A Multi-Institutional Description of Processes and Outcomes of Postbaccalaureate Research Education Programs in the Mid-Atlantic Region.

Outcome data from 6 National Institutes of Health-funded Postbaccalaureate Research Education Programs (PREPs) in the Mid-Atlantic region were combined to give a multi-institutional perspective on their scholars' characteristics and progress through biomedical research training. The institutions hosting these programs were Johns Hopkins University School of Medicine, the Medical University of South Carolina, the University of Maryland School of Medicine, the University of North Carolina at Chapel Hill, Virginia Commonwealth University, and Virginia Polytechnic Institute and State University. The authors summarize the institutional pathways, demographics, undergraduate institutions, and graduate institutions for a total of 384 PREP scholars who completed the programs by June 2021.

Engineering the common cold to be a live-attenuated SARS-CoV-2 vaccine.

According to the American Centers for Disease Control and Prevention, people in all age groups catch two or more "colds" per year, at least half of which are caused by human rhinoviruses. Despite decades of effort, there are no vaccines or drugs against rhinovirus infections and even social distancing measures that were effective in reducing the spread of the pandemic coronavirus, SARS-CoV-2, did not reduce the rate of rhinovirus detection. Fortunately, most rhinovirus strains are naturally attenuated in that they are not associated with serious illness, hospitalization or mortality.

Sex differences in the MB49 syngeneic, murine model of bladder cancer.

Objective: The MB49 syngeneic, murine model of bladder cancer has been widely used for more than 35 years. In humans, bladder cancer is one third as prevalent in women as in men, with a trend toward lower prevalence in parous compared to nulliparous women. Our objective was to determine if the MB49 bladder cancer model reproduces the sex differences observed in humans, and to determine its sensitivity to testosterone and the pregnancy hormone, human chorionic gonadotropin (hCG).

Polymer-enhanced delivery increases adenoviral gene expression in an orthotopic model of bladder cancer.

Gene therapy has garnered significant attention as a therapeutic approach for bladder cancer but efficient delivery and gene expression remain major hurdles. The goal of this study was to determine if cationic polymers can enhance adenoviral gene expression in cells that are difficult to transduce in vitro and to subsequently investigate lead candidates for their capacity to increase adenoviral gene expression in an orthotopic in vivo model of bladder cancer. In vitro screening of linear polyamine-based and aminoglycoside-based polymer libraries identified several candidates that enhanced adenoviral reporter gene expression in vitro.

An orthotopic bladder cancer model for gene delivery studies.

Bladder cancer is the second most common cancer of the urogenital tract and novel therapeutic approaches that can reduce recurrence and progression are needed. The tumor microenvironment can significantly influence tumor development and therapy response. It is therefore often desirable to grow tumor cells in the organ from which they originated.

Histone deacetylase inhibitors restore cell surface expression of the coxsackie adenovirus receptor and enhance CMV promoter activity in castration-resistant prostate cancer cells.

Adenoviral gene therapy using the death receptor ligand TRAIL as the therapeutic transgene can be safely administered via intraprostatic injection but has not been evaluated for efficacy in patients. Here we investigated the efficacy of adenoviral TRAIL gene therapy in a model of castration resistant prostate cancer and found that intratumoral injections can significantly delay tumor growth but cannot eliminate established lesions. We hypothesized that an underlying cause is inefficient adenoviral delivery.

Adenoviral infectivity of exfoliated viable cells in urine: implications for the detection of bladder cancer.

Background: Bladder cancer, the 5th most common malignancy in the USA, is often detected as a result of incidental findings or by presenting hematuria. Once diagnosed the disease is one of the costliest cancers to treat due to frequent, invasive and often lifelong follow-up procedures. Because cells are shed into urine, there has been an emerging effort to develop non-invasive tests for the detection of bladder cancer.

Salivary glands act as mucosal inductive sites via the formation of ectopic germinal centers after site-restricted MCMV infection.

We investigated the hypothesis that salivary gland inoculation stimulates formation of ectopic germinal centers (GCs), transforming the gland into a mucosal inductive site. Intraglandular infection of mice with murine cytomegalovirus (MCMV; control: UV-inactivated MCMV) induces salivary gland ectopic follicles comprising cognate interactions between CD4(+) and B220(+) lymphocytes, IgM(+) and isotype-switched IgG(+) and IgA(+) B cells, antigen presenting cells, and follicular dendritic cells. B cells coexpressed the GC markers GCT (57%) and GL7 (52%), and bound the lectin peanut agglutinin.

Polymer-enhanced adenoviral transduction of CAR-negative bladder cancer cells.

The application of adenoviral gene therapy for cancer is limited by immune clearance of the virus as well as poor transduction efficiency, since the protein used for viral entry (CAR) serves physiological functions in adhesion and is frequently decreased among cancer cells. Cationic polymers have been used to enhance adenoviral gene delivery, but novel polymers with low toxicity are needed to realize this approach. We recently identified polymers that were characterized by high transfection efficiency of plasmid DNA and a low toxicity profile.

Oxidative stress sensitizes bladder cancer cells to TRAIL mediated apoptosis by down-regulating anti-apoptotic proteins.

Purpose: TRAIL, an endogenous protein involved in immunosurveillance and a novel drug in clinical trials, is of particular interest as cancer therapy because it can induce apoptosis in cancer cells but not in normal cells. Since some cancers develop resistance to TRAIL, safe and effective methods of TRAIL sensitization are of clinical interest. We explored how chemotherapy and oxidative stress affect TRAIL sensitivity and expression of proteins in the apoptotic pathway.

Doxorubicin generates a proapoptotic phenotype by phosphorylation of elongation factor 2.

We have previously shown that doxorubicin sensitizes prostate cancer cells to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL). Sensitization correlated with decreased expression of the antiapoptotic cellular FLICE-like inhibitor protein (cFLIP(S)). The decrease in cFLIP(S) could not be explained by transcriptional regulation or increased degradation, leading us to focus on translational mechanisms.

A focused salivary gland infection with attenuated MCMV: an animal model with prevention of pathology associated with systemic MCMV infection.

While the salivary gland has been recognized as an important effector site of the common mucosal immune system, a useful model for studying anti-viral salivary gland immune responses in vivo and for exploring the role of the salivary gland within the common mucosal system has been lacking. Murine cytomegalovirus (MCMV) is a beta-herpesvirus that displays a strong tropism for the salivary gland and produces significant morbidity in susceptible mice when introduced by intraperitoneal (i.p.

Immunoglobulin gene implicated in murine herpes stromal keratitis is not associated with the human disease.

Purpose: Susceptibility to herpes stromal keratitis (HSK) is strongly influenced by genetic factors, as shown by multiple rodent models using human herpes simplex virus. A single gene, encoding the immunoglobulin G (IgG) 2a heavy chain protein, confers susceptibility or resistance through a mechanism involving molecular mimicry in one mouse model. However, other rodent studies have produced contradictory results.

Barriers to coliphage infection of commensal intestinal flora of laboratory mice.

Background: Growth characteristics of coliphage viruses indicate that they are adapted to live with their Eschericia coli hosts in the intestinal tract. However, coliphage experimentally introduced by ingestion persist only transiently if at all in the gut of humans and other animals. This study attempted to identify the barriers to long term establishment of exogenous coliphage in the gastrointestinal (GI) tracts of laboratory mice.

CD13/aminopeptidase N and murine cytomegalovirus infection.

CD13/aminopeptidase N is a membrane-bound metalloproteinase implicated in human cytomegalovirus (HCMV) infection and pathogenesis. Anti-CD13 antibodies can neutralize HCMV infectivity, and HCMV viremia after bone marrow transplantation induces anti-CD13 autoantibodies which correlate with development of chronic graft vs. host disease.

Use of genetically engineered phage to deliver antimicrobial agents to bacteria: an alternative therapy for treatment of bacterial infections.

The emergence and increasing prevalence of multidrug-resistant bacterial pathogens emphasizes the need for new and innovative antimicrobial strategies. Lytic phages, which kill their host following amplification and release of progeny phage into the environment, may offer an alternative strategy for combating bacterial infections. In this study, however, we describe the use of a nonlytic phage to specifically target and deliver DNA encoding bactericidal proteins to bacteria.

The role of infectious agents in the pathogenesis of systemic sclerosis.

Over the past few years, increasing evidence has accumulated to implicate infectious agents in the etiology of systemic sclerosis (SSc) and Raynaud phenomenon. Infection rates in patients with SSc compared with those in control populations do not provide clear support for any specific pathogen. However, increased antibody titers, a preponderance of specific strains in patients with SSc, and evidence of molecular mimicry inducing autoimmune responses suggest mechanisms by which infectious agents may contribute to the development and progression of SSc.

Overcoming the phage replication threshold: a mathematical model with implications for phage therapy.

Prior observations of phage-host systems in vitro have led to the conclusion that susceptible host cell populations must reach a critical density before phage replication can occur. Such a replication threshold density would have broad implications for the therapeutic use of phage. In this report, we demonstrate experimentally that no such replication threshold exists and explain the previous data used to support the existence of the threshold in terms of a classical model of the kinetics of colloidal particle interactions in solution.