Wu Zhang

The University of Hong Kong, Hong Kong, Hong Kong

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Publications (13)46.79 Total impact

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    ABSTRACT: Activation of the stem cell transcriptional circuitry is an important event in cancer development. Although cancer cells demonstrate a stem cell-like gene expression signature, the epigenetic regulation of pluripotency-associated genes in cancers remains poorly understood. In this study, we characterized the epigenetic regulation of the pluripotency-associated genes NANOG, OCT4, c-MYC, KLF4, and SOX2 in a variety of cancer cell lines and in primary tumor samples, and investigated the re-activation of pluripotency regulatory circuits in cancer progression. Differential patterns of DNA methylation, histone modifications, and gene expression of pluripotent genes were demonstrated in different types of cancers, which may reflect their tissue origins. NANOG promoter hypomethylation and gene upregulation were found in metastatic human liver cancer cells and human hepatocellular carcinoma (HCC) primary tumor tissues. The upregulation of NANOG, together with p53 depletion, was significantly associated with clinical late stage of HCC. A pro-metastatic role of NANOG in colon cancer cells was also demonstrated, using a NANOG-overexpressing orthotopic tumor implantation mouse model. Demethylation of NANOG promoter was observed in CD133+(high) cancer cells. In accordance, overexpression of NANOG resulted in an increase in the population of CD133+(high) cells. In addition, we demonstrated a cross-regulation between OCT4 and NANOG in cancer cells via reprogramming of promoter methylation. Taken together, epigenetic reprogramming of NANOG can lead to the acquisition of stem cell-like properties. These results underscore the restoration of pluripotency circuits in cancer cells as a potential mechanism for cancer progression.
    PLoS ONE 01/2013; 8(9):e72435. · 3.53 Impact Factor
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    ABSTRACT: Liver transplantation (LT) is a cure for many liver diseases. Blood chimerism of donor origin can develop after LT, which raises the possibility of the existence of hematopoietic stem/progenitor cells (HSPCs) in the liver. We characterized the blood chimerism in a large cohort of 249 LT patients and analyzed putative HSPCs in adult human livers. The overall incidence of chimerism was 6.43%, of which 11.11% was among short-term (1 day to 6 months) and 3.77% was among long-term (6 months to 8 years) LT patients. Hematopoietic Lin(-) CD34(+) CD38(-) CD90(+) populations have been demonstrated to generate long-term lymphomyeloid grafts in transplantations. In human adult livers, we detected Lin(-) CD34(+) CD38(-) CD90(+) populations accounting for 0.03% ± 0.017% of the total single liver cells and for 0.05% ± 0.012% of CD45(+) liver cells. Both Lin(-) CD34(+) and Lin(-) CD45(+) liver cells, from extensively perfused human liver grafts, were capable of forming hematopoietic myeloid-lineage and erythroid-lineage methylcellulose colonies. More importantly, Lin(-) CD45(+) or CD45(+) liver cells could be engrafted into hematopoietic cells in an immunodeficient mouse model. These results are the first evidence of the presence of putative HSPC populations in the adult human liver, where the liver is a good ectopic niche. The discovery of the existence of HSPCs in the adult liver have implications for the understanding of extramarrow hematopoiesis, liver regeneration, mechanisms of tolerance in organ transplantation, and de novo cancer recurrence in LT patients. Conclusion: The human adult liver contains a small population of HSPCs. In LT patients, there are two types of chimerisms: transient chimerism, resulting from mature leucocytes, and long-term chimerism, derived from putative HSPCs in the liver graft. (HEPATOLOGY 2012).
    Hepatology 04/2012; 56(4):1557-66. · 12.00 Impact Factor
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    ABSTRACT: Notch signaling, a critical pathway for tissue development, also contributes to tumorigenesis in many cancers, but its pathological function in liver cancer is not well defined. In our study, Notch1 expression and its clinicopathological parameters were evaluated in 82 human hepatocellular carcinoma (HCC) patients. Plasmid-based siNotch1 shRNA was transiently or stably transfected into metastatic HCC cells and subsequently evaluated for the effects on orthotopic liver tumor metastasis in a mouse model as well as the effects on downstream pathways. Aberrant high expression of Notch1 was significantly associated with metastatic disease parameters in HCC patients, such as tumor-node-metastasis Stages III-IV and tumor venous invasion. Knocking-down Notch1 reduced cell motility in vitro and orthotopic tumor metastasis from the liver to the lung in vivo in a mouse model. In metastatic HCC cells, abnormal expression of Notch1 was associated with increased expression of Snail1 and repressed expression of E-cadherin; the Notch1-Snail1-E-cadherin association can also be found in HCC patient tumors. Inhibition of Notch1 by shRNA abolished Snail1 expression, which further resulted in the re-establishment of repressed E-cadherin in metastatic HCC cells. Thus, abnormal Notch1 expression was strongly associated with HCC metastatic disease, which might be mediated through the Notch1-Snail1-E-cadherin pathway. Knock-down of Notch1 reversed HCC tumor metastasis in a mouse model. Therefore, these data suggest that effective targeting of Notch signaling might also inhibit tumor metastasis.
    International Journal of Cancer 11/2011; 131(3):E163-72. · 6.20 Impact Factor
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    ABSTRACT: This article describes the synthesis and characterization of a new ladder-type poly (p-phenylene) (LPFC) containing alkylcarbazole and dialkylfluorene units in backbone, and its optical and electrochemical properties as well as its light-emitting device performance. LPFC shows the well-defined structure, high molecular weights, excellent thermal stability, and good solubility in common organic solvents. And it also shows strongly blue emission (λmax = 465 nm) with quantum efficiency of 70% in solution, while its solid emission (λmax = 470 nm) is almost the same as its solution. Electrochemical studies show that the highest occupied molecular orbital (HOMO) energy levels of LPFC is up to 5.29 eV, which is significantly higher than that of LPPP without carbazole in backbone, indicating an enhanced ability of hole injection from anodes. Furthermore, the single layer light-emitting device using LPFC as the active layer shows blue emission (λmax = 470 nm) with maximum luminescence of ∼ 2000 cd/m2 and maximum luminance efficiency of 0.43 cd/A. The attractive properties exhibited from new ladder-type polymer establish LPFC as a good candidate for the potential application as transporting and emitting layer in polymeric light emitting diodes. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3120–3127, 2008
    Journal of Polymer Science Part A Polymer Chemistry 03/2008; 46(9):3120 - 3127. · 3.54 Impact Factor
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    ABSTRACT: A series of well-defined poly[2,7-(9,9-dihexylfluorenyl)-co-bipyridinyl] [F-(BPY)x] with varied BPY (bipyridine) unit contents from 0 to 50% were synthesized using palladium(0) catalyzed Suzuki cross-coupling reactions, and well characterized using 1H NMR, IR, and GPC. Their photophysical and electrochemical properties were investigated. These copolymers showed pure blue photoluminescence (440 nm) in dilute solutions with the fluorescence quantum yield >0.6. Electron-affinity potentials (LUMO levels) of these polymers estimated from cyclic voltammetry were significantly decreased with the increase of BPY content in the polymer backbone, and a level of 2.43 eV for alternating BPY-fluorene polymer (50% BPY) was achieved, making them good candidates for electron injection and transport materials in EL devices. A further great decrease in LUMO level up to 2.99 eV was found when Zn2+ was chelated into polymers. The experimental observations were supported by the quantum chemical calculations on these polymers, which provided the proof for the intuitive notion of an intramolecular charge transfer band in polymer chain.
    Synthetic Metals 01/2008; 158(5):194-199. · 2.11 Impact Factor
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    ABSTRACT: The stability of fluorene-based compounds and polymers, especially at the bridged C-9 position under photoirradiation and thermal treatment, has claimed much attention. The emission of fluorenone formed by degradation of the 9-site is regarded as the origin of the low emission band at 2.2-2.3 eV in polyfluorene-based conjugated materials. We have investigated the role of nonemissive quenchers such as alkyl ketones, which were also one of the products of polyfluorene degradation, for the low-energy emission in polyfluorenes. The spectral characteristics of a blend system of polyfluorene/nonemissive quencher/fluorenone are found to accord well with the kinetics of actual polyfluorene degradation. Our results indicate that strong green emission in degraded polyfluorene would be not caused only by fluorenone, but also by nonemissive quenchers for their effectively quenching bulk emission.
    The Journal of Physical Chemistry B 10/2007; 111(36):10639-44. · 3.61 Impact Factor
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    ABSTRACT: To reveal the nature of the zinc(II)-ion-induced ionochromic effect of bipyridine (bpy)-containing pi-conjugated polymers, we proposed an electrostatic interaction mechanism to illustrate our recent experimental findings [Tian, L., et al. J. Phys. Chem. B 2005 109 (15), 6944]. Our theoretical analysis was based on the semiempirical (INDO/2) calculation of spectral properties and electronic structures of difluorene-substituted bpy model compounds. Our calculations show that the zinc(II)-induced ionochromic effect can be attributed to the electrostatic interaction between the zinc(II) ion and the polymer. Zinc(II) ion acts as a positive point charge with varied charge quantities, which is responsible for the red-shifted absorption spectra compared with those of the metal-free compound. The counterion ionochromic effect of the zinc(II) ion is also discussed. The proposed mechanism is possibly applied to the ionochromic effect induced by other metal ions such as Cd(II) and Hg(II).
    The Journal of Physical Chemistry B 09/2006; 110(34):16846-51. · 3.61 Impact Factor
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    ABSTRACT: The stability of fluorene-based compounds and polymers, especially at the bridged C-9 position under photoirradiation and thermal treatment, has claimed wide attention. We report the electronic, vibrational, and MALDI-TOF mass spectral combined studies for the fluorene oligomers with alkyl and aromatic substitutions under UV-light irradiation. The low-energy emission and the formation of ketonic defects after degradation highly depend on the proportion of alkyl substitution. The oligomer with fully aromatic substitution shows good stability, but when the proportion of alkyl substitution increases, their photostability rapidly decreases. The mass spectra show not only the mass of the fluorenone-fluorene trimer but also another new degradation product with a large mass (pristine oligomer plus 14) from alkyl oxidation, which testify to the assistance of alkyl side chain during degradation. We propose that the degradation of fluorene is a radical chain process propagated by alkyl side chains, and then the different stability between alkyl and aromatic substitution can be well explained.
    The Journal of Physical Chemistry B 08/2006; 110(28):13734-40. · 3.61 Impact Factor
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    ABSTRACT: We have investigated the thermal degradation in air by Fourier transform infrared spectroscopy of a ladder-type copolymer containing fluorene units in the backbone (Me-LPF), to reveal the formation of the ketonic defects. As thermal treatment of Me-LPF film at 200 degrees C in air proceeds, a new group of complex absorption bands due to degradation products arises in the range between 1800 and 1600 cm(-1). The observed overlapping bands were separated and assigned by utilizing the second-derivative IR spectral analysis, which can narrow the peak width to one-third of the originals and thereby eases the analysis. The degraded products were assigned as fluorenone (1718 cm(-1)) and benzophenone (Ar-(C=O)-Ar) (1665 cm(-1)), formed by the oxidation of the backbone, and acylphenone (Ar-(C=O)-R) (1685 cm(-1)) from the side chain. The fluorenone was found to be the major component among the degraded products in the main chain, and the time and temperature dependence indicated that the oxidation is a kind of autocatalytic radical-chain process. The oxidation can reach a very high degree (approximately 30% for 6 h oxidation at 240 degrees C estimated by absorption of the alkyl). Our results suggest the possibility of the oxidation of the 9-bialkylfluorene sites. We propose that the degradation of the alkyl in the side chain can help the radicals to propagate in the chain reaction.
    The Journal of Physical Chemistry B 01/2006; 109(49):23366-70. · 3.61 Impact Factor
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    ABSTRACT: A series of fluorene and bipyridine (bpy) copolymers were synthesized, and their optical properties were investigated in the presence of zinc(II). By adjusting the bpy content in the polymer backbone, the emitting color of the polymer solution could be tuned from initial blue to green to white and violet when it interacted with zinc(II) ions. The counteranions of zinc(II) ions were also found to influence the optical properties of copolymers greatly.
    The Journal of Physical Chemistry B 01/2005; 109(15):6944-6947. · 3.61 Impact Factor
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    ABSTRACT: A type of soluble and thermally stable semiladder polyphenylenes containing carbazole moieties (SLPFCs) have been prepared with a facile and short synthetic route. The full characterizations of structures and properties as well as the performances of electroluminescence devices of the new polymers are presented. The conjugated backbone of the SLPFCs contained three kinds of constituents: fluorene, ladder-type tetraphenylene, and ladder-type hexaphenylene. The SLPFCs exhibit pure-blue fluorescence (λ max) 445 nm) with high efficiency up to 90% in solution. Electrochemical studies indicate that the introduction of carbazole moieties raises the HOMO energy levels. Furthermore, the single-layer light-emitting devices using the SLPFCs as the active layer show pure-blue emission (λmax) 447 nm, CIE coordinates: 0.15, 0.05) with maximum luminescence of 5500 cd/m 2 and maximum luminance efficiency of 0.556 cd/A. The attractive properties exhibited by the new semiladder polymers establish them as good candidates for active layers in stable pure-blue light-emitting devices.
    Macromolecules. 01/2005; 38(16).
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    ABSTRACT: A series of π-conjugated co-polymers {(P)[Re] x (x) 0.1, 0.2, and 0.5)} incorporated with fac-(bpy)Re(I)-(CO) 3 Cl (bpy) 2,2′-bipyridine, Re) rhenium) chromophores in the backbones have been synthesized. The Re(I) chromophore contents were accurately controlled by the contents of bpy segments in (P)[bpy] x (x) 0.1, 0.2, and 0.5) co-polymers. The structures of (P)[Re] x co-polymers were characterized by 1 H nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) analysis, and their optical and electronic properties were measured by electronic absorption, steady-state and time-resolved fluorescence, and field-induced surface photovoltaic spectroscopy (SPS). At room temperature, the characteristic metal-to-ligand charge-transfer (1 MLCT) absorption band and red emission of 3 MLCT from fac-(bpy)Re(I)(CO) 3 Cl chromophores can be observed. Electroluminescence (EL) devices that use (P)[Re] x co-polymers as the active layers showed enhanced red 3 MLCT emission. However, the photoluminescence (PL) and EL efficiency of (P)[Re] x co-polymers were lower, compared to those of a fac-(bpy)Re(I)(CO) 3 Cl molecularly doped polymers. The lower emission of (P)[Re] x co-polymers is conceivably related to the charge carrier separation of localized electron-hole pairs (excitions) in the sites of fac-(bpy)Re(I)(CO) 3 Cl as they became incorporated with extensive π-conjugation chains. Further studies of density functional theory (DFT) calculation and SPS provided proof of charge carrier separation in (P)[Re] x co-polymers. The efficient charge carrier separation would decrease the efficiency of PL and EL but enhance the photovoltaic efficiency, which meant a more suitable application of the types of π-conjugated polymers incorporated with transition-metal complexes in their backbones.
    Journal of Physical Chemistry B - J PHYS CHEM B. 01/2004; 108(35).
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    ABSTRACT: The fluorescence quenching effect of the conjugated polymers P1 and P2 (the molecular recognitions are twisted 2,2′-bipyridine (bpy) and planar 1,10-phenanthrolin (phen), respectively) films upon the addition of metal ions has been studied. And the results showed that P2 exhibited stronger fluorescence quenching ability upon the addition of both transition metal ions and main group metal ions compared with that of P1. The 20° twist angle between the two consecutive pyridine rings of bpy unit in the P1 main chain is the reason for the weaker fluorescence quenching ability compared with P2, in which the planar phen unit can chelate with metal ions relatively freely without the conformational transition. So P2 is a kind of material with better properties for solid film devices, such as sensors for metal ions recognition.
    Chinese Science Bulletin 49(3). · 1.37 Impact Factor