Digital Commons Network^™

Cancer Organoids As Reliable Disease Models To Drive Clinical Development Of Novel Therapies, Giovanni Blandino, Ronit Satchi-Fainaro, Ingeborg Tinhofer, Giovanni Tonon, Sarah C Heilshorn, Ana Pestana, Luca Pompili, Aurora Puce, Sara Iachettini, Annalisa Tocci, Sofia Karkampouna, Marianna Kruithof-De Julio, Piera Tocci, Nicla Porciello, Klizia Maccaroni, Daniela Rutigliano, Xiling Shen, Gennaro Ciliberto

Faculty, Staff and Student Publications

On September 23-24 (2024) the 6th Workshop IRE on Translational Oncology, titled "Cancer Organoids as Reliable Disease Models to Drive Clinical Development of Novel Therapies," took place at the IRCCS Regina Elena Cancer Institute in Rome. This prominent international conference focused on tumor organoids, bringing together leading experts from around the world.A central challenge in precision oncology is modeling the dynamic tumor ecosystem, which encompasses numerous elements that evolve spatially and temporally. Patient-derived 3D culture models, including organoids, explants, and engineered or bioprinted systems, have recently emerged as sophisticated tools capable of capturing the complexity and diversity of cancer cells …

Development And Evaluation Of An Implementation Strategy To Increase Hpv Vaccination Among Underserved Youth Across Texas: A Protocol Paper, Mayra Aguilar Mcbride

Faculty, Staff and Student Publications

BACKGROUND: All for Them is a theory-based and evidence-informed multilevel, multicomponent program delivered through schools to increase HPV vaccination among medically underserved youth across Texas. Given the potential logistical challenges of program implementation, understanding how to best support the implementation and sustainment of the program is critical. The overall goals of this study are twofold: 1) develop a multifaceted implementation strategy, Implementing All for Them (IM-AFT); and 2) evaluate the impact of IM-AFT on implementation outcomes for schools and healthcare providers to successfully implement All for Them in their respective settings.

METHODS: This study is underpinned by a comprehensive and …

Improving Pediatric Magnetic Resonance Imaging Safety By Enhanced Non-Technical Skills And Team Collaboration, Masashi Uramatsu, Hidekuni Takahashi, Paul Barach, Yoshikazu Fujisawa, Megumi Takahashi, Shiro Mishima, Gaku Yamanaka

College of Population Health Faculty Papers

BACKGROUND: Safe pediatric magnetic resonance imaging (MRI) ideally relies on non-sedative techniques, as avoiding risky sedation is inherently safer. However, in practice, sedation often becomes unavoidable, particularly for younger children or those with anxiety, to ensure motion-free, high-quality imaging. This narrative review explores the current practices and proposes strategies to enhance safety in pediatric MRI examinations.

METHODS: We identified and analyzed 247 studies addressing various aspects of pediatric MRI safety, including sedation protocols, patient monitoring, and team-based management approaches.

RESULTS: Safe sedation requires careful drug selection tailored to individual needs, continuous monitoring, and robust emergency preparedness. While efforts are underway …

A Conceptual Framework To Assess The Health, Socioeconomic And Environmental Burden Of Chronic Kidney Disease, Charlotte Johnston-Webber, Isaac Bencomo-Bermudez, George Wharton, Robin Van Kessel, Salvatore Barone, Francisco Brotons Muntó, Steven Chadban, Juan Jose Garcia Sanchez, Janwillem Kocks, Kyra Obolensky, Petra Sandow, Neil Skolnik, Ming-Hui Zhao, Alexei Volaco, David Wheeler, Alistair Mcguire, Elias Mossialos

Department of Medicine Faculty Papers

Chronic kidney disease (CKD) is a global health challenge that affects patients, caregivers, healthcare systems, the environment and national economies. Despite its far-reaching impact, there is no framework to systematically evaluate national CKD prevention and management programmes or evaluate the societal burden of disease. This paper has two objectives: first, to introduce a comprehensive framework to assess national programmes, which recognises gaps and weaknesses and identifies feasible policy interventions to reduce overall CKD burden; second, to present some key challenges and success stories in delivering CKD services delivered in eight different country settings. A literature review informed an initial version …

Glucose-Lowering Agents Developed In The Last Two Decades And Their Perioperative Implications, Basavana Goudra, Geno Merli, Michael Green

Department of Anesthesiology Faculty Papers

The last two decades have provided far more options f both patients and their physicians in the treatment of diabetes mellitus. While dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been approved for nearly two decades, sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are relatively new. Of interest to perioperative physicians, these drugs present specific perioperative concerns, prompting many societies to issue guidelines. Retained gastric contents due to slow gastric emptying is a significant drawback of GLP-1RAs, increasing the risk of aspiration. Recommendations include withholding GLP-1RAs for a predefined period of time, performing gastric ultrasound to evaluate gastric …

An Ontology-Based Approach For Understanding Appendicectomy Processes And Associated Resources, Xubing Hao, Licong Cui, Ping Yu

Faculty, Staff and Student Publications

Background: Traditional methods for analysing surgical processes often fall short in capturing the intricate interconnectedness between clinical procedures, their execution sequences, and associated resources such as hospital infrastructure, staff, and protocols.

Aim: This study addresses this gap by developing an ontology for appendicectomy, a computational model that comprehensively represents appendicectomy processes and their resource dependencies to support informed decision making and optimise appendicectomy healthcare delivery.

Methods: The ontology was developed using the NeON methodology, drawing knowledge from existing ontologies, scholarly literature, and de-identified patient data from local hospitals.

Results: The resulting ontology comprises 108 classes, including 11 top-level classes and …

Inhibition Of Microrna-660-5p Decreases Breast Cancer Progression Through Direct Targeting Of Tmem41b, Valeria Villarreal-García, José Roberto Estupiñan-Jiménez, Vianey Gonzalez-Villasana, Pablo E Vivas-Mejía, Marienid Flores-Colón, Patricio Adrián Zapata-Morín, José Manuel Vázquez-Guillen, Cristina Rodríguez-Padilla, Recep Bayraktar, Mohamed H Rashed, Cristina Ivan, Gabriel Lopez-Berestein, Diana Reséndez-Pérez

Faculty, Staff and Student Publications

Background: Breast cancer is the most prevalent cancer among women worldwide. Most breast cancer-related deaths result from metastasis and drug resistance. Novel therapies are imperative for targeting metastatic and drug-resistant breast cancer cells. Accumulating evidence suggests that dysregulated microRNAs (miRNAs) promote breast cancer progression, metastasis, and drug resistance. Compared with healthy breast tissue, miR-660-5p is notably overexpressed in breast cancer tumor tissues. However, the downstream effectors of miR-660-5p in breast cancer cells have not been fully elucidated. Our aim was to investigate the role of miR-660-5p in breast cancer cell proliferation, migration, invasion, and angiogenesis and to identify its potential …

Novel Digital Anomalies, Hippocampal Atrophy, And Mutations Expand The Genotypic And Phenotypic Spectra Of Cnksr2 In The Houge Type Of X-Linked Syndromic Intellectual Development Disorder (Mrxshg), Mohammad Reza Ghasemi, Sahand Tehrani Fateh, Afif Ben-Mahmoud, Vijay Gupta, Lara G. Stühn, Gaetan Lesca, Nicolas Chatron, Konrad Platzer, Patrick Edery, Hossein Sadeghi, Bertrand Isidor, Benjamin Cogné, Heidi L. Schulz, Ilona Krauspe-Stübecke, Radhakrishnan Periyasamy, Sheela Nampoothiri, Reza Mirfakhraie, Sahar Alijanpour, Steffen Syrbe, Ulrich Pfeifer, Stephanie Spranger, Kathrin Grundmann-Hauser, Tobias B. Haack, Maria T. Papadopoulou, Tayrine Da Silva Gonçalves, Eleni Panagiotakaki, Alexis Arzimanoglou, Seyed Hassan Tonekaboni, Yves Lacassie, Et Al

School of Medicine Faculty Publications

The Houge type of X-linked syndromic intellectual developmental disorder (MRXSHG) encompasses a spectrum of neurodevelopmental disorders characterized by intellectual disability (ID), language/speech delay, attention issues, and epilepsy. These conditions arise from hemizygous or heterozygous deletions, along with point mutations, affecting CNKSR2, a gene located at Xp22.12. CNKSR2, also known as CNK2 or MAGUIN, functions as a synaptic scaffolding molecule within the neuronal postsynaptic density (PSD) of the central nervous system. It acts as a link connecting postsynaptic structural proteins, such as PSD95 and S-SCAM, by employing multiple functional domains crucial for synaptic signaling and protein–protein interactions. Predominantly expressed in dendrites, …

Womb, Gravity, And Space: Shifting Towards The Cerebellum-Basal Ganglia Paradigm In Dystonia, Diego Iacono

Department of Neurology Faculty Papers

No abstract provided.

The Camden Study - A Pregnancy Cohort Study Of Pregnancy Complications And Birth Outcomes In Camden, New Jersey, Usa., Stephanie Shiau, Xinhua Chen, Ayana April-Sanders, Ellen C Francis, Shristi Rawal, Megan Hansel, Kehinde Adeyemi, Zorimar Rivera-Núñez, Emily S Barrett

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Pregnancy is a unique stage of the life course characterized by trade-offs between the nutritional, immune, and metabolic needs of the mother and fetus. The Camden Study was originally initiated to examine nutritional status, growth, and birth outcomes in adolescent pregnancies and expanded to study dietary and molecular predictors of pregnancy complications and birth outcomes in young women.

METHODS: From 1985-2006, 4765 pregnant participants aged 12 years and older were recruited from Camden, NJ, one of the poorest cities in the US. The cohort reflects a population under-represented in perinatal cohort studies (45% Hispanic, 38% non-Hispanic Black, 17% White …

Notes From The Field: School-Based Surveillance Of Mycoplasma Pneumoniae Trends And Impact On School Attendance By Students And Staff Members - Missouri, Fall 2024., Olivia M. Almendares, Brittney Fritschmann, Rangaraj Selvarangan, Brian R. Lee, Chris Edens, Maureen Diaz, Brett Whitaker, Shannon Tilsworth, Janelle Porter, Nibha Sagar, Jennifer E. Schuster, Jennifer Goldman, Hannah L. Kirking

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Assessing Tolerability With The Functional Assessment Of Cancer Therapy Item Gp5: Psychometric Evidence From Libretto-531, A Phase 3 Trial Of Selpercatinib In Medullary Thyroid Cancer, Antoine Regnault, Laurine Bunod, Angely Loubert, Marcia S. Brose, Lisa M. Hess, Patricia Maeda, Yan Lin, Rebecca M. Speck, Adrienne M. Gilligan, Nalin Payakachat

Department of Medical Oncology Faculty Papers

BACKGROUND: This psychometric analysis generated evidence to support the use of the Functional Assessment of Cancer Therapy item GP5 (GP5) as a measure of tolerability and confirms the appropriateness of categorizing "high side-effect burden" using a rating of 3 or 4 (score ranges 0-4) in patients with advanced/metastatic RET-mutant medullary thyroid cancer (MTC).

METHODOLOGY: Blinded, pooled interim data from the safety population (n=290) enrolled in the phase 3 LIBRETTO-531 trial (NCT04211337) were used. Intraclass correlation coefficients (ICC) were calculated for test-retest reliability using data from cycles 1-2 post-baseline. Construct validity was evaluated by examining the correlations of GP5 ratings with …

Epilepsy Therapies Symposium | Do We Really "Outgrow" Seizures?, Mohammed Ilyas, Dean Naritoku, Alica M Goldman

Faculty, Staff and Students Publications

Initiation and maintenance of antiseizure therapy can be relatively straightforward in most patients. Depending on epilepsy type, patients may be more or less likely to enter remission or a resolution of their epilepsy and the International League Against Epilepsy developed clinically guiding definitions in this regard. The mechanisms by which resolution or remission are achieved are poorly understood which complicates clinical decision making and risk estimate for future seizure relapse. The impetus for the maintenance of medical therapy in a seizure-free patient is also age-dependent. In children, one ought to consider the unknown effects of antiseizure medications on the developing …

Il-12 Encoding Ondv Synergizes With Car-T Cells In Orthotopic Models Of Non-Small Cell Lung Cancer, Eric Tu, Greyson W Biegert, Sonia Agrawal, Nicholas Durham, Malcolm K Brenner, Masataka Suzuki

Faculty, Staff and Students Publications

Systemic administration of oncolytic viruses (OVs) is a promising approach for targeting metastatic solid tumors, but their anti-tumor activity is limited by pre-existing neutralizing antibodies against common human viruses. Therefore, investigators have developed OVs derived from non-human host viruses. Successful implementation of this strategy requires that the viral vector selectively infects and replicates within human cancer cells. Newcastle disease virus (NDV) is an avian paramyxovirus that, as NDV-based OVs (oNDVs), has demonstrated safety and activity against multiple human tumors in clinical trials. Their use as a single agent, however, is insufficient to cure tumors. Similarly, chimeric antigen receptor-modified T cells …

Oculomotor Nerve Palsy Recovery Following Microsurgery Vs. Endovascular Treatment Of Posterior Communicating Artery Aneurysms: A Comparative Meta-Analysis Of Short- And Long-Term Outcomes, Rahim Abo Kasem, Conor Cunningham, Sameh Samir Elawady, Mohammad Mahdi Sowlat, Sofia Babool, Saad Hulou, Zachary Hubbard, Atakan Orscelik, Basel Musmar, Alejandro Spiotta

Department of Neurosurgery Faculty Papers

Recent advancements in endovascular treatment (EVT) and different views on optimal management for posterior communicating artery (PComA) aneurysms with oculomotor nerve palsy (ONP) highlight a need to compare recovery timelines between microsurgery and EVT; heterogeneous outcomes and influencing factors may also affect results. A comprehensive systematic review and meta-analysis were conducted by searching PubMed, Embase, Scopus, and Web of Science databases. The extracted data encompassed patient demographics, details on treatment modalities and timing, and characteristics of PComA aneurysms ONP caused by either unruptured or ruptured aneurysms. The primary outcome was ONP favorable recovery, defined as the resolution of admission symptoms, …

Navigating Life After The Nicu: A Developmental Guide For Preterm And High-Risk Infants And Toddlers, Reagan Lachaussee, Mary Jan Greer Phd, Otr, Theresa Mensi

Fall 2024 OTD Capstone Symposium

Premature and medically fragile infants are at high risk for developmental delays and benefit from ongoing support. Parents often feel overwhelmed and uncertain about how to support their child’s development at home. This project addressed gaps in caregiver education and support by developing the PEARLS Program (Promoting Early Achievements, Resilience, and Life Skills), a practical resource tailored to the needs of families and healthcare providers.

A needs assessment and provider feedback guided the program’s development, identifying challenges such as information overload, confusion around corrected age, and feeding difficulties. The PEARLS Program empowers families with digestible, actionable resources, including …

Feasibility Of Large Language Models For Ceus Li-Rads Categorization Of Small Liver Nodules In Patients At Risk For Hepatocellular Carcinoma, Jiayan Huang, Rui Yang, Xiaotong Huang, Keyu Zeng, Yan Liu, Jun Luo, Andrej Lyshchik, Qiang Lu

Department of Radiology Faculty Papers

BACKGROUND: Large language models (LLMs) offer opportunities to enhance radiological applications, but their performance in handling complex tasks remains insufficiently investigated.

PURPOSE: To evaluate the performance of LLMs integrated with Contrast-enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) in diagnosing small (≤20mm) hepatocellular carcinoma (sHCC) in high-risk patients.

MATERIALS AND METHODS: From November 2014 to December 2023, high-risk HCC patients with untreated small (≤20mm) focal liver lesions (sFLLs), were included in this retrospective study. ChatGPT-4.0, ChatGPT-4o, ChatGPT-4o mini, and Google Gemini were integrated with imaging features from structured CEUS LI-RADS reports to assess their diagnostic performance for sHCC. …

Multi-Antigen Elephant Endotheliotropic Herpesvirus (Eehv) Mrna Vaccine Induces Humoral And Cell-Mediated Responses In Mice, Rongsheng Peng, Jie Tan, Paul D Ling

Faculty, Staff and Students Publications

Background/Objectives: Elephant endotheliotropic herpesvirus (EEHV) causes lethal hemorrhagic disease (HD) in Asian and African elephants in human care and the wild. It is the leading cause of death for young Asian elephants in North American and European zoos despite sensitive diagnostic tests and improved treatments. Thus, there is a critical need to develop an effective vaccine to prevent severe illness and reduce mortality from EEHV-HD. We generated a multi-antigenic EEHV mRNA vaccine to address this need that encodes the EEHV1A-subtype glycoproteins gB, gH, gL, and gO. These conserved proteins are the entry machinery for several herpesviruses in the betaherpesvirus subfamily …

Artificial Intelligence-Based Methodologies For Early Diagnostic Precision And Personalized Therapeutic Strategies In Neuro-Ophthalmic And Neurodegenerative Pathologies, Rahul Kumar, Ethan Waisberg, Joshua Ong, Phani Paladugu, Dylan Amiri, Jeremy Saintyl, Jahnavi Yelamanchi, Robert Nahouraii, Ram Jagadeesan, Alireza Tavakkoli

SKMC Student Presentations and Publications

Advancements in neuroimaging, particularly diffusion magnetic resonance imaging (MRI) techniques and molecular imaging with positron emission tomography (PET), have significantly enhanced the early detection of biomarkers in neurodegenerative and neuro-ophthalmic disorders. These include Alzheimer's disease, Parkinson's disease, multiple sclerosis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein antibody disease. This review highlights the transformative role of advanced diffusion MRI techniques-Neurite Orientation Dispersion and Density Imaging and Diffusion Kurtosis Imaging-in identifying subtle microstructural changes in the brain and visual pathways that precede clinical symptoms. When integrated with artificial intelligence (AI) algorithms, these techniques achieve unprecedented diagnostic precision, facilitating early detection of neurodegeneration and …

Guidelines For Returning To Dance Following Concussion: Adaptations From Sport Concussion Literature, Sheyi Ojofeitimi, Lauren Mcintyre, Elizabeth Barchi, Sarah S. Rae, Brittney Winnitoy, Jeffrey A. Russell

Department of Family & Community Medicine Faculty Papers

Sport concussion receives substantial attention as a public health concern. Conversely, performing artists, including dancers, sustain concussions, but these aesthetic athletes do not receive the same level of consideration nor care for this injury as that offered to traditional athletes. The concussion literature pertaining to dance is sparse, and, to our knowledge, no recommendations exist for the crucial aspect of care related to returning to dance following a concussion. The purpose of this article is to assimilate the current knowledge about post-concussion return to activity management in sport—the closest analog of the physical demands required in dance—as a means to …

The Revised Cdc Chronic Pain Guidelines And Payer Opioid Analgesic Policies In Michigan, Victoria Tutag Lehr, Cynthia L. Arfken

Michigan Journal of Public Health

Abstract

The 2016 publication of A Guideline for Prescribing Opioids for Chronic Pain by the Centers for Disease Control and Prevention motivated commercial and Medicaid payers to restrict their opioid prescribing policies including the imposition of hard limits on opioid daily dosages and duration. One result of these policies was an increase in abrupt opioid discontinuation and rapid tapering events for patients receiving long-term opioid therapy. Responding to this misapplication of the 2016 guideline, the 2022 revised guidelines emphasized individualized opioid therapy and exclusion of certain chronic diseases. However, it is not known if the payers changed their policies to …

Feasibility Of A Low-Intensity Intervention To Influence Antibiotic Prescribing Rates Use In Outpatient Settings: A Cluster Randomized Controlled Clinical Trial, Brigid M. Wilson, Sunah Song, Robin L.P. Jump, Federico Perez

Faculty Scholarship

Background. Primary care providers (PCPs) may modify their antibiotic prescription practices if aware of their potentially damaging impact. Methods. We conducted a cluster randomized controlled trial at 12 Veterans Affairs community-based outpatient clinics. PCPs at clinics randomized to the intervention group received quarterly antibiotic use reports with feedback about antibiotics prescribed for acute respiratory infections and adverse event letters alerting about Clostridioides difficile infection or antibiotic-resistant gram-negative bacteria among their patients. The main outcome, antibiotic prescriptions in primary care visits, was compared in the preintervention (April–September 2020), intervention (October 2020 to September 2021), and postintervention periods (September 2021 to September …

Enhancing Dignity Amongst Persons With Dementia Through Occupational Engagement, Habeeba Ahmed, Amy Lyons-Brown Ms, Otd, Otr/L

Fall 2024 OTD Capstone Symposium

Dementia is a cognitive impairment that impacts an individual's memory, judgement, safety awareness, and emotions which can interfere with their activities of daily living. As the condition progresses, the person living with dementia (PLWD) may require a care partner to help them complete their daily tasks. Having a care partner and being a care partner can be challenging for both, the PLWD and their care partner, as there begins to be a shift in their independence. The PLWD must rely on their care partner to help them throughout their day, leading to a decrease in independence and occupational engagement. When …

After-Hours, Severity, And Distance Are Associated With Non-Vha Emergency Department Use For Older Veterans: Insights From A Regional Health Information Exchange, Elina Kurkurina, Kimberly M. Judon, Ula Hwang, Kenneth S. Boockvar, Juan Wisnivesky, Matthew R. Augustine

Journal of Geriatric Emergency Medicine

Background: Older adults treated in emergency departments (EDs) are at higher risk for adverse outcomes. Using multiple facilities can worsen this issue through service duplication and poor care transitions. Veterans with dual insurance coverage can access both Veterans Health Administration (VHA) and non-VHA EDs. This study aimed to identify factors associated with non-VHA ED use among veterans.

Methods: We conducted a retrospective observational study of patients aged ≥ 65 who had primary care at the James J Peters VA Medical Center and at least one VHA or non-VHA ED visit between October 2017 and February 2020. Data were collected from …

Effectiveness Of An Improved Leprosy Lakar Training On Knowledge And Skills Among Healthcare Workers In Primary Healthcare In Pahang Malaysia., Nuraihan Zafirah Zainal Abidin

Student Works (2020-2029)

Leprosy, a neglected chronic tropical disease caused by Mycobacterium leprae, poses significant health challenges due to its potential for irreversible disabilities and disfigurement. Adequate leprosy training for healthcare workers (HCWs) is crucial for early detection and prompt treatment, thereby preventing complications and reducing transmission risks. This study aimed to revise and evaluate the effectiveness of leprosy LaKAR* training on knowledge and skills of leprosy among HCWs in primary healthcare in Pahang, Malaysia. The study employed a sequential exploratory, mixed-method design consisting of two phases. Phase 1a was a qualitative study identifying gaps in current LaKAR training among HCWs at …

Blinatumomab Maintenance After Allogeneic Hematopoietic Cell Transplantation For B-Lineage Acute Lymphoblastic Leukemia, Yuanxin Wang, Merve Dede, Vakul Mohanty, Jinzhuang Dou, Ziyi Li

Faculty, Staff and Student Publications

Decoding cellular state transitions is crucial for understanding complex biological processes in development and disease. While recent advancements in single-cell RNA sequencing (scRNA-seq) offer insights into cellular trajectories, existing tools primarily study expressional rather than regulatory state shifts. We present CellTran, a statistical approach utilizing paired-gene expression correlations to detect transition cells from scRNA-seq data without explicitly resolving gene regulatory networks. Applying our approach to various contexts, including tissue regeneration, embryonic development, preinvasive lesions, and humoral responses post-vaccination, reveals transition cells and their distinct gene expression profiles. Our study sheds light on the underlying molecular mechanisms driving cellular state transitions, …

A Statistical Approach For Systematic Identification Of Transition Cells From Scrna-Seq Data, Yuanxin Wang, Merve Dede, Vakul Mohanty, Jinzhuang Dou, Ziyi Li

Faculty, Staff and Student Publications

Decoding cellular state transitions is crucial for understanding complex biological processes in development and disease. While recent advancements in single-cell RNA sequencing (scRNA-seq) offer insights into cellular trajectories, existing tools primarily study expressional rather than regulatory state shifts. We present CellTran, a statistical approach utilizing paired-gene expression correlations to detect transition cells from scRNA-seq data without explicitly resolving gene regulatory networks. Applying our approach to various contexts, including tissue regeneration, embryonic development, preinvasive lesions, and humoral responses post-vaccination, reveals transition cells and their distinct gene expression profiles. Our study sheds light on the underlying molecular mechanisms driving cellular state transitions, …

Development Of A Ripk1 Degrader To Enhance Antitumor Immunity, Rishi Ram Paudel, Hanfeng Lin, Bryan L Holloman, Feng Jin, Longyong Xu, Lang Ding, Weiyi Peng, Meng C Wang, Xi Chen, Jin Wang

Faculty, Staff and Students Publications

The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo. Degradation of RIPK1 by LD4172 triggers immunogenic cell death, enhances tumor-infiltrating lymphocyte responses, and sensitizes tumors to anti-PD1 therapy in female C57BL/6J mice. This work reports …

The American Cancer Society National Lung Cancer Roundtable Strategic Plan: Advancing Comprehensive Biomarker Testing In Non-Small Cell Lung Cancer, Adam H Fox, Raymond U Osarogiagbon, Farhood Farjah, James R Jett, Bruce E Johnson, Robert A Smith, Gerard A Silvestri

Faculty, Staff and Student Publications

Comprehensive biomarker testing is a crucial requirement for the optimal treatment of advanced-stage non-small cell lung cancer (NSCLC), with emerging relevance in the adjuvant treatment setting. To advance its goal of ensuring optimal therapy for persons diagnosed with lung cancer, the American Cancer Society National Lung Cancer Roundtable (ACS NLCRT) held The Summit on Optimizing Lung Cancer Biomarkers in Practice in September 2020 to align its partners toward the goal of ensuring comprehensive biomarker testing for all eligible patients with NSCLC. The ACS NLCRT's Strategic Plan for Advancing Comprehensive Biomarker Testing in NSCLC, a product of the summit, comprises actions …

The American Cancer Society National Lung Cancer Roundtable Strategic Plan: Methods For Improving Turnaround Time Of Comprehensive Biomarker Testing In Non-Small Cell Lung Cancer, Sinchita Roy-Chowdhuri, Haresh Mani, Adam H Fox, Anne Tsao, Lynette M Sholl, Bruce E Johnson, M Patricia Rivera, Gerard A Silvestri, Robert A Smith, Ignacio I Wistuba

Faculty, Staff and Student Publications

Comprehensive biomarker testing for patients with non-small cell lung cancer is critical for selecting appropriate targeted therapy or immunotherapy. Ensuring timely ordering, processing, and reporting is key to optimizing patient outcomes. However, various factors can prevent or delay patients from being offered the option of treatment selection based on comprehensive biomarker testing. These factors include problems with access to testing, tissue adequacy, turnaround time, and health insurance coverage and billing practices. Turnaround time depends on several logistical and tissue handling factors, which involve institutional policies, processes, resources, testing methodology, and testing algorithms that vary across different practices. In this article, …