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https://www.readbyqxmd.com/read/28800395/using-chemistry-to-target-neuroblastoma
#1
Jeanne N Hansen, Xingguo Li, Y George Zheng, Louis T Lotta, Abhishek Dedhe, Nina F Schor
Neuroblastoma is a cancer of the neural crest almost exclusively seen in childhood. While children with single, small primary tumors are often cured with surgery alone, the 65% of children with neuroblastoma whose disease has metastasized have less than a 50% chance of surviving five years after diagnosis. Innovative pharmacological strategies are critically needed for these children. Efforts to identify novel targets that afford ablation of neuroblastoma with minimal toxicity to normal tissues are underway...
August 11, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28780888/anti-gd2-immunotherapy-for-neuroblastomas
#2
Sameer Sait, Shakeel I Modak
Current therapeutic approaches for high-risk neuroblastoma (HR-NB) include high-dose chemotherapy, surgery and radiotherapy; interventions that are associated with long and short-term toxicities. Effective immunotherapy holds particular promise for improving survival and quality of life by reducing exposure to cytotoxic agents. GD2, a surface glycolipid is the most common target for immunotherapy. Areas covered: We review the status of anti-GD2 immunotherapies currently in clinical use for neuroblastomas and novel GD2-targeted strategies in preclinical development...
August 7, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28748630/transverse-myelitis-as-an-unexpected-complication-following-treatment-with-dinutuximab-in-pediatric-patients-with-high-risk-neuroblastoma-a-case-series
#3
Yang-Yang Ding, Jessica Panzer, John M Maris, Alicia Castañeda, Marta Gomez-Chiari, Jaume Mora
Immunotherapy with the anti-GD2 monoclonal antibody ch14.18, or dinutuximab, represents an important therapeutic advance in the treatment of pediatric high-risk neuroblastoma and is now considered part of standard of care in this patient population. To date, transverse myelitis as a result of dinutuximab therapy has not been reported in clinical trials or in the published literature. We describe three patients with clinical symptoms of transverse myelitis, confirmed via magnetic resonance imaging, shortly following initiation of dinutuximab...
July 27, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28737939/several-gd-m-heterometal-organic-frameworks-with-gdn-as-nodes-tunable-structures-and-magnetocaloric-effect
#4
Peng-Fei Shi, Chun-Shuai Cao, Chu-Ming Wang, Bin Zhao
Tunable structures and magnetocaloric effect (MCE) of seven MOFs with [Gdn] as nodes are explored. The [Gdn] node is realized from mononuclear [Gd] to binuclear paddle-wheel [Gd2], tetranuclear tetrahedral [Gd4], and pentanuclear trigonal bipyramidal [Gd5]. Meanwhile, the magnetic entropy changes from 19.4 to 46.0 J·kg(-1)·K(-1). The results reveal that the effect of magnetic density on MCE plays a dominant role for Gd(3+)-based compounds, and high spin ground state of Mn(2+) (S = 5/2) is more favorable to achieve high MCE than that with Zn(2+), Co(2+), and Ni(2+) (Co(2+), S = 3/2; Ni(2+), S = 1)...
August 7, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28737787/coming-full-circle-constructing-a-gd6-wheel-dimer-by-dimer-and-the-importance-of-spin-topology
#5
Thomas N Hooper, Stuart K Langley, Silvia Gómez-Coca, Giulia Lorusso, Eliseo Ruiz, Keith S Murray, Marco Evangelisti, Euan K Brechin
The syntheses, structures, magnetic and thermodynamic properties of three related triethanolamine-based Gd(III) complexes are described. The smallest, a dimer ([Gd2]), can be viewed as the subunit from which the two larger complexes, a linear tetramer ([Gd2]2) and a cyclic hexamer ([Gd2]3), are composed by further deprotonation of the triethanolamine ligand. In all cases, nearest neighbour magnetic ions are weakly correlated by antiferromagnetic isotropic exchange, whose strength does not change significantly from one complex to another; J ranging from -0...
July 24, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28733263/consolidation-therapy-for-newly-diagnosed-pediatric-patients-with-high-risk-neuroblastoma-using-busulfan-melphalan-autologous-hematopoietic-cell-transplantation-anti-gd2-antibody-granulocyte-macrophage-colony-stimulating-factor-interleukin-2-and-haploidentical
#6
Aimee C Talleur, Brandon M Triplett, Sara Federico, Ewelina Mamcarz, William Janssen, Jianrong Wu, David Shook, Wing Leung, Wayne L Furman
The treatment of pediatric high-risk neuroblastoma is intensive and multimodal. Despite the introduction of immunotherapy for minimal residual disease, survival rates remain suboptimal and new therapies are needed. As part of a phase 2 trial, we are using a consolidation therapy regimen that combines a busulfan/melphalan conditioning schema, autologous hematopoietic cell transplantation (AHCT), and experimental immunotherapy with hu14.18K322A (a humanized anti-GD2 monoclonal antibody), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-2, with or without the adoptive transfer of haploidentical natural killer cells (NKs)...
July 18, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28709807/identification-of-a-new-b4galnact1-gm2-gd2-ga2-synthase-isoform-and-regulation-of-enzyme-stability-and-intracellular-transport-by-arginine-based-motif
#7
Fumi Shishido, Satoshi Uemura, Madoka Kashimura, Jin-Ichi Inokuchi
Glycosphingolipids (GSLs) are abundant in plasma membranes of mammalian cells, and their synthesis is strictly regulated in the Golgi apparatus. Disruption of GSL homeostasis is the cause of numerous diseases. Hundreds of molecular species of GSLs exist, and the detailed mechanisms underlying their homeostasis remain unclear. We investigated the physiological significance of isoform production for β1,4-N-acetyl-galactosaminyl transferase 1/B4GALNT1 (B4GN1), an enzyme involved in synthesis of ganglio-series GSLs GM2/GD2/GA2...
July 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28681513/enhanced-green-emissions-of-er-3-yb-3-co-doped-gd2-moo4-3-by-co-excited-up-conversion-processes
#8
Haoyue Hao, Hongyu Lu, Guanghong Ao, Yinglin Song, Yuxiao Wang, Xueru Zhang
Improving the emission from rare earth ions doped materials is of great importance to broaden their application in bio-imaging, photovoltaics and temperature sensing. The green emissions of Gd2 (MoO4 )3 :Er(3+) /Yb(3+) powder upon co-excitation with 980 and 808 nm lasers were investigated in this paper. Distinct enhancement of green emissions was observed compared with single laser excitation. Based on the energy level structure of Er(3+) , the enhancement mechanism was discussed. Moreover, the result of temperature-dependent enhancement revealed that the enhancement factor reached its maximum (2...
July 6, 2017: Luminescence: the Journal of Biological and Chemical Luminescence
https://www.readbyqxmd.com/read/28680755/bispecific-antibody-does-not-induce-t-cell-death-mediated-by-chimeric-antigen-receptor-against-disialoganglioside-gd2
#9
Sayed Shahabuddin Hoseini, Konstantin Dobrenkov, Dmitry Pankov, Xiaoliang L Xu, Nai-Kong V Cheung
Chimeric antigen receptors (CAR) and bispecific antibodies (BsAb) are two powerful immunotherapy approaches for retargeting lymphocytes toward cancer cells. Despite their success in lymphoblastic leukemia, solid tumors have been more recalcitrant. Identifying therapeutic barriers facing CAR-modified (CART) or BsAb-redirected T (BsAb-T) cells should facilitate their clinical translation to solid tumors. Novel lentiviral vectors containing low-affinity or high-affinity 4-1BB second-generation anti-GD2 (disialoganglioside) CARs were built to achieve efficient T cell transduction...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28680104/alkaline-earth-metals-doped-pyrochlore-gd2zr2o7-as-oxygen-conductors-for-improved-no2-sensing-performance
#10
Fulan Zhong, Jiwu Zhao, Lanqian Shi, Yihong Xiao, Guohui Cai, Yong Zheng, Jinlin Long
This work proposed a novel strategy to fabricate highly-stable NO2 sensor based on a pyrochlore-phase Gd2Zr2O7 oxygen conductor. The incorporation of alkaline-earth metals distinctly enhances the sensing performance of the Gd2Zr2O7 based sensors. The excellent sensor based on Gd1.95Ca0.05Zr2O7+δ exhibits rapid response-recovery characteristics with the maximum response current value (ΔI = 6.4 μA), extremely short 90% responce (3 s) and 90% recovery (35 s) time towards 500 ppm NO2 at 500 °C, which is better than that of commercial YSZ under the same condition...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28678088/treatment-of-transient-peripheral-neuropathy-during-chimeric-14-18-antibody-therapy-in-children-with-neuroblastoma-a-case-series
#11
Pranathi Ari, Michelle Kars, Holly Meany, Sophie Pestieau
Children with high-risk neuroblastoma are currently treated with a chimeric monoclonal antibody against GD2 ganglioside (chimeric 14.18). The treatment improves survival but causes transient neuropathic pain-like syndrome. We retrospectively studied 16 children with neuroblastoma receiving GD2 therapy. To manage pain, all patients received morphine via nurse-controlled analgesia or patient-controlled analgesia. Mean daily pain scores ranged from 0 to 5 and all children had a 0 pain score upon discharge. No major side effects were noted, suggesting morphine via nurse-controlled analgesia/patient-controlled analgesia is effective in controlling transient neuropathic pain in children receiving GD2 antibody therapy...
July 3, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28659916/hla-bw4-i-80-isoform-differentially-influences-clinical-outcome-as-compared-to-hla-bw4-t-80-and-hla-a-bw4-isoforms-in-rituximab-or-dinutuximab-based-cancer-immunotherapy
#12
Amy K Erbe, Wei Wang, Patrick K Reville, Lakeesha Carmichael, KyungMann Kim, Eneida A Mendonca, Yiqiang Song, Jacquelyn A Hank, Wendy B London, Arlene Naranjo, Fangxin Hong, Michael D Hogarty, John M Maris, Julie R Park, M F Ozkaynak, Jeffrey S Miller, Andrew L Gilman, Brad Kahl, Alice L Yu, Paul M Sondel
Killer-cell immunoglobulin-like receptors (KIRs) are a family of glycoproteins expressed primarily on natural killer cells that can regulate their function. Inhibitory KIRs recognize MHC class I molecules (KIR-ligands) as ligands. We have reported associations of KIRs and KIR-ligands for patients in two monoclonal antibody (mAb)-based trials: (1) A Children's Oncology Group (COG) trial for children with high-risk neuroblastoma randomized to immunotherapy treatment with dinutuximab (anti-GD2 mAb) + GM-CSF + IL-2 + isotretinion or to treatment with isotretinoin alone and (2) An Eastern Cooperative Oncology Group (ECOG) trial for adults with low-tumor burden follicular lymphoma responding to an induction course of rituximab (anti-CD20 mAb) and randomized to treatment with maintenance rituximab or no-maintenance rituximab...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28650722/optimized-dna-vaccine-enhanced-by-adjuvant-il28b-induces-protective-immune-responses-against-herpes-simplex-virus-type-2-in-mice
#13
Yan Zhou, Ziyan Wang, Yongqing Xu, Zeqiang Zhang, Rui Hua, Wei Liu, Chunlai Jiang, Yan Chen, Wenying Yang, Wei Kong
Antigen-specific immune responses determine the efficacy of herpes simplex virus type 2 (HSV-2) vaccines. To optimize the immunogenicity of the antigen gD2, we developed the gD2ΔUL25 DNA vaccine encoding HSV-2 glycoprotein D and UL25 gene encoding viral capsid vertex proteins in this study. The gD2 and gD2ΔUL25 DNA vaccines were compared with formalin-inactivated HSV-2 (FI-HSV-2), and results showed a greater protective immune response induced by gD2ΔUL25 than by gD2. Therefore, gD2ΔUL25 was chosen to evaluate further using the IL28B adjuvant...
June 26, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28636755/technical-note-combination-of-multiple-epid-imager-layers-improves-image-quality-and-tracking-performance-of-low-contrast-to-noise-objects
#14
Stephen Sf Yip, Joerg Rottmann, Haijian Chen, Daniel Morf, Rony Füglistaller, Josh Star-Lack, George Zentai, Ross Berbeco
PURPOSE: We hypothesized that combining multiple amorphous silicon flat panel layers increases photon detection efficiency in an electronic portal imaging device (EPID), improving image quality and tracking accuracy of low contrast targets during radiotherapy METHODS: The prototype imager evaluated in this study contained 4 individually programmable layers each with a copper converter layer, Gd2 O2 S scintillator and active-matrix flat panel imager (AMFPI). The imager was placed on a Varian TrueBeam linac and a Las Vegas phantom programmed with sinusoidal motion (peak-to-peak amplitude=20mm, Period=3...
June 21, 2017: Medical Physics
https://www.readbyqxmd.com/read/28614387/global-sensing-of-the-antigenic-structure-of-herpes-simplex-virus-gd-using-high-throughput-array-based-spr-imaging
#15
Tina M Cairns, Noah T Ditto, Huan Lou, Benjamin D Brooks, Doina Atanasiu, Roselyn J Eisenberg, Gary H Cohen
While HSV-2 typically causes genital lesions, HSV-1 is increasingly the cause of genital herpes. In addition, neonatal HSV infections are associated with a high rate of mortality and HSV-2 may increase the risk for HIV or Zika infections, reinforcing the need to develop an effective vaccine. In the GSK Herpevac trial, doubly sero-negative women were vaccinated with a truncated form of gD2 [gD2(284t)], then examined for anti-gD serum titers and clinical manifestations of disease. Surprisingly, few vaccinees were protected against genital HSV-2 but 86% were protected from genital HSV-1...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28602436/car-t-cells-administered-in-combination-with-lymphodepletion-and-pd-1-inhibition-to-patients-with-neuroblastoma
#16
Andras Heczey, Chrystal U Louis, Barbara Savoldo, Olga Dakhova, April Durett, Bambi Grilley, Hao Liu, Mengfeng F Wu, Zhuyong Mei, Adrian Gee, Birju Mehta, Huimin Zhang, Nadia Mahmood, Haruko Tashiro, Helen E Heslop, Gianpietro Dotti, Cliona M Rooney, Malcolm K Brenner
Targeting disialoganglioside (GD2) on neuroblastoma (NB) with T cells expressing a first-generation chimeric antigen receptor (CAR) was safe, but the cells had poor expansion and long-term persistence. We developed a third-generation GD2-CAR (GD2-CAR3) and hypothesized that GD2-CAR3 T cells (CARTs) would be safe and effective. This phase 1 study enrolled relapsed or refractory NB patients in three cohorts. Cohort 1 received CART alone, cohort 2 received CARTs plus cyclophosphamide and fludarabine (Cy/Flu), and cohort 3 was treated with CARTs, Cy/Flu, and a programmed death-1 (PD-1) inhibitor...
June 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28594418/microemulsion-made-gadolinium-carbonate-hollow-nanospheres-showing-magnetothermal-heating-and-drug-release
#17
J Jung-König, M Sanhaji, R Popescu, C Seidl, E Zittel, U Schepers, D Gerthsen, I Hilger, C Feldmann
Gadolinium carbonate (Gd2(CO3)3) hollow nanospheres and their suitability for drug transport and magnetothermally-induced drug release are presented. The hollow nanospheres are prepared via a microemulsion-based synthesis using tris(tetramethylcyclopentadienyl)gadolinium(iii) and CO2 as the starting materials. Size, structure and composition of the as-prepared Gd2(CO3)3 hollow nanospheres are comprehensively validated by several independent analytical methods (HRTEM, HAADF-STEM, DLS, EDXS, XRD, FT-IR, DTA-TG)...
June 8, 2017: Nanoscale
https://www.readbyqxmd.com/read/28583105/characteristics-and-potentials-of-stem-cells-derived-from-human-degenerated-nucleus-pulposus-potential-for-regeneration-of-the-intervertebral-disc
#18
Xiao-Chuan Li, Yong Tang, Jian-Hong Wu, Pu-Shan Yang, De-Li Wang, Di-Ke Ruan
BACKGROUND: Eliminating the symptoms during treatment of intervertebral disc degeneration (IVDD) is only a temporary solution that does not cure the underlying cause. A biological method to treat this disorder may be possible by the newly discovered nucleus pulposus derived stem cells (NPDCs). However, the uncertain characteristics and potential of NPDCs calls for a comprehensive study. METHODS: In the present study, nucleus pulposus samples were obtained from 5 patients with IVDD undergoing discectomy procedure and NPDCs were harvested using fluorescence activated cell sorting (FACS) by the co-expression of GD2(+) and Tie2(+)...
June 5, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28574176/a-photosensitizer-lanthanide-nanoparticle-formulation-that-induces-singlet-oxygen-with-direct-light-excitation-but-not-by-photon-or-x-ray-energy-transfer
#19
Rima Chouikrat, Francis Baros, Jean-Claude André, Régis Vanderesse, Bruno Viana, Anne-Laure Bulin, Christophe Dujardin, Philippe Arnoux, Marc Verelst, Céline Frochot
We report the design and synthesis of europium-doped gadolinium oxysulfide nanoscintillators Gd2 O2 S:Eu(3+) conjugated with two different photosensitizers (PSs): a zinc chlorin (ZnTPC) and a zinc phtalocyanine (ZnPc) by covalent bonding through a layer of N-(3-trimethoxysilylpropyl)diethylenetriamine (TPDA). These conjugates were designed to be activated under X-ray excitation to allow a photodynamic effect, although this desired outcome was not achieved in this study. The monodispersed nanoparticles of ∼70 nm diameter were pegylated to be stabilized in aqueous suspension...
June 2, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28570663/rectal-administration-of-a-chlamydial-subunit-vaccine-protects-against-genital-infection-and-upper-reproductive-tract-pathology-in-mice
#20
Roshan Pais, Yusuf Omosun, Qing He, Uriel Blas-Machado, Carolyn Black, Joseph U Igietseme, Kohtaro Fujihashi, Francis O Eko
In this study, we tested the hypothesis that rectal immunization with a VCG-based chlamydial vaccine would cross-protect mice against heterologous genital Chlamydia trachomatis infection and Chlamydia-induced upper genital tract pathologies in mice. Female mice were immunized with a C. trachomatis serovar D-derived subunit vaccine or control or live serovar D elementary bodies (EBs) and the antigen-specific mucosal and systemic immune responses were characterized. Vaccine efficacy was determined by evaluating the intensity and duration of genital chlamydial shedding following intravaginal challenge with live serovar E chlamydiae...
2017: PloS One
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