Publications by authors named "Xianjun Cao"

8 Publications

  • Page 1 of 1

Free-standing NiCoSe nanostructure on Ni foam via electrodeposition as high-performance asymmetric supercapacitor electrode.

Nanotechnology 2020 Aug 27;31(33):335706. Epub 2020 Apr 27.

School of Materials and Energy, University of Electronic Science and Technology of China, Chengdu 610054, People's Republic of China.

Designing a high-energy-density and power-density electrode for supercapacitors has become an increasingly important concept in the energy storage community. In this article, NiCoSe nanostructures were electrodeposited on nickel (Ni) foam and directly used as electrodes for supercapacitors. The effect on the morphology and electrochemical performance of NiCoSe prepared under different scan rates was measured through scanning electron microscopy and various electrochemical measurements. The resultant NiCoSe prepared with 5 mV s exhibits a cross-linked porous nanostructure and a high specific capacitance of 2185 F g at a current density of 1 A g. Taking advantage of these features, an ASC is constructed by using NiCoSe on Ni foam as the positive electrode and an active carbon electrode as the negative electrode with 3 M KOH as the electrolyte. The ASC displays a high-energy density of 41.8 Wh kg, an ultrahigh power output of 8 kW kg, as well as a long cycling life (91.4% capacity retention after 10 000 cycles). The excellent electrochemical performance makes the porous NiCoSe nanostructures a promising alternative in energy storage devices.
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http://dx.doi.org/10.1088/1361-6528/ab8d6aDOI Listing
August 2020

Therapeutic Effects of FGF23 c-tail Fc in a Murine Preclinical Model of X-Linked Hypophosphatemia Via the Selective Modulation of Phosphate Reabsorption.

J Bone Miner Res 2017 Oct 25;32(10):2062-2073. Epub 2017 Aug 25.

Center for Therapeutic Innovation, Pfizer, New York, NY, USA.

Fibroblast growth factor 23 (FGF23) is the causative factor of X-linked hypophosphatemia (XLH), a genetic disorder effecting 1:20,000 that is characterized by excessive phosphate excretion, elevated FGF23 levels and a rickets/osteomalacia phenotype. FGF23 inhibits phosphate reabsorption and suppresses 1α,25-dihydroxyvitamin D (1,25D) biosynthesis, analytes that differentially contribute to bone integrity and deleterious soft-tissue mineralization. As inhibition of ligand broadly modulates downstream targets, balancing efficacy and unwanted toxicity is difficult when targeting the FGF23 pathway. We demonstrate that a FGF23 c-tail-Fc fusion molecule selectively modulates the phosphate pathway in vivo by competitive antagonism of FGF23 binding to the FGFR/α klotho receptor complex. Repeated injection of FGF23 c-tail Fc in Hyp mice, a preclinical model of XLH, increases cell surface abundance of kidney NaPi transporters, normalizes phosphate excretion, and significantly improves bone architecture in the absence of soft-tissue mineralization. Repeated injection does not modulate either 1,25D or calcium in a physiologically relevant manner in either a wild-type or disease setting. These data suggest that bone integrity can be improved in models of XLH via the exclusive modulation of phosphate. We posit that the selective modulation of the phosphate pathway will increase the window between efficacy and safety risks, allowing increased efficacy to be achieved in the treatment of this chronic disease. © 2017 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816679PMC
October 2017

Novel Anti-TM4SF1 Antibody-Drug Conjugates with Activity against Tumor Cells and Tumor Vasculature.

Mol Cancer Ther 2015 Aug 18;14(8):1868-76. Epub 2015 Jun 18.

The Center for Vascular Biology Research and the Departments of Pathology, Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School, Boston, Massachusetts.

Antibody-drug conjugates (ADC) represent a promising therapeutic modality for managing cancer. Here, we report a novel humanized ADC that targets the tetraspanin-like protein TM4SF1. TM4SF1 is highly expressed on the plasma membranes of many human cancer cells and also on the endothelial cells lining tumor blood vessels. TM4SF1 is internalized upon interaction with antibodies. We hypothesized that an ADC against TM4SF1 would inhibit cancer growth directly by killing cancer cells and indirectly by attacking the tumor vasculature. We generated a humanized anti-human TM4SF1 monoclonal antibody, v1.10, and armed it with an auristatin cytotoxic agent LP2 (chemical name mc-3377). v1.10-LP2 selectively killed cultured human tumor cell lines and human endothelial cells that express TM4SF1. Acting as a single agent, v1.10-LP2 induced complete regression of several TM4SF1-expressing tumor xenografts in nude mice, including non-small cell lung cancer and pancreas, prostate, and colon cancers. As v1.10 did not react with mouse TM4SF1, it could not target the mouse tumor vasculature. Therefore, we generated a surrogate anti-mouse TM4SF1 antibody, 2A7A, and conjugated it to LP2. At 3 mpk, 2A7A-LP2 regressed several tumor xenografts without noticeable toxicity. Combination therapy with v1.10-LP2 and 2A7A-LP2 together was more effective than either ADC alone. These data provide proof-of-concept that TM4SF1-targeting ADCs have potential as anticancer agents with dual action against tumor cells and the tumor vasculature. Such agents could offer exceptional therapeutic value and warrant further investigation. Mol Cancer Ther; 14(8); 1868-76. ©2015 AACR.
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http://dx.doi.org/10.1158/1535-7163.MCT-15-0188DOI Listing
August 2015

Successful surgical treatment of descending aorta interruption in a 29-year-old woman with acute paraplegia and subarachnoid hemorrhage: a case report.

J Cardiothorac Surg 2015 Jun 6;10:80. Epub 2015 Jun 6.

US Department of Cardiothoracic Surgery, Linköping Heart Center, Linköping, Sweden.

Interruption of the descending aorta is an extremely rare great vessel malformation. In this report, we describe a very unusual case of a 29-year-old female with a 13-year history of hypertension who was found to have an interruption of the descending aorta when she was hospitalized with a subarachnoid hemorrhage and symptoms of acute paraplegia. We successfully surgically corrected the defect using a Gore-Tex® graft to bypass the aortic interruption. The patient's blood pressure postoperatively returned to normal, and the patient recovered completely from her paraplegia by the time of her 5-month follow-up visit.
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http://dx.doi.org/10.1186/s13019-015-0285-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458336PMC
June 2015

Antibodies directed to alpha6beta4 highlight the adhesive and signaling functions of the integrin in breast cancer cell lines.

Cancer Biol Ther 2010 Mar 8;9(6):437-45. Epub 2010 Mar 8.

Biogen Idec, San Diego, CA, USA.

Integrin alpha6beta4 signaling interactions have been implicated in tumor progression, and beta4 expression has been linked to poor prognosis in certain breast cancer subtypes. We generated human antibodies to alpha6beta4 to further evaluate its role in tumor cell signaling. Biochemical characterization indicated these antibodies are specific for alpha6beta4, recognize distinct epitopes and have low nanomolar affinities for both human and murine protein. The antibodies demonstrated differing effects on alpha6beta4-mediated cellular adhesion, highlighting the existence of different functional epitopes on alpha6beta4. Interestingly however both antibodies blocked adhesion-independent growth in a panel of breast cancer cell lines. Antibody induced apoptosis and inhibition of phosphoinositide 3-kinase (PI3K) signaling were also observed within the context of matrix adhesion. Enhanced inhibitory effects were observed when the alpha6beta4 antibodies were used in combination with antibodies to epidermal growth factor receptor (EGFR) or erythoblastic leukemia viral oncogene homolog 2 (ErbB2). These findings illustrate a role for both the adhesive and signaling functions of alpha6beta4 in breast cancer cell survival. The antibodies and data generated herein advance our understanding of alpha6beta4 in regulating tumorigenic processes, and suggest that combination therapies involving alpha6beta4 may be therapeutically effective in breast cancer.
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http://dx.doi.org/10.4161/cbt.9.6.10893DOI Listing
March 2010

Characterization of inhibitory anti-insulin-like growth factor receptor antibodies with different epitope specificity and ligand-blocking properties: implications for mechanism of action in vivo.

J Biol Chem 2009 Apr 11;284(15):10254-67. Epub 2009 Feb 11.

Biogen Idec, San Diego, California 92130 and Applied Photophysics Limited, Leatherhead, Surrey KT22 7PB, United Kingdom.

Therapeutic antibodies directed against the type 1 insulin-like growth factor receptor (IGF-1R) have recently gained significant momentum in the clinic because of preliminary data generated in human patients with cancer. These antibodies inhibit ligand-mediated activation of IGF-1R and the resulting down-stream signaling cascade. Here we generated a panel of antibodies against IGF-1R and screened them for their ability to block the binding of both IGF-1 and IGF-2 at escalating ligand concentrations (>1 microm) to investigate allosteric versus competitive blocking mechanisms. Four distinct inhibitory classes were found as follows: 1) allosteric IGF-1 blockers, 2) allosteric IGF-2 blockers, 3) allosteric IGF-1 and IGF-2 blockers, and 4) competitive IGF-1 and IGF-2 blockers. The epitopes of representative antibodies from each of these classes were mapped using a purified IGF-1R library containing 64 mutations. Most of these antibodies bound overlapping surfaces on the cysteine-rich repeat and L2 domains. One class of allosteric IGF-1 and IGF-2 blocker was identified that bound a separate epitope on the outer surface of the FnIII-1 domain. Using various biophysical techniques, we show that the dual IGF blockers inhibit ligand binding using a spectrum of mechanisms ranging from highly allosteric to purely competitive. Binding of IGF-1 or the inhibitory antibodies was associated with conformational changes in IGF-1R, linked to the ordering of dynamic or unstructured regions of the receptor. These results suggest IGF-1R uses disorder/order within its polypeptide sequence to regulate its activity. Interestingly, the activity of representative allosteric and competitive inhibitors on H322M tumor cell growth in vitro was reflective of their individual ligand-blocking properties. Many of the antibodies in the clinic likely adopt one of the inhibitory mechanisms described here, and the outcome of future clinical studies may reveal whether a particular inhibitory mechanism leads to optimal clinical efficacy.
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http://dx.doi.org/10.1074/jbc.M809709200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2665079PMC
April 2009

Functional characterization of integrin alpha6beta4 adhesion interactions using soluble integrin constructs reveals the involvement of different functional domains in the beta4 subunit.

Cell Commun Adhes 2008 Nov;15(4):317-31

Biogen Idec, San Diego, California, USA.

Integrin alpha6beta4-mediated adhesion interactions play key roles in keratinocyte and epithelial tumor cell biology. In order to evaluate how alpha6beta4 adhesion interactions contribute to these important cellular processes, the authors generated soluble versions of the integrin by recombinant expression of the subunit ectodomains fused to a human immunoglobulin G (IgG) Fc constant domain. Coexpression of the appropriate subunits enabled dimerization, secretion and purification of stable Fc-containing alpha6beta4 heterodimers. The soluble proteins exhibited the same metal ion and ligand dependency in their binding characteristics as intact alpha6beta4. Using these reagents in combination with anti-beta4 antibodies, the authors identified two distinct functional epitopes on the beta4 subunit. They demonstrated the involvement of one epitope in adhesion interactions and the other in regulating adhesion-independent growth in alpha6beta4-expressing tumor cell lines. The availability of these soluble integrin reagents and the data provided herein help to further delineate the structure-function relationships regulating alpha6beta4 signaling biology.
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http://dx.doi.org/10.1080/15419060802428356DOI Listing
November 2008

An intermediate pH unfolding transition abrogates the ability of IgE to interact with its high affinity receptor FcepsilonRIalpha.

J Biol Chem 2006 Oct 11;281(41):30755-67. Epub 2006 Aug 11.

Biogen Idec, San Diego, California 92122, USA.

The interaction between IgE-Fc (Fcepsilon) and its high affinity receptor FcepsilonRI on the surface of mast cells and basophils is a key event in allergen-induced allergic inflammation. Recently, several therapeutic strategies have been developed based on this interaction, and some include Fcepsilon-containing moieties. Unlike well characterized IgG therapeutics, the stability and folding properties of IgE are not well understood. Here, we present comparative biophysical analyses of the pH stability and thermostability of Fcepsilon and IgG1-Fc (Fcgamma). Fcepsilon was found to be significantly less stable than Fcgamma under all pH and NaCl conditions tested. Additionally, the Cepsilon3Cepsilon4 domains of Fcepsilon were shown to become intrinsically unfolded at pH values below 5.0. The interaction between Fcepsilon and an Fcgamma-FcepsilonRIalpha fusion protein was studied between pH 4.5 and 7.4 using circular dichroism and a combination of differential scanning calorimetry and isothermal titration calorimetry. Under neutral pH conditions, the apparent affinity of Fcepsilon for the dimeric fusion protein was extremely high compared with published values for the monomeric receptor (KD < 10(-12) m). Titration to pH 6.0 did not significantly change the binding affinity, and titration to pH 5.5 only modestly attenuated affinity. At pH values below 5.0, the receptor binding domains of Fcepsilon unfolded, and interaction of Fcepsilon with the Fcgamma-FcepsilonRIalpha fusion protein was abrogated. The unusual pH sensitivity of Fcepsilon may play a role in antigen-dependent regulation of receptor-bound, non-circulating IgE.
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http://dx.doi.org/10.1074/jbc.M605190200DOI Listing
October 2006
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