published and represents the first broadband asteroseismology measurement using a GW detector.

BM6, a new semi-synthetic vinca alkaloid, exhibits its potent in vivo anti-tumor activities via its high binding affinity for tubulin and improved pharmacokinetic profiles.

Abstract: The aim of this study was to evaluate the anti-tumor activities and to establish the mechanism of the action of 3-decarboxyl-acetyloxylmethyl-anhydrovinblastine (BM6), a new semi-synthetic Vinca alkaloid, in an effort towards finding the favorable therapeutics of Vinca alkaloid derivatives. BM6 was characterized by its superior in vivo activity to vinorelbine in preclinical tumor models, though BM6 exerted in vitro cytotoxic activity against a wide spectrum of tumor cell lines with IC50 values generally 10-fold higher than the classic Vinca alkaloids. Of note, BM6 displayed more potent cytotoxic activity against multidrug-resistant sublines. We further found that BM6 shared the mitotic arresting and tubulin-interacting properties comparable with other Vinca alkaloids. BM6 also induced significant cell cycle arrested in mitosis and cytoskeleton disruption via interacting with the Vinca binding site on tubulin. Encouragingly, the features in term of its higher tubulin binding affinities and better pharmacok...

Chromosome 8 BAC array comparative genomic hybridization and expression analysis identify amplification and overexpression of TRMT12 in breast cancer

Abstract: Genomic changes in chromosome 8 are commonly observed in breast cancer cell lines and tumors. To fine map such genomic changes by comparative genomic hybridization (CGH), a high resolution (100 kb) chromosome 8 array that can detect single copy changes was developed using Phi29 DNA polymerase amplified BAC (bacterial artificial chromosome) DNA. The BAC array CGH resolved the two known amplified regions (8q21 and 8q24) of a breast cancer cell line (SKBR3) into nine separate regions including six amplicons and three deleted regions, all of which were verified by Fluorescence in situ hybridization. The extent of the gain/loss for each region was validated by qPCR. CGH was performed with a total of 8 breast cancer cell lines, and common regions of genomic amplification/deletion were identified by segmentation analysis. A 1.2-Mb region (125.3–126.5 Mb) and a 1.0-Mb region (128.1–129.1 Mb) in 8q24 were amplified in 7/8 cell lines. A global expression analysis was performed to evaluate expression changes associated with genomic amplification/deletion: a novel gene, TRMT12 (at 125.5 Mb), amplified in 7/8 cell lines, showed highest expression in these cell lines. Further analysis by RT-qPCR using RNA from 30 breast tumors showed that TRMT12 was overexpressed >2 fold in 87% (26/30) of the tumors. TRMT12 is a homologue of a yeast gene encoding a tRNA methyltransferase involved in the posttranscriptional modification of tRNAPhe, and exploring the biological consequence of its altered expression, may reveal novel pathways in tumorigenesis. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. Published 2007 Wiley-Liss, Inc.

Silencing of Lactotransferrin expression by methylation in prostate cancer progression.

Abstract: Background: Cancer cells gain selection advantages by the coordinated silencing of protective and by the activation of cell proliferation/cell survival genes. Evaluations of epithelial cell transcriptome of benign and malignant prostate glands by laser capture microdissection (LCM) identified Lactotransferrin (LTF) as the most significantly downregulated gene in prostate cancer (CaP) cells (P

First cross-correlation analysis of interferometric and resonant-bar gravitational-wave data for stochastic backgrounds

Abstract: Data from the LIGO Livingston interferometer and the ALLEGRO resonant-bar detector, taken during LIGO’s fourth science run, were examined for cross correlations indicative of a stochastic gravitational-wave background in the frequency range 850–950 Hz, with most of the sensitivity arising between 905 and 925 Hz. ALLEGRO was operated in three different orientations during the experiment to modulate the relative sign of gravitational-wave and environmental correlations. No statistically significant correlations were seen in any of the orientations, and the results were used to set a Bayesian 90% confidence level upper limit of Ω_(gw)(f)≤1.02, which corresponds to a gravitational-wave strain at 915 Hz of 1.5×10^(−23) Hz^(−1/2). In the traditional units of h^2_(100)Ω_(gw)(f), this is a limit of 0.53, 2 orders of magnitude better than the previous direct limit at these frequencies. The method was also validated with successful extraction of simulated signals injected in hardware and software.