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The Dhodh Inhibitor Ptc299 Arrests Sars-Cov-2 Replication And Suppresses Induction Of Inflammatory Cytokines, Jeremy Luban, Caterina Strambio De Castilla, Yetao Wang, Allan Jacobson, Stuart Peltz 2020 University of Massachusetts Medical School

The Dhodh Inhibitor Ptc299 Arrests Sars-Cov-2 Replication And Suppresses Induction Of Inflammatory Cytokines, Jeremy Luban, Caterina Strambio De Castilla, Yetao Wang, Allan Jacobson, Stuart Peltz

University of Massachusetts Medical School Faculty Publications

The coronavirus disease 2019 (COVID-19) pandemic has created an urgent need for therapeutics that inhibit the SARS-CoV-2 virus and suppress the fulminant inflammation characteristic of advanced illness. Here, we describe the anti-COVID-19 potential of PTC299, an orally available compound that is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme of the de novo pyrimidine biosynthesis pathway. In tissue culture, PTC299 manifests robust, dose-dependent, and DHODH-dependent inhibition of SARS CoV-2 replication (EC50 range, 2.0 to 31.6 nM) with a selectivity index >3,800. PTC299 also blocked replication of other RNA viruses, including Ebola virus. Consistent with known ...


Convalescent Plasma Therapy In Coronavirus Disease 2019 (Covid-19) Patients: A Brief Review, Muhammad Arif Khan, Ikram Ullah 2020 The University of Haripur

Convalescent Plasma Therapy In Coronavirus Disease 2019 (Covid-19) Patients: A Brief Review, Muhammad Arif Khan, Ikram Ullah

The University of Louisville Journal of Respiratory Infections

The recent outbreak of the COVID-19 pandemic has reevaluated effectiveness of the convalescent plasma therapy (CPT). This review was carried out to assess the usefulness of CPT in critically COVID-19 patients, based on the published data to date. To the best of our knowledge, this is the second review of the usefulness of CPT in COVID-19 patients. PubMed, Google Scholar, Medline and EMBASE databases were searched for the relevant reports up to June 21, 2020. All the records of the published data were analyzed according to eligibility criteria protocols. Five different studies on CPT for COVID-19 critically ill patients were ...


Transgenic Goats Producing An Improved Version Of Cetuximab In Milk, Götz Laible, Sally Cole, Brigid Brophy, Paul Maclean, Li How Chen, Dan P. Pollock, Lisa A. Cavacini, Nathalie Fournier, Christophe De Romeuf, Nicholas C. Masiello, William G. Gavin, David N. Wells, Harry M. Meade 2020 University of Auckland

Transgenic Goats Producing An Improved Version Of Cetuximab In Milk, Götz Laible, Sally Cole, Brigid Brophy, Paul Maclean, Li How Chen, Dan P. Pollock, Lisa A. Cavacini, Nathalie Fournier, Christophe De Romeuf, Nicholas C. Masiello, William G. Gavin, David N. Wells, Harry M. Meade

University of Massachusetts Medical School Faculty Publications

Therapeutic monoclonal antibodies (mAbs) represent one of the most important classes of pharmaceutical proteins to treat human diseases. Most are produced in cultured mammalian cells which is expensive, limiting their availability. Goats, striking a good balance between a relatively short generation time and copious milk yield, present an alternative platform for the cost-effective, flexible, large-scale production of therapeutic mAbs. Here, we focused on cetuximab, a mAb against epidermal growth factor receptor, that is commercially produced under the brand name Erbitux and approved for anti-cancer treatments. We generated several transgenic goat lines that produce cetuximab in their milk. Two lines were ...


Mathematical Modeling Of The Car T-Cell Therapy, Emek Kose, Elizabeth Zollinger, Samantha Elliott 2020 St. Mary's College of Maryland

Mathematical Modeling Of The Car T-Cell Therapy, Emek Kose, Elizabeth Zollinger, Samantha Elliott

Biology and Medicine Through Mathematics Conference

No abstract provided.


147— The Effect Of A Histone Deacetylase Inhibitor On Pd-L1, Hla-Abc, Hla-E, And Hla-G On Human Breast Cancer Cell Lines, Nikhil Reddy, Alec Toufexis 2020 SUNY Geneseo

147— The Effect Of A Histone Deacetylase Inhibitor On Pd-L1, Hla-Abc, Hla-E, And Hla-G On Human Breast Cancer Cell Lines, Nikhil Reddy, Alec Toufexis

GREAT Day

Increased expression of human leukocyte antigen (HLA) allows tumor cells to be more easily detected by the immune system. In previous research, epigenetic modifiers including the histone deacetylase inhibitor 3 (HDAC3), RGFP966, has been shown to decrease PD-L1 expression. PD-L1 expression inhibits T cell cytotoxicity, and decreasing it can enhance the immune response. We hope to elucidate whether or not HLA-ABC expression similarly decreases upon exposure to the HDAC3 inhibitor which would be detrimental to immune detection. Two breast cancer cell lines that express HLA-ABC are MCF-7 and MDA-MB-231. Our initial results show that HLA-ABC is expressed on the MDA-MB-231 ...


Timely Development Of Vaccines Against Sars-Cov-2, Shan Lu 2020 University of Massachusetts Medical School

Timely Development Of Vaccines Against Sars-Cov-2, Shan Lu

COVID-19 Publications by UMMS Authors

The rapidly emerging SARS-2-CoV (SARS-2) has been spreading through China and entering many parts of the world with easy human-to-human transmission and thousands of deaths. Development of a vaccine, and a vaccine which can be quickly deployed on a global scale, is no longer merely a discussion or part of a debate whether such a vaccine is ultimately needed.


Diabetes Mellitus Type 2 Is Associated With Increased Tumor Expression Of Programmed Death-Ligand 1 (Pd-L1) In Surgically Resected Non-Small Cell Lung Cancer - A Matched Case-Control Study, Christopher A. Febres-Aldana, Robert Poppiti, John M. Varlotto, Rick Voland, Michael Zaleski, Setareh Sharzehi, Negar Rassaei 2020 Mount Sinai Medical Center

Diabetes Mellitus Type 2 Is Associated With Increased Tumor Expression Of Programmed Death-Ligand 1 (Pd-L1) In Surgically Resected Non-Small Cell Lung Cancer - A Matched Case-Control Study, Christopher A. Febres-Aldana, Robert Poppiti, John M. Varlotto, Rick Voland, Michael Zaleski, Setareh Sharzehi, Negar Rassaei

Open Access Articles

OBJECTIVES: Programmed death-ligand 1 (PD-L1) expression is a biomarker for cancer immunotherapy. Diabetes mellitus type-2 is a comorbid disease associated with adverse outcomes in Non-Small Cell Lung Cancer (NSCLC). We aimed to investigate the differences in PD-L1 expression in diabetics.

METHODS: A matched case-control cohort of surgically-resected NSCLC was assembled from an early multicenter study (PMID: 19152440). PD-L1 immunohistochemistry (Clone 22C3) was graded by a tumor positive score (TPS) system (TPS0: no staining; TPS1: < 1%; TPS2: 1-49%; TPS3: > /=50%). Variables showing significance at univariate survival analysis were fit in a Cox regression survival model.

RESULTS: Diabetics (n=40) and nondiabetics (n=39) showed no ...


The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine 2020 Virginia Commonwealth University

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute ...


Immunotherapy: Therapy Vs. Enhancement, Mariah Daly 2020 Rollins College

Immunotherapy: Therapy Vs. Enhancement, Mariah Daly

Honors Program Theses

The battle against cancer is a long-standing struggle that has resulted in new information and the development of novel medical technologies. Current research aims to figure out a way to reprogram cells and bodily mechanisms to eliminate those cells that are cancerous without destroying healthy cells in the process. Methods which use the body’s own mechanisms, such as immunotherapy, have shown and continue to show potential for specifically targeting cancer cells. Adoptive T cell therapy is one form of immunotherapy that has gained significant attention and focus in the field. Therapies improve conditions up to the normal state of ...


Identification Of Imiquimod As A Potential Combination For Anti-Cd47 Antibodies In Cancer Therapy, Nicole Brittaney Pang 2020 Scripps College

Identification Of Imiquimod As A Potential Combination For Anti-Cd47 Antibodies In Cancer Therapy, Nicole Brittaney Pang

Scripps Senior Theses

The avenues of targeted immunotherapy offers a promise of less toxic treatment options for those battling different forms of cancer. Specifically, the process of hijacking a patient’s own immune system to fight cancer from within versus using external treatments like chemotherapy which is extremely damaging to the patient. One such avenue includes the usage of monoclonal antibodies as an effective modality for immunotherapy. Cluster of Differentiation 47 (CD47), also known as the ‘don’t eat me signal’, aids in cell proliferation and evasion of phagocytosis and has been found to be a target for stopping tumorigenesis. Previous research has ...


Role Of Gonococcal Neisserial Surface Protein A (Nspa) In Serum Resistance And Comparison Of Its Factor H Binding Properties With Those Of Its Meningococcal Counterpart, Lisa A. Lewis, Peter A. Rice, Sanjay Ram 2019 University of Massachusetts Medical School

Role Of Gonococcal Neisserial Surface Protein A (Nspa) In Serum Resistance And Comparison Of Its Factor H Binding Properties With Those Of Its Meningococcal Counterpart, Lisa A. Lewis, Peter A. Rice, Sanjay Ram

Infectious Diseases and Immunology Publications

Neisseria gonorrhoeae, the causative agent of gonorrhea, has evolved several mechanisms to subvert complement, including binding of the complement inhibitor factor H (FH). We previously reported FH binding to N. gonorrhoeae independently of lipooligosaccharide (LOS) sialylation. Here we report that factor H-like protein 1 (FHL-1), which contains FH domains 1 through 7 and possesses complement-inhibitory activity, also binds to N. gonorrhoeae The ligand for both FH and FHL-1 was identified as neisserial surface protein A (NspA), which has previously been identified as a ligand for these molecules on Neisseria meningitidis As with N. meningitidis NspA (Nm-NspA), N. gonorrhoeae NspA (Ng-NspA ...


Probiotic Therapy - Recruiting Old Friends To Fight New Foes, Roy D. Sleator 2010 Alimentary Pharmabiotic Centre; University College Cork; Cork, Ireland; Department of Biological Sciences; Cork Institute of Technology; Cork, Ireland.

Probiotic Therapy - Recruiting Old Friends To Fight New Foes, Roy D. Sleator

Dept. of Biological Sciences Publications

Against a backdrop of increasing antibiotic resistance, and the emergence of new and evolving pathogens, clinicians are increasingly forced to consider alternative therapies - probiotics are one such alternative.


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