13,835 results match your criteria type chimeric

Animal Models of COVID-19. I. Comparative Virology and Disease Pathogenesis.

ILAR J 2021 Apr 9. Epub 2021 Apr 9.

Department of Comparative Medicine, John Hopkins School of Medicine, Baltimore, Maryland, USA.

The Coronavirus Disease 2019 (COVID-19) pandemic has fueled unprecedented development of animal models to understand disease pathogenesis, test therapeutics, and support vaccine development. Models previously developed to study severe acute respiratory syndrome coronavirus (SARS-CoV) have been rapidly deployed to study SARS-CoV-2. However, it has become clear that despite the common use of ACE2 as a receptor for both viruses, the host range of the 2 viruses does not entirely overlap. Read More

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Over-Expression of Intestinal Alkaline Phosphatase Attenuates Atherosclerosis.

Circ Res 2021 Apr 9. Epub 2021 Apr 9.

Internal Medicine, VCU Medical Center, UNITED STATES.

Intestinal Alkaline Phosphatase (IAP) is secreted by enterocytes and is present on the apical surface. It not only detoxifies bacterial endotoxin lipopolysaccharide (LPS) in the gut lumen and limits intestinal inflammation but also restricts translocation of LPS into systemic circulation. Diet-induced intestinal barrier dysfunction and subsequent development of metabolic endotoxemia seen in diabetes and heart disease is associated with reduced IAP levels. Read More

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Anti-CLL1 chimeric antigen receptor T cell therapy in children with relapsed/refractory acute myeloid leukemia.

Clin Cancer Res 2021 Apr 8. Epub 2021 Apr 8.

Guangzhou Medical University.

Purpose: The survival rate of children with refractory/relapsed acute myeloid leukemia (R/R-AML) by salvage chemotherapy is minimal. Treatment with chimeric antigen receptor T cells (CAR-T) has emerged as a novel therapy to improve malignancies treatment. C-type lectin-like molecule 1 (CLL1) is highly expressed on AML leukemia stem cells, blast cells, and monocytes, but not on normal hematopoietic stem cells, indicating the therapeutic potential of anti-CLL1 CAR-T in AML treatment. Read More

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Pancreatic islet transplantation under the kidney capsule of mice: model of refinement for molecular and graft analysis.

Lab Anim 2021 Apr 8:236772211004051. Epub 2021 Apr 8.

Translational Research for Diabetes, Inserm, University of Lille, France.

Diabetes cell therapy by human islet transplantation can restore an endogenous insulin secretion and normal glycaemic control in type 1 diabetic patients for as long as 10 years post transplantation. Before transplantation, each clinical islet preparation undergoes extensive and quality controls. The quality control assay consists of transplanting human islets under the kidney capsule of immunocompromised mice. Read More

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Novel COL4A1-VEGFD gene fusion in myofibroma.

J Cell Mol Med 2021 Apr 8. Epub 2021 Apr 8.

de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.

Myofibroma is a benign pericytic tumour affecting young children. The presence of multicentric myofibromas defines infantile myofibromatosis (IMF), which is a life-threatening condition when associated with visceral involvement. The disease pathophysiology remains poorly characterized. Read More

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Rational engraftment of quaternary-interactive acidic loops for anti-HIV-1 antibody improvement.

J Virol 2021 Apr 7. Epub 2021 Apr 7.

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA

Broadly neutralizing antibodies (bNAbs) are the focus of increasing interest for human immunodeficiency virus type-1 (HIV-1) prevention and treatment. Although several bNAbs are already under clinical evaluation, the development of antibodies with even greater potency and breadth remains a priority. Recently, we reported a novel strategy for improving bNAbs against the CD4-binding site (CD4bs) of gp120 by engraftment of the elongated framework region 3 (FR3) from VRC03, which confers the ability to establish quaternary interactions with a second gp120 protomer. Read More

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The Kunitz-type serine protease inhibitor Spint2 is required for cellular cohesion, coordinated cell migration and cell survival during zebrafish hatching gland development.

Dev Biol 2021 Apr 4. Epub 2021 Apr 4.

Institute of Zoology - Developmental Biology, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany. Electronic address:

We have previously shown that the Kunitz-type serine protease inhibitor Spint1a, also named Hai1a, is required in the zebrafish embryonic epidermis to restrict the activity of the type II transmembrane serine protease (TTSP) Matriptase1a/St14a, thereby ensuring epidermal homeostasis. A closely related Kunitz-type inhibitor is Spint2/Hai2, which in mammals plays multiple developmental roles that are either redundant or non-redundant with those of Spint1. However, the molecular bases for these non-redundancies are not fully understood. Read More

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Novel therapies emerging in oncology to target the TGF-β pathway.

J Hematol Oncol 2021 Apr 6;14(1):55. Epub 2021 Apr 6.

Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

The TGF-β signaling pathway governs key cellular processes under physiologic conditions and is deregulated in many pathologies, including cancer. TGF-β is a multifunctional cytokine that acts in a cell- and context-dependent manner as a tumor promoter or tumor suppressor. As a tumor promoter, the TGF-β pathway enhances cell proliferation, migratory invasion, metastatic spread within the tumor microenvironment and suppresses immunosurveillance. Read More

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Development of non-viral, ligand-dependent, EPHB4-specific chimeric antigen receptor T cells for treatment of rhabdomyosarcoma.

Mol Ther Oncolytics 2021 Mar 5;20:646-658. Epub 2021 Mar 5.

Department of Pediatrics, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Ephrin type-B receptor 4 (EPHB4), expressed in tumors including rhabdomyosarcoma, is a suitable target for chimeric antigen receptor (CAR)-T cells. Ligand-independent activation of EPHB4 causes cell proliferation and malignant transformation in rhabdomyosarcoma, whereas ligand-dependent stimulation of EPHB4 induces apoptosis in rhabdomyosarcoma. Therefore, we hypothesized that ligand-based, EPHB4-specific CAR-T cells may kill rhabdomyosarcoma cells without stimulating downstream cell proliferation mechanisms. Read More

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Cytotoxic Efficacy and Resistance Mechanism of a TRAIL and VEGFA-Peptide Fusion Protein in Colorectal Cancer Models.

Int J Mol Sci 2021 Mar 19;22(6). Epub 2021 Mar 19.

Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.

TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein capable of selectively inducing apoptosis in cancer cells by binding to its cognate receptors. Here, we examined the anticancer efficacy of a recently developed chimeric AD-O51.4 protein, a TRAIL fused to the VEGFA-originating peptide. Read More

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Detection of a New Resistance-Mediating Plasmid Chimera in a -Positive Strain at a German University Hospital.

Microorganisms 2021 Mar 31;9(4). Epub 2021 Mar 31.

Institute for Medical Microbiology, University Medical Center Göttingen, 37075 Göttingen, Germany.

Mobile genetic elements, such as plasmids, facilitate the spread of antibiotic resistance genes in Enterobacterales. In line with this, we investigated the plasmid-resistome of seven gene-carrying isolates, which were isolated between 2013 and 2014 at the University Medical Center in Göttingen, Germany. All isolates were subjected to complete genome sequencing including the reconstruction of entire plasmid sequences. Read More

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Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment.

Int J Mol Sci 2021 Mar 28;22(7). Epub 2021 Mar 28.

Department of Obstetrics, Gynaecology and Maternity Care, Medical University of Bialystok, Szpitalna 37 Street, 15-295 Bialystok, Poland.

Our increased understanding of tumour biology gained over the last few years has led to the development of targeted molecular therapies, e.g., vascular endothelial growth factor A (VEGF-A) antagonists, poly[ADP-ribose] polymerase 1 (PARP1) inhibitors in hereditary breast and ovarian cancer syndrome ( and mutants), increasing survival and improving the quality of life. Read More

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CTX-CNF1 Recombinant Protein Selectively Targets Glioma Cells In Vivo.

Toxins (Basel) 2021 Mar 8;13(3). Epub 2021 Mar 8.

Neuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy.

Current strategies for glioma treatment are only partly effective because of the poor selectivity for tumoral cells. Hence, the necessity to identify novel approaches is urgent. Recent studies highlighted the effectiveness of the bacterial protein cytotoxic necrotizing factor 1 (CNF1) in reducing tumoral mass, increasing survival of glioma-bearing mice and protecting peritumoral neural tissue from dysfunction. Read More

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Emerging Roles of PETase and MHETase in the Biodegradation of Plastic Wastes.

Appl Biochem Biotechnol 2021 Apr 1. Epub 2021 Apr 1.

Indian Academy Degree College-Autonomous, Bangalore, Karnataka, 560043, India.

Polyethylene terephthalate (PET) is extensively used in plastic products, and its accumulation in the environment has become a global concern. Being a non-degradable pollutant, a tremendous quantity of PET-bearing plastic materials have already accumulated in the environment, posing severe challenges towards the existence of various endangered species and consequently threatening the ecosystem and biodiversity. While conventional recycling and remediation methodologies so far have been ineffective in formulating a "green" degradation protocol, the bioremediation strategies-though nascent-are exhibiting greater promises towards achieving the target. Read More

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EIN2-directed histone acetylation requires EIN3-mediated positive feedback regulation in response to ethylene.

Plant Cell 2020 Dec 7. Epub 2020 Dec 7.

Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA.

Ethylene is an important phytohormone with pleotropic roles in plant growth, development, and stress responses. ETHYLENE INSENSITIVE2 (EIN2) mediates the transduction of the ethylene signal from the endoplasmic reticulum membrane to the nucleus, where its C-terminus (EIN2-C) regulates histone acetylation to mediate transcriptional regulation by EIN3. However, no direct interaction between EIN2-C and EIN3 has been detected. Read More

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December 2020

Development of Triantennary N-Acetylgalactosamine Conjugates as Degraders for Extracellular Proteins.

ACS Cent Sci 2021 Mar 4;7(3):499-506. Epub 2021 Mar 4.

School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 56305, United States.

Targeted protein degradation (TPD) technology has drawn significant attention from researchers in both academia and industry. It is rapidly evolved as a new therapeutic modality and also a useful chemical tool in selectively depleting various protein targets. As most efforts focus on cytosolic proteins using PROteolysis TArgeting Chimera (PROTAC), LYsosome TArgeting Chimera (LYTAC) recently emerged as a promising technology to deliver extracellular protein targets to lysosome for degradation through the cation-independent mannose-6-phosphate receptor (CI-M6PR). Read More

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Research advances in chimeric antigen receptor-modified T-cell therapy (Review).

Exp Ther Med 2021 May 16;21(5):484. Epub 2021 Mar 16.

Institute of Tissue Engineering and Stem Cells, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.

Chimeric antigen receptor (CAR)-modified T-cells are T-cells that have been genetically engineered to express CAR molecules to target specific surface antigens on tumor cells. CAR T-cell therapy, a novel cancer immunotherapy, has been attracting increasing attention, since it exhibited notable efficacy in the treatment of hematological tumors in clinical trials. However, for this type of therapy, challenges must be overcome in the treatment of solid tumors. Read More

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Genome Editing in Commercial Wheat Varieties.

Front Plant Sci 2021 15;12:648841. Epub 2021 Mar 15.

Division of Applied Genetics, Institute of Agrobiological Sciences, National Agriculture and Food Research Organization (NARO), Tsukuba, Japan.

Limitations for the application of genome editing technologies on elite wheat ( L.) varieties are mainly due to the dependency on culture and regeneration capabilities. Recently, we developed an particle bombardment (iPB) method which has increased process efficiency since no culture steps are required to create stably genome-edited wheat plants. Read More

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Generation and identification of endothelial-specific Hrh2 knockout mice.

Transgenic Res 2021 Mar 30. Epub 2021 Mar 30.

Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force, 212 Daguan Rd, Kunming, 650032, China.

Histamine H receptor (HRH2) is closely associated with the development of cardiovascular and cerebrovascular diseases. However, systematic Hrh2 knockout mice did not exactly reflect the HRH2 function in specific cell or tissue types. To better understand the physiological and pathophysiological functions of endothelial HRH2, this study constructed a targeting vector that contained loxp sites flanking the ATG start codon located in Hrh2 exon 2 upstream and a neomycin (Neo) resistance gene flanked by self-deletion anchor sites within the mouse Hrh2 allele. Read More

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Signal transduction through Cys-loop receptors is mediated by the nonspecific bumping of closely apposed domains.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801;

One of the most fundamental questions in the field of Cys-loop receptors (pentameric ligand-gated ion channels, pLGICs) is how the affinity for neurotransmitters and the conductive/nonconductive state of the transmembrane pore are correlated despite the ∼60-Å distance between the corresponding domains. Proposed mechanisms differ, but they all converge into the idea that interactions between wild-type side chains across the extracellular-transmembrane-domain (ECD-TMD) interface are crucial for this phenomenon. Indeed, the successful design of fully functional chimeras that combine intact ECD and TMD modules from different wild-type pLGICs has commonly been ascribed to the residual conservation of sequence that exists at the level of the interfacial loops even between evolutionarily distant parent channels. Read More

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Any closer to successful therapy of multiple myeloma? CAR-T cell is a good reason for optimism.

Stem Cell Res Ther 2021 Mar 29;12(1):217. Epub 2021 Mar 29.

Department of Virology, Pasteur Institute of Iran, Tehran, Iran.

Despite many recent advances on cancer novel therapies, researchers have yet a long way to cure cancer. They have to deal with tough challenges before they can reach success. Nonetheless, it seems that recently developed immunotherapy-based therapy approaches such as adoptive cell transfer (ACT) have emerged as a promising therapeutic strategy against various kinds of tumors even the cancers in the blood (liquid cancers). Read More

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Effective degradation of EGFR mutant proteins by CRBN-based PROTACs through both proteosome and autophagy/lysosome degradation systems.

Eur J Med Chem 2021 Mar 7;218:113328. Epub 2021 Mar 7.

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai, 201210, China; Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China. Electronic address:

Targeted therapy of treating patients with specific tyrosine kinase inhibitors (TKIs) is currently the standard care for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer. However, the inevitably developed drug resistance in patients to EGFR TKIs is the biggest obstacle for cancer targeted therapy. About 60% of drug resistance to the 1st generation of EGFR TKIs was resulted from an acquired T790M mutation in the kinase domain of EGFR protein. Read More

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Rituximab hypersensitivity reactions and tolerance of ofatumumab therapy.

Clin Exp Rheumatol 2021 Mar 25. Epub 2021 Mar 25.

Department of Clinical Immunology and Allergy, Royal Adelaide Hospital, and Department of Immunology, SA Pathology, Adelaide, Australia.

B-cell depleting agents play a key role in a variety of disease entities. Rituximab, a murine-human chimeric anti-CD20 monoclonal antibody, as one of these major agents, has been associated with hypersensitivity reactions, which not only include the classic hypersensitivity ranging from immediate (type 1) to delayed (type IV), but also infusion-related reactions (IRRs). Whilst these typical hypersensitivity reactions occur in the setting of prior exposure, IRRs may occur in first exposure. Read More

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and functional characterization of human HLA-DRB1∗04 restricted T cell receptors.

J Transl Autoimmun 2021 3;4:100087. Epub 2021 Mar 3.

Division of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.

Recent advances in single-cell sequencing technologies enable the generation of large-scale data sets of paired TCR sequences from patients with autoimmune disease. Methods to validate and characterize patient-derived TCR data are needed, as well as relevant model systems that can support the development of antigen-specific tolerance inducing drugs. We have generated a pipeline to allow streamlined generation of 'artificial' T cells in a robust and reasonably high throughput manner for and studies of antigen-specific and patient-derived immune responses. Read More

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Anti-CD19 CARs displayed at the surface of lentiviral vector particles promote transduction of target-expressing cells.

Mol Ther Methods Clin Dev 2021 Jun 24;21:42-53. Epub 2021 Feb 24.

Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany.

Recently, a rare type of relapse was reported upon treating a B cell acute lymphoblastic leukemia (B-ALL) patient with anti-CD19 chimeric antigen receptor (CAR)-T cells caused by unintentional transduction of residual malignant B cells (CAR-B cells). We show that anti-CD19 and anti-CD20 CARs are presented on the surface of lentiviral vectors (LVs), inducing specific binding to the respective antigen. Binding of anti-CD19 CAR-encoding LVs containing supernatant was reduced by CD19-specific blocking antibodies in a dose-dependent manner, and binding was absent for unspecific LV containing supernatant. Read More

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T Cell Subsets During Early Life and Their Implication in the Treatment of Childhood Acute Lymphoblastic Leukemia.

Front Immunol 2021 4;12:582539. Epub 2021 Mar 4.

Division of Paediatric Oncology and Paediatric Surgery, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

The immune system plays a major role in recognizing and eliminating malignant cells, and this has been exploited in the development of immunotherapies aimed at either activating or reactivating the anti-tumor activity of a patient's immune system. A wide range of therapeutic approaches involving T lymphocytes, such as programmed cell death protein ligand-1 (PDL-1) inhibitors, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) blockers, and CD19-targeted T-cell therapy through chimeric antigen receptor (CAR)-T cells or CD19/CD3 bi-specific T-cell engagers, have been introduced to the field of oncology, leading to significant improvements in overall survival of adult cancer patients. During the past few years, the availability and approval of T-cell based immunotherapies have become a reality also for the treatment of childhood cancers. Read More

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Hematopoietic expression of a chimeric murine-human CALR oncoprotein allows the assessment of anti-CALR antibody immunotherapies in vivo.

Am J Hematol 2021 Mar 24. Epub 2021 Mar 24.

Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

Myeloproliferative neoplasms (MPNs) are characterised by a pathologic expansion of myeloid lineages. Mutations in JAK2, CALR and MPL genes are known to be three prominent MPN disease drivers. Mutant CALR (mutCALR) is an oncoprotein that interacts with and activates the thrombopoietin receptor (MPL) and represents an attractive target for targeted therapy of CALR mutated MPN. Read More

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Fluorescent In Situ Hybridization Must be Preferred to pan-TRK Immunohistochemistry to Diagnose NTRK3-rearranged Gastrointestinal Stromal Tumors (GIST).

Appl Immunohistochem Mol Morphol 2021 Mar 22. Epub 2021 Mar 22.

Department of Pathology Cytogenetics Unit, Department of Genetics, CHRU Brest Registre des cancers digestifs du Finistère EA7479 SPURBO, Université de Bretagne Occidentale Ouest Pathologie Univ Brest, Inserm, CHU de Brest, LBAI, Brest Departement of Pathology, CHU Rennes Ouest Pathologie, Rennes Ouest Pathologie, Quimper, France.

Tyrosine kinase inhibitors have revolutionized the treatment of patients with gastrointestinal stromal tumors (GISTs). Nevertheless, some GISTs do not contain any targetable KIT or PDGFRA mutations classically encountered in this field. Novel approved therapies targeting TRK chimeric proteins products of NTRK genes fusions consist in a promising approach to treat some patients with GISTs lacking any identified driver oncogenic mutation in KIT, PDGFRA or BRAF genes. Read More

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Fusion transcript discovery using RNA sequencing in formalin-fixed paraffin-embedded specimen.

Crit Rev Oncol Hematol 2021 Mar 20;160:103303. Epub 2021 Mar 20.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Cancer Genetics Research Unit, Reza Radiotherapy and Oncology Center, Mashhad, Iran. Electronic address:

Chimeric transcripts are critical for diagnosis or prognosis and could constitute effective therapeutic targets. Fresh tissues are the major source for the identification of these fusion transcripts. The quality and quantity of the extracted RNA directly affect fusion transcript discovery. Read More

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Multi-headed loop chimera states in coupled oscillators.

Chaos 2021 Jan;31(1):013135

Division of Dynamics, Lodz University of Technology, Stefanowskiego 1/15, 90-924 Lodz, Poland.

In this paper, we introduce a novel type of chimera state, characterized by the geometrical distortion of the coherent ring topology of coupled oscillators. The multi-headed loop chimeras are examined for a simple network of locally coupled pendulum clocks, suspended on the vertical platform. We determine the regions of the occurrence of the observed patterns, their structure, and possible co-existence. Read More

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January 2021