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Hung C Tran, Zesheng Wan, Michael A Sheard, Jianping Sun, Jeremy R Jackson, Jemily Malvar, Yibing Xu, Larry Wang, Richard Sposto, Eugene S Kim, Shahab Asgharzadeh, Robert C Seeger
PURPOSE: Immunotherapy of high-risk neuroblastoma using the anti-GD2 antibody dinutuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC). Galunisertib, an inhibitor of TGFβR1, was examined for its ability to enhance the efficacy of dinutuximab in combination with human ex vivo activated NK (aNK) cells against neuroblastoma. EXPERIMENTAL DESIGN: TGFB1 and TGFBR1 mRNA expression was determined for 249 primary neuroblastoma tumors by microarray analysis...
October 10, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Soumya Mukherjee, Jingjing Lu, Gunasekaran Velmurugan, Shweta Singh, Gopalan Rajaraman, Jinkui Tang, Sujit K Ghosh
A coordination complex family comprising of six new dinuclear symmetric lanthanide complexes, namely, [Ln2(Lx)2(L')2(CH3OH)2]·yG (H2Lx: three related yet distinct Schiff-base linkers; x = 1-3, according to the nomenclature of the Schiff-base linker employed herein. HL': 2,6-dimethoxyphenol. yG refers to crystallographically assigned guest solvent species in the respective complexes; y = number of solvent molecules; Ln(III) = Dy/Gd) were isolated employing a mixed-ligand strategy stemming out of a strategic variation of the functionalities introduced among the constituent Schiff-base linkers...
October 11, 2016: Inorganic Chemistry
Martine Cordeau, Assila Belounis, Martin Lelaidier, Paulo Cordeiro, Hervé Sartelet, Sabine Herblot, Michel Duval
High-risk neuroblastoma (NB) remains a major therapeutic challenge despite the recent advent of disialoganglioside (GD2)-antibody treatment combined with interleukin (IL)-2 and granulocyte monocyte-colony stimulating factor (GM-CSF). Indeed, more than one third of the patients still die from this disease. Here, we developed a novel approach to improve the current anti-GD2 immunotherapy based on NK cell stimulation using toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDCs). We demonstrated that this strategy led to the efficient killing of NB cells...
2016: PloS One
Jan Müller, Robin Reichel, Sebastian Vogt, Stefan P Müller, Wolfgang Sauerwein, Wolfgang Brandau, Angelika Eggert, Alexander Schramm
Neuroectodermal tumours are characterized by aberrant processing of disialogangliosides concomitant with high expression of GD2 or GD3 on cell surfaces. Antibodies targeting GD2 are already in clinical use for therapy of neuroblastoma, a solid tumour of early childhood. Here, we set out to identify peptides with high affinity to human disialoganglioside GD2. To this end, we performed a combined in vivo and in vitro screen using a recombinant phage displayed peptide library. We isolated a phage displaying the peptide sequence WHWRLPS that specifically binds to the human disialoganglioside GD2...
2016: PloS One
Elwira Szychot, Jarosław Peregud-Pogorzelski, Paweł Wawryków, Andrzej Brodkiewicz
Neuroblastoma is the most common extra-cranial malignancy of childhood, with the highest incidence in children younger than 4 years. The prognosis depends on many factors, such as age at diagnosis, stage of disease and molecular genetic subtype. More than 50% of children who present with the disease are deemed to have high-risk neuroblastoma. The standard therapy for children with high-risk neuroblastoma consists of intensive chemotherapy, surgery, radiotherapy, myeloablative consolidation with autologous haematopoietic stem cell rescue followed by the treatment of minimal residual disease with 13-cis-retinoic acid...
September 28, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
Tokiaki Yamaguchi, Yoshio Yamauchi, Keiko Furukawa, Yuhsuke Ohmi, Yuki Ohkawa, Qing Zhang, Tetsuya Okajima, Koichi Furukawa
Alzheimer's disease (AD) is the most prevalent form of dementia characterized by the extracellular accumulation of amyloid β (Aβ) peptides, which are produced by proteolytic cleavages of amyloid precursor protein (APP). Gangliosides are involved in AD pathophysiology including Aβ deposition and APP processing, yet the detailed mechanisms are not fully understood. Here we examined how changes in the carbohydrate moiety of gangliosides alter APP processing in human melanoma cells, neuroectoderm-derived cells...
September 30, 2016: Scientific Reports
Wan-Ling Ho, Wen-Ming Hsu, Min-Chuan Huang, Kenji Kadomatsu, Akira Nakagawara
Glycosylation is the most complex post-translational modification of proteins. Altered glycans on the tumor- and host-cell surface and in the tumor microenvironment have been identified to mediate critical events in cancer pathogenesis and progression. Tumor-associated glycan changes comprise increased branching of N-glycans, higher density of O-glycans, generation of truncated versions of normal counterparts, and generation of unusual forms of terminal structures arising from sialylation and fucosylation. The functional role of tumor-associated glycans (Tn, sTn, T, and sLe(a/x)) is dependent on the interaction with lectins...
September 29, 2016: Journal of Hematology & Oncology
Pingju Ge, Fugeng Sheng, Yiguang Jin, Li Tong, Lina Du, Lei Zhang, Ning Tian, Gongjie Li
Magnetic resonance (MR) is currently used for diagnosis of osteosarcoma but not well even though contrast agents are administered. Here, we report a novel bone-targeted MR imaging contrast agent, Gd2-diethylenetriaminepentaacetate-bis(alendronate) (Gd2-DTPA-BA) for the diagnosis of osteosarcoma. It is the conjugate of a bone cell-seeking molecule (i.e., alendronate) and an MR imaging contrast agent (i.e., Gd-DTPA). Its physicochemical parameters were measured, including pKa, complex constant, and T1 relaxivity...
September 25, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ž Antić, S Kuzman, V Đorđević, M D Dramićanin, T Thundat
Here we report the synthesis and structural, morphological, and photoluminescence analysis of white- and blue-light-emitting Dy(3) (+) - and Tm(3) (+) -doped Gd2 Ti2 O7 nanophosphors. Single-phase cubic Gd2 Ti2 O7 nanopowders consist of compact, dense aggregates of nanoparticles with an average size of ~25 nm for Dy(3) (+) -doped and ~50 nm for Tm(3) (+) -doped samples. The photoluminescence results indicated that ultraviolet (UV) light excitation of the Dy(3) (+) -doped sample resulted in direct generation of white light, while a dominant yellow emission was obtained under blue-light excitation...
September 15, 2016: Luminescence: the Journal of Biological and Chemical Luminescence
Florian C Maier, Julia Schmitt, Andreas Maurer, Walter Ehrlichmann, Gerald Reischl, Konstantin Nikolaou, Rupert Handgretinger, Bernd J Pichler, Wolfgang M Thaiss
Antibody-based therapies gain momentum in clinical therapy, thus the need for accurate imaging modalities with respect to target identification and therapy monitoring are of increasing relevance. Cerenkov luminescence imaging (CLI) are a novel method detecting charged particles emitted during radioactive decay with optical imaging. Here, we compare Position Emission Tomography (PET) with CLI in a multimodal imaging study aiming at the fast and efficient screening of monoclonal antibodies (mAb) designated for targeting of the neuroblastoma-characteristic epitope disialoganglioside GD2...
September 1, 2016: Oncotarget
Kazuki Miyaji, Jun-Ichi Furukawa, Youichi Suzuki, Naoki Yamamoto, Yasuro Shinohara, Nobuhiro Yuki
There is a case report of a patient with overlapping Guillain-Barré syndrome and Bickerstaff brainstem encephalitis after infection with herpes simplex virus type 1 (HSV-1), who carried high titers of serum anti-GQ1b IgG antibodies. Several studies have linked viral infection to the modulation of ganglioside expression such as human T-lymphotropic virus to GD2 and simian virus 40 to GM3. Also, enhancement of the expression of GM2 on the cell membrane after cytomegalovirus infection has been reported. The objective of this study was to unveil the relationship between HSV-1 infection and the alteration of cellular ganglioside expression in neuronal and glial cell lines...
August 18, 2016: Carbohydrate Research
Bipin Kumar Gupta, Satbir Singh, Pawan Kumar, Yean Lee, Garima Kedawat, Tharangattu N Narayanan, Sajna Antony Vithayathil, Liehui Ge, Xiaobo Zhan, Sarika Gupta, Angel A Martí, Robert Vajtai, Pulickel M Ajayan, Benny Abraham Kaipparettu
Nanoparticles exhibiting both magnetic and luminescent properties are need of the hour for many biological applications. A single compound exhibiting this combination of properties is uncommon. Herein, we report a strategy to synthesize a bifunctional luminomagnetic Gd2-xEuxO3 (x = 0.05 to 0.5) nanorod, with a diameter of ~20 nm and length in ~0.6 μm, using hydrothermal method. Gd2O3:Eu(3+) nanorods have been characterized by studying its structural, optical and magnetic properties. The advantage offered by photoluminescent imaging with Gd2O3:Eu(3+) nanorods is that this ultrafine nanorod material exhibits hypersensitive intense red emission (610 nm) with good brightness (quantum yield more than 90%), which is an essential parameter for high-contrast bioimaging, especially for overcoming auto fluorescent background...
2016: Scientific Reports
Beate Hintersteiner, Nico Lingg, Peiqing Zhang, Susanto Woen, Kong Meng Hoi, Stefan Stranner, Susanne Wiederkum, Oliver Mutschlechner, Manfred Schuster, Hans Loibner, Alois Jungbauer
We identified active isoforms of the chimeric anti-GD2 antibody, ch14.18, a recombinant antibody produced in Chinese hamster ovary cells, which is already used in clinical trials. (1,2,3) We separated the antibody by high resolution ion-exchange chromatography with linear pH gradient elution into acidic, main and basic charge variants on a preparative scale yielding enough material for an in-depth study of the sources and the effects of microheterogeneity. The binding affinity of the charge variants toward the antigen and various cell surface receptors was studied by Biacore...
August 25, 2016: MAbs
Ling Han, Elena N Kitova, John S Klassen
This study reports on the use of the catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS) assay, combined with glycomicelles, as a method for detecting specific interactions between water-soluble proteins and glycolipids (GLs) in aqueous solution. The B subunit homopentamers of cholera toxin (CTB5) and Shiga toxin type 1 B (Stx1B5) and the gangliosides GM1, GM2, GM3, GD1a, GD1b, GT1b, and GD2 served as model systems for this study. The CTB5 exhibits broad specificity for gangliosides and binds to GM1, GM2, GM3, GD1a, GD1b, and GT1b; Stx1B5 does not recognize gangliosides...
November 2016: Journal of the American Society for Mass Spectrometry
Ming-Yi Ho, Alice L Yu, John Yu
Glycosphingolipids (GSLs) are composed of complex glycans linked to sphingosines and various fatty acid chains. Antibodies against several GSLs designated as stage-specific embryonic antigens (SSEAs), have been widely used to characterize differentiation of embryonic stem (ES) cells. In view of the cross-reactivities of these antibodies with multiple glycans, a few laboratories have employed advanced mass spectrometry (MS) technologies to define the dynamic changes of surface GSLs upon ES differentiation. However, the amphiphilic nature and heterogeneity of GSLs make them difficult to decipher...
August 22, 2016: Glycoconjugate Journal
Adrienne H Long, Steven L Highfill, Yongzhi Cui, Jillian P Smith, Alec J Walker, Sneha Ramakrishna, Rana El-Etriby, Susana Galli, Maria G Tsokos, Rimas J Orentas, Crystal L Mackall
Genetically engineered T cells expressing CD19-specific chimeric antigen receptors (CAR) have shown impressive activity against B-cell malignancies, and preliminary results suggest that T cells expressing a first-generation disialoganglioside (GD2)-specific CAR can also provide clinical benefit in patients with neuroblastoma. We sought to assess the potential of GD2-CAR therapies to treat pediatric sarcomas. We observed that 18 of 18 (100%) of osteosarcomas, 2 of 15 (13%) of rhabdomyosarcomas, and 7 of 35 (20%) of Ewing sarcomas expressed GD2...
October 2016: Cancer Immunology Research
Yutaka Itokazu, Yi-Tzang Tsai, Robert K Yu
The structural diversity and localization of cell surface glycosphingolipids (GSLs), including gangliosides, in glycolipid-enriched microdomains (GEMs, also known as lipid rafts) render them ideally suited to play important roles in mediating intercellular recognition, interactions, adhesion, receptor function, and signaling. Gangliosides, sialic acid-containing GSLs, are most abundant in the nerve tissues. The quantity and expression pattern of gangliosides in brain change drastically throughout development and these changes are mainly regulated through stage-specific expression of glycosyltransferase genes...
August 19, 2016: Glycoconjugate Journal
Vinit, K S Sujith, C N Ramachandran
Density functional theoretical calculations were performed to study the stability and magnetic properties of nitrogen-encapsulated C60, C59N, and their respective dimers at B3LYP/6-311G* and B3LYP-GD2/6-311G* levels of theory. For the most stable spin state of each of the above complexes, spin density transfer and spin-spin coupling between different components are investigated. The nature of bonding between the guest and the host is analyzed based on the highest occupied molecular orbital-lowest unoccupied molecular orbital energy gap and the respective molecular orbital diagrams...
September 8, 2016: Journal of Physical Chemistry. A
Alice L Yu, Jung-Tung Hung, Ming-Yi Ho, John Yu
All mammalian cells display an array of surface glycans that can modulate cellular interactions, and regulate the development of an organism. In spite of their important implications in health and disease, investigations of glycans pose a great challenge, given their inherent heterogeneity, and the frequently observed cross-reactivities of antibodies against glycosphingolipids (GSLs) with multiple glycans, which may lead to erroneous interpretation and conclusion. We employed matrix-assisted laser desorption ionization- mass spectrometry (MALDI-MS) and tandem MS/MS analyses to systematically delineate changes in GSLs during differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells into various derivatives...
August 9, 2016: Stem Cells and Development
Qing Lu, Kirk A Peterson
Using the 3rd-order Douglas-Kroll-Hess (DKH3) Hamiltonian, all-electron correlation consistent basis sets of double-, triple-, and quadruple-zeta quality have been developed for the lanthanide elements La through Lu. Basis sets designed for the recovery of valence correlation (defined here as 4f5s5p5d6s), cc-pVnZ-DK3, and outer-core correlation (valence + 4s4p4d), cc-pwCVnZ-DK3, are reported (n = D, T, and Q). Systematic convergence of both Hartree-Fock and correlation energies towards their respective complete basis set (CBS) limits are observed...
August 7, 2016: Journal of Chemical Physics
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