HNF1α and CDX2 transcriptional factors bind to cadherin-17 (CDH17) gene promoter and modulate its expression in hepatocellular carcinoma

Cadherin-17 (CDH17) belongs to the cell adhesion cadherin family with a prominent role in tumorigenesis. It is highly expressed in human hepatocellular carcinoma (HCC) and is proposed to be a biomarker and therapeutic molecule for liver malignancy. The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC. A 1-kb upstream sequence of CDH17 gene was cloned and the promoter activity was studied by luciferase reporter assay. By bioinformatics analysis, deletion and mutation assays, and chromatin immunoprecipitation studies, we identified hepatic nuclear factor 1a (HNF1a) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L). A consistent down-regulation of CDH17 and the two transcriptional activators (HNF1a and CDX2) expression was found in the liver of mouse during development, as well as in human liver cancer cells with less metastatic potential. Suppression of HNF1a and CDX2 expression by small interfering RNA (siRNA) significantly down-regulated expressions of CDH17 and its downstream target cyclin D1 and the viability of HCC cells in vitro. In summary, we identified the minimal promoter region of CDH17 that is regulated by HNF1a and CDX2 transcriptional factors. The present findings enhance our understanding on the regulatory mechanisms of CDH17 oncogene in HCC, and may shed new insights into targeting CDH17 expression as potential therapeutic intervention for cancer treatment. © 2010 Wiley-Liss, Inc.preprin

Miniaturized Via-Free Magneto-Electric Dipole Antenna Fed by Substrate Integrated Coaxial Line on Reactive Impedance Surface

A wideband via-free magneto-electric (ME) dipole antenna is conceived for millimeter wave band applications. Herein, the electric dipole patch and a half-wavelength radiating slot are excited in phase on the patch layer by a substrate integrated coaxial line (SICL) to fulfill the complementary conditions as a ME dipole. The proposed antenna omits the deployment of the vertically oriented shorted patch, which relieves the typical quarter-wavelength height constraint and fabrication complexity of the conventional ME dipole antennas. The antenna is further loaded with the capacitive reactive impedance surface (RIS) to achieve size miniaturization and bandwidth enhancement. The finalized dimension (excluding the RIS) is 0.36 λ0 × 0.48 λ0 × 0.13 λ0, where λ0 denotes the wavelength in free-space at the center frequency. A wide impedance bandwidth of 64.8% (17.1 GHz - 33.5 GHz) is achieved for SWR ≤ 2, in which the antenna gain varies from 5.9 dBi to 8.8 dBi. Besides, a consistent unidirectional radiation pattern can be observed across the operating frequency band. In the sequel, the same antenna is aggregated into an 8-element linear array which is fed by a designated 8-way SICL network

Miniaturized Via-Free Magneto-Electric Dipole Antenna Fed by Substrate Integrated Coaxial Line on Reactive Impedance Surface

A wideband via-free magneto-electric (ME) dipole antenna is conceived for millimeter wave band applications. Herein, the electric dipole patch and a half-wavelength radiating slot are excited in phase on the patch layer by a substrate integrated coaxial line (SICL) to fulfill the complementary conditions as a ME dipole. The proposed antenna omits the deployment of the vertically oriented shorted patch, which relieves the typical quarter-wavelength height constraint and fabrication complexity of the conventional ME dipole antennas. The antenna is further loaded with the capacitive reactive impedance surface (RIS) to achieve size miniaturization and bandwidth enhancement. The finalized dimension (excluding the RIS) is 0.36 λ0 × 0.48 λ0 × 0.13 λ0, where λ0 denotes the wavelength in free-space at the center frequency. A wide impedance bandwidth of 64.8% (17.1 GHz - 33.5 GHz) is achieved for SWR ≤ 2, in which the antenna gain varies from 5.9 dBi to 8.8 dBi. Besides, a consistent unidirectional radiation pattern can be observed across the operating frequency band. In the sequel, the same antenna is aggregated into an 8-element linear array which is fed by a designated 8-way SICL network. Finally, an active simulation has been performed to verify the ability of the array in beam scanning

Study of motoring operation of in-wheel switched reluctance motor drives for electric vehicles

Author name used in this publication: X. D. XueAuthor name used in this publication: K. W. E. ChengAuthor name used in this publication: N. C. CheungAuthor name used in this publication: Z. ZhangAuthor name used in this publication: J. K. LinRefereed conference paper2008-2009 > Academic research: refereed > Refereed conference paperVersion of RecordPublishe

The Embryotrophic Activity of Oviductal Cell-derived Complement C3b and iC3b, a Novel Function of Complement Protein in Reproduction

The oviduct-derived embryotrophic factor, ETF-3, enhances the development of trophectoderm and the hatching process of treated embryos. Monoclonal anti-ETF-3 antibody that abolishes the embryotrophic activity of ETF-3 recognized a 115-kDa protein from the conditioned medium of immortalized human oviductal cells. Mass spectrometry analysis showed that the protein was complement C3. Western blot analysis using an antibody against C3 confirmed the cross-reactivities between anti-C3 antibody with ETF-3 and anti-ETF-3 antibody with C3 and its derivatives, C3b and iC3b. Both derivatives, but not C3, were embryotrophic. iC3b was most efficient in enhancing the development of blastocysts with larger size and higher hatching rate, consistent with the previous reported embryotrophic activity of ETF-3. Embryos treated with iC3b contained iC3b immunoreactivity. The oviductal epithelium produced C3 as evidenced by the presence of C3 immunoreactivity and mRNA in the human oviduct and cultured oviductal cells. Cyclical changes in the expression of C3 immunoreactivity and mRNA were also found in the mouse oviduct with the highest expression at the estrus stage. Molecules involving in the conversion of C3b to iC3b and binding of iC3b were present in the human oviduct (factor I) and mouse preimplantation embryo (Crry and CR3), respectively. In conclusion, the present data showed that the oviduct produced C3/C3b, which was converted to iC3b to stimulate embryo development.postprin

Global Regulation on microRNA in Hepatitis B Virus-Associated Hepatocellular Carcinoma

Recent work has revealed the causative links between deregulation of microRNAs (miRNAs) and cancer development. In hepatocellular carcinoma (HCC), aberrant expression of miRNAs has been observed, but the molecular mechanisms that contribute to such changes remains to be elucidated. Here, we reported the analysis of miRNA expression in 94 pairs of tumor and adjacent nontumor tissues from HBV-associated HCC in Chinese patients. We found miRNAs were aberrantly expressed in HCC tissues. To investigate the cause of such deregulation, we detected changes in DNA copy number by measuring locus-specific hybridization intensity, and found changes in expression of several miRNAs are correlated with genomic amplification or deletion. For example, the genomic regions of miR-30d and miR-151 were amplified in ∼50% of HCC tumor tissues, and the expressions of these miRNAs are significantly correlated with DNA copy number. We also employed cDNA microarray data, and provide evidence that key regulators of the miRNA biosynthetic pathway, including DROSHA, DGCR8, AGO1, and AGO2, are frequently overexpressed in HCC. This study provides molecular clues that may contribute to the global changes of miRNA expression in HCC. Copyright © 2011, Mary Ann Liebert, Inc.published_or_final_versio

Anti-cadherin-17 antibody modulates Beta-catenin signaling and tumorigenicity of hepatocellular carcinoma

published_or_final_versio

Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome

Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.published_or_final_versio

Exhaled breath condensate pH as a biomarker of COPD severity in ex-smokers

Endogenous airway acidification, as assessed by exhaled breath condensate (EBC) pH, is present in patients with stable COPD. The aim of this study was to measure EBC pH levels in a large cohort of COPD patients and to evaluate associations with functional parameters according to their smoking status

In patient stroke rehabilitation efficiency: Influence of organization of service delivery and staff numbers

<p>Abstract</p> <p>Background</p> <p>Outcomes of inpatient stroke rehabilitation need to be reviewed in terms of optimal resource utilization (staff time, service organization, and duration of stay). We compared FIM efficiency scores between three hospitals, and also variation in FIM scores over a ten year period in one hospital undergoing reduction in staff numbers, to examine the relationship between outcome and service characteristics.</p> <p>Method</p> <p>This is a retrospective study comparing the mean FIM efficiency for stroke patients (FIM score – FIM admission score) divided by duration of stay for 2005 among three rehabilitation hospitals adjusting for age and baseline FIM score, and a longitudinal study of changes in mean FIM efficiency during a ten year period in one hospital, to examine the effects of different service organization and staff numbers.</p> <p>Results</p> <p>FIM efficiency (FIMEG) was inversely associated with age, and positively associated with admission FIM score. FIMEG was higher in the hospital with a coordinated care plan involving medical, nursing, occupational, physiotherapy staff and other healthcare providers working as a team, with a seamless interface with community rehabilitation services. Over a ten year period, reduction in staff numbers was associated with reduction in FIMEG, which may be offset to some extent by service re-engineering.</p> <p>Conclusion</p> <p>Within hospital organization of stroke rehabilitation services may influence outcome. A critical number of staff may be identified for the provision of services, below which rehabilitation efficiency may be affected.</p