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Small Extracellular Vesicle-Mediated Itgb6 Sirna Delivery Downregulates The Αvβ6 Integrin And Inhibits Adhesion And Migration Of Recipient Prostate Cancer Cells, Shiv Ram Krishn, Vaughn Garcia, Nicole M Naranjo, Fabio Quaglia, Christopher D Shields, Maisha A Harris, Andrew V Kossenkov, Qin Liu, Eva Corey, Dario C Altieri, Lucia R Languino 2022 Thomas Jefferson University

Small Extracellular Vesicle-Mediated Itgb6 Sirna Delivery Downregulates The Αvβ6 Integrin And Inhibits Adhesion And Migration Of Recipient Prostate Cancer Cells, Shiv Ram Krishn, Vaughn Garcia, Nicole M Naranjo, Fabio Quaglia, Christopher D Shields, Maisha A Harris, Andrew V Kossenkov, Qin Liu, Eva Corey, Dario C Altieri, Lucia R Languino

Department of Cancer Biology Faculty Papers

The αVβ6 integrin, an epithelial-specific cell surface receptor absent in normal prostate and expressed during prostate cancer (PrCa) progression, is a therapeutic target in many cancers. Here, we report that transcript levels of ITGB6 (encoding the β6 integrin subunit) are significantly increased in metastatic castrate-resistant androgen receptor-negative prostate tumors compared to androgen receptor-positive prostate tumors. In addition, the αVβ6 integrin protein levels are significantly elevated in androgen receptor-negative PrCa patient derived xenografts (PDXs) compared to androgen receptor-positive PDXs. In vitro, the androgen receptor-negative PrCa cells express high levels of the αVβ6 integrin compared to androgen receptor-positive PrCa cells. Additionally, expression ...


Defining The Cooperation Between Mhc-I And Mhc-Ii Neoantigen-Driven T Cell Responses To Develop Effective Personalized Immunotherapies, Charmelle Williams 2022 The University of Texas MD Anderson Cancer Center

Defining The Cooperation Between Mhc-I And Mhc-Ii Neoantigen-Driven T Cell Responses To Develop Effective Personalized Immunotherapies, Charmelle Williams

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Immune checkpoint therapy (ICT) (e.g. anti-CTLA-4 (α-CTLA-4), anti-PD-1 (α-PD-1)) enables durable T cell-dependent anti-tumor immunity in certain cancer patients. Since a subset of patients respond to ICT, this work aims at developing a more in-depth understanding of T-cell responses to MHC class I (MHC-I) and MHC class II (MHC-II) tumor antigens that are derived from aberrant expression of non-mutant antigens or driver and passenger somatic alterations that can function as tumor neoantigens. We used a poorly immunogenic Brafv600e Pten-/- Cdkn2a-/- YUMM1.7 (Y1.7) murine melanoma line with a paucity of endogenous neoantigens that is unresponsive to ICT ...


Real-World Third Covid-19 Vaccine Dosing And Antibody Response In Patients With Hematologic Malignancies, Michael A. Thompson, Sigrun Hallmeyer, Veronica E. Fitzpatrick, Yunqi Liao, Michael P. Mullane, Stephen C. Medlin, Kenneth Copeland, James L. Weese 2022 Aurora Cancer Care, Advocate Aurora Health

Real-World Third Covid-19 Vaccine Dosing And Antibody Response In Patients With Hematologic Malignancies, Michael A. Thompson, Sigrun Hallmeyer, Veronica E. Fitzpatrick, Yunqi Liao, Michael P. Mullane, Stephen C. Medlin, Kenneth Copeland, James L. Weese

Journal of Patient-Centered Research and Reviews

Purpose: This study sought to describe the changes in immune response to a third dose of either Pfizer’s or Moderna’s COVID-19 mRNA vaccine (3V) among patients with hematologic malignancies, as well as associated characteristics

Methods: This retrospective cohort study analyzed pre-3V and post-3V data on 493 patients diagnosed with hematologic malignancies across a large Midwestern health system between August 28, 2021, and November 1, 2021. For antibody testing, S1 spike antigen of the SARS-CoV-2 virus titer was used to determine serostatus.

Results: Among 493 participants, 274 (55.6%) were seropositive both pre- and post-3V (+/+) while 115 (23.3 ...


B- And T-Cell Subset Abnormalities In Monogenic Common Variable Immunodeficiency, Saba Fekrvand, Shaghayegh Khanmohammadi, Hassan Abolhassani, Reza Yazdani 2022 Tehran University of Medical Sciences

B- And T-Cell Subset Abnormalities In Monogenic Common Variable Immunodeficiency, Saba Fekrvand, Shaghayegh Khanmohammadi, Hassan Abolhassani, Reza Yazdani

Department of Neurology Faculty Papers

Common variable immunodeficiency (CVID) is a heterogeneous group of inborn errors of immunity characterized by reduced serum concentrations of different immunoglobulin isotypes. CVID is the most prevalent symptomatic antibody deficiency with a broad range of infectious and non-infectious clinical manifestations. Various genetic and immunological defects are known to be involved in the pathogenesis of CVID. Monogenic defects account for the pathogenesis of about 20-50% of CVID patients, while a variety of cases do not have a defined genetic background. Deficiencies in molecules of B cell receptor signaling or other pathways involving B-cell development, activation, and proliferation could be associated with ...


Genomic Features Underlie The Co-Option Of Sva Transposons As Cis-Regulatory Elements In Human Pluripotent Stem Cells, Samantha M Barnada, Andrew Isopi, Daniela Tejada-Martinez, Clément Goubert, Sruti Patoori, Luca Pagliaroli, Mason Tracewell, Marco Trizzino 2022 Thomas Jefferson University

Genomic Features Underlie The Co-Option Of Sva Transposons As Cis-Regulatory Elements In Human Pluripotent Stem Cells, Samantha M Barnada, Andrew Isopi, Daniela Tejada-Martinez, Clément Goubert, Sruti Patoori, Luca Pagliaroli, Mason Tracewell, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Domestication of transposable elements (TEs) into functional cis-regulatory elements is a widespread phenomenon. However, the mechanisms behind why some TEs are co-opted as functional enhancers while others are not are underappreciated. SINE-VNTR-Alus (SVAs) are the youngest group of transposons in the human genome, where ~3,700 copies are annotated, nearly half of which are human-specific. Many studies indicate that SVAs are among the most frequently co-opted TEs in human gene regulation, but the mechanisms underlying such processes have not yet been thoroughly investigated. Here, we leveraged CRISPR-interference (CRISPRi), computational and functional genomics to elucidate the genomic features that underlie SVA ...


A Single Dose Of The Deactivated Rabies-Virus Vectored Covid-19 Vaccine, Coravax, Is Highly Efficacious And Alleviates Lung Inflammation In The Hamster Model, Drishya Kurup, Christoph Wirblich, Leila Zabihi Diba, Rachael Lambert, Megan Watson, Noor Shaikh, Holly Ramage, Charalambos Solomides, Matthias J Schnell 2022 Thomas Jefferson University

A Single Dose Of The Deactivated Rabies-Virus Vectored Covid-19 Vaccine, Coravax, Is Highly Efficacious And Alleviates Lung Inflammation In The Hamster Model, Drishya Kurup, Christoph Wirblich, Leila Zabihi Diba, Rachael Lambert, Megan Watson, Noor Shaikh, Holly Ramage, Charalambos Solomides, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

Without sufficient herd immunity through either vaccination or natural infection, the coronavirus disease 2019 pandemic is unlikely to be controlled. Waning immunity with the currently approved vaccines suggests the need to evaluate vaccines causing the induction of long-term responses. Here, we report the immunogenicity and efficacy of our adjuvanted single-dose Rabies-vectored SARS-CoV-2 S1 vaccine, CORAVAX, in hamsters. CORAVAX induces high SARS-CoV-2 S1-specific and virus-neutralizing antibodies (VNAs) that prevent weight loss, viral loads, disease, lung inflammation, and the cytokine storm in hamsters. We also observed high Rabies VNA titers. In summary, CORAVAX is a promising dual-antigen vaccine candidate for clinical evaluation ...


Antigen Staining For Detection Of Muc13 And Muc16 Expression In Carcinoma Tissue, Jose A. Benitez 2022 The University of Texas Rio Grande Valley

Antigen Staining For Detection Of Muc13 And Muc16 Expression In Carcinoma Tissue, Jose A. Benitez

MEDI 9331 Scholarly Activities Clinical Years

MUC13 and MUC16 are epithelial expressed proteins implicated in various carcinomas. Overexpression of these biomarkers appear to play a role in tumor growth; this discovery has paved a road for multiple studies discussing the potential of targeting mucin proteins and optimize immunotherapy approaches against carcinomas. Our study serves to investigate the level of expression of MUC13 and MUC16 in cancerous and normal tissue and to discuss the implications our findings may have for the utilization of these biomarkers for cancer therapy.


A Within-Host Modeling Framework For Sars-Cov-2 Infection To Support Vaccine Strategies, Morgan Rose, Rachel Jennings, Jeffry Schroeter 2022 Applied Research Associates, Inc.

A Within-Host Modeling Framework For Sars-Cov-2 Infection To Support Vaccine Strategies, Morgan Rose, Rachel Jennings, Jeffry Schroeter

Biology and Medicine Through Mathematics Conference

No abstract provided.


Cathelicidin Anti-Microbial Peptide (Camp) Is Toxic During Neonatal Influenza Virus Infection, Nneka Ugwu 2022 Tower Health

Cathelicidin Anti-Microbial Peptide (Camp) Is Toxic During Neonatal Influenza Virus Infection, Nneka Ugwu

St. Chris Research Day

No abstract provided.


A Suspected Case Of Vaccine Induced Thrombosis With Thrombocytopenia Following Sars Cov2 Vaccine, Maryam Soliman 2022 Rowan University

A Suspected Case Of Vaccine Induced Thrombosis With Thrombocytopenia Following Sars Cov2 Vaccine, Maryam Soliman

Stratford Campus Research Day

With the new development of the SARS-CoV vaccine and the majority of the population receiving this vaccine, it is important to recognize some of the rare side effects associated with it.

VITT is a rare complication of the COVID vaccine

Diagnostic criteria: COVID vaccine 4-24 days prior to symptom onset, any venous or arterial thrombosis, thrombocytopenia <150, positive PF4 HIT ELISA, markedly elevated D-dimer >4x ULN.

Vaccine Induced Thrombosis with Thrombocytopenia is a potentially life-threatening diagnosis that must be recognized and treated correctly to prevent poor outcomes.


The Role Of Obesity In Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer., Katharina Marietta Scheurlen 2022 University of Louisville

The Role Of Obesity In Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer., Katharina Marietta Scheurlen

Electronic Theses and Dissertations

Early-onset colon cancer (EOCC) is a leading cause of cancer death among people younger than 50 years of age in the United States and is associated with metabolic dysfunction and obesity. Anti-inflammatory tumor-associated macrophages (TAM) and low Peroxisome Proliferator Activated Receptor Gamma (PPARγ) gene expression in colon cancer (CC) tissue promote tumor progression and decreased patient survival. Obesity-related hormones, such as leptin and adiponectin, have the potential to affect gene expression in TAM to promote CC progression and thereby link obesity and EOCC. The aim of this project was to identify target genes in human CC and to investigate the ...


Variations In Antibody Response To Aspergillus Fumigatus Inhalation In Mice, Andrea Wells 2022 Minnesota State University Moorhead

Variations In Antibody Response To Aspergillus Fumigatus Inhalation In Mice, Andrea Wells

Student Academic Conference

Studies have configured immunological responses to Aspergillus fumigatus in mice, leading to advanced understandings. However, the comparisons of the immune responses between juvenile (younger than 6 weeks) male and female C57BL/6J mice after A. fumigatus exposure, remains uninvestigated. In this study, we intranasally inoculated 3 week old male and female mice with Aspergillus fumigatus spores dilution of 2 106spores per 40 l. They were exposed to the allergen once a week for 8 consecutive weeks and euthanized on day 28 post the last inoculation. As compared to our last report, we increased the sample size for each group in ...


Cellular Dynamics And Disease Outcome Of Type 3 Streptococcus Pneumoniae Clinical Isolates Differ Between Strains, Taylor Rae Plunkett White 2022 University of Tennessee Health Science Center

Cellular Dynamics And Disease Outcome Of Type 3 Streptococcus Pneumoniae Clinical Isolates Differ Between Strains, Taylor Rae Plunkett White

Theses and Dissertations (ETD)

Streptococcus pneumoniae is a bacterial pathogen that continues to be a major cause of disease around the world. It is not only the number one cause of bacterial pneumonia but also the cause of about 15% of the deaths of children under 5 around the world. There is a lot of research done on this organism, but with around 100 known serotypes and each one producing a unique capsule, there is still much more to be studied. The Etiology of Pneumonia in the Community (EPIC) study conducted by the CDC observed the burden of hospitalizations caused by pneumonia while determining ...


Medical Factors Associated With Caregiver Intention To Vaccinate Their Children Against Covid-19, Thao-Ly Phan, Paul T Enlow, Michael King, Amanda M Lewis, Anne E Kazak, Jonathan M Miller 2022 Thomas Jefferson University

Medical Factors Associated With Caregiver Intention To Vaccinate Their Children Against Covid-19, Thao-Ly Phan, Paul T Enlow, Michael King, Amanda M Lewis, Anne E Kazak, Jonathan M Miller

Department of Medicine Faculty Papers

Objective: To describe medical factors that are associated with caregiver intention to vaccinate their children against COVID-19.

Methods: We conducted a cross-sectional study of families receiving primary care in a mid-Atlantic pediatric healthcare system, linking caregiver-reported data from a survey completed March 19 to April 16, 2021 to comprehensive data from the child's EHR.

Results: 513 families were included (28% Black, 16% Hispanic, 44% public insurance, 21% rural, child age range 0-21 years). 44% of caregivers intended to vaccinate their children against COVID-19, while 41% were not sure and 15% would not. After adjusting for socio-demographics, the only medical ...


T Cell Therapy: Underlying Mechanisms And Current Advancements, Griffin McCloy 2022 Liberty University

T Cell Therapy: Underlying Mechanisms And Current Advancements, Griffin Mccloy

Senior Honors Theses

As the second leading cause of death in 2016, cancer is one of the most serious diseases facing the world today. T cell therapy is a current area of research attempting to address the disease with two primary division: CAR-T and TCR-T cell therapy. The immune system naturally produces T lymphocytes to aid in the recognition and removal of cells infected with viruses or transformed into cancer. Under normal circumstances, T lymphocytes identify and destroy cancerous cells; however, some cancerous cell types can evade this system. With the use of genetic editing technology, T lymphocytes can gain the ability to ...


Arsenic Toxicity On Metabolism And Autophagy In Adipose And Muscle Tissues, Seung-Hyun Ro, Jiyoung Bae, Yura Jang, Jacob Myers, Soonkyu Chung, Jiujiu Yu, Sathish Kumar Natarajan, Rodrigo Franco, Hyun-Seob Song 2022 University of Nebraska-Lincoln

Arsenic Toxicity On Metabolism And Autophagy In Adipose And Muscle Tissues, Seung-Hyun Ro, Jiyoung Bae, Yura Jang, Jacob Myers, Soonkyu Chung, Jiujiu Yu, Sathish Kumar Natarajan, Rodrigo Franco, Hyun-Seob Song

Department of Microbiology and Immunology Faculty Papers

Arsenic, a naturally occurring metalloid derived from the environment, has been studied worldwide for its causative effects in various cancers. However, the effects of arsenic toxicity on the development and progression of metabolic syndrome, including obesity and diabetes, has received less attention. Many studies suggest that metabolic dysfunction and autophagy dysregulation of adipose and muscle tissues are closely related to the development of metabolic disease. In the USA, arsenic contamination has been reported in some ground water, soil and grain samples in major agricultural regions, but the effects on adipose and muscle tissue metabolism and autophagy have not been investigated ...


Creation Of An Influenza A Virus Neuraminidase Consensus Vaccine In An Adenoviral Vector, Leigh Jahnke 2022 University of Nebraska - Lincoln

Creation Of An Influenza A Virus Neuraminidase Consensus Vaccine In An Adenoviral Vector, Leigh Jahnke

Honors Theses, University of Nebraska-Lincoln

In the last decade, the estimated annual burden of the flu includes 12,000-52,000 deaths, 140,000-710,000 hospitalizations, and 9 million – 41 million illnesses (Centers for Disease Control and Prevention: Disease burden of the flu). Influenza A virus can mutate and infect a variety of different hosts, which results in frequent antigenic changes and even pandemics. This has led to increased attention on the creation of a universal Influenza A vaccine containing broader immunogenic coverage than current vaccines. Our research involved detailing the steps of the cloning process utilizing a consensus neuraminidase antigen. We utilized the pAdEasy Adenoviral ...


T-Cell Responses To Immunodominant Listeria Epitopes Limit Vaccine-Directed Responses To The Colorectal Cancer Antigen, Guanylyl Cyclase C, John C. Flickinger, Jagmohan Singh, Yanki Yarman, Robert D Carlson, Joshua Barton, Scott A Waldman, Adam E. Snook 2022 Thomas Jefferson University

T-Cell Responses To Immunodominant Listeria Epitopes Limit Vaccine-Directed Responses To The Colorectal Cancer Antigen, Guanylyl Cyclase C, John C. Flickinger, Jagmohan Singh, Yanki Yarman, Robert D Carlson, Joshua Barton, Scott A Waldman, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The Gram-positive bacterium Listeria monocytogenes (Lm) is an emerging platform for cancer immunotherapy. To date, over 30 clinical trials have been initiated testing Lm cancer vaccines across a wide variety of cancers, including lung, cervical, colorectal, and pancreatic. Here, we assessed the immunogenicity of an Lm vaccine against the colorectal tumor antigen GUCY2C (Lm-GUCY2C). Surprisingly, Lm-GUCY2C vaccination did not prime naïve GUCY2C-specific CD8+ T-cell responses towards the dominant H-2Kd-restricted epitope, GUCY2C254-262. However, Lm-GUCY2C produced robust CD8+ T-cell responses towards Lm-derived peptides suggesting that GUCY2C254-262 peptide may be subdominant to Lm-derived peptides. Indeed, incorporating immunogenic Lm peptides into an adenovirus-based GUCY2C ...


Rapid Assessment Of Opisthorchis Viverrini Igg Antibody In Serum: A Potential Diagnostic Biomarker To Predict Risk Of Cholangiocarcinoma In Regions Endemic For Opisthorchiasis., Rutchanee Rodpai, Vor Luvira, Lakkhana Sadaow, Wattana Sukeepaisarnjaroen, Amnat Kitkhuandee, Krisada Paonariang, Oranuch Sanpool, Wannaporn Ittiprasert, Victoria H. Mann, Pewpan M Intapan, Paul J. Brindley, Wanchai Maleewong 2022 George Washington University

Rapid Assessment Of Opisthorchis Viverrini Igg Antibody In Serum: A Potential Diagnostic Biomarker To Predict Risk Of Cholangiocarcinoma In Regions Endemic For Opisthorchiasis., Rutchanee Rodpai, Vor Luvira, Lakkhana Sadaow, Wattana Sukeepaisarnjaroen, Amnat Kitkhuandee, Krisada Paonariang, Oranuch Sanpool, Wannaporn Ittiprasert, Victoria H. Mann, Pewpan M Intapan, Paul J. Brindley, Wanchai Maleewong

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Opisthorchiasis is caused by an infection with fish-borne liver flukes of the genus Opisthorchis. Opisthorchiasis frequently leads to chronic inflammation in the biliary tract and is classified as a group 1 biological carcinogen by the International Agency for Research on Cancer: a definitive risk for cholangiocarcinoma (CCA).

METHODS: We used the rapid immunochromatographic test (ICT) to detect anti-Opisthorchis viverrini IgG and IgG4 subclass antibodies in sera of patients with CCA. The ICT kits were developed based on soluble antigens excreted and secreted by O. viverrini adult worms.

RESULTS: ICT indicated sera was positive for IgG and IgG4 antibodies, respectively ...


Similarly Efficacious Anti-Malarial Drugs Sj733 And Pyronaridine Differ In Their Ability To Remove Circulating Parasites In Mice, Arya SheelaNair, Aleksandra S. Romanczuk, Rosemary A. Aogo, Rohit Nemai Haldar, Lianne I. M. Lansink, Deborah Cromer, Yandira G. Salinas, R. Kiplin Guy, James S. McCarthy, Miles P. Davenport, Ashraful Haque, David S. Khoury 2022 QIMR Berghofer Medical Research Institute, Australia

Similarly Efficacious Anti-Malarial Drugs Sj733 And Pyronaridine Differ In Their Ability To Remove Circulating Parasites In Mice, Arya Sheelanair, Aleksandra S. Romanczuk, Rosemary A. Aogo, Rohit Nemai Haldar, Lianne I. M. Lansink, Deborah Cromer, Yandira G. Salinas, R. Kiplin Guy, James S. Mccarthy, Miles P. Davenport, Ashraful Haque, David S. Khoury

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the "parasite clearance curve", has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation.

METHODS: In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine ...


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