Digital Commons Network^™

Immunologic Predictors For Clinical Responses During Immune Checkpoint Blockade In Patients With Myelodysplastic Syndromes, Sung-Eun Lee, Feng Wang, Maison Grefe, Abel Trujillo-Ocampo, Wilfredo Ruiz-Vasquez, Hussein A Abbas, Dinler Amaral Antunes, Gheath Al-Atrash, Naval Daver, Jeffrey J Molldrem, Andrew Futreal, Guillermo Garcia-Manero, Jin S Im

Faculty, Staff and Student Publications

PURPOSE: The aim of this study is to determine immune-related biomarkers to predict effective antitumor immunity in myelodysplastic syndrome (MDS) during immunotherapy (IMT, αCTLA-4, and/or αPD-1 antibodies) and/or hypomethylating agent (HMA).

EXPERIMENTAL DESIGN: Peripheral blood samples from 55 patients with MDS were assessed for immune subsets, T-cell receptor (TCR) repertoire, mutations in 295 acute myeloid leukemia (AML)/MDS-related genes, and immune-related gene expression profiling before and after the first treatment.

RESULTS: Clinical responders treated with IMT ± HMA but not HMA alone showed a significant expansion of central memory (CM) CD8+ T cells, diverse TCRβ repertoire pretreatment with increased clonality and …

Ragd Auto-Activating Mutations Impair Mit/Tfe Activity In Kidney Tubulopathy And Cardiomyopathy Syndrome, Irene Sambri, Marco Ferniani, Giulia Campostrini, Marialuisa Testa, Viviana Meraviglia, Mariana E G De Araujo, Ladislav Dokládal, Claudia Vilardo, Jlenia Monfregola, Nicolina Zampelli, Francesca Del Vecchio Blanco, Annalaura Torella, Carolina Ruosi, Simona Fecarotta, Giancarlo Parenti, Leopoldo Staiano, Milena Bellin, Lukas A Huber, Claudio De Virgilio, Francesco Trepiccione, Vincenzo Nigro, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

Heterozygous mutations in the gene encoding RagD GTPase were shown to cause a novel autosomal dominant condition characterized by kidney tubulopathy and cardiomyopathy. We previously demonstrated that RagD, and its paralogue RagC, mediate a non-canonical mTORC1 signaling pathway that inhibits the activity of TFEB and TFE3, transcription factors of the MiT/TFE family and master regulators of lysosomal biogenesis and autophagy. Here we show that RagD mutations causing kidney tubulopathy and cardiomyopathy are "auto- activating", even in the absence of Folliculin, the GAP responsible for RagC/D activation, and cause constitutive phosphorylation of TFEB and TFE3 by mTORC1, without affecting the phosphorylation …

Observations On The Present And The Future Of Hip Surgery, Alberto Di Martino

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

Feature Selection From Clinical Surveys Using Semantic Textual Similarity, Benjamin Warner

McKelvey School of Engineering Graduate Student Theses & Dissertations

Survey data collected from human subjects can contain a high number of features while having a comparatively low quantity of examples. Machine learning models that attempt to predict outcomes from survey data under these conditions can overfit and result in poor generalizability. One remedy to this issue is feature selection, which attempts to select an optimal subset of features to learn upon. A relatively unexplored source of information in the feature selection process is the usage of textual names of features, which may be semantically indicative of which features are relevant to a target outcome. The relationships between feature names …

Lipoxin A4 (Lxa4) Reduces Alkali-Induced Corneal Inflammation And Neovascularization And Upregulates A Repair Transcriptome, Jiucheng He, Thang L. Pham, Azucena H. Kakazu, Abhilash Ponnath, Khanh V. Do, Haydee E.P. Bazan

School of Graduate Studies Faculty Publications

Purpose: To investigate the anti-inflammatory and anti-angiogenic effects of the bioactive lipid mediator LXA4 on a rat model of severe corneal alkali injury. Methods: To induce a corneal alkali injury in the right eyes of anesthetized Sprague Dawley rats. They were injured with a Φ 4 mm filter paper disc soaked in 1 N NaOH placed on the center of the cornea. After injury, the rats were treated topically with LXA4 (65 ng/20 μL) or vehicle three times a day for 14 days. Corneal opacity, neovascularization (NV), and hyphema were recorded and evaluated in a blind manner. Pro-inflammatory cytokine expression …

Structure Of A Eukaryotic Cholinephosphotransferase-1 Reveals Mechanisms Of Substrate Recognition And Catalysis

Faculty, Staff and Students Publications

Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic cell membranes. In eukaryotes, two highly homologous enzymes, cholinephosphotransferase-1 (CHPT1) and choline/ethanolamine phosphotransferase-1 (CEPT1) catalyze the final step of de novo PC synthesis. CHPT1/CEPT1 joins two substrates, cytidine diphosphate-choline (CDP-choline) and diacylglycerol (DAG), to produce PC, and Mg2+ is required for the reaction. However, mechanisms of substrate recognition and catalysis remain unresolved. Here we report structures of a CHPT1 from Xenopus laevis (xlCHPT1) determined by cryo-electron microscopy to an overall resolution of ~3.2 Å. xlCHPT1 forms a homodimer, and each protomer has 10 transmembrane helices (TMs). The first 6 TMs carve …

Functional Variants Identify Sex-Specific Genes And Pathways In Alzheimer’S Disease, Minh Pham, Dillon Shapiro, Yashwanth Lagisetty, Shirin Soleimani, Samantha Mota, Kevin Wilhelm, Maryam Samieinasab, Young Won Kim, Eunna Huh, Jennifer Asmussen, Panagiotis Katsonis, Juan Botas, Olivier Lichtarge

Faculty, Staff and Students Publications

The incidence of Alzheimer's Disease in females is almost double that of males. To search for sex-specific gene associations, we build a machine learning approach focused on functionally impactful coding variants. This method can detect differences between sequenced cases and controls in small cohorts. In the Alzheimer's Disease Sequencing Project with mixed sexes, this approach identified genes enriched for immune response pathways. After sex-separation, genes become specifically enriched for stress-response pathways in male and cell-cycle pathways in female. These genes improve disease risk prediction in silico and modulate Drosophila neurodegeneration in vivo. Thus, a general approach for machine learning on …

Dynamic Conformational Switching Underlies Tfiih Function In Transcription And Dna Repair And Impacts Genetic Diseases, Jina Yu, Chunli Yan, Thomas Dodd, Chi-Lin Tsai, John A Tainer, Ivaylo Ivanov

Faculty, Staff and Student Publications

Transcription factor IIH (TFIIH) is a protein assembly essential for transcription initiation and nucleotide excision repair (NER). Yet, understanding of the conformational switching underpinning these diverse TFIIH functions remains fragmentary. TFIIH mechanisms critically depend on two translocase subunits, XPB and XPD. To unravel their functions and regulation, we build cryo-EM based TFIIH models in transcription- and NER-competent states. Using simulations and graph-theoretical analysis methods, we reveal TFIIH's global motions, define TFIIH partitioning into dynamic communities and show how TFIIH reshapes itself and self-regulates depending on functional context. Our study uncovers an internal regulatory mechanism that switches XPB and XPD activities …

Magnetic Resonance Image-Based Estimates Of Hepatic Blood Flow In Children With And Without Obesity; Implications For Physiologically-Based Pharmacokinetic Models, Yoon Cho, Sherwin S. Chan, Chance S. Friesen, Valentina Shakhnovich

Research Days

Background: Physiologically based pharmacokinetic models for simulating drug pharmacokinetics are useful to guide drug dosing for pediatric patients. Hepatic blood flow could be a useful variable to use in these models.

Objectives/Goal: In this study, we explored 2-D phase contrast non-invasive magnetic resonance imaging (MRI) to measure hepatic blood flow in children with and without obesity.

Methods/Design: In this IRB-approved study, we imaged pediatric patients with abdominal MRI with 2D phase contrast imaging of the descending aorta (AO) at the diaphragm, the inferior vena cava (IVC) at the right atrium, and inferior to hepatic drainage above the renal vein confluence …

Program (Pdf), Department Of Obstetrics & Gynecology

Dept. of Obstetrics & Gynecology Resident Research Day

The 35th Annual LSU School of Medicine Department of Obstetrics & Gynecology Resident Research Day was held on Friday, May 12, 2023 at the Human Development Center (HDC).

The Keynote Speaker was Erin Teeter Carey, MD, MSCR.
8 oral presentations were included.

Session Moderators
Session 1 - Obstetrics : Sarah Buzhardt, MD and Tabitha Quebedeaux, MD, PhD
Session 2 - Office Practice : Stacey Scheib, MD and La’Nasha Tanner, MD
Session 3 - Gynecology : Tara Castellano, MD and Neelima Sukhavasi, MD

Browse the attached program for schedule and abstracts.

Dynamic Role Of Exosome Micrornas In Cancer Cell Signaling And Their Emerging Role As Noninvasive Biomarkers, Jaya Aseervatham

Department of Neurology Faculty Papers

Exosomes are extracellular vesicles that originate from endosomes and are released by all cells irrespective of their origin or type. They play an important role in cell communication and can act in an autocrine, endocrine, or paracrine fashion. They are 40–150 nm in diameter and have a similar composition to the cell of origin. An exosome released by a particular cell is unique since it carries information about the state of the cell in pathological conditions such as cancer. miRNAs carried by cancer-derived exosomes play a multifaceted role by taking part in cell proliferation, invasion, metastasis, epithelial–mesenchymal transition, angiogenesis, apoptosis, …

Ethical Considerations Of Clinical Research In Emergency Care Settings: A Review, Adith Velavan

Honors Scholar Theses

Emergency and acute care settings are some of the most volatile and high intensity areas of any healthcare operation. Better understanding of systems and treatments in these spaces are critical to improving outcomes for the high risk patients that are treated there. Clinical research serves as a cornerstone of modern medical research, and is critical to the further improvement of clinical care in these settings. This thesis serves to explore the ethicality of such research given the constraints of emergency medicine settings. Not only does this thesis provide a strong foundation regarding the history and current practices of clinical research, …

Clinical Characteristics And Survival Of Pulmonary Arterial Hypertension With Or Without Interstitial Lung Disease In Systemic Sclerosis, Joanne Sahhar, Kathleen Morrisroe, Diane Apostolopoulous, Nava Ferdowsi, Michelle Wilson, Maryam Tabesh, Wendy Stevens, Mandana Nikpour

Faculty, Staff and Student Publications

Objectives

To describe the clinical phenotype and prognosis of people in the Australian Scleroderma (SSc) Cohort Study with pulmonary arterial hypertension (PAH) with or without interstitial lung disease (ILD).

Methods

Participants meeting ACR/EULAR criteria for SSc were divided into four mutually exclusive groups: those meeting criteria for PAH (PAH-only), ILD (ILD-only), concurrent PAH and ILD (PAH-ILD) or neither PAH nor ILD (SSc-only). Logistic or linear regression analyses were used for associations between clinical features, health-related quality of life (HRQoL) and physical function. Survival analysis was performed using Kaplan–Meier estimates and Cox-regression modelling.

Results

Of 1561 participants, 7% fulfilled criteria for …

Efficient Cancer Modeling Through Crispr-Cas9/Hdr-Based Somatic Precision Gene Editing In Mice, Yongchao Dou, Jazmin Urrutia, Wen Jiang, Fei Yue, Luyu Jia, Ahmed Atef Ibrahim, Bing Zhang, Shixia Huang, Yi Li

Faculty, Staff and Student Publications

CRISPR-Cas9 has been used successfully to introduce indels in somatic cells of rodents; however, precise editing of single nucleotides has been hampered by limitations of flexibility and efficiency. Here, we report technological modifications to the CRISPR-Cas9 vector system that now allows homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic tissues to generate tumor models with high flexibility and efficiency. Somatic editing of either

Pustular Psoriasis And The Potential Therapeutic Usage Of An Il-36 Receptor Monoclonal Antibody, Jeannel T. Miclat, Shafik Habal

Research Day

Pustular psoriasis is an uncommon subtype of psoriasis that dramatically affects the quality of life of affected patients. Pustules can emerge anywhere along the trunk, limbs, soles, palms, and fingers, which debilitates the functionality of these appendages. Currently, there are no approved treatments for pustular psoriasis in the US; off-label usage of psoriasis vulgaris medications is usually prescribed. These treatments are insufficient for patients with difficult to manage or severe forms of pustular psoriasis. Psoriasis vulgaris biologic medications mainly target the IL-17 and IL-23 axis. However, novel clinical findings have demonstrated that pustular psoriasis’s central inflammatory axis depends on the …

An Investigation Of Oral Sex As A Risk Factor For Recurrent Vaginitis: A Case Study, Humza M. Baig, Kate B. Barker, Joy Zarandy

Research Day

Background:

Recurrent Vaginitis is defined as having three or more confirmed episodes within a year. Recurrence rates of vaginitis have been reported in up to 60% of previously infected women. The most common bacterial cause is due to Gardnerella vaginalis, while Candida albicans is the most common fungal cause; both microorganisms can cause opportunistic infections when imbalances occur in the vaginal environment. Commonly known risk factors include multiple sex partners, unprotected sex, douching, recent antibiotic use, and estrogen therapy.

Case Presentation:

A healthy 34-year-old female is complaining of recurrent episodes of vaginitis since the birth of her son two years …

Contributions To Auditory System Conduction Velocity: Insights With Multi-Modal Neuroimaging And Machine Learning In Children With Asd And Xyy Syndrome, Jeffrey I. Berman, Luke Bloy, Lisa Blaskey, Carissa R. Jackel, Judith S. Miller, Judith Ross, J. Christopher Edgar, Thimothy P.L. Roberts

Department of Pediatrics Faculty Papers

Introduction: The M50 electrophysiological auditory evoked response time can be measured at the superior temporal gyrus with magnetoencephalography (MEG) and its latency is related to the conduction velocity of auditory input passing from ear to auditory cortex. In children with autism spectrum disorder (ASD) and certain genetic disorders such as XYY syndrome, the auditory M50 latency has been observed to be elongated (slowed).

Methods: The goal of this study is to use neuroimaging (diffusion MR and GABA MRS) measures to predict auditory conduction velocity in typically developing (TD) children and children with autism ASD and XYY syndrome.

Results: Non-linear TD …

The Effect Of Microglial Cell Dysfunction On Multi-Modal Pre-Pulse Inhibition, Michelle Besser

Dissertations, 2020-current

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication, restricted behaviors, and executive functioning deficits. Mutations in fractalkine signaling, particularly in CX3CR1, in the brain have been linked to ASD and other neurodevelopmental disorders. This investigation examined wild-type mice and mice with one or two copies of mutated CX3CR1 and their uni-modal (auditory and somatosensory) and multi-modal (combined) pre-pulse inhibitions (PPI). PPI is an unconditioned response – a decrement in the acoustic startle reflex when the mouse detects a non-startling stimulus presented a few hundred ms before the startling sound. In this study, the …

Rational Design Of Highly Potent And Selective Covalent Map2k7 Inhibitors, Kristine K Deibler, Hasan H Munshi, Cory Seth Bridges, Taylor Jie Chen, Xiaoyu Zhang, H Daniel Lacorazza, Karl A Scheidt

Faculty, Staff and Students Publications

The mitogen-activated protein kinase signaling cascade is conserved across eukaryotes, where it plays a critical role in the regulation of activities including proliferation, differentiation, and stress responses. This pathway propagates external stimuli through a series of phosphorylation events, which allows external signals to influence metabolic and transcriptional activities. Within the cascade, MEK, or MAP2K, enzymes occupy a molecular crossroads immediately upstream to significant signal divergence and cross-talk. One such kinase, MAP2K7, also known as MEK7 and MKK7, is a protein of great interest in the molecular pathophysiology underlying pediatric T cell acute lymphoblastic leukemia (T-ALL). Herein, we describe the rational …

3-Phosphoinositide-Dependent Kinase 1 Drives Acquired Resistance To Osimertinib, Feng Meng, Lihui Gao, Ruping Shao, Renduo Song, Feng Li, Yonathan Lissanu, Huiqin Chen, Min Jin Ha, Qi Wang, Jing Wang, Elizabeth Shpall, Sung Yun Jung, Franziska Haderk, Philippe Gui, Jonathan Wesley Riess, Victor Olivas, Trever G Bivona, Jack A Roth

Faculty, Staff and Students Publications

Osimertinib sensitive and resistant NSCLC NCI-H1975 clones are used to model osimertinib acquired resistance in humanized and non-humanized mice and delineate potential resistance mechanisms. No new EGFR mutations or loss of the EGFR T790M mutation are found in resistant clones. Resistant tumors grown under continuous osimertinib pressure both in humanized and non-humanized mice show aggressive tumor regrowth which is significantly less sensitive to osimertinib as compared with parental tumors. 3-phosphoinositide-dependent kinase 1 (PDK1) is identified as a potential driver of osimertinib acquired resistance, and its selective inhibition by BX795 and CRISPR gene knock out, sensitizes resistant clones. In-vivo inhibition of …

Co-Clinical Imaging Metadata Information (Cimi) For Cancer Research To Promote Open Science, Standardization, And Reproducibility In Preclinical Imaging, Richard Laforest, Gregory D Ayers, Cristian T Badea, Andriy Y Fedorov, Paul E Kinahan, Matthew Holbrook, Peder E Z Larson, Renuka Sriram, Thomas L Chenevert, Dariya Malyarenko, John Kurhanewicz, A Mcgarry Houghton, Brian D Ross, Stephen Pickup, James C Gee, Rong Zhou, Seth T Gammon, Henry Charles Manning, Raheleh Roudi, Heike E Daldrup-Link, Michael T Lewis, Daniel L Rubin, Thomas E Yankeelov, Kooresh I Shoghi

Faculty, Staff and Students Publications

Preclinical imaging is a critical component in translational research with significant complexities in workflow and site differences in deployment. Importantly, the National Cancer Institute's (NCI) precision medicine initiative emphasizes the use of translational co-clinical oncology models to address the biological and molecular bases of cancer prevention and treatment. The use of oncology models, such as patient-derived tumor xenografts (PDX) and genetically engineered mouse models (GEMMs), has ushered in an era of co-clinical trials by which preclinical studies can inform clinical trials and protocols, thus bridging the translational divide in cancer research. Similarly, preclinical imaging fills a translational gap as an …

Meqtl Mapping In The Genoa Study Reveals Genetic Determinants Of Dna Methylation In African Americans, Lulu Shang, Wei Zhao, Yi Zhe Wang, Zheng Li, Jerome J Choi, Thomas H Mosley, Jennifer A Smith, Xiang Zhou

Faculty, Staff and Student Publications

Identifying genetic variants that are associated with variation in DNA methylation, an analysis commonly referred to as methylation quantitative trait locus (meQTL) mapping, is an important first step towards understanding the genetic architecture underlying epigenetic variation. Most existing meQTL mapping studies have focused on individuals of European ancestry and are underrepresented in other populations, with a particular absence of large studies in populations with African ancestry. We fill this critical knowledge gap by performing a large-scale cis-meQTL mapping study in 961 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We identify a total of 4,565,687 cis-acting meQTLs …

Five-Year Follow-Up Of Zuma-1 Supports The Curative Potential Of Axicabtagene Ciloleucel In Refractory Large B-Cell Lymphoma, Sattva S Neelapu, Caron A Jacobson, Armin Ghobadi, David B Miklos, Lazaros J Lekakis, Yi Lin, Brian T Hill, John M Timmerman, Abhinav Deol, Patrick M Reagan, Patrick Stiff, Ian W Flinn, Umar Farooq, Andre H Goy, Peter A Mcsweeney, Javier Munoz, Tanya Siddiqi, Julio C Chavez, Alex F Herrera, Nancy L Bartlett, Adrian A Bot, Rhine R Shen, Jinghui Dong, Kanwarjit Singh, Harry Miao, Jenny J Kim, Yan Zheng, Frederick L Locke

Faculty, Staff and Student Publications

In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we assessed outcomes in ZUMA-1 after 5 years of follow-up. Eligible adults received lymphodepleting chemotherapy followed by axi-cel (2 × 106 cells per kg). Investigator-assessed response, survival, safety, and pharmacokinetics were assessed in patients who had received treatment. The objective response rate in these 101 patients was 83% (58% complete response rate); with a median follow-up of 63.1 months, responses were ongoing in 31% …

Sepsis-Induced Acute Lung Injury (Ali) And The Development Of Bronchopulmonary Dysplasia (Bpd) In Premature Infants., Jacob S. Ward, Hung-Wen Yeh, Megan Tucker, Venkatesh Sampath

Research Days

Background: Bronchopulmonary dysplasia (BPD) is a significant cause of morbidity and mortality in premature infants with several known risk factors. Recent literature described the harmful effect of inflammation on the developing lung. Recently, we showed that late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) causes acute lung injury (ALI) in preterm infants as measured by increases in pulmonary severity scores (PSS). The aim of this study was to investigate the association between LOS-induced ALI and BPD outcomes. We hypothesized that LOS would increase the likelihood of developing BPD, and the associated LOS-induced ALI will add to the ability to predict development …

Maintenance Of Chronicity Signatures In Fibroblasts Isolated From Recessive Dystrophic Epidermolysis Bullosa Chronic Wound Dressings Under Culture Conditions, Cristian De Gregorio, Evelyng Catalán, Gabriel Garrido, Pilar Morandé, Jimena Castillo Bennett, Catalina Muñoz, Glenda Cofré, Ya-Lin Huang, Bárbara Cuadra, Paola Murgas, Margarita Calvo, Fernando Altermatt, María Joao Yubero, Francis Palisson, Andrew P. South, Marcelo Ezquer, Ignacia Fuentes

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the COL7A1 gene, coding for type VII collagen (C7), an important component of anchoring fibrils in the basement membrane of the epidermis. RDEB patients suffer from skin fragility starting with blister formation and evolving into chronic wounds, inflammation and skin fibrosis, with a high risk of developing aggressive skin carcinomas. Restricted therapeutic options are limited by the lack of in vitro models of defective wound healing in RDEB patients.

RESULTS: In order to explore a more efficient, non-invasive in vitro model for RDEB studies, …

Sensor-Controlled Digital Game For Heart Failure Self-Management: Protocol For A Randomized Controlled Trial, Rachel Tunis, Grace Lee, Angelica Rangel, James Custer, Tom Baranowski, Paul J Rathouz, Miyong T Kim

Faculty, Staff and Students Publications

BACKGROUND: Heart failure (HF) is the leading cause of hospitalization among older adults in the United States. There are substantial racial and geographic disparities in HF outcomes, with patients living in southern US states having a mortality rate 69% higher than the national average. Self-management behaviors, particularly daily weight monitoring and physical activity, are extremely important in improving HF outcomes; however, patients typically have particularly low adherence to these behaviors. With the rise of digital technologies to improve health outcomes and motivate health behaviors, sensor-controlled digital games (SCDGs) have become a promising approach. SCDGs, which leverage sensor-connected technologies, offer the …

Exrna-Eclip Intersection Analysis Reveals A Map Of Extracellular Rna Binding Proteins And Associated Rnas Across Major Human Biofluids And Carriers, David Chen, Anne C Starner, Emmanuel Esquivel, Eric Alsop, Andrew R Jackson, Ionita Ghiran, Getulio Pereira, Joel Rozowsky, Justin Chang, Mark B Gerstein, Roger P Alexander, Matthew E Roth, Jeffrey L Franklin, Robert J Coffey, Robert L Raffai, Isabelle M Mansuy, Stavros Stavrakis, Andrew J Demello, Louise C Laurent, Yi-Ting Wang, Chia-Feng Tsai, Tao Liu, Jennifer Jones, Kendall Van Keuren-Jensen, Eric Van Nostrand, Bogdan Mateescu, Aleksandar Milosavljevic

Faculty, Staff and Students Publications

Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small …

Physician Views On The Provision Of Information On Immune Checkpoint Inhibitor Therapy To Patients With Cancer And Pre-Existing Autoimmune Disease: A Qualitative Study, Hussein Tawbi, Cassandra Calabrese, Natalia I Heredia, Robert J Volk, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) have improved cancer outcomes but can cause severe immune-related adverse events (irAEs) and flares of autoimmune conditions in cancer patients with pre-existing autoimmune disease. The objective of this study was to identify the information physicians perceived as most useful for these patients when discussing treatment initiation with ICIs. Twenty physicians at a cancer institution with experience in the treatment of irAEs were interviewed. Qualitative thematic analysis was performed to organize and interpret data. The physicians were 11 medical oncologists and 9 non-oncology specialists. The following themes were identified: (1) current methods used by physicians to provide …

Late Health Outcomes Among Survivors Of Wilms Tumor Diagnosed Over Three Decades: A Report From The Childhood Cancer Survivor Study, Brent R Weil, Andrew J Murphy, Qi Liu, Rebecca M Howell, Susan A Smith, Elizabeth A Mullen, Wendy M Leisenring, Joseph P Neglia, Lucie M Turcotte, Kevin C Oeffinger, Amanda M Termuhlen, Sogol Mostoufi-Moab, Jennifer M Levine, Kevin R Krull, Yutaka Yasui, Leslie L Robison, Gregory T Armstrong, Eric J Chow, Saro H Armenian

Faculty, Staff and Student Publications

Purpose: To evaluate long-term morbidity and mortality among unilateral, nonsyndromic Wilms tumor (WT) survivors according to conventional treatment regimens.

Methods: Cumulative incidence of late mortality (≥ 5 years from diagnosis) and chronic health conditions (CHCs) were evaluated in WT survivors from the Childhood Cancer Survivor Study. Outcomes were evaluated by treatment, including nephrectomy combined with vincristine and actinomycin D (VA), VA + doxorubicin + abdominal radiotherapy (VAD + ART), VAD + ART + whole lung radiotherapy, or receipt of ≥ 4 chemotherapy agents.

Results: Among 2,008 unilateral WT survivors, 142 deaths occurred (standardized mortality ratio, 2.9, 95% CI, 2.5 to …

Immune Checkpoint B7-H3 Is A Therapeutic Vulnerability In Prostate Cancer Harboring Pten And Tp53 Deficiencies, Wei Shi, Yin Wang, Yuehui Zhao, Justin Jimin Kim, Haoyan Li, Feiyu Chen, Duncan H Mak, Vivien Van, Javier Leo, Brad St Croix, Ana Aparicio, Di Zhao

Faculty, Staff and Student Publications

Checkpoint immunotherapy has yielded meaningful responses across many cancers but has shown modest efficacy in advanced prostate cancer. B7 homolog 3 protein (B7-H3/CD276) is an immune checkpoint molecule and has emerged as a promising therapeutic target. However, much remains to be understood regarding B7-H3's role in cancer progression, predictive biomarkers for B7-H3-targeted therapy, and combinatorial strategies. Our multi-omics analyses identified B7-H3 as one of the most abundant immune checkpoints in prostate tumors containing PTEN and TP53 genetic inactivation. Here, we sought in vivo genetic evidence for, and mechanistic understanding of, the role of B7-H3 in PTEN/TP53-deficient prostate …