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https://www.readbyqxmd.com/read/29691398/galectin-3-deficiency-drives-lupus-like-disease-by-promoting-spontaneous-germinal-centers-formation-via-ifn-%C3%AE
#1
Cristian Gabriel Beccaria, María Carolina Amezcua Vesely, Facundo Fiocca Vernengo, Ricardo Carlos Gehrau, María Cecilia Ramello, Jimena Tosello Boari, Melisa Gorosito Serrán, Juan Mucci, Eliane Piaggio, Oscar Campetella, Eva Virginia Acosta Rodríguez, Carolina Lucía Montes, Adriana Gruppi
Germinal centers (GC) are important sites for high-affinity and long-lived antibody induction. Tight regulation of GC responses is critical for maintaining self-tolerance. Here, we show that Galectin-3 (Gal-3) is involved in GC development. Compared with WT mice, Gal-3 KO mice have more GC B cells and T follicular helper cells, increased percentages of antibody-secreting cells and higher concentrations of immunoglobulins and IFN-γ in serum, and develop a lupus-like disease. IFN-γ blockade in Gal-3 KO mice reduces spontaneous GC formation, class-switch recombination, autoantibody production and renal pathology, demonstrating that IFN-γ overproduction sustains autoimmunity...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29691200/crispr-cas9-genome-editing-fueling-the-revolution-in-cancer-immunotherapy
#2
REVIEW
Xiaojun Liu, Yangbing Zhao
The development of genomic editing technologies expands the landscape of T cell engineering for adoptive cell therapy. Among the multiple tools that can be used, CRISPR/Cas9 has been shown to be relatively easy to use, simple to design and cost effective with highly efficient multiplex genome engineering capabilities. Allogeneic universal chimeric antigen receptor (CAR) T cells can be produced by disrupting T cell receptor (TCR) and beta-2-microglobulin (B2M) in CAR T cells or by directly knocking in a CAR at the disrupted TRAC locus...
April 21, 2018: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/29691064/novel-ace2-fc-chimeric-fusion-provides-long-lasting-hypertension-control-and-organ-protection-in-mouse-models-of-systemic-renin-angiotensin-system-activation
#3
Pan Liu, Jan Wysocki, Tomokazu Souma, Minghao Ye, Veronica Ramirez, Bisheng Zhou, Lisa D Wilsbacher, Susan E Quaggin, Daniel Batlle, Jing Jin
Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that potently degrades angiotensin II to angiotensin 1-7. Previous studies showed that injection of the enzymatic ectodomain of recombinant ACE2 (rACE2) markedly increases circulatory levels of ACE2 activity, and effectively lowered blood pressure in angiotensin II-induced hypertension. However, due to the short plasma half-life of rACE2, its therapeutic potential for chronic use is limited. To circumvent this, we generated a chimeric fusion of rACE2 and the Ig fragment Fc segment to increase its plasma stability...
April 21, 2018: Kidney International
https://www.readbyqxmd.com/read/29687382/induction-of-skin-allograft-transplantation-tolerance-in-mice-using-human-adipose-derived-stromal-cells
#4
Anthony D Foster, Nicholas Clark, Thomas A Davis
Murine models of allograft transplantation are valuable for understanding the immunological mechanisms of allograft acceptance and rejection, the evaluation of immunosuppressive drugs and strategies, and the restoration of functional defects. Herein, we describe methods to create a skin murine allograft surgical model and how to administer adipose-derived stromal cells (ASC) with limited numbers of donor bone marrow to create stable multilineage donor cell chimerism and indefinite immunological tolerance.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29687248/a-versatile-and-sensitive-lateral-flow-immunoassay-for-the-rapid-diagnosis-of-visceral-leishmaniasis
#5
Laura Anfossi, Fabio Di Nardo, Margherita Profiti, Chiara Nogarol, Simone Cavalera, Claudio Baggiani, Cristina Giovannoli, Giulia Spano, Ezio Ferroglio, Walter Mignone, Sergio Rosati
Visceral leishmaniasis (VL) is a zoonotic infectious disease with a severe impact on humans and animals. Infection is transmitted by phlebotomine sand flies, and several domestic and wild mammals act as reservoirs for the infection, so the prompt detection of infected hosts is crucial to preventing and controlling the spread of the disease and its transmission to humans. A rapid and portable tool for VL diagnosis based on the lateral flow immunoassay (LFIA) technology is described herein. The device exploits a highly specific chimeric recombinant antigen as the recognition element for capturing anti-leishmanial antibodies, and protein A labelled with gold nanoparticles as the signal reporter...
April 23, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29687032/enhanced-expression-of-anti-cd19-chimeric-antigen-receptor-in-piggybac-transposon-engineered-t-cells
#6
Daisuke Morita, Nobuhiro Nishio, Shoji Saito, Miyuki Tanaka, Nozomu Kawashima, Yusuke Okuno, Satoshi Suzuki, Kazuyuki Matsuda, Yasuhiro Maeda, Matthew H Wilson, Gianpietro Dotti, Cliona M Rooney, Yoshiyuki Takahashi, Yozo Nakazawa
Adoptive T cell therapy using chimeric antigen receptor (CAR)-modified T cells is a promising cancer immunotherapy. We previously developed a non-viral method of gene transfer into T cells using a piggyBac transposon system to improve the cost-effectiveness of CAR-T cell therapy. Here, we have further improved our technology by a novel culture strategy to increase the transfection efficiency and to reduce the time of T cell manufacturing. Using a CH2CH3-free CD19-specific CAR transposon vector and combining irradiated activated T cells (ATCs) as feeder cells and virus-specific T cell receptor (TCR) stimulation, we achieved 51...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29686617/a-chimeric-nav1-8-channel-expression-system-based-on-hek293t-cell-line
#7
Xi Zhou, Yunxiao Zhang, Dongfang Tang, Songping Liang, Ping Chen, Cheng Tang, Zhonghua Liu
Among the nine voltage-gated sodium channel (NaV) subtypes, NaV1.8 is an attractive therapeutic target for pain. The heterologous expression of recombinant NaV1.8 currents is of particular importance for its electrophysiological and pharmacological studies. However, NaV1.8 expresses no or low-level functional currents when transiently transfected into non-neuronal cell lines. The present study aims to explore the molecular determinants limiting its functional expression and accordingly establish a functional NaV1...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29686080/systemic-surfaceome-profiling-identifies-target-antigens-for-immune-based-therapy-in-subtypes-of-advanced-prostate-cancer
#8
John K Lee, Nathanael J Bangayan, Timothy Chai, Bryan A Smith, Tiffany E Pariva, Sangwon Yun, Ajay Vashisht, Qingfu Zhang, Jung Wook Park, Eva Corey, Jiaoti Huang, Thomas G Graeber, James Wohlschlegel, Owen N Witte
Prostate cancer is a heterogeneous disease composed of divergent molecular and histologic subtypes, including prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC). While PrAd is the major histology in prostate cancer, NEPC can evolve from PrAd as a mechanism of treatment resistance that involves a transition from an epithelial to a neurosecretory cancer phenotype. Cell surface markers are often associated with specific cell lineages and differentiation states in normal development and cancer...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29685843/clinical-units-to-set-up-chimeric-antigen-receptor-t-cell-therapy-car-t-cells-based-on-the-recommendations-of-the-francophone-society-of-bone-marrow-transplantation-and-cellular-therapy-sfgm-tc
#9
Ibrahim Yakoub-Agha
The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) hold its eighth practice harmonization workshops on September 2017. In a workshop dedicated to chimeric antigen receptor T-cell therapy (CAR T-cells), the society issued recommendations regarding the prerequisite for hematopoietic cellular therapy programs to set up CAR T-cell therapy. In this article we focused on the prerequisite needed, in France, for a hematopoietic transplantation unit to start a CAR T-cell program with industrial manufactured cells within investigational products or after market access authorization...
April 20, 2018: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/29685392/cellular-therapies-day-by-day-all-the-way
#10
REVIEW
Erden Atilla, Pelin Kilic, Gunhan Gurman
Tremendous effort and knowledge have elucidated a new era of 'cellular therapy,' also called "live" or "living" drugs. There are currently thousands of active clinical trials that are ongoing, seeking hope for incurable conditions thanks to the increased accessibility and reliability of gene editing and cellular reprogramming. Accomplishments in various adoptive T cell immunotherapies and chimeric antigen receptor (CART) T cell therapies oriented researchers to the field. Cellular therapies are believed to be the next generation of curative therapeutics in many ways, the classification and nomenclature for these applications have not yet reached a consensus...
April 18, 2018: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/29685162/mir-153-suppresses-ido1-expression-and-enhances-car-t-cell-immunotherapy
#11
Qian Huang, Jiajia Xia, Lei Wang, Xu Wang, Xiaodong Ma, Qipan Deng, Yong Lu, Munish Kumar, Zhiyuan Zhou, Ling Li, Zhaoyang Zeng, Ken H Young, Qing Yi, Mingzhi Zhang, Yong Li
BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first and rate-limiting step in converting tryptophan to kynurenine. Chimeric antigen receptor (CAR) T cells are T cells with recombinant receptors targeting tumor-associated antigens. The Food and Drug Administration has approved CAR T cells that target CD19 for treatment of advanced B cell leukemia and lymphoma. However, CAR T cell therapy in solid tumors has been hampered by multiple obstacles. Preclinical and clinical studies suggest that combinatorial immune checkpoint blockade and IDO1 inhibition provide durable therapeutic efficacy against cancer...
April 23, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29684562/bmt-following-non-myeloablative-treosulfan-conditioning-is-curative-in-a-murine-model-of-sickle-cell-disease
#12
Divya Devadasan, Chiao-Wang Sun, Erik R Westin, Li-Chen Wu, Kevin M Pawlik, Tim M Townes, Frederick D Goldman
Allogeneic hematopoietic stem cell transplantation (HSCT) can be curative for patients with sickle cell disease (SCD). However, morbidity associated with myeloablative conditioning and graft versus host disease has limited its utility. To this end, autologous HSCT for SCD using lentiviral gene-modified bone marrow (BM) or peripheral blood stem cells has been undertaken, though toxicities of fully ablative conditioning with busulfan and incomplete engraftment have been encountered. Treosulfan, a busulfan analog with a low extra-medullary toxicity profile, has been employed successfully as part of a myeloablative conditioning regimen in the allogeneic setting in SCD...
April 20, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29684061/the-kinetics-of-tem1-antibiotic-degrading-enzymes-that-are-displayed-on-ure2-protein-nanofibrils-in-a-flow-reactor
#13
Benjamin Schmuck, Mats Sandgren, Torleif Härd
Enzymatic functionalization of cross-β structured protein nanofibrils has hitherto resulted in a severe reduction of the catalytic efficiency of high turnover biocatalysts. It has been speculated that steric restrictions and mass transport pose limits on the attached enzymes, but detailed kinetics analyzing this have not yet been reported. For a more comprehensive understanding, we studied protein nanofibrils endowed with TEM1, a β-lactamase from Escherichia coli. The packing density of TEM1 along the fibrils was controlled by co-fibrillation; in other words, the N-terminal ureidosuccinate transporter Ure2(1-80) from Saccharomyces cerevisiae was simultaneously aggregated with the chimeric proteins TEM1-Ure2(1-80)...
2018: PloS One
https://www.readbyqxmd.com/read/29683766/displaying-31rg-1-peptide-on-the-surface-of-hpv16-l1-by-use-of-a-human-papillomavirus-chimeric-virus-like-particle-induces-cross-neutralizing-antibody-responses-in-mice
#14
Xue Chen, Ting Zhang, Hongyang Liu, Yaru Hao, Guoyang Liao, Xuemei Xu
Current available human papillomavirus (HPV) vaccines are based on the major capsid protein L1 virus-like particles (VLPs), which mainly induce type-specific neutralizing antibodies against vaccine types. Continuing to add more types of VLPs in a vaccine raises the complexity and cost of production which remains the principal impediment to achieve broad implementation of HPV vaccines, particularly in developing regions. In this study, we constructed 16L1-31L2 chimeric VLP (cVLP) by displaying HPV31 L2 aa.17-38 on the h4 coil surface region of HPV16 L1, and assessed its immunogenicity in mouse model...
April 23, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29682973/response-to-comparison-and-evaluation-of-clustering-algorithms-for-tandem-mass-spectra
#15
Johannes Griss, Yasset Perez-Riverol, Matthew The, Lukas Käll, Juan A Vizcaíno
In the recent benchmarking article entitled "Comparison and Evaluation of Clustering Algorithms for Tandem Mass Spectra", Rieder et al. compared several different approaches to cluster MS/MS spectra. While we certainly recognize the value of the manuscript, here, we report some shortcomings detected in the original analyses. For most analyses, the authors only clustered single MS/MS runs. In one of the reported analyses, three MS/MS runs were processed together, which already led to computational performance issues in many of the tested approaches...
April 23, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29682573/antibody-mediated-osseous-regeneration-for-bone-tissue-engineering-in-canine-segmental-defects
#16
A Khojasteh, S Hosseinpour, M M Dehghan, F Mashhadiabbas, M Rezai Rad, S Ansari, S Farzad Mohajeri, H H Zadeh
Among many applications of therapeutic monoclonal antibodies (mAbs), a unique approach for regenerative medicine has entailed antibody-mediated osseous regeneration (AMOR). In an effort to identify a clinically relevant model of craniofacial defect, the present study investigated the efficacy of mAb specific for bone morphogenetic protein- (BMP-) 2 to repair canine segmental mandibular continuity defect model. Accordingly, a 15 mm unilateral segmental defect was created in mandible and fixated with a titanium plate...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29682521/immune-escape-mechanisms-and-future-prospects-for-immunotherapy-in-neuroblastoma
#17
REVIEW
Thitinee Vanichapol, Somchai Chutipongtanate, Usanarat Anurathapan, Suradej Hongeng
Neuroblastoma (NB) is the most common extracranial solid tumor in childhood with 5-year survival rate of 40% in high-risk patients despite intensive therapies. Recently, adoptive cell therapy, particularly chimeric antigen receptor (CAR) T cell therapy, represents a revolutionary treatment for hematological malignancies. However, there are challenges for this therapeutic strategy with solid tumors, as a result of the immunosuppressive nature of the tumor microenvironment (TME). Cancer cells have evolved multiple mechanisms to escape immune recognition or to modulate immune cell function...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29681751/utilization-of-transcription-factors-for-controlling-floral-morphogenesis-in-horticultural-plants
#18
REVIEW
Katsutomo Sasaki
Transcription factors play important roles not only in the development of floral organs but also in the formation of floral characteristics in various plant species. Therefore, transcription factors are reasonable targets for modifying these floral traits and generating new flower cultivars. However, it has been difficult to control the functions of transcription factors because most plant genes, including those encoding transcription factors, exhibit redundancy. In particular, it has been difficult to understand the functions of these redundant genes by genetic analysis...
January 2018: Breeding Science
https://www.readbyqxmd.com/read/29681468/discrimination-against-rna-backbones-by-a-ssdna-binding-protein
#19
Neil R Lloyd, Deborah S Wuttke
Pot1 is the shelterin component responsible for the protection of the single-stranded DNA (ssDNA) overhang at telomeres in nearly all eukaryotic organisms. The C-terminal domain of the DNA-binding domain, Pot1pC, exhibits non-specific ssDNA recognition, achieved through thermodynamically equivalent alternative binding conformations. Given this flexibility, it is unclear how specificity for ssDNA over RNA, an activity required for biological function, is achieved. Examination of the ribose-position specificity of Pot1pC shows that ssDNA specificity is additive but not uniformly distributed across the ligand...
April 18, 2018: Structure
https://www.readbyqxmd.com/read/29680236/chimeric-small-antibody-fragments-as-strategy-to-deliver-therapeutic-payloads
#20
Sandra Aguiar, Joana Dias, Ana M Manuel, Roberto Russo, Pedro M P Gois, Frederico A da Silva, Joao Goncalves
Antibody-drug conjugates (ADCs) represent an innovative class of biopharmaceuticals, which aim at achieving a site-specific delivery of cytotoxic agents to the target cell. The use of ADCs represents a promising strategy to overcome the disadvantages of conventional pharmacotherapy of cancer or neurological diseases, based on cytotoxic or immunomodulatory agents. ADCs consist of monoclonal antibodies attached to biologically active drugs by means of cleavable chemical linkers. Advances in technologies for the coupling of antibodies to cytotoxic drugs promise to deliver greater control of drug pharmacokinetic properties and to significantly improve pharmacodelivery applications, minimizing exposure of healthy tissue...
2018: Advances in Protein Chemistry and Structural Biology
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