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https://www.readbyqxmd.com/read/28538502/successful-reduced-intensity-allogeneic-transplant-with-full-donor-chimerism-and-good-quality-of-life-in-adolescent-patient-with-wiskott-aldrich-syndrome
#1
Salah Ali, Anna Gacsadi, Elizabeth McDougall, Christine Armstrong, Joerg Krueger, Tal Schechter, Muhammad Ali
Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by microthrombocytopenia, eczema, immune deficiency, and autoimmune phenomena. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment. Myeloablative conditioning is the most common regimen used for HSCT in patients with WAS to avoid the risk of mixed donor chimerism and autoimmunity post-HSCT. There is limited data on the use of reduced intensity conditioning for HSCT in patients with WAS. Here, we report a case with severe phenotype of WAS transplanted successfully with reduced intensity conditioning, which is an acceptable conditioning regimen and can be considered in patients with WAS with significantly impaired organ functions...
May 22, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28537891/multiplex-pcr-approach-to-simultaneously-identify-several-mutations-in-fine-needle-cytology-thyroid-samples
#2
Emilia Vuttariello, Marco Borra, Elvira Mauriello, Celeste Calise, Barbara D'Andrea, Anna Capiluongo, Franco Fulciniti, Anna Cipolletta, Mario Monaco, Luciano Pezzullo, Gennaro Chiappetta
The most frequent initial manifestation of thyroid cancer is the appearance of a nodule. More than 20% of the general population has a palpable thyroid nodule and the percentage rises to 70% based on ultrasound identification. In 95% of cases the nodule is simply a hyperplastic or benign lesion. The most reliable diagnostic test for thyroid nodules is fine needle aspiration (FNA), but cytological discrimination between malignant and benign follicular neoplasms remains difficult. Cytological analysis is now, almost routinely, being combined with molecular genetics to enable the pathologist to make a more objective diagnosis...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533894/a-scaffold-merging-approach-to-hsp90-c-terminal-inhibition-synthesis-and-evaluation-of-a-chimeric-library
#3
Rachel E Davis, Zheng Zhang, Brian S J Blagg
Inhibition of the Hsp90 C-terminus is an attractive therapeutic paradigm for the treatment of cancer, however the developmental space of C-terminal inhibitors is limited. It was hypothesized that the combination of two previously identified scaffolds into a single structure could provide a platform for which to probe the three-dimensional space within the Hsp90 C-terminal binding pocket. The resulting chimeric compounds displayed anti-proliferative activity at low micromolar concentrations and manifested inhibitory activity in an Hsp90-dependent rematuration assay...
March 1, 2017: MedChemComm
https://www.readbyqxmd.com/read/28533359/selective-regulation-of-notch-ligands-during-angiogenesis-is-mediated-by-vimentin
#4
Daniel Antfolk, Marika Sjöqvist, Fang Cheng, Kimmo Isoniemi, Camille L Duran, Adolfo Rivero-Muller, Christian Antila, Rasmus Niemi, Sebastian Landor, Carlijn V C Bouten, Kayla J Bayless, John E Eriksson, Cecilia M Sahlgren
Notch signaling is a key regulator of angiogenesis, in which sprouting is regulated by an equilibrium between inhibitory Dll4-Notch signaling and promoting Jagged-Notch signaling. Whereas Fringe proteins modify Notch receptors and strengthen their activation by Dll4 ligands, other mechanisms balancing Jagged and Dll4 signaling are yet to be described. The intermediate filament protein vimentin, which has been previously shown to affect vascular integrity and regenerative signaling, is here shown to regulate ligand-specific Notch signaling...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533272/chimeric-pd-1-28-receptor-upgrades-low-avidity-t-cells-and-restores-effector-function-of-tumor-infiltrating-lymphocytes-for-adoptive-cell-therapy
#5
Ramona Schlenker, Luis Felipe Olguín-Contreras, Matthias Leisegang, Julia Schnappinger, Anja Disovic, Svenja Rühland, Peter J Nelson, Heinrich Leonhardt, Hartmann Harz, Susanne Wilde, Dolores J Schendel, Wolfgang Uckert, Gerald Willimsky, Elfriede Noessner
Inherent intermediate-to-low affinity T cell receptors (TCR) that develop during the natural course of immune responses may not allow sufficient activation for tumor elimination, making the majority of T cells suboptimal for adoptive T cell therapy (ATT). TCR affinity enhancement has been implemented to provide stronger T cell activity but carries the risk of creating undesired cross-reactivity leading to potential serious adverse effects in clinical application. We demonstrate here that engineering of low-avidity T cells recognizing a naturally processed and presented tumor-associated antigen with a chimeric PD-1:28 receptor increases effector function to levels seen with high-avidity T cells of identical specificity...
May 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28531189/tandem-duplications-lead-to-novel-expression-patterns-through-exon-shuffling-in-drosophila-yakuba
#6
Rebekah L Rogers, Ling Shao, Kevin R Thornton
One common hypothesis to explain the impacts of tandem duplications is that whole gene duplications commonly produce additive changes in gene expression due to copy number changes. Here, we use genome wide RNA-seq data from a population sample of Drosophila yakuba to test this 'gene dosage' hypothesis. We observe little evidence of expression changes in response to whole transcript duplication capturing 5' and 3' UTRs. Among whole gene duplications, we observe evidence that dosage sharing across copies is likely to be common...
May 22, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28531161/development-of-optimized-inhibitor-rnas-allowing-multisite-targeting-of-the-hcv-genome
#7
Cristina Romero-López, Thomas Lahlali, Beatriz Berzal-Herranz, Alfredo Berzal-Herranz
Engineered multivalent drugs are promising candidates for fighting infection by highly variable viruses, such as HCV. The combination into a single molecule of more than one inhibitory domain, each with its own target specificity and even a different mechanism of action, results in drugs with potentially enhanced therapeutic properties. In the present work, the anti-HCV chimeric inhibitor RNA HH363-10, which has a hammerhead catalytic domain and an aptamer RNA domain, was subjected to an in vitro selection strategy to isolate ten different optimised chimeric inhibitor RNAs...
May 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28530644/intestinal-fungi-contribute-to-development-of-alcoholic-liver-disease
#8
An-Ming Yang, Tatsuo Inamine, Katrin Hochrath, Peng Chen, Lirui Wang, Cristina Llorente, Sena Bluemel, Phillipp Hartmann, Jun Xu, Yukinori Koyama, Tatiana Kisseleva, Manolito G Torralba, Kelvin Moncera, Karen Beeri, Chien-Sheng Chen, Kim Freese, Claus Hellerbrand, Serene Ml Lee, Hal M Hoffman, Wajahat Z Mehal, Guadalupe Garcia-Tsao, Ece A Mutlu, Ali Keshavarzian, Gordon D Brown, Samuel B Ho, Ramon Bataller, Peter Stärkel, Derrick E Fouts, Bernd Schnabl
Chronic liver disease with cirrhosis is the 12th leading cause of death in the United States, and alcoholic liver disease accounts for approximately half of all cirrhosis deaths. Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet we understand little about the contribution of intestinal fungi, or mycobiota, to alcoholic liver disease. Here we have demonstrated that chronic alcohol administration increases mycobiota populations and translocation of fungal β-glucan into systemic circulation in mice...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28529898/preclinical-rationale-for-combining-radiation-therapy-and-immunotherapy-beyond-checkpoint-inhibitors-i-e-cart
#9
REVIEW
James P Flynn, Mark H O'Hara, Saumil J Gandhi
An increasing appreciation for the role of the immune system in targeting cancer cells over the last decade has led to the development of several immunomodulatory agents aimed at enhancing the systemic antitumor immune response. One such method is the use of T cells that are genetically engineered to express chimeric antigen receptors (CARs). The remarkable success of this approach in advanced hematologic malignancies has garnered much enthusiasm for using this novel tool in treating other cancers. However, multiple challenges have hampered the application of this therapy to a broader set of solid tumors, most notably lung cancer...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529511/characterization-of-cd4-t-cell-epitopes-of-infliximab-and-rituximab-identified-from-healthy-donors
#10
Moustafa Hamze, Sylvain Meunier, Anette Karle, Abdelaziz Gdoura, Amélie Goudet, Natacha Szely, Marc Pallardy, Franck Carbonnel, Sebastian Spindeldreher, Xavier Mariette, Corinne Miceli-Richard, Bernard Maillère
The chimeric antibodies anti-CD20 rituximab (Rtx) and anti-TNFα infliximab (Ifx) induce antidrug antibodies (ADAs) in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. With the perspective to anticipate immunogenicity of therapeutic antibodies, identification of the CD4 T cell epitopes was performed using cells collected in healthy donors. Nine T cell epitopes were identified in the variable chains of both antibodies by deriving CD4 T cell lines raised against either Rtx or Ifx...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28528708/depletion-of-the-chimeric-drug-rituximab-from-biological-samples
#11
Benita K Book, Mark D Pescovitz, Lili Guo, Eric A Wiebke
No abstract text is available yet for this article.
May 18, 2017: Human Immunology
https://www.readbyqxmd.com/read/28526770/therapeutic-ige-antibodies-harnessing-a-macrophage-mediated-immune-surveillance-mechanism-against-cancer
#12
REVIEW
Sophia N Karagiannis, Debra H Josephs, Heather J Bax, James F Spicer
IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surveillance and superior effector cell potency against cancer cells. In our recent article, we elaborate our proof-of-concept studies of a mouse/human chimeric IgE antibody (MOv18 IgE), which is specific for the cancer-associated antigen folate receptor alpha...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28526067/the-chimeric-monoclonal-antibody-mhcsz-123-against-human-von-willebrand-factor-a3-domain-inhibits-high-shear-arterial-thrombosis-in-a-rhesus-monkey-model
#13
Shundong Ji, Miao Jiang, Bin Yan, Fei Shen, Yang He, Aini Wan, Lijun Xia, Changgeng Ruan, Yiming Zhao
BACKGROUND: SZ-123, a murine monoclonal antibody that targets the human von Willebrand factor (VWF) A3 domain and blocks the binding of collagen, is a powerful antithrombotic. In a Rhesus monkey model of thrombosis, SZ-123 had no side effects, such as bleeding or thrombocytopenia. METHODS: The mouse/human chimeric version of SZ-123, MHCSZ-123, was developed and maintained inhibitory capacities in vitro and ex vivo after injection into monkeys. CHO-S cells were selected for stable expression of MHCSZ-123...
May 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28525963/the-use-of-transgenic-parasites-in-malaria-vaccine-research
#14
Ahmad Syibli Othman, Catherin Marin-Mogollon, Ahmed M Salman, Blandine M Franke-Fayard, Chris J Janse, Shahid M Khan
Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas Covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection...
May 19, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28525878/vaccine-development-for-respiratory-syncytial-virus
#15
REVIEW
Barney S Graham
Respiratory syncytial virus (RSV) is an important and ubiquitous respiratory pathogen for which no vaccine is available notwithstanding more than 50 years of effort. It causes the most severe disease at the extremes of age and in settings of immunodeficiency. Although RSV is susceptible to neutralizing antibody, it has evolved multiple mechanisms of immune evasion allowing it to repeatedly infect people despite relatively little genetic diversity. Recent breakthroughs in determining the structure and antigenic content of the fusion (F) glycoprotein in its metastable untriggered prefusion form (pre-F) and the stable rearranged postfusion form (post-F) have yielded vaccine strategies that can induce potent neutralizing antibody responses and effectively boost pre-existing neutralizing activity...
May 16, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28525538/chimeraviz-a-tool-for-visualizing-chimeric-rna
#16
Stian Lågstad, Sen Zhao, Andreas M Hoff, Bjarne Johannessen, Ole Christian Lingjærde, Rolf I Skotheim
Summary: Advances in high-throughput RNA sequencing have enabled more efficient detection of fusion transcripts, but the technology and associated software used for fusion detection from sequencing data often yield a high false discovery rate. Good prioritization of the results is important, and this can be helped by a visualization framework that automatically integrates RNA data with known genomic features. Here we present chimeraviz , a Bioconductor package that automates the creation of chimeric RNA visualizations...
May 19, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28523907/unexpected-position-dependent-effects-of-ribose-g-quartets-in-g-quadruplexes
#17
Jun Zhou, Samir Amrane, Frédéric Rosu, Gilmar F Salgado, Yunqiang Bian, Hisae Tateishi-Karimata, Eric Largy, Dursun Nizam Korkut, Anne Bourdoncle, Daisuke Miyoshi, Jian Zhang, Huangxian Ju, Wei Wang, Naoki Sugimoto, Valérie Gabelica, Jean-Louis Mergny
To understand the role of ribose G-quartets and how they affect the properties of G-quadruplex structures, we studied three systems in which one, two, three, or four deoxyribose G-quartets were substituted with ribose G-quartets. These systems were a parallel DNA intramolecular G-quadruplex d(TTGGGTGGGTTGGGTGGGTT) and two tetramolecular G-quadruplexes d(TGGGT) and d(TGGGGT). Thermal denaturation experiments revealed that ribose G-quartets have position-dependent and cumulative effects on G-quadruplex stability...
May 19, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28523432/novel-t-cells-with-improved-in-vivo-anti-tumor-activity-generated-by-rna-electroporation
#18
Xiaojun Liu, Shuguang Jiang, Chongyun Fang, Hua Li, Xuhua Zhang, Fuqin Zhang, Carl H June, Yangbing Zhao
The generation of T cells with maximal anti-tumor activities will significantly impact the field of T-cell-based adoptive immunotherapy. In this report, we found that OKT3/IL-2-stimulated T cells were phenotypically more heterogeneous, with enhanced anti-tumor activity in vitro and when locally administered in a solid tumor mouse model. To further improve the OKT3/IL-2-based T cell manufacturing procedure, we developed a novel T cell stimulation and expansion method in which peripheral blood mononuclear cells were electroporated with mRNA encoding a chimeric membrane protein consisting of a single-chain variable fragment against CD3 and the intracellular domains of CD28 and 4-1BB (OKT3-28BB)...
May 18, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28522730/11%C3%AE-hsd1-suppresses-cardiac-fibroblast-cxcl2-cxcl5-and-neutrophil-recruitment-to-the-heart-post-mi
#19
Katie J Mylonas, Neil A Turner, Sumia A Bageghni, Christopher J Kenyon, Christopher I White, Kieran McGregor, Robert A Kimmitt, Richard Sulston, Valerie Kelly, Brian R Walker, Karen E Porter, Karen E Chapman, Gillian A Gray
We have previously demonstrated that neutrophil recruitment to the heart following myocardial infarction (MI) is enhanced in mice lacking 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that regenerates active glucocorticoid within cells from intrinsically inert metabolites. The present study aimed to identify the mechanism of regulation. In a mouse model of MI, neutrophil mobilization to blood and recruitment to the heart were higher in 11β-HSD1-deficient (Hsd11b1(-)(/)(-) ) relative to wild-type (WT) mice, despite similar initial injury and circulating glucocorticoid...
June 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28520587/complementary-roles-of-nod2-in-hematopoietic-and-nonhematopoietic-cells-in-preventing-gut-barrier-dysfunction-dependent-on-mlck-activity
#20
Ziad Al Nabhani, Nicolas Montcuquet, Maryline Roy, Monique Dussaillant, Jean-Pierre Hugot, Frédérick Barreau
BACKGROUND: Crohn's disease (CD) pathogenesis is multifactorial involving genetic and environmental factors. Loss of function mutations in the nucleotide oligomerization domain 2 (NOD2) gene are the main genetic risk factor for CD. Like patients with CD, Nod2 mice are characterized by an enhanced Th1 immune response and a defective mucosal barrier function evidenced by increased intestinal permeability. We previously showed that the latter is related to hematopoietic Nod2 deficiency. Our aim was to explore the mechanisms by which Nod2 expressed in the hematopoietic and in the nonhematopoietic compartments interplay to control epithelial paracellular permeability...
May 16, 2017: Inflammatory Bowel Diseases
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