scholarly journals USP18 is differentially expressed in SARS and MERS coronavirus infection models.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Mouse Models ◽  
Microarray Data ◽  
Middle Eastern ◽  
Experimental Models ◽  
Differentially Expressed ◽  
Infection Models ◽  
Coronavirus Infection

COVID19 is caused by infection with the seventh virus of the coronavirus family capable of infecting humans, now known as Severe Acute Respiratory Syndrome 2, or SARS-CoV-2 (1-3). We mined published and public microarray data from coronavirus infection models to identify genes whose expression changed most significantly following infection with coronaviruses (4-9). In two in vivo mouse models of SARS coronavirus infection, the deubiquitinase USP18 was among the genes whose expression changed most significantly in the lungs of mice infected with SARS-CoV. In the blood of ferrets after intranasal infection with SARS-CoV-1, and in human cells in vitro after infection with the Middle Eastern Respiratory Syndrome (MERS) Usp18 was also found to be differentially expressed when compared to mock-infected tissues or uninfected cells. Differential expression of Usp18 following infection with coronaviruses can be observed in experimental models in vivo and in vitro, and across species.

scholarly journals The MAX dimerization protein MXD1 is differentially expressed and transcriptionally induced in multiple models of coronavirus infection.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Cellular Response ◽  
Differentially Expressed ◽  
Human Coronavirus ◽  
Lack Of Information ◽  
Infection Models ◽  
Mammalian Tissues ◽  
Coronavirus Infection ◽  
Human Coronavirus 229E

The coronavirus COVID19 pandemic is an emerging biosafety threat to the nation and the world (1). There are no treatments approved for coronavirus infection in humans (2) and there is a lack of information available regarding the basic transcriptional behavior of human cells and mammalian tissues following coronavirus infection. We mined independent public (3) and published (4, 5) datasets, containing transcriptome data from infection models of the human coronavirus 229E, severe acute respiratory syndrome (SARS) coronavirus and Middle East (MERS) coronavirus to discover genes that are differentially expressed in coronaviruses and identify potential therapeutic targets and host cell vulnerabilities. We identified MXD1 as differentially expressed genes following coronavirus infection in vivo and in vitro, conserved across HCoV, MERS-CoV, and SARS-CoV. MXD1 may be involved in the cellular response to COVID19 infection.

scholarly journals Experimental Models for Studying HPV-Positive and HPV-Negative Penile Cancer: New Tools for An Old Disease

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 460
Author(s):  
Beatriz Medeiros-Fonseca ◽  
Antonio Cubilla ◽  
Haissa Brito ◽  
Tânia Martins ◽  
Rui Medeiros ◽  
...  
Keyword(s):  
Mouse Models ◽  
Cell Lines ◽  
Penile Cancer ◽  
Hpv Infection ◽  
Experimental Models ◽  
In Vivo Models ◽  
Recent Developments ◽  
Key Aspects

Penile cancer is an uncommon malignancy that occurs most frequently in developing countries. Two pathways for penile carcinogenesis are currently recognized: one driven by human papillomavirus (HPV) infection and another HPV-independent route, associated with chronic inflammation. Progress on the clinical management of this disease has been slow, partly due to the lack of preclinical models for translational research. However, exciting recent developments are changing this landscape, with new in vitro and in vivo models becoming available. These include mouse models for HPV+ and HPV− penile cancer and multiple cell lines representing HPV− lesions. The present review addresses these new advances, summarizing available models, comparing their characteristics and potential uses and discussing areas that require further improvement. Recent breakthroughs achieved using these models are also discussed, particularly those developments pertaining to HPV-driven cancer. Two key aspects that still require improvement are the establishment of cell lines that can represent HPV+ penile carcinomas and the development of mouse models to study metastatic disease. Overall, the growing array of in vitro and in vivo models for penile cancer provides new and useful tools for researchers in the field and is expected to accelerate pre-clinical research on this disease.

scholarly journals IFI44 is differentially expressed in models of coronavirus infection in vivo.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Host Cell ◽  
Cellular Response ◽  
Distress Syndrome ◽  
Differentially Expressed Gene ◽  
Differentially Expressed ◽  
Lack Of Information ◽  
Infection Models ◽  
Mammalian Tissues ◽  
Coronavirus Infection

The coronavirus COVID19 pandemic is an emerging biosafety threat to the nation and the world (1). There are no treatments approved for coronavirus infection in humans (2) and there is a lack of information available regarding the basic transcriptional behavior of human cells and mammalian tissues following coronavirus infection. We mined two independent published datasets (3-4), containing transcriptome data from infection models of the severe acute respiratory distress syndrome SARS coronavirus in mice and in ferrets to discover genes that are differentially expressed in coronaviruses in vivo and identify potential therapeutic targets and host cell vulnerabilities. We identified IFI44 as a conserved differentially expressed gene following coronavirus infection in the blood of infected ferrets and in the lungs of infected mice. IFI44 may be involved in the cellular response to COVID19 infection or a host cell vulnerability, exploited by coronaviruses.

scholarly journals ELK3 is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Experimental Models ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Invasion And Migration ◽  
And Migration

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the ETS family transcription factor ELK3 was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at lower levels in the tumors of patients treated with trastuzumab. Thus, the use of trastuzumab in patients with breast cancer is associated with increased expression of a molecule that can promote the invasion and migration of breast cancer cells in vitro, support metastasis of breast cancer in experimental models in vivo, and specify the definitive neural crest (5-8).

scholarly journals Human Norovirus: Experimental Models of Infection

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 151 ◽  
Author(s):  
Kyle Todd ◽  
Ralph Tripp
Keyword(s):  
Animal Models ◽  
Experimental Models ◽  
Reverse Genetic ◽  
Infection Models ◽  
Human Volunteers ◽  
Genetic Systems ◽  
Therapeutic Development ◽  
Insight Into

Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis worldwide. HuNoV infections lead to substantial societal and economic burdens. There are currently no licensed vaccines or therapeutics for the prevention or treatment of HuNoVs. A lack of well-characterized in vitro and in vivo infection models has limited the development of HuNoV countermeasures. Experimental infection of human volunteers and the use of related viruses such as murine NoV have provided helpful insights into HuNoV biology and vaccine and therapeutic development. There remains a need for robust animal models and reverse genetic systems to further HuNoV research. This review summarizes available HuNoV animal models and reverse genetic systems, while providing insight into their usefulness for vaccine and therapeutic development.

scholarly journals Induction of methyl-CpG-binding domain proteins in coronavirus infection.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Microarray Data ◽  
Binding Proteins ◽  
Significant Differential Expression ◽  
Coronavirus Infection ◽  
Human Coronaviruses ◽  
Vitro Analysis ◽  
Transcriptional Induction ◽  
In Vitro Analysis

Coronavirus SARS-CoV-2 (“COVID-19”) has infected close to 20,000,000 people worldwide (1, 2). We mined published and public microarray data (3-8) to determine in an unbiased fashion genes most transcriptionally perturbed in the host following coronavirus infection with a series of human coronaviruses, including SARS-CoV-1, MERS-CoV and HCoV-229E. We observed significant transcriptional induction of the methyl-CpG-binding proteins MBD5 and MeCP2 following infection with two genetically distinct MERS-CoV isolates in human cells in vitro. Analysis of independent microarray data revealed less significant differential expression of MBD5 and MeCP2 in the lungs of mice following infection with SARS-CoV-1 in vivo. Epigenetic mechanisms involving methyl-CpG-binding proteins may be important to establishment of coronavirus infection in the human host.

Neutralization of a Low Molecular Weight Heparin (LHN-1) and Conventional Heparin by Protamine Sulfate in Rats

1986 ◽  
Vol 56 (03) ◽  
pp. 318-322 ◽  
Author(s):  
V Diness ◽  
P B Østergaard
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Thrombus Formation ◽  
Experimental Models ◽  
Protamine Sulfate ◽  
Low Molecular Weight ◽  
Antithrombotic Effect ◽  
Higher Doses

SummaryThe neutralization of a low molecular weight heparin (LHN-1) and conventional heparin (CH) by protamine sulfate has been studied in vitro and in vivo. In vitro, the APTT activity of CH was completely neutralized in parallel with the anti-Xa activity. The APTT activity of LHN-1 was almost completely neutralized in a way similar to the APTT activity of CH, whereas the anti-Xa activity of LHN-1 was only partially neutralized.In vivo, CH 3 mg/kg and LHN-1 7.2 mg/kg was given intravenously in rats. The APTT and anti-Xa activities, after neutralization by protamine sulfate in vivo, were similar to the results in vitro. In CH treated rats no haemorrhagic effect in the rat tail bleeding test and no antithrombotic effect in the rat stasis model was found at a protamine sulfate to heparin ratio of about 1, which neutralized APTT and anti-Xa activities. In LHN-1 treated rats the haemorrhagic effect was neutralized when APTT was close to normal whereas higher doses of protamine sulfate were required for neutralization of the antithrombotic effect. This probably reflects the fact that in most experimental models higher doses of heparin are needed to induce bleeding than to prevent thrombus formation. Our results demonstrate that even if complete neutralization of APTT and anti-Xa activities were not seen in LHN-1 treated rats, the in vivo effects of LHN-1 could be neutralized as efficiently as those of conventional heparin. The large fall in blood pressure caused by high doses of protamine sulfate alone was prevented by the prior injection of LHN-1.

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez
Keyword(s):  
Pulmonary Tuberculosis ◽  
Antimicrobial Peptides ◽  
Experimental Models ◽  
New Drugs ◽  
World Health ◽  
Public Health Issue ◽  
Health Organization ◽  
Drug Resistant Strains

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

627 The DLL3-targeted half-life extended bispecific T cell engager (HLE BiTE®) immune-oncology therapy AMG 757 has potent antitumor activity in neuroendocrine cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A663-A663
Author(s):  
Keegan Cooke ◽  
Juan Estrada ◽  
Jinghui Zhan ◽  
Jonathan Werner ◽  
Fei Lee ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Mouse Models ◽  
T Cell Activation ◽  
Phase 1 ◽  
Phase 1 Study ◽  
Human T Cells

BackgroundNeuroendocrine tumors (NET), including small cell lung cancer (SCLC), have poor prognosis and limited therapeutic options. AMG 757 is an HLE BiTE® immune therapy designed to redirect T cell cytotoxicity to NET cells by binding to Delta-like ligand 3 (DLL3) expressed on the tumor cell surface and CD3 on T cells.MethodsWe evaluated activity of AMG 757 in NET cells in vitro and in mouse models of neuroendocrine cancer in vivo. In vitro, co-cultures of NET cells and human T cells were treated with AMG 757 in a concentration range and T cell activation, cytokine production, and tumor cell killing were assessed. In vivo, AMG 757 antitumor efficacy was evaluated in xenograft NET and in orthotopic models designed to mimic primary and metastatic SCLC lesions. NSG mice bearing established NET were administered human T cells and then treated once weekly with AMG 757 or control HLE BiTE molecule; tumor growth inhibition was assessed. Pharmacodynamic effects of AMG 757 in tumors were also evaluated in SCLC models following a single administration of human T cells and AMG 757 or control HLE BiTE molecule.ResultsAMG 757 induced T cell activation, cytokine production, and potent T cell redirected killing of DLL3-expressing SCLC, neuroendocrine prostate cancer, and other DLL3-expressing NET cell lines in vitro. AMG 757-mediated redirected lysis was specific for DLL3-expressing cells. In patient-derived xenograft and orthotopic models of SCLC, single-dose AMG 757 effectively engaged human T cells administered systemically, leading to a significant increase in the number of human CD4+ and CD8+ T cells in primary and metastatic tumor lesions. Weekly administration of AMG 757 induced significant tumor growth inhibition of SCLC (figure 1) and other NET, including complete regression of established tumors and clearance of metastatic lesions. These findings warranted evaluation of AMG 757 (NCT03319940); the phase 1 study includes dose exploration (monotherapy and in combination with pembrolizumab) and dose expansion (monotherapy) in patients with SCLC (figure 2). A study of AMG 757 in patients with neuroendocrine prostate cancer is under development based on emerging data from the ongoing phase 1 study.Abstract 627 Figure 1AMG 757 Significantly reduced tumor growth in orthotopic SCLC mouse modelsAbstract 627 Figure 2AMG 757 Phase 1 study designConclusionsAMG 757 engages and activates T cells to kill DLL3-expressing SCLC and other NET cells in vitro and induces significant antitumor activity against established xenograft tumors in mouse models. These preclinical data support evaluation of AMG 757 in clinical studies of patients with NET.Ethics ApprovalAll in vivo work was conducted under IACUC-approved protocol #2009-00046.

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