Medical Specialties Commons^™

Case Report: Selexipag In Pediatric Pulmonary Hypertension: Initiation, Transition, And Titration, Jenna M Faircloth, Neelam D Bhatt, Corey A Chartan, Ryan D Coleman, Natalie Villafranco, Fadel E Ruiz, Raysa Morales-Demori, Elise Whalen, Erin Ely, Rozmeen Fombin, Nidhy P Varghese

Faculty, Staff and Students Publications

Selexipag, a selective prostacyclin receptor agonist, is approved for treating pulmonary arterial hypertension in WHO Group 1 adult patients. Compared to parenteral prostacyclin formulations, selexipag offers a significant improvement in patient’s and caregiver’s quality of life because of its oral formulation, frequency of administration, and mechanism of action. Although experience in the pediatric population is limited and selexipag is not FDA-approved for use in the pediatric pulmonary hypertension population, many US pediatric centers are expanding the use of this therapy to this younger population. We report our institution's experience in the use of selexipag to treat pulmonary hypertension in children …

Clinical Characterization Of Data-Driven Diabetes Clusters Of Pediatric Type 2 Diabetes, Mahsan Abbasi, Mustafa Tosur, Marcela Astudillo, Ahmad Refaey, Ashutosh Sabharwal, Maria J Redondo

Faculty, Staff and Students Publications

BACKGROUND: Pediatric Type 2 diabetes (T2D) is highly heterogeneous. Previous reports on adult-onset diabetes demonstrated the existence of diabetes clusters. Therefore, we set out to identify unique diabetes subgroups with distinct characteristics among youth with T2D using commonly available demographic, clinical, and biochemical data.

METHODS: We performed data-driven cluster analysis (K-prototypes clustering) to characterize diabetes subtypes in pediatrics using a dataset with 722 children and adolescents with autoantibody-negative T2D. The six variables included in our analysis were sex, race/ethnicity, age, BMI

RESULTS: We identified five distinct clusters of pediatric T2D, with different features, treatment regimens and risk of diabetes complications: …

Clinical Hypoxemia Score For Outpatient Child Pneumonia Care Lacking Pulse Oximetry In Africa And South Asia, Holly B Schuh, Shubhada Hooli, Salahuddin Ahmed, Carina King, Arunangshu D Roy, Norman Lufesi, Asmd Ashraful Islam, Tisungane Mvalo, Nabidul H Chowdhury, Amy Sarah Ginsburg, Tim Colbourn, William Checkley, Abdullah H Baqui, Eric D Mccollum

Faculty, Staff and Students Publications

BACKGROUND: Pulse oximeters are not routinely available in outpatient clinics in low- and middle-income countries. We derived clinical scores to identify hypoxemic child pneumonia.

METHODS: This was a retrospective pooled analysis of two outpatient datasets of 3-35 month olds with World Health Organization (WHO)-defined pneumonia in Bangladesh and Malawi. We constructed, internally validated, and compared fit & discrimination of four models predicting SpO

RESULTS: 12,712 observations were included. The independent and composite LASSO models discriminated moderately (both C-statistic 0.77) between children with a SpO

CONCLUSIONS: In the absence of pulse oximeters, both LASSO models better identified outpatient hypoxemic pneumonia cases …

Cholestasis Impairs Gut Microbiota Development And Bile Salt Hydrolase Activity In Preterm Neonates, Lauren E Lynch, Amy B Hair, Krishnakant G Soni, Heeju Yang, Laura A Gollins, Monica Narvaez-Rivas, Kenneth D R Setchell, Geoffrey A Preidis

Faculty, Staff and Students Publications

Cholestasis refers to impaired bile flow from the liver to the intestine. In neonates, cholestasis causes poor growth and may progress to liver failure and death. Normal bile flow requires an intact liver-gut-microbiome axis, whereby liver-derived primary bile acids are transformed into secondary bile acids. Microbial bile salt hydrolase (BSH) enzymes are responsible for the first step, deconjugating glycine- and taurine-conjugated primary bile acids. Cholestatic neonates often are treated with the potent choleretic bile acid ursodeoxycholic acid (UDCA), although interactions between UDCA, gut microbes, and other bile acids are poorly understood. To gain insight into how the liver-gut-microbiome axis develops …

The Covert Symphony: Cellular And Molecular Accomplices In Breast Cancer Metastasis, Hongjiang Si, Madelyn Esquivel, Erika Mendoza Mendoza, Kevin Roarty

Faculty, Staff and Students Publications

Breast cancer has emerged as the most commonly diagnosed cancer and primary cause of cancer-related deaths among women worldwide. Although significant progress has been made in targeting the primary tumor, the effectiveness of systemic treatments to prevent metastasis remains limited. Metastatic disease continues to be the predominant factor leading to fatality in the majority of breast cancer patients. The existence of a prolonged latency period between initial treatment and eventual recurrence in certain patients indicates that tumors can both adapt to and interact with the systemic environment of the host, facilitating and sustaining the progression of the disease. In order …

Sphingolipids In Neurodegenerative Diseases, Xueyang Pan, Debdeep Dutta, Shenzhao Lu, Hugo J Bellen

Faculty, Staff and Students Publications

Neurodegenerative Diseases (NDDs) are a group of disorders that cause progressive deficits of neuronal function. Recent evidence argues that sphingolipid metabolism is affected in a surprisingly broad set of NDDs. These include some lysosomal storage diseases (LSDs), hereditary sensory and autonomous neuropathy (HSAN), hereditary spastic paraplegia (HSP), infantile neuroaxonal dystrophy (INAD), Friedreich’s ataxia (FRDA), as well as some forms of amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). Many of these diseases have been modeled in Drosophila melanogaster and are associated with elevated levels of ceramides. Similar changes have also been reported in vertebrate cells and mouse models. Here, we …

Ageing And Rejuvenation Of Tissue Stem Cells And Their Niches, Anne Brunet, Margaret A Goodell, Thomas A Rando

Faculty, Staff and Students Publications

Most adult organs contain regenerative stem cells, often organized in specific niches. Stem cell function is critical for tissue homeostasis and repair upon injury, and it is dependent on interactions with the niche. During ageing, stem cells decline in their regenerative potential and ability to give rise to differentiated cells in the tissue, which is associated with a deterioration of tissue integrity and health. Ageing-associated changes in regenerative tissue regions include defects in maintenance of stem cell quiescence, differentiation ability and bias, clonal expansion and infiltration of immune cells in the niche. In this Review, we discuss cellular and molecular …

Cefepime Dosing In A Critically Ill Neonate Receiving Continuous Renal Replacement Therapy With The Cardio-Renal Pediatric Dialysis Emergency Machine (Carpediem), Cynthia Toy, Grant Stimes, Megan Moore, Poyyapakkam Srivaths, Ayse Akcan Arikan

Faculty, Staff and Students Publications

We report on a former 27-week gestational age infant who was placed on the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM) at 4 months post-menstrual age while receiving cefepime treatment for an Enterobacter cloacae bacteremia and persistent peritonitis secondary to an infected peritoneal dialysis catheter. Using therapeutic drug monitoring while assessing the clearance of cefepime on continuous renal replacement therapy (CRRT), we were able to successfully treat this patient's infection while also minimizing the risk of side effects from this medication. Current literature supports dosing in adult patients on all modalities of CRRT with effluent flow rates of 20 to 25 …

Protocol For The Promoting Resilience In Stress Management (Prism) Intervention: A Multi-Site Randomized Controlled Trial For Adolescents With Type 1 Diabetes, Maeve B O'Donnell, Samantha R Scott, Britney M Ellisor, Viena T Cao, Chuan Zhou, Miranda C Bradford, Catherine Pihoker, Daniel J Desalvo, Faisal S Malik, Marisa E Hilliard, Abby R Rosenberg, Joyce P Yi-Frazier

Faculty, Staff and Students Publications

BACKGROUND: Adolescents with type 1 diabetes (T1D) are at high risk for elevated diabetes distress, which greatly impacts diabetes management, glycemic outcomes and overall quality of life. Developing protective skills and "resilience resources" to navigate adversity and manage diabetes distress has high potential to help adolescents with T1D achieve optimal behavioral, psychological, and health outcomes. The "Promoting Resilience in Stress Management" (PRISM) program is a manualized, brief, skills-based intervention delivered over 6 months via two 45-60 min one-on-one sessions and a family meeting with a PRISM coach, and supplemented by booster calls and a digital app. This trial (PRISM versus …

Long-Term Neuropsychological Outcomes In Children With Febrile Infection-Related Epilepsy Syndrome (Fires) Treated With Anakinra, Anima Shrestha, E Lynne Wood, Gretchen Berrios-Siervo, Coral M Stredny, Katrina Boyer, Clemente Vega, Srishti Nangia, Eyal Muscal, Krista Eschbach

Faculty, Staff and Students Publications

BACKGROUND: Febrile-infection related epilepsy syndrome (FIRES) is a rare epilepsy syndrome in which a previously healthy individual develops refractory status epilepticus in the setting of a preceding febrile illness. There are limited data regarding detailed long-term outcomes. This study aims to describe the long-term neuropsychological outcomes in a series of pediatric patients with FIRES.

METHODS: This is a retrospective multi-center case series of pediatric patients with a diagnosis of FIRES treated acutely with anakinra who had neuropsychological testing at least 12 months after status epilepticus onset. Each patient underwent comprehensive neuropsychological evaluation as part of routine clinical care. Additional data …

A Population-Based Assessment Of Metastatic Hepatoblastoma In Texas Reveals Ethnic Disparities, Andres F Espinoza, Michael E Scheurer, Tiffany M Chambers, Sanjeev A Vasudevan, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Hepatoblastoma (HB) is the most common primary liver cancer in children with emerging evidence that incidence is increasing globally. While overall survival for low risk hepatoblastoma is >90%, children with metastatic disease have worse survival. As identifying factors associated with high-risk disease is critical for improving outcomes for these children, a need for a further understanding of the epidemiology of hepatoblastoma is warranted. Therefore, we conducted a population-based epidemiologic study of hepatoblastoma in Texas, a large state characterized by ethnic and geographic diversity.

METHODS: Information on children diagnosed with hepatoblastoma at 0-19 years of age for the period of …

Oocyte-Specific Wee1-Like Protein Kinase 2 Is Dispensable For Fertility In Mice, Kaori Nozawa, Zian Liao, Yuhkoh Satouh, Ting Geng, Masahito Ikawa, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Wee1-like protein kinase 2 (WEE2) is an oocyte-specific protein tyrosine kinase involved in the regulation of oocyte meiotic arrest in humans. As such, it has been proposed as a candidate for non-hormonal female contraception although pre-clinical models have not been reported. Therefore, we developed two novel knockout mouse models using CRISPR/Cas9 to test loss-of-function of Wee2 on female fertility. A frameshift mutation at the Wee2 translation start codon in exon 2 had no effect on litter size, litter production, or the ability of oocytes to maintain prophase I arrest. Because of the lack of a reproductive phenotype, we additionally generated …

Disease Modeling Of Adamts9-Related Nephropathy Using Kidney Organoids Reveals Its Roles In Tubular Cells And Podocytes, Seyoung Yu, Yo Jun Choi, John Hoon Rim, Hye-Youn Kim, Nasim Bekheirnia, Sarah Jane Swartz, Hongzheng Dai, Shen Linda Gu, Soyeon Lee, Ryuichi Nishinakamura, Friedhelm Hildebrandt, Mir Reza Bekheirnia, Heon Yung Gee

Faculty, Staff and Students Publications

INTRODUCTION: Mutations in ADAMTS9 cause nephronophthisis-related ciliopathies (NPHP-RC), which are characterized by multiple developmental defects and kidney diseases. Patients with NPHP-RC usually have normal glomeruli and negligible or no proteinuria. Herein, we identified novel compound-heterozygous ADAMTS9 variants in two siblings with NPHP-RC who had glomerular manifestations, including proteinuria.

METHODS: To investigate whether ADAMTS9 dysfunction causes NPHP and glomerulopathy, we differentiated ADAMTS9 knockout human induced pluripotent stem cells (hiPSCs) into kidney organoids. Single-cell RNA sequencing was utilized to elucidate the gene expression profiles from the ADAMTS9 knockout kidney organoids.

RESULTS:ADAMTS9 knockout had no effect on nephron differentiation; however, it reduced …

5-Aminolevulinic Acid, Fluorescein Sodium, And Indocyanine Green For Glioma Margin Detection: Analysis Of Operating Wide-Field And Confocal Microscopy In Glioma Models Of Various Grades, Evgenii Belykh, Liudmila Bardonova, Irakliy Abramov, Vadim A Byvaltsev, Talgat Kerymbayev, Kwanha Yu, Debbie R Healey, Ernesto Luna-Melendez, Benjamin Deneen, Shwetal Mehta, James K Liu, Mark C Preul

Faculty, Staff and Students Publications

INTRODUCTION: Surgical resection remains the first-line treatment for gliomas. Several fluorescent dyes are currently in use to augment intraoperative tumor visualization, but information on their comparative effectiveness is lacking. We performed systematic assessment of fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), and indocyanine green (ICG) fluorescence in various glioma models using advanced fluorescence imaging techniques.

METHODS: Four glioma models were used: GL261 (high-grade model), GB3 (low-grade model), and an

RESULTS: Our systematic analysis showed that wide-field imaging of highly malignant gliomas is equally efficient with 5-ALA, FNa, and ICG, although FNa is associated with more false-positive staining of …

Primary Spinal Intramedullary Anaplastic Ganglioglioma In A Pediatric Patient, Huy Dang, Abdul Basit Khan, Nisha Gadgil, Marc Prablek, Frank Y Lin, Melissa M Blessing, Guillermo Aldave, David Bauer

Faculty, Staff and Students Publications

BACKGROUND: Gangliogliomas (GGs) are rare tumors of the central nervous system composed of neoplastic neural and glial cells and are typically low-grade. Intramedullary spinal anaplastic GGs (AGG) are rare, poorly understood, and often aggressive tumors that can result in widespread progression along the craniospinal axis. Due to the rarity of these tumors, data are lacking to guide clinical and pathologic diagnosis and standard of care treatment. Here, we present a case of pediatric spinal AGG to provide information on our institutional approach to work-up and to highlight unique molecular pathology.

CASE DESCRIPTION: A 13-year-old female presented with signs of spinal …

Bridging Science And Spirituality: The Intersection Of Religion And Public Health In The Covid-19 Pandemic, Shahana Ayub, Gibson O Anugwom, Tajudeen Basiru, Vishi Sachdeva, Nazar Muhammad, Anil Bachu, Maxwell Trudeau, Gazal Gulati, Amanda Sullivan, Saeed Ahmed, Lakshit Jain

Faculty, Staff and Students Publications

BACKGROUND: The COVID-19 pandemic has had global impacts on social interactions and religious activities, leading to a complex relationship between religion and public health policies. This article reviews impact of the COVID-19 pandemic on religious activities and beliefs in relation to the spread of the virus, as well as the potential of religious leaders and faith communities in mitigating the impact of the pandemic through public health measures and community engagement.

METHODS: A literature review was conducted using PubMed and Google Scholar, with search terms including "religion," "COVID-19," "pandemic," "coronavirus," and "spirituality." We included English articles published between January 2020 …

Efficient Recognition And Closed Reduction Of Locked Lateral Patella Dislocation, Justin Aflatooni, Scott D Mckay

Faculty, Staff and Students Publications

Patellar dislocation is not an uncommon injury in the general population that can often be managed in the emergency room with a closed reduction. However, rarely, the patella can become impacted on the lateral femoral condyle and become resistant to closed reduction techniques, which is known as a locked patellar dislocation. This injury is reported in the literature as requiring advanced imaging with a costly workup, operative intervention, or extensive manipulation under general anesthesia, and, to our knowledge, has never been documented to be closed reduced outside the operating room. In this report, we present a 17-year-old male with a …

Atrial Standstill In The Pediatric Population: A Multi-Institution Collaboration, Taylor S Howard, David Y Chiang, Scott R Ceresnak, Virginie Beausejour Ladouceur, Robert D Whitehill, Richard J Czosek, Timothy K Knilans, Agnethe M Ahnfeldt, Malene Lando Borresen, Edgar Jaeggi, Sharmila Udupa, Robert Gow, Jeremy P Moore, Roberto G Galloti, Doug Y Mah, Jeffrey J Kim, Santiago O Valdes, Dianna M Milewicz, Christina Y Miyake

Faculty, Staff and Students Publications

Background: Atrial standstill (AS) is a rare condition characterized by absence of electrical activity within the atria. Studies to date have been limited.

Objectives: The authors sought to describe the clinical characteristics, genetics, and outcomes of patients with AS.

Methods: This was a retrospective multicenter study of patients < 18 years at AS diagnosis, defined as absence of atrial activity documented during an electrophysiology study, device placement, or noninvasive rhythm tracings and confirmed by echocardiogram. Patients with acquired disorders were excluded. Clinical details and genetic variants were recorded and analyzed.

Results: Twenty patients were diagnosed at a median age of 6.6 years (IQR: 2.9-10.8 years). Arrhythmias included 16 (80%) with atrial/supraventricular arrhythmias and 8 (40%) with ventricular tachycardia, including 4 with cardiac arrests. A type 1 Brugada pattern was documented in 4. Pacemakers were implanted in 18 (90%). Although atrial leads were …

Acute Liver Failure And Unique Challenges Of Pediatric Liver Transplantation Amidst A Worldwide Cluster Of Adenovirus-Associated Hepatitis, Anna M Banc-Husu, Elizabeth A Moulton, Henry Shiau, Luz Helena Gutierrez Sanchez, Moreshwar S Desai, Dana Cerminara, Flor M Munoz, Leanne M Buffaloe, Kristen G Valencia-Deray, N Thao N Galvan, Julu Bhatnagar, Lindsey Estetter, Negar Rassaei, Sarah Reagan-Steiner, Jason Wicker, James J Dunn, Carl E Allen, Kalyani R Patel, Sanjiv Harpavat, John A Goss, Daniel H Leung

Faculty, Staff and Students Publications

Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue …

Perspective: Developing Future Veterans Affairs Scientists Through A Diversity, Equity, And Inclusion Program, Darius B Dawson, Valerie Lewis, Terri L Fletcher, Robert Hal Scofield

Faculty, Staff and Students Publications

For >95 years, the Department of Veterans Affairs Office of Research and Development (ORD) has been improving the lives of Veterans and all Americans through health care discovery and innovation. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives and creativity to address complex health-related problems, which helps to foster scientific innovation, improve quality of research, and advance the likelihood that underserved populations participate in and benefit from clinical and health services research. In this study, we will discuss our experiences in developing future scientists through mentored research supplements supported by ORD.

Lymphocytic Panhypophysitis Mimicking Glaucoma: Case Report, Phillip Howard Keys, Patrick J Hunt, Clement Anozie, Samir Cayenne, Pamela Davila-Siliezar, Noor Laylani, Andrew G Lee

Faculty, Staff and Students Publications

Lymphocytic hypophysitis (LH) is a primary inflammatory disorder of the pituitary gland and infundibulum that commonly manifests in both mass effect and endocrinologic symptoms. Although the exact pathophysiology remains unclear, it has been increasingly linked to an autoimmune process. Complications arise by two separate mechanisms. Inflammation in the sella can lead to headaches and visual field defects. Pituitary inflammation and, chronically, fibrosis interfere with the gland's hormone-secreting capacity, often resulting in various endocrinopathies such as polyuria, polydipsia, amenorrhea, and others. While final histologic classification requires pathologic evaluation, diagnosis can often be made clinically with appropriate imaging. Treatment often consists of …

Safety Procedures To Work With West Nile Virus In Biosafety Level 3 Facilities, Freedom M Green, Shannon E Ronca

Faculty, Staff and Students Publications

West Nile virus (WNV) can cause severe and sometimes fatal disease, but we do not have treatments or therapeutics to manage these outcomes. Since its introduction to the USA in 1999, WNV has been handled in a biosafety level 3 laboratory to decrease risk to researchers, requiring strict safety protocols and important considerations with planning experiments. Recent changes in US guidelines suggest that WNV can be handled at a lower biosafety level due to its endemicity in the USA and generally minor symptoms, but some research still requires the use of the agent at biosafety level 3. This chapter will …

Ai-Powered Discovery Of A Novel P53-Y220c Reactivator, Shan Zhou, Dafei Chai, Xu Wang, Praveen Neeli, Xinfang Yu, Aram Davtyan, Ken Young, Yong Li

Faculty, Staff and Students Publications

Introduction

The p53-Y220C mutation is one of the most common mutations that play a major role in cancer progression.

Methods

In this study, we applied artificial intelligence (AI)-powered virtual screening to identify small-molecule compounds that specifically restore the wild-type p53 conformation from p53-Y220C. From 10 million compounds, the AI algorithm selected a chemically diverse set of 83 high-scoring hits, which were subjected to several experimental assays using cell lines with different p53 mutations.

Results

We identified one compound, H3, that preferentially killed cells with the p53-Y220C mutation compared to cells with other p53 mutations. H3 increased the amount of folded …

The Role Of Neural And Genetic Processes In Learning To Read And Specific Reading Disabilities: Implications For Instruction, Jessica A Church, Elena L Grigorenko, Jack M Fletcher

Faculty, Staff and Students Publications

To learn to read, the brain must repurpose neural systems for oral language and visual processing to mediate written language. We begin with a description of computational models for how alphabetic written language is processed. Next, we explain the roles of a dorsal sublexical system in the brain that relates print and speech, a ventral lexical system that develops the visual expertise for rapid orthographic processing at the word level, and the role of cognitive control networks that regulate attentional processes as children read. We then use studies of children, adult illiterates learning to read, and studies of poor readers …

Editorial: Peripheral Stimulation: Neuromodulation Of The Central Nervous System Through Existing Pathways, Musa Ozturk, Julio Cesar Hernandez-Pavon, Alexander Kent, Jose L Pons, Ilknur Telkes, Arjun Tarakad

Faculty, Staff and Students Publications

No abstract provided.

Editorial: Surgical Techniques For The Management Of Pain, Anthony K Allam, Ashwin Viswanathan, Jason M Schwalb, Parag G Patil, M Benjamin Larkin

Faculty, Staff and Students Publications

No abstract provided.

Clinical Approach To Evaluation Of Underlying Cardiac Device Infection In Patients Hospitalized With Bacteremia, Dierdre B Axell-House, Sarwat Khalil, M Rizwan Sohail

Faculty, Staff and Students Publications

More than 400,000 cardiac implantable electronic devices (CIEDs), including permanent pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices, are implanted every year in the United States (US). Infection is a serious complication of CIED therapy and is associated with high morbidity and mortality. While CIED pocket infection can be diagnosed based on clinical exam findings, positive blood culture may be the only manifestation of CIED lead infection. Thus, management of bacteremia in patients living with CIEDs requires special consideration. This review summarizes contemporary data in the context of the recently updated 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for …

Real-World Experience With Cefiderocol Therapy For Pseudomonas Aeruginosa And Other Multidrug Resistant Gram-Negative Infections Within The Veterans Health Administration, 2019–2022, Andrew Chou, David Ramsey, Eva Amenta, Barbara W Trautner

Faculty, Staff and Students Publications

OBJECTIVE: Single-center and regional studies have reported outcomes after treatment with cefiderocol, a novel siderophore cephalosporin. We report on real-world use, clinical outcomes, and microbiological outcomes with cefiderocol therapy within the Veterans' Health Administration (VHA).

DESIGN: Prospective, observational descriptive study.

SETTING: Veterans' Health Administration, 132 sites across the United States, during 2019-2022.

PATIENTS: This study included patients admitted to any VHA medical center who received cefiderocol for ≥2 days.

METHODS: Data were obtained from the VHA Corporate Data Warehouse and through manual chart review. We extracted clinical and microbiologic characteristics and outcomes.

RESULTS: In total, 8,763,652 patients received 1,142,940,842 prescriptions …

Tanshinone Iia Inhibits Cell Viability And Promotes Puma-Mediated Apoptosis Of Oral Squamous Cell Carcinoma, Shuangze Han, Xinfang Yu, Ruirui Wang, Xiaocong Wang, Lulu Liu, Qing Zhao, Rongbo Xie, Ming Li, Zhong Su Zhou

Faculty, Staff and Students Publications

Apoptosis alteration is responsible for tumorigenesis and tumor resistance to therapies. The natural product Tanshinone IIA (Tan IIA) exhibits potent inhibitory effects against various tumors. However, the effect of Tan IIA on apoptosis and its underlying mechanism remains elusive in oral squamous cell carcinoma (OSCC). Here, we demonstrated that Tan IIA dose-dependently suppressed cell viability and colony formation in CAL27, SCC4, and SCC25 cells. Moreover, Tan IIA inhibited Akt activation from inducing Foxo3a dephosphorylation and PUMA-mediated apoptosis. PUMA or Foxo3a knockdown compromised the inhibitory effect of Tan IIA on OSCC cells. Tan IIA administration inhibited CAL27-deprived xenograft tumor growth and …

Novel Banana Lectin Car-T Cells To Target Pancreatic Tumors And Tumor-Associated Stroma, Mary K Mckenna, Ada Ozcan, Daniel Brenner, Norihiro Watanabe, Maureen Legendre, Dafydd G Thomas, Christopher Ashwood, Richard D Cummings, Challice Bonifant, David M Markovitz, Malcolm K Brenner

Faculty, Staff and Students Publications

BACKGROUND: Cell therapies for solid tumors are thwarted by the hostile tumor microenvironment (TME) and by heterogeneous expression of tumor target antigens. We address both limitations with a novel class of chimeric antigen receptors based on plant lectins, which recognize the aberrant sugar residues that are a 'hallmark' of both malignant and associated stromal cells. We have expressed in T cells a modified lectin from banana, H84T BanLec, attached to a chimeric antigen receptor (H84T-CAR) that recognizes high-mannose (asparagine residue with five to nine mannoses). Here, we tested the efficacy of our novel H84T CAR in models of pancreatic ductal …