54,126 results match your criteria preclinical models


The road (not) taken - Placental transfer and interspecies differences.

Placenta 2021 Sep 22;115:70-77. Epub 2021 Sep 22.

Placenta Lab, Department of Obstetrics, University Hospital Jena, Am Klinikum 1, 07747, Jena, Germany.

Species differences are among the main reasons for the high failure rate of preclinical studies. A better awareness and understanding of these differences might help to improve the outcome of preclinical research. In reproduction, the placenta is the central organ regulating fetal exposure to a substance circulating in the maternal organism. Read More

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September 2021

Amplifying the antidiabetic actions of GLP-1: potential benefits of new adjunct therapies.

Diabet Med 2021 Sep 25:e14699. Epub 2021 Sep 25.

Diabetes Research Group, School of Biomedical Sciences, Ulster University, Coleraine, Co, Londonderry, BT52 1SA, Northern Ireland, UK.

Clinically approved for the treatment of diabetes and obesity, glucagon-like peptide-1 (GLP-1) receptor agonists display prominent glucose- and weight-lowering effects as well as positive cardio- and neuro-protective actions. Despite these benefits, bariatric surgery remains superior in producing robust and sustained weight loss alongside improvements in metabolic control with possible diabetes remission. The current review considers the potential for adjunct therapies to augment the therapeutic actions of GLP-1 receptor agonists. Read More

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September 2021

A Method for Orthotopic Transplantation of Lung Cancer in Mice.

Methods Mol Biol 2022 ;2374:231-242

Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research and Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Preclinical mouse models of lung cancer have been vital experimental tools to elucidate cancer biology and test novel therapeutic regimens. Two main models are most commonly used-genetically engineered mouse models and xenograft transplantation models. The most common xenograft model employs subcutaneous transplantation of tumor cells. Read More

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January 2022

Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study.

Invest New Drugs 2021 Sep 25. Epub 2021 Sep 25.

Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Carboplatin and paclitaxel (CT) is one of the standard chemotherapy regimens used in various tumor types. Preclinical models have suggested that selinexor, a first-in-class oral potent selective inhibitor of nuclear export Exportin-1, and CT exerts antitumor activity in multiple malignancies.

Methods: This was a single-center, multi-arm phase Ib study utilizing a "basket type" expansion. Read More

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September 2021

The Potential Role of Dexmedetomidine on Neuroprotection and its Possible Mechanisms: Evidence from In Vitro and In Vivo Studies.

Eur J Neurosci 2021 Sep 24. Epub 2021 Sep 24.

Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

Neurological disorders following brain injuries and neurodegeneration are on the rise worldwide, and cause disability and suffering in patients. It is crucial to explore novel neuroprotectants. Dexmedetomidine, a selective α2-adrenoceptor agonist, is commonly used for anxiolysis, sedation, and analgesia in clinical anesthesia and critical care. Read More

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September 2021

Pharmacologic treatments in preclinical tinnitus models with special focus on Ginkgo biloba leaf extract EGb 761®.

Mol Cell Neurosci 2021 Sep 21:103669. Epub 2021 Sep 21.

Experimental Otolaryngology, ENT-Hospital, Head and Neck Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany. Electronic address:

Tinnitus is defined as the perception of sound in the absence of external acoustic stimuli. Frequent comorbidities or associated factors are depression, anxiety, concentration problems, insomnia, resignation, helplessness, headache, bruxism, or social isolation, just to name a few. Although many therapeutic approaches have already been tested with varying success, there still is no cure available for tinnitus. Read More

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September 2021

Clinical and therapeutic significance of genetic variation in the GRIN gene family encoding NMDARs.

Neuropharmacology 2021 Sep 21:108805. Epub 2021 Sep 21.

Institute of Human Genetics, Leipzig Medical Center, Leipzig, Germany.

Considerable genetic variation of N-methyl-d-aspartate receptors (NMDARs) has recently become apparent, with many hundreds of de novo variants identified through widely available clinical genetic testing. Individuals with GRIN variants present with neurological conditions such as epilepsy, autism, intellectual disability (ID), movement disorders, schizophrenia and behavioral disorders. Determination of the functional consequence of genetic variation for NMDARs should lead to precision therapeutics. Read More

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September 2021

Loss of cancer cell STAT1 improves response to radiation therapy and promotes T cell activation in head and neck squamous cell carcinoma.

Cancer Immunol Immunother 2021 Sep 24. Epub 2021 Sep 24.

Department of Radiation Oncology, University of Colorado, Anschutz Medical Campus, 1665 Aurora Court Suite 1032, Aurora, Colorado, 80045, USA.

Resistance to radiation therapy (RT) remains an obstacle in HPV-negative head and neck squamous cell carcinomas (HNSCCs)-even with a combined RT-immunotherapy approach. Jak-Stat proteins have long been studied for both their immune regulatory role in the host immune response as well as their cancer cell signaling role in shaping the tumor microenvironment (TME). Here, we identify STAT1 as a mediator of radioresistance in HPV-negative preclinical mouse models of HNSCC, by which knockout of STAT1 in the cancer cell (STAT1 KO)-but not in the host-resulted in decreased tumor growth alongside increased immune activation. Read More

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September 2021

Effect of the Histone Deacetylase Inhibitor FRM-0334 on Progranulin Levels in Patients With Progranulin Gene Haploinsufficiency: A Randomized Clinical Trial.

JAMA Netw Open 2021 Sep 1;4(9):e2125584. Epub 2021 Sep 1.

FORUM Pharmaceuticals Incorporated, Waltham, Massachusetts.

Importance: Histone deacetylase inhibitors have been repeatedly shown to elevate progranulin levels in preclinical models. This report describes the first randomized clinical trial of a histone deacetylase inhibitor in frontotemporal dementia (FTD) resulting from progranulin (GRN) gene variations.

Objective: To characterize the safety, tolerability, plasma pharmacokinetics, and pharmacodynamic effects of oral FRM-0334 on plasma progranulin and other exploratory biomarkers, including fluorodeoxyglucose (FDG)-positron emission tomography (PET), in individuals with GRN haploinsufficiency. Read More

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September 2021

Preliminary examination of early neuroconnectivity features in the R6/1 mouse model of Huntington's disease by ultra-high field diffusion MRI.

Neural Regen Res 2022 May;17(5):983-986

Instituto de Fisiología Biología Molecular y Neurociencias-IFIBYNE-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.

During the last decades, advances in the understanding of genetic, cellular, and microstructural alterations associated to Huntington's disease (HD) have improved the understanding of this progressive and fatal illness. However, events related to early neuropathological events, neuroinflammation, deterioration of neuronal connectivity and compensatory mechanisms still remain vastly unknown. Ultra-high field diffusion MRI (UHFD-MRI) techniques can contribute to a more comprehensive analysis of the early microstructural changes observed in HD. Read More

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Bone Morphogenetic Protein-2 Rapidly Heals Two Distinct Critical Sized Segmental Diaphyseal Bone Defects in a Porcine Model.

Mil Med 2021 Sep 24. Epub 2021 Sep 24.

Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Introduction: Segmental bone defects (SBDs) are devastating injuries sustained by warfighters and are difficult to heal. Preclinical models that accurately simulate human conditions are necessary to investigate therapies to treat SBDs. We have developed two novel porcine SBD models that take advantage of similarities in bone healing and immunologic response to injury between pigs and humans. Read More

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September 2021

Fecal Microbiota Transplantation as a Tool for Therapeutic Modulation of Non-gastrointestinal Disorders.

Front Med (Lausanne) 2021 7;8:665520. Epub 2021 Sep 7.

Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.

Fecal microbiota transplantation has been primarily investigated as a therapeutic tool for a number of gut disorders. Optimistic results from clinical studies on Clostridium difficile infection, inflammatory bowel disease and irritable bowel syndrome have stimulated the expansion of possible indications in which FMT might represent a game changing approach. Microbial dysbiosis was shown in a number of non-gastrointestinal disorders. Read More

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September 2021

Literature Mining and Mechanistic Graphical Modelling to Improve mRNA Vaccine Platforms.

Front Immunol 2021 7;12:738388. Epub 2021 Sep 7.

Data Science and Computational Vaccinology, GSK, Siena, Italy.

RNA vaccines represent a milestone in the history of vaccinology. They provide several advantages over more traditional approaches to vaccine development, showing strong immunogenicity and an overall favorable safety profile. While preclinical testing has provided some key insights on how RNA vaccines interact with the innate immune system, their mechanism of action appears to be fragmented amid the literature, making it difficult to formulate new hypotheses to be tested in clinical settings and ultimately improve this technology platform. Read More

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September 2021

Synthetic SARS-CoV-2 Spike-Based DNA Vaccine Elicits Robust and Long-Lasting Th1 Humoral and Cellular Immunity in Mice.

Front Microbiol 2021 7;12:727455. Epub 2021 Sep 7.

Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) calls for an urgent development of effective and safe prophylactic and therapeutic measures. The spike (S) glycoprotein of severe acute respiratory syndrome-coronavirus (SARS-CoV-2) is a major immunogenic and protective protein and plays a crucial role in viral pathogenesis. In this study, we successfully constructed a synthetic codon-optimized DNA-based vaccine as a countermeasure against SARS-CoV-2, denoted VIU-1005. Read More

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September 2021

Individual Differences in Different Measures of Opioid Self-Administration in Rats Are Accounted for by a Single Latent Variable.

Front Psychiatry 2021 7;12:712163. Epub 2021 Sep 7.

Hennepin Healthcare Research Institute, Minneapolis, MN, United States.

Individual differences in vulnerability to addiction have been widely studied through factor analysis (FA) in humans, a statistical method that identifies "latent" variables (variables that are not measured directly) that reflect the common variance among a larger number of observed measures. Despite its widespread application in behavioral genetics, FA has not been used in preclinical opioid addiction research. The current study used FA to examine the latent factor structure of four measures of i. Read More

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September 2021

Characterizing the Retinal Phenotype of the Thy1-h[A30P]α-syn Mouse Model of Parkinson's Disease.

Front Neurosci 2021 7;15:726476. Epub 2021 Sep 7.

Research Group of Neural Circuit Development and Regeneration, Department of Biology, KU Leuven, Leuven, Belgium.

Despite decades of research, disease-modifying treatments of Parkinson's disease (PD), the second most common neurodegenerative disease worldwide, remain out of reach. One of the reasons for this treatment gap is the incomplete understanding of how misfolded alpha-synuclein (α-syn) contributes to PD pathology. The retina, as an integral part of the central nervous system, recapitulates the PD disease processes that are typically seen in the brain, and retinal manifestations have emerged as prodromal symptoms of the disease. Read More

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September 2021

Surface-fill hydrogel attenuates the oncogenic signature of complex anatomical surface cancer in a single application.

Nat Nanotechnol 2021 Sep 23. Epub 2021 Sep 23.

Chemical Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.

Tumours growing in a sheet-like manner on the surface of organs and tissues with complex topologies represent a difficult-to-treat clinical scenario. Their complete surgical resection is difficult due to the complicated anatomy of the diseased tissue. Residual cancer often responds poorly to systemic therapy and locoregional treatment is hindered by the limited accessibility to microscopic tumour foci. Read More

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September 2021

3D-bioprinted cancer-on-a-chip: level-up organotypic in vitro models.

Trends Biotechnol 2021 Sep 20. Epub 2021 Sep 20.

Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal. Electronic address:

Combinatorial conjugation of organ-on-a-chip platforms with additive manufacturing technologies is rapidly emerging as a disruptive approach for upgrading cancer-on-a-chip systems towards anatomic-sized dynamic in vitro models. This valuable technological synergy has potential for giving rise to truly physiomimetic 3D models that better emulate tumor microenvironment elements, bioarchitecture, and response to multidimensional flow dynamics. Herein, we showcase the most recent advances in bioengineering 3D-bioprinted cancer-on-a-chip platforms and provide a comprehensive discussion on design guidelines and possibilities for high-throughput analysis. Read More

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September 2021

A novel 3D culture model recapitulates primary FL B cell features and promotes their survival.

Blood Adv 2021 Sep 23. Epub 2021 Sep 23.

INSERM U1053, Bordeaux, France.

Non-Hodgkin B-cell lymphomas (B-NHL) mainly develop within lymph nodes (LN) as densely packed aggregates of tumor cells and their surrounding microenvironment, creating a tumor niche specific to each lymphoma subtypes. In vitro preclinical models mimicking biomechanical forces, cellular microenvironment, and 3D organization of B-cell lymphomas remain scarce, while all these parameters constitute key determinants of lymphomagenesis and drug resistance. Using a microfluidic method based on cell encapsulation inside permeable, elastic, and hollow alginate microspheres, we developed a new tunable 3D-model incorporating lymphoma B cells, extracellular matrix (ECM), and/or tonsil stromal cells (TSC). Read More

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September 2021

From antibodies to living drugs: Quo vadis cancer immunotherapy?

Biol Futur 2021 Mar 1;72(1):85-99. Epub 2021 Feb 1.

Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Egyetem tér 1., 4032, Debrecen, Hungary.

In the last few decades, monoclonal antibodies targeting various receptors and ligands have shown significant advance in cancer therapy. However, still a great percentage of patients experiences tumor relapse despite persistent antigen expression. Immune cell therapy with adoptively transferred modified T cells that express chimeric antigen receptors (CAR) is an engaging option to improve disease outcome. Read More

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Adaptation of laser interstitial thermal therapy for tumor ablation under MRI monitoring in a rat orthotopic model of glioblastoma.

Acta Neurochir (Wien) 2021 Sep 23. Epub 2021 Sep 23.

Department of Neurosurgery, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI, 48202-2689, USA.

Background: Laser interstitial thermal therapy (LITT) under magnetic resonance imaging (MRI) monitoring is being increasingly used in cytoreductive surgery of recurrent brain tumors and tumors located in eloquent brain areas. The objective of this study was to adapt this technique to an animal glioma model.

Methods: A rat model of U251 glioblastoma (GBM) was employed. Read More

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September 2021

JNJ-67569762, A 2-Aminotetrahydropyridine-Based Selective BACE1 Inhibitor Targeting the S3 Pocket: From Discovery to Clinical Candidate.

J Med Chem 2021 Sep 23. Epub 2021 Sep 23.

Janssen Research & Development, Janssen Pharmaceutica N. V., Turnhoutseweg 30, Beerse B-2340, Belgium.

The discovery of a novel 2-aminotetrahydropyridine class of BACE1 inhibitors is described. Their pK and lipophilicity were modulated by a pending sulfonyl group, while good permeability and brain penetration were achieved via intramolecular hydrogen bonding. BACE1 selectivity over BACE2 was achieved in the S3 pocket by a novel bicyclic ring system. Read More

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September 2021

Developmental programming by maternal obesity: lessons from animal models.

Diabet Med 2021 Sep 23:e14694. Epub 2021 Sep 23.

Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, CB2 OQQ, United Kingdom.

The obesity epidemic has led to more women entering pregnancy overweight or obese. In addition to adverse short-term outcomes, maternal obesity and/or gestational diabetes predisposes offspring to developing obesity, type 2 diabetes and cardiovascular disease in adulthood through developmental programming. Human epidemiological studies, although vital in identifying associations, are often unable to address causality and mechanistic studies can be limited by the lack of accessibility of key metabolic tissues. Read More

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September 2021

Treatment of glioblastoma with current oHSV variants reveals differences in efficacy and immune cell recruitment.

Mol Ther Oncolytics 2021 Sep 29;22:444-453. Epub 2021 Jul 29.

Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15219, USA.

Oncolytic herpes simplex viruses (oHSVs) have demonstrated efficient lytic replication in human glioblastoma tumors using immunodeficient mouse models, but early-phase clinical trials have reported few complete responses. Potential reasons for the lack of efficacy are limited vector potency and the suppressive glioma tumor microenvironment (TME). Here we compare the oncolytic activity of two HSV-1 vectors, a KOS-strain derivative KG4:T124 and an F-strain derivative rQNestin34. Read More

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September 2021

Gut microbiome depletion and repetitive mild traumatic brain injury differentially modify bone development in male and female adolescent rats.

Bone Rep 2021 Dec 8;15:101123. Epub 2021 Sep 8.

Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.

Dysregulation of the gut microbiome has been shown to disrupt both bone formation and bone resorption in several preclinical and clinical models. However, the role of microbiome in adolescent bone development remains poorly understood. This effect of disrupted bone development may be more pronounced during adolescence, when bone development is vulnerable to environmental stimuli and external insults (e. Read More

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December 2021

LC-MS/MS Estimation of Rociletinib Levels in Human Liver Microsomes: Application to Metabolic Stability Estimation.

Drug Des Devel Ther 2021 15;15:3915-3925. Epub 2021 Sep 15.

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Background: Rociletinib (CO-1686; RLC) is a new, small molecule that is orally administered to inhibit mutant-selective covalent inhibitor of most epidermal growth factor receptor (EGFR)-mutated forms, including T790M, L858R, and exon 19 deletions, but not exon 20 insertions. Non-small-cell lung cancer (NSCLC) with a gene mutation that encodes EGFR is sensitive to approved EGFR inhibitors, but usually resistance develops, which is frequently mediated by T790M EGFR mutation. RLC is an EGFR inhibitor found to be active in preclinical models of EGFR-mutated NSCLC with or without T790M. Read More

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September 2021

Biologically informed deep neural network for prostate cancer discovery.

Nature 2021 Sep 22. Epub 2021 Sep 22.

Dana-Farber Cancer Institute, Boston, MA, USA.

The determination of molecular features that mediate clinically aggressive phenotypes in prostate cancer remains a major biological and clinical challenge. Recent advances in interpretability of machine learning models as applied to biomedical problems may enable discovery and prediction in clinical cancer genomics. Here we developed P-NET-a biologically informed deep learning model-to stratify patients with prostate cancer by treatment-resistance state and evaluate molecular drivers of treatment resistance for therapeutic targeting through complete model interpretability. Read More

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September 2021

Fecal filtrate transplantation protects against necrotizing enterocolitis.

ISME J 2021 Sep 22. Epub 2021 Sep 22.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disorder afflicting preterm infants, which is currently unpreventable. Fecal microbiota transplantation (FMT) is a promising preventive therapy, but the transfer of pathogenic microbes or toxic compounds raise concern. Removal of bacteria from donor feces by micropore filtering may reduce this risk of bacterial infection, while residual bacteriophages could maintain the NEC-preventive effects. Read More

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September 2021

Antitumor activity of the novel BTK inhibitor TG-1701 is associated with disruption of Ikaros signaling in patients with B-cell non-Hodgkin lymphoma.

Clin Cancer Res 2021 Sep 22. Epub 2021 Sep 22.

Lymphoma Translational group, Josep Carreras Leukaemia Research Institute

Purpose: Despite the remarkable activity of BTK inhibitors (BTKi) in relapsed B-cell non-Hodgkin lymphoma (B-NHL), no clinically-relevant biomarker has been associated to these agents so far. The relevance of phosphoproteomic profiling for the early identification of BTKi responders remains underexplored.

Experimental Design: A set of six clinical samples from an ongoing phase 1 trial dosing chronic lymphocytic leukemia (CLL) patients with TG-1701, a novel irreversible and highly specific BTKi, were characterized by phosphoproteomic and RNA-seq analysis. Read More

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September 2021

ImmunoPET: harnessing antibodies for imaging immune cells.

Mol Imaging Biol 2021 Sep 22. Epub 2021 Sep 22.

Molecular Imaging &Therapy Svc, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Dramatic, but uneven, progress in the development of immunotherapies for cancer has created a need for better diagnostic technologies including innovative non-invasive imaging approaches. This review discusses challenges and opportunities for molecular imaging in immuno-oncology and focuses on the unique role that antibodies can fill. ImmunoPET has been implemented for detection of immune cell subsets, activation and inhibitory biomarkers, tracking adoptively transferred cellular therapeutics, and many additional applications in preclinical models. Read More

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September 2021