Combination of SAHA and bortezomib up-regulates CDKN2A and CDKN1A and induces apoptosis of Epstein-Barr virus-positive Wp-restricted Burkitt lymphoma and lymphoblastoid cell lines

Epstein-Barr virus (EBV) latent proteins exert anti-apoptotic effects on EBV-transformed lymphoid cells by down-regulating BCL2L11 (BIM), CDKN2A (p16(INK4A) ) and CDKN1A (p21(WAF1) ). However, the potential therapeutic effects of targeting these anti-apoptotic mechanisms remain unexplored. Here, we tested both in vitro and in vivo effects of the combination of histone deacetylase (HDAC) and proteasome inhibitors on the apoptosis of six endemic Burkitt lymphoma (BL) lines of different latency patterns (types I and III and Wp-restricted) and three lymphoblastoid cell lines (LCLs). We found that the combination of HDAC and proteasome inhibitors (e.g. SAHA/bortezomib) synergistically induced the killing of Wp-restricted and latency III BL and LCLs but not latency I BL cells. The synergistic killing was due to apoptosis, as evidenced by the high percentage of annexin V positivity and strong cleavage of PARP1 (PARP) and CASP3 (caspase-3). Concomitantly, SAHA/bortezomib up-regulated the expression of CDKN2A and CDKN1A but did not affect the level of BCL2L11 or BHRF1 (viral homologue of BCL2). The apoptotic effects were dependent on reactive oxygen species generation. Furthermore, SAHA/bortezomib suppressed the growth of Wp-restricted BL xenografts in nude mice. This study provides the rationale to test the novel application of SAHA/bortezomib on the treatment of EBV-associated Wp-restricted BL and post-transplant lymphoproliferative disorder.postprin

Electroluminescence from AlN nanowires grown on p-SiC substrate

2010-2011 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Effects of controllable biaxial strain on the Raman spectra of monolayer graphene prepared by chemical vapor deposition

Author name used in this publication: Hui, Yeung YuAuthor name used in this publication: Lau, Shu PingAuthor name used in this publication: Hao, Jianhua2012-2013 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

X-ray photoemission spectroscopy of nonmetallic materials : electronic structures of boron and BᵪOᵧ

Author name used in this publication: H. Huang2003-2004 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Application of a graphene buffer layer for the growth of high quality SnS films on GaAs(100) substrate

Tin mono-sulfide (SnS) thin films have been grown by molecular beam epitaxy (MBE) on two different substrates, GaAs (100) and soda lime glass at 400°C. High resolution X-ray Diffraction (HXRD) and Scanning Electron Microscopy (SEM) are used to characterize the structural properties of the as grown SnS films. By introducing a graphene buffer layer between the SnS thin film and the substrate, the XRD rocking curve's full width at half maximum (FWHM) of the SnS film grown on GaAs (100) and soda lime glass decrease from 2.92° to 0.37° and from 6.58° to 2.04° respectively, indicating a significant improvement of SnS thin films.Department of Applied PhysicsDepartment of Electronic and Information EngineeringAuthor name used in this manuscript: W. K. FongAuthor name used in this manuscript: C. SuryaRefereed conference pape

Molecular beam epitaxy growth of high quality p-doped SnS van der Waals epitaxy on a graphene buffer layer

Author name used in this publication: W. K. FongAuthor name used in this publication: C. Surya2011-2012 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in Buruli ulcer lesions

A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tisischemia could contribute to the development of the tissue necrosis seen in BU lesions

Adiponectin gene variant +276G>T independently predicts incident coronary heart disease in men: a 16-year prospective study

Adiponectin gene variant +276G>T independently predicts incident coronary heart disease in men: a 16-year prospective studypublished_or_final_versio

CNx-modified Fe3O4 as Pt nanoparticle support for the oxygen reduction reaction

A novel electrocatalyst support material, nitrogendoped carbon (CNx)-modified Fe3O4 (Fe3O4-CNx), was synthesized through carbonizing a polypyrrole-Fe3O4 hybridized precursor. Subsequently, Fe3O4-CNx-supported Pt (Pt/Fe3O4-CNx) nanocomposites were prepared by reducing Pt precursor in ethylene glycol solution and evaluated for the oxygen reduction reaction (ORR). The Pt/Fe3O4-CNx catalysts were characterized by X-ray diffraction, Raman spectra, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy. The electrocatalytic activity and stability of the as-prepared electrocatalysts toward ORR were studied by cyclic voltammetry and steady-state polarization measurements. The results showed that Pt/ Fe3O4-CNx catalysts exhibited superior catalytic performance for ORR to the conventional Pt/C and Pt/C-CNx catalysts.Web of Scienc

Study of Bˉ0→D0μ+μ−\bar B^0 \to D^0 \mu^+\mu^- Decay in Perturbative QCD Approach

Within the perturbative QCD approach and ignoring the contributions of long distance and subleading penguin loops, we investigate $\bar B^0 \to D^0 \mu^+\mu^-$ decay in the large recoiling kinematic region in the Standard Model. At the tree level, $\bar B^0$ decays to $D^0$ by exchanging a $W$ boson accompanied by a virtual photon emission from the valence quarks of $\bar B^0$ and $D^0$ meson, then the virtual photon decays to the lepton pair. Numerically, we find that the branching ratio decreases rapidly as the $q^2$ increases, and the branching ratio of $\bar B^0\to D^0\mu^+\mu^-$ is $(9.7_{-3.2}^{+4.2})\times 10^{-6}$ in the region $q^2 \in [1,5] \mathrm{GeV}^2$. The order of the branching ratio shows a possibility to study this interesting channel in the current $B$ factories and the Large Hadron Collider. The precise experimental data will help us to test the factorization approach and the QCD theory, in general.Comment: 9 pages, 5 figures, Final version to be published in JHE