Life Sciences Commons^™

Consensus Recommendations For Hyperpolarized [1- 13c]Pyruvate Mri Multi-Center Human Studies, Shonit Punwani, Peder E Z Larson, Christoffer Laustsen, Jan Vandermeulen, Jan Henrik Ardenkjær-Larsen, Adam W Autry, James A Bankson, Jenna Bernard, Robert Bok, Lotte Bonde Bertelsen, Jenny Che, Albert P Chen, Rafat Chowdhury, Arnaud Comment, Charles H Cunningham, Duy Dang, Ferdia A Gallagher, Adam Gaunt, Yangcan Gong, Jeremy W Gordon, Ashley Grimmer, James Grist, Esben Søvsø Szocska Hansen, Mathilde Hauge Lerche, Richard L Hesketh, Jan-Bernd Hoevener, Ching-Yi Hsieh, Kayvan R Keshari, Sebastian Kozerke, Titus Lanz, Dirk Mayer, Mary Mclean, Jae Mo Park, Jim Slater, Damian Tyler, Jean-Luc Vanderheyden, Cornelius Von Morze, Fulvio Zaccagna, Vlad Zaha, Duan Xu, Daniel Vigneron

Faculty, Staff and Student Publications

MRI of hyperpolarized (HP) [1‐13C]pyruvate allows in vivo assessment of metabolism and has translated into human studies across diseases at 15 centers worldwide. To determine consensus on best practice for multi‐center studies for development of clinical applications. This paper presents the results of a two‐round formal consensus building exercise carried out by experts with HP [1‐13C]pyruvate human study experience. Twenty‐nine participants from 13 sites brought together expertise in pharmacy methods, MR physics, translational imaging, and data analysis with the goal of providing recommendations and best practice statements on conduct of multi‐center human studies of HP [1‐13C]pyruvate MRI. Overall, the group …

Isoform-Level Analyses Of 6 Cancers Uncover Extensive Genetic Risk Mechanisms Undetected At The Gene-Level, Yung-Han Chang, Sean T Bresnahan, S Taylor Head, Tabitha A Harrison, Yao Yu, Chad D Huff, Bogdan Pasaniuc, Sara Lindström, Arjun Bhattacharya

Faculty, Staff and Student Publications

Background: Integrating genome-wide association study (GWAS) and transcriptomic datasets can identify mediators for genetic risk of cancer. Traditional methods often are insufficient as they rely on total gene expression measures and overlook alternative splicing, which generates different transcript-isoforms with potentially distinct effects.

Methods: We integrate multi-tissue isoform expression data from the Genotype Tissue-Expression Project with GWAS summary statistics (all N > ~20,000 cases) to identify isoform- and gene-level associations with six cancers (breast, endometrial, colorectal, lung, ovarian, prostate) and six related cancer subtype classifications (N = 12 total).

Results: Directly modeling isoforms using transcriptome-wide association studies (isoTWAS) significantly improves discovery of …

Performance Characteristics For Physiological Measures Of Progressive Pulmonary Fibrosis, Chad A Newton, Ashwatha Thenappan, Gabrielle Y Liu, Leda Yazbeck, Cathryn T Lee, Janelle Vu Pugashetti, Jennifer M Wang, Ethan White, Kevin R Flaherty, Elizabeth A Belloli, Jamie S Sheth, Nisha Mohan, Nazanin Nazemi, Andrew R Yu, Sahand Ghodrati, Kerri A Johannson, Veronica Marcoux, Jolene H Fisher, Deborah Assayag, Helene Manganas, Nasreen Khalil, Martin Kolb, Julie Morisset, Christine Kim Garcia, Felix Chua, Mary E Strek, Yet H Khor, Ayodeji Adegunsoye, Christopher J Ryerson, Philip L Molyneaux, Justin M Oldham

Faculty, Staff and Student Publications

Rationale: Clinical measures of progressive pulmonary fibrosis (PPF) have been proposed, but their clinical utility remains unclear.

Objectives: To determine performance characteristics of lung function-based PPF measures, including new guideline criteria for discriminating clinically relevant outcomes.

Methods: A multicenter retrospective cohort analysis was performed to assess the performance characteristics of eight categorical measures of FVC and DlCO decline, together with PPF guideline criteria (requiring two of the following: worsening respiratory symptoms, absolute decline in FVC ⩾5% or DlCO ⩾15%, or radiological progression) for discriminating 2-year death or lung transplant among patients fibrotic interstitial lung disease from the United States, United …

Associations Of High Attenuation Area-Related Proteomic Biomarkers With Fibrotic Or Subpleural Interstitial Lung Abnormalities, John S Kim, Catherine L Debban, Daniel E Guzman, Riley T Hannan, Mary Salvatore, Claire Mcgroder, David Zhang, Anna J Podolanczuk, Daniel A Duprez, Shwu-Fan Ma, Yong Huang, Jeffrey M Sturek, Stephen S Rich, Jerome I Rotter, Rajat Deo, Ruth F Dubin, Janelle Vu Pugashetti, Jennifer M Wang, Meilan K Han, Justin M Oldham, Imre Noth, Prescott G Woodruff, Victor E Ortega, Julie C Fanburg-Smith, Edward B Stelow, Christopher A Moskaluk, Eric A Hoffman, Christine Kim Garcia, Russell P Bowler, Peter Ganz, R Graham Barr, Ani Manichaikul

Faculty, Staff and Student Publications

No abstract provided.

Engaging Chinese And Korean American Communities In Dementia Research: A Journey Of Inclusivity And Partnership, Jing Wang, Xiang Qi, Mary S Mittelman, Eunjung Ko, Yaolin Pei, I Tek Leong, Sungji Park, Katherine Wang, Weiyu Mao, Cynthia Epstein, Bei Wu

Faculty, Staff and Student Publications

Introduction: The New York University Caregiver Intervention plus Enhanced Support Project is a randomized controlled trial of a family-based psychosocial intervention to enhance social support and reduce cardiometabolic risk for Chinese and Korean American dementia caregivers, using culturally tailored recruitment strategies.

Methods: We reviewed reflections from research staff, weekly meeting minutes, debriefing sessions, and progress reports, to identify key challenges and approaches to engaging participants.

Results: Key challenges included reluctance to involve family members, dementia stigma, and resistance to involving family. In response, we engaged online communities, partnered with local organizations, participated in events, and adapted recruitment messages to cultural …

Impact Of A Focused Best Practice Workshop On Athletic Trainer Confidence, Jaclyn B. Arduini, Jennifer L. Volberding, Zachary A. Murray

Clinical Practice in Athletic Training

Athletic trainers are required to be proficient in emergency management skills, without review these skills may decay creating a potentially dangerous knowledge gap. Confidence measures of emergency management skills were taken before and after a workshop to determine if they changed due to the review of material. All 11 confidence measures increased post workshop, seven significantly, including rectal temperature, hemostatic agents, external hemostatic modalities, in-line stabilization, measurement and application of a cervical collar, football and other equipment removal. ATs should aim to incorporate emergency management review into continuing education choices.

Examining Burnout Among Athletic Trainers Employed In The College And Secondary School Settings, Stephanie M. Singe, Dayna Liu, Alexandrya Cairns

Clinical Practice in Athletic Training

Burnout continues to be an important concern for athletic trainers working traditional employment settings. The purpose of this study was to compare the secondary school and collegiate settings in relation to burnout. Both secondary school and collegiate athletic trainers participated in a self-reported, online cross-sectional design (Qualtrics) to collect data on their experiences with burnout. Data collection occurred during the second week of October 2023 and ceased during the early weeks of November. Collegiate athletic trainers reported moderate burnout overall (54.56 ±15.89) on the CBI whereas secondary school athletic trainers reported low burnout overall (46.67 ±16.57). On the personal-related burnout …

Use Of An Electronic Dynamometer Following Pitching To Identify Fatigue In Softball Pitchers, Bethany L. Hansberger, Peter Lisman

Clinical Practice in Athletic Training

This study used a case-series design to collect in-game fatigue measures for collegiate softball pitchers immediately after pitching during the competitive season. Five softball pitchers (age = 19.8 ± 1.5 years; height = 169.9±6.1 cm; body mass = 79.1±22.6 kg) from one Division I program were recruited. Isometric internal and external rotation, scaption, and grip strength measures were collected using an electronic dynamometer at the beginning and conclusion of the fall non-traditional season, and at the beginning of preseason in January. Strength measures were also obtained during the competitive season at the conclusion of pitching in a game and compared …

Suturing Education For Athletic Trainers: An Evidence-To-Practice Review, Morgan K. Webb, Brett T. Heim, Allyson E. Ritchey, Kenya Moore, Zachary K. Winkelmann

Clinical Practice in Athletic Training

Teaching suturing skills to medical students is a critical component of their education. Implementing suturing into a comprehensive framework is developed from how professors teach the skill. Suturing is a required skill by the General Medical Council that all medical students must have, and how it is being introduced to new students is changing. This review aimed to summarize different educational interventions and determine the most efficient and cost-effective way to teach future suturing skills. The original systematic review included 25 articles in the final data synthesis. Fourteen studies were randomized control trials, six were quasi-experimental, and five were observational. …

Hungry Minds: Analyzing The Impact Of Food Insecurity And Food Assistance Programs On Neurocognitive Development And Childhood Mental Health, Kayla A. Davenport

Senior Theses

Introduction: Food insecurity affects millions of children in the United States and is increasingly recognized as a significant risk factor for poor nutritional intake and adverse health outcomes. However, less is known about how the experience of food insecurity disrupts healthy development and well-being, particularly among American youth. This thesis had two aims: (1) to examine the relationship between household food insecurity and children’s neurocognitive and mental health outcomes and (2) to evaluate how major food assistance programs address, or fail to address, these developmental risks.

Methods: This thesis uses a mixed-methods approach, integrating a narrative literature review, a cross-sectional …

Cul3 Postnatal Homozygous Deletion In Forebrain Results In Behavioral Differences, Prathibha Sekar, Qiang‐Qiang Xia, Alex C. Stokes, Feiyu Quan, Jeffrey Singer, Craig M. Powell

Biology Faculty Publications and Presentations

Large-scale human genetic studies implicate multiple genes that regulate protein ubiquitination in autism spectrum disorder (ASD). De novo loss-of-function mutations in the gene CULLIN3 (CUL3) are implicated in autism and intellectual disability (ID). CUL3 is an essential component of an E3 ubiquitin ligase complex required for ubiquitination of substrates, often a signal for proteasomal degradation. Homozygous deletion of Cul3 is embryonically lethal. Recent studies show heterozygous deletion of Cul3 results in phenotypes with some face validity for autism in constitutive and conditional Cul3 heterozygotes. To understand the function of Cul3 in late postnatal development and function in the brain, we …

Exploring The Diversity And Biology Of Unique Giant Broad Host Range Bacteriophages In Natural Environments, Tannaz Mohammadi

Theses and Dissertations

Microbial interactions within the rhizosphere play a crucial role in shaping bacterial community diversity and function. To explore these dynamics, we isolated 21 bacterial strains from soil and plant root samples collected near Rocky Branch Creek on the University of South Carolina campus. Our findings revealed that a significant proportion of these bacteria are lysogenic for CbK-like phages belonging to the Dolichocephalovirinae subfamily. Additionally, we isolated free bacteriophages directly from the same soil samples and found them to be closely related to those harbored within lysogenic bacteria. Surprisingly, despite predictions of a narrow host range, most of these phages, both …

Unveiling Caulocovert: Conserved Phage And Gene Transfer Agent In Caulobacter, Talia Neco

Theses and Dissertations

Bacteriophage play an important role in bacterial evolution, population control, and horizontal gene transfer within microbial ecosystems. This study focuses on the discovery and characterization of Caulocovert, an active bacteriophage identified in multiple Caulobacter strains. Using genome annotation tools such as Artemis and Mauve, we identified multiple key phage genes, including the major capsid protein, head-tail connector, portal protein, and major tail protein. These phage genes are present in CB13 and several other strains, such as C. vibriodies CB15 and CB2, C. segnis CBR1, Caulobacter sp. FWC26, and the distantly related Caulobacter sp. D5 strain. The location of these genes …

Evaluating The Performance And Feasibility Of A Device-Agnostic Approach To Compare Raw Accelerometry And Hr Data From Consumer Wearables To Research Grade Devices In Young Adults, Candy Bryan Mrudula Yalla

Theses and Dissertations

INTRODUCTION: Wearable technologies are increasingly used to monitor physical activity and heart rate in both research and everyday settings. This study aimed to compare accelerometery and heart rate (HR) data from two consumer wearables Apple Watch Series 7 and Google Pixel Watch Series 2, with research-grade devices: the ActiGraph GT9X Link and ActiHeart 5.

METHODS: Twenty-four young adults aged 18–24 years (mean age = 22.4; 54.2% female) participated in a 90-minute activity protocol while wearing the devices. The protocol included structured tasks ranging from rest to vigorous intensity. Consumer wearables and ActiGraph were worn on the non-dominant wrist, and the …

Hcmv Infection Of Terminally Differentiated Neurons Disrupts Microtubule Organization, Resulting In Neurite Retraction, Jacob W. Adelman, Andrew T. Sukowaty, Kaitlyn J. Partridge, Jessica E. Gawrys, Allison Akins, Scott S. Terhune, Allison D. Ebert

Biological Sciences Faculty Research and Publications

Human cytomegalovirus (HCMV) is a prolific human herpesvirus that infects most individuals by adulthood. While typically asymptomatic in adults, congenital infection can induce serious neurological symptoms, including hearing loss, visual deficits, cognitive impairment, and microcephaly in 10%–15% of cases. HCMV has been shown to infect most neural cells, with our group recently demonstrating this capacity in stem cell-derived forebrain neurons. Infection of neurons induces deleterious effects on calcium dynamics and electrophysiological function paired with gross restructuring of neuronal morphology. Here, we utilize an induced pluripotent stem cell-derived model of the human forebrain to demonstrate how HCMV infection induces syncytia, drives …

Memories Of Trees Past: Coexistence Implications Of Legacy Conspecific Density Dependence, Lukas J. Magee, Daniel J.B. Smith, David Bauman, Po-Ju Ke, Helene C. Muller-Laudau, Kristina J. Anderson-Teixeira, Jessica Shue, David A. Orwig, Sean M. Mcmahon, Stephanie Bohlman, Raelene M. Crandall, Ben Weinstein, Sergio Marconi, Jeremy W. Lichstein, James F. Gillooly, Robert Bagchi, Joseph A. Lamanna, Daniel J. Johnson

Biological Sciences Faculty Research and Publications

The Janzen-Connell Hypothesis posits that plant species diversity is maintained by a reduction in seedling survival near living conspecific trees relative to heterospecifics–known as negative conspecific density dependence (CDD). CDD facilitates coexistence if stronger than heterospecific density dependence (HDD). However, whether and how long CDD persists after trees die is unknown. In a three-year study across three forests, we monitored seedling survival near living and dead trees, both conspecific and heterospecific, across a seven-year chrono-sequence since tree death. CDD persisted for at least 5 years after tree death (‘legacy CDD’), and most species showed stronger CDD relative to HDD through …

Dynamic Rewiring Of Microrna Networks In The Brainstem Autonomic Control Circuits During Hypertension Development In The Female Spontaneously Hypertensive Rat, Alison Moss, Ankita Srivastava, Lakshmi Kuttippurathu, James S. Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We describe global microRNA (miRNA) changes in the central autonomic control circuits during the development of neurogenic hypertension. Using the female spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto (WKY), we analyzed the dynamic miRNA expression changes in three brainstem regions-the nucleus of the solitary tract, caudal ventrolateral medulla, and rostral ventrolateral medulla-as a time series beginning at 8 wk of age before hypertension onset through to extended chronic hypertension. Our analysis yielded nine miRNAs that were significantly differentially regulated in all three regions between SHR and WKY over time. We collated computationally predicted gene targets of these nine …

Sulforaphane And Non-Clustered Tumor/Non-Tumor Suppressor Micrornas Regulate Akt And Its Downstream Genes In Mda-Mb-231 Cancer Cells, Omobolanle David Garuba

Dissertations (2016-Present)

Cancer is a complex pathological condition characterized mainly by uncontrolled rapid cell divisions caused by several factors, which include genetics and environmental factors. Of all cancer types, breast cancer (BC) remains the second most diagnosed among women worldwide; thus, BC burden has become a global health issue. Of all known breast cancer subtypes, triple-negative breast cancer (TNBC) is the only primary subtype without effective therapy as a result of their lack of the essential estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) common to other BCs and are the usual therapeutic targets for treatment. …

Detection Of Microplastics In Household Dust From Suburban Texas And Toxicological Assessment Of Polystyrene Microparticles In Lung Epithelial Cells: Nf-Kb Pathway Activation And Inflammatory Responses, Nirupama Surubhotla

Dissertations (2016-Present)

Microplastics are emerging contaminants that have raised global concern due to their persistence, ubiquity, and potential impacts on human health. Indoor environments are increasingly recognized as significant sources of microplastic exposure through household dust inhalation. This study aimed to detect the presence of microplastics in household dust from suburban regions of Texas, USA, and to investigate the cytotoxic and inflammatory effects of polystyrene microparticles in a lung epithelial cell model (A549). Household dust samples were collected and analyzed using Raman spectroscopy, confirming the presence of a mixture of microplastics. To assess biological responses, A549 cells were exposed to defined sizes …

Curcumin And Compound-20 (A Synthetic Curcumin) Ameliorates Effects Of Acrolein In Rat Kidney By Improving Renal Autophagy, Sandra Isioma Erue

Dissertations (2016-Present)

Study aim is to determine the role of p38-MAPK/Nrf2 and NF-κB signaling in acrolein-induced kidney injury. Evaluate autophagy modulation and whether curcumin and Compound 20 mitigate acrolein-induced kidney injury by modulating p38-MAPK/Nrf2 and NF-κB pathways. Male Sprague–Dawley rats were randomly divided into groups (n = 5) for control and treatment. All rats were fasted for 4–5 hours daily throughout the 10-day study period. Male Sprague–Dawley rats were administered peanut butter, curcumin, or Compound-20 mixed with peanut butter via voluntary oral consumption, followed by intraperitoneal (IP) administration of acrolein. The animals were randomly divided into groups (n = 5) for control …

Hooks For Four-Dimensional Ecology Education (4dee) Teaching With Differing Audiences Of Nonmajors, Sara E. Scanga, Vikki L. Rodgers, Loren B. Byrne, Justin R. St. Juliana, Jon M. Honea, Erica S. Tietjen, George Middendorf

Arts & Sciences Faculty Publications

Nonmajors (i.e., undergraduate students not majoring in the natural sciences) constitute a majority of United States college graduates and are a large potential audience for courses with ecology content. However, nonmajors may be unmotivated to learn about ecology because they perceive it to be uninteresting and irrelevant to their everyday lives or career goals. Although the Four-Dimensional Ecology Education (4DEE) framework can be adapted for nonmajors courses as a starting point to improve student engagement, we suggest that nonmajors ecology instructors also use ecology hooks as effective gateways to 4DEE that will motivate and deepen student learning. Selecting and developing …

Investigating The Effect Of Gene Ncu07872 Deletion On Spore Killing By Neurospora Sk-3, Allison Rimmey

Senior Theses – Biological Sciences

The selfish genetic element Spore killer-3 (Sk-3) is found in some Neurospora fungi. Sk-3 is considered selfish because it has evolved the capacity to bias its transmission to the next generation through spore killing. The mechanism of spore killing requires at least two genes, a gene that produces a resistance protein (an antidote) and a gene that produces a killer protein (a poison). The Sk-3 genetic element is millions of base pairs long and contains hundreds of genes. Although the antidote gene has been identified, the identity of the poison gene has remained elusive. Previous research has identified a DNA …

Cephalopod Consciousness: Asking The Right Questions, Gordon Burghardt

Animal Sentience

Jennifer Mather has provided a comprehensive and fascinating overview of the various cognitive accomplishments of cephalopods and their sensory, behavioral, and neurophysiological attributes. The advances in our understanding of a clade that has been separated from vertebrate evolution by well over half a billion years is a testament to advances in both methodology and the questions we now feel free to address. Mather embeds her review in the issue of consciousness, which is certainly a perennial issue in mental evolution, going back to Romanes and earlier. I argue that the term “consciousness” has such a checkered history and is used …

Smart Search Results For Growth And Economic Performance Comparison Of Twenty-Year-Old ... Refine Results For Arkansas Net Energy: A Productive Energy System Sensitive To Broiler Performance And Body Composition Arkansas Net Energy: A Productive Energy System Sensitive To Broiler Performance And Body Composition 21 Of 94 Arkansas Net Energy: A Productive Energy System Sensitive To Broiler Performance And Body Composition, Diego A. Martinez, Nawin Suesuttajit, Cole Umberson, Craig N. Coon

Poultry Science Faculty Publications and Presentations

This study determined the sensitivity of productive energy (PE; Arkansas Net Energy) to performance and body composition and developed predictive models based on PE. Chicks (2,148 day-old ones) were placed in 96 pens and assigned to one of 12 dietary treatments, including varying concentrations of total digestible amino acids (TDAA), digestible CP (dCP), digestible fat (dFat), digestible starch, and non-starch polysaccharides (NSP). Eight replications per treatment, one per block, were used, being the block consecutive groups of birds weekly starting the seven-day experimental period. In each block, birds were control fed to meet similar ME intake, placed in calorimetry chambers …

Effects Of Heat Stress And Depressed Feed Intake On The Cecal And Ileal Microbiota Of Broiler Chickens, Philip M. Campos, Elizabeth S. Greene, Monika Proszkowiec-Weglarz, Sami Dridi

Poultry Science Faculty Publications and Presentations

Chronic heat stress (HS) is known to depress feed intake (FI) and growth in broiler chickens, and may alter the gut microbiota and health, however, the amplitude and duration of each (HS and depressed FI) effect on gut microbiota is still unclear. This study aimed to determine the effects of chronic and acute HS on the cecal and ileal microbiota profiles. Broilers were subjected to thermoneutral (TN, 23 degrees C) or chronic cyclic HS (CHS, 8 h/d, 35 degrees C) condition from d29-42, and one group to acute HS (AHS, 2 h, 35 degrees C) at d42. To distinguish between …

Divergent Sensory Transcriptomic Profiles In Positive And Negative Learning In Bicyclus Anynana Butterflies, Yi Ting Ter, Erica L. Westerman

Biological Sciences Faculty Publications and Presentations

Mate preference learning, where individuals learn to prefer or avoid specific phenotypes during mate selection, is pervasive across animal taxa and influences reproductive isolation and trait evolution. Despite its significance, the genetic basis underlying the associated valence attribution (whether to prefer or avoid) remains largely unclear. Both in terms of what genes are associated with attributing valence, and whether valence attribution is associated with transcriptional changes in both sensory tissues and neural circuits in the brain, or is restricted to the brain. Here, we investigate the neurogenomic basis of positive and negative mate preference learning using Bicyclus anynana butterflies. We …

Trichome Density And Herbivore Behaviour On Tomato Is Influenced By Herbivory, Plant Age, And Leaf Surface, Sunil Aryal, Manish Gautam, Justin George, Gadi V.P. Reddy, Rupesh Kariyat

Entomology and Plant Pathology Faculty Publications and Presentations

Leaf trichomes in plants act as the first line of physical defence against herbivory, in addition to many other reported functions. Although trichomes have been found to vary intraspecifically and can be induced by herbivory, their interactive effects under additional factors, such as plant age and abaxial vs. adaxial leaf surfaces, are less understood. Here, using five common tomato varieties, we explored the effects of these factors and their interactions on trichome type and density. We quantified the densities of Type VI glandular trichomes, non-glandular trichomes, and total trichomes on abaxial and adaxial leaf surfaces, and total leaf trichomes with …

Physicochemical And Structural Optimization Of Date (Phoenix Dactylifera L.) Syrup: Impact Of Extraction Temperatures And Pectin Addition, Afna Thaivalappil Abdul Asiz

Theses

This thesis focuses on the optimization of date (Phoenix dactylifera L.) syrup, an emerging natural sweetener rich in glucose, fructose, and bioactive compounds, by investigating how extraction temperature and pectin incorporation influence its physicochemical and structural properties. Therefore, the main objective of this study was to examine how extraction temperatures (25°C, 50°C, 75°C, and 90°C), and the incorporation of lowmethoxyl pectin (LMP, DE 31%) and high-methoxyl pectin (HMP, DE 85%) prior to concentration, affect the quality, stability, and functionality of date syrup. The results showed that increasing extraction temperatures increased the total soluble solids (16 °Brix at 25°C to …

Precemtabart Tocentecan, An Anti-Ceacam5 Antibody-Drug Conjugate, In Metastatic Colorectal Cancer: A Phase 1 Trial, Scott Kopetz, Valentina Boni, Ken Kato, Kanwal P S Raghav, Maria Vieito, Athanasios Pallis, Christina Habermehl, Abdul Siddiqui, Perrine Courlet, Willem Sloot, Sabine Raab-Westphal, Felix Hart, Ildefonso Rodriguez-Rivera

Faculty, Staff and Student Publications

CEACAM5, a cell surface protein, is overexpressed in colorectal cancer (CRC). Precemtabart tocentecan (Precem-TcT, previously M9140) is an anti-CEACAM5 antibody–drug conjugate with the topoisomerase 1 inhibitor exatecan as payload. Precem-TcT demonstrated strong antitumor activity and potent bystander activity in preclinical models. Its toxicity profile in cynomolgus monkeys was consistent with that of exatecan. In the dose-escalation stage of the phase 1 trial of Precem-TcT (PROCEADE-CRC-01), 40 heavily pretreated patients with irinotecan-refractory metastatic CRC received Precem-TcT every 3 weeks across seven dose levels (DLs, 0.6–3.2 mg kg−1). Primary endpoints were dose-limiting toxicities (DLTs), adverse events and preliminary clinical activity to establish …

Lesion Absorbed Dose-Response Relationship In Patients With Metastatic Castration-Resistant Prostate Cancer Undergoing [177lu]Lu-Psma-617 Radiopharmaceutical Therapy, Milan Grkovski, Simone S Krebs, Joseph A O'Donoghue, Jonathan Kuten, Audrey Mauguen, Parnian Shobeiri, Daniel Lafontaine, Maria Thor, Finn Augensen, Josef J Fox, Neeta Pandit-Taskar, Mark P Dunphy, Lisa Bodei, John L Humm, Heiko Schöder

Faculty, Staff and Student Publications

The relationship between lesion absorbed dose (AD) and response in patients with metastatic castration-resistant prostate cancer undergoing [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) remains poorly understood. The objective of this work was to investigate the AD-response relationship at both the patient and lesion levels.

Methods: Sixty-five patients underwent serial SPECT/CT imaging after receiving 7.31 ± 0.27 GBq of [177Lu]Lu-PSMA-617. Single-time-point (STP) (Hänscheid approximation at 72 h) and multiple-time-point voxelwise dosimetry were performed. Patient response was evaluated by changes in serum prostate-specific antigen level before and after cycle 1 of RPT. The response of individual lesions was evaluated by the change in the …