Digital Commons Network^™

Test-Retest Apparent Diffusion Coefficient Reproducibility In Head And Neck Cancer Using A 15-T Mr-Linac, Brigid A Mcdonald, Dina El-Habashy, Renjie He, Sam Mulder, Sarah Mirbahaeddin, Abdallah S R Mohamed, Sara Ahmed, Yao Ding, Jihong Wang, Stephen Y Lai, Alex Dresner, John Christodouleas, Clifton D Fuller

Faculty, Staff and Student Publications

Purpose

To evaluate the reproducibility of apparent diffusion coefficient (ADC) measurements in head and neck squamous cell carcinoma (HNSCC) using a 1.5-T MR-linac (MRI-guided linear accelerator) system.

Materials and Methods

In this retrospective study, conducted between February 2021 and January 2024, patients with HNSCC lesions underwent echo-planar imaging diffusion-weighted MRI on a 1.5-T MR-linac system at two time points before the start of radiation therapy. Mean and median ADC values and volumes were measured for each lesion. Absolute and percent reproducibility coefficients (RCs) were calculated. Linear regression analyses and F tests were performed to determine whether the lesion volume or …

Metastasis-Directed Radiotherapy For Oligometastatic Urothelial Carcinoma Of The Bladder And Upper Tract, Patrick Carriere, Omar Alhalabi, Jianjun Gao, Amishi Shah, Sangeeta Goswami, Matthew Campbell, Ruitao Lin, Lauren Mayo, Osama Mohamad, Karen Hoffman, Henry Mok, Charmaigne Lozano, Ashish Kamat, Neema Navai, Kelly Bree, Byron Lee, Charles Guo, Michael Rooney, Chad Tang, Seungtaek Choi, Comron Hassanzadeh

Faculty, Staff and Student Publications

Background: Metastasis-directed therapy (MDT) for oligometastatic cancer is utilized for genitourinary malignancies including prostate and kidney cancers. Clinical research on MDT for urothelial carcinoma (UC) remains sparse, especially as systemic therapy advances have improved outcomes.

Objective: We investigated the role of MDT, specifically radiotherapy, for patients with oligometastatic bladder or upper-tract UC.

Methods: Data were collated on patients with metastatic UC with 5 or fewer metastatic sites undergoing MDT with ablative radiotherapy with or without preceding systemic therapy during January 2016 to July 2024. Endpoints were progression-free survival (PFS), and overall survival (OS). Cox proportional hazards analysis was conducted to …

Congenital Syphilis: From Near-Elimination To Crisis, Chad J Abresch, Irene A Stafford, Regan M Johnson, Kayode Olabanji, Ashleigh M Sutphen, Helen E Cejtin, Ashley Hoover

Faculty, Staff and Student Publications

This analytic essay examines the transformation of congenital syphilis (CS) in the United States from near-elimination to crisis. Drawing from the January 2025 Congenital Syphilis Summit in Atlanta, Georgia-convening public health leaders, Tribal health departments, the National Coalition of STD Directors, and Centers for Disease Control and Prevention experts-we contrast prevention systems during near-elimination (1998-2005) with the current crisis (2018-2025). Evidence revealed how dismantling public health infrastructure produced dramatically different outcomes, with CS cases increasing 937% over the past decade and racial/ethnic disparities worsening. American Indian/Alaska Native communities face rates up to 100 times higher than White populations in some …

Glaucoma Risk With Metformin And Sulfonylurea Therapies In Type 2 Diabetes: A Retrospective Cohort Study., Jared Lim, Jingru Zhou, Hulin Wu, Ziqi Liu, David A Lee

Faculty, Staff and Student Publications

Background: Research on metformin, sulfonylureas, and open-angle glaucoma risk in type 2 diabetes mellitus (T2DM) has yielded inconsistent findings. This study examined associations between hypoglycemic treatments and glaucoma diagnosis rates.

Methods: This retrospective cohort study analyzed electronic health records of newly diagnosed T2DM patients from the Merative™ Explorys® Therapeutic Dataset (2010-2022), comparing three groups: metformin monotherapy, sulfonylureas plus metformin combination, and untreated controls. Propensity score matching balanced demographics, glycemic control, body mass index, blood pressure, lipid levels, and comorbidities. Cox proportional hazards models calculated adjusted hazard ratios for incident glaucoma.

Results: After 1:1 propensity score matching, metformin monotherapy (N=100,387) showed …

Biomechanical And Computational Modeling Of Metastatic Acetabular Defects: Influence Of Tumor Location On The Risk Of Fracture, Jacob Doddridge, Hongjia He, Rui Yang, E U Conrad, Nicholas Dunbar

Faculty, Staff and Student Publications

Background: Metastatic bone disease can lead to pathologic fracture of the pelvis which affects quality of life. There are limited validated approaches for biomechanical modeling, classification, or surgical treatment of metastatic acetabular defects.

Methods: An artificial hemipelvis bone was used to calibrate a computed tomography-based computational model of the pelvis with varying locations and sizes of acetabular defects. Metastatic defects affecting the anterior and posterior column, medial wall, and their combinations were created. Mechanical testing was performed on each defect, and images of the lateral surface of the acetabulum were analyzed by digital image correlation to measure peak surface strains. …

Personalized Management Of Chronic Rhinosinusitis In The Context Of Immune Deficiency, Christopher M Bell, Amber U Luong, Chadi A Makary

Faculty, Staff and Student Publications

Primary and secondary immunodeficiency as a cause of recalcitrant or difficult to treat chronic rhinosinusitis (CRS) and recurrent acute rhinosinusitis (RARS) are under-appreciated etiologies. Patients with persistent symptoms, frequent exacerbations despite appropriate medical therapy, or other sinopulmonary conditions known to be related to an immunodeficient state warrant further testing for immunodeficiency, as up to 20% of this cohort of patients may have underlying immunodeficiency. Testing for immunodeficiency includes CBC with differential, immunoglobulin levels, and pneumococcal vaccine titres before and after administration. Regarding secondary immunodeficiency, these patients may present with atypical symptoms, harbor atypical bacteria, or even present with severe complications …

Collision Tumors Involving Metastatic Carcinoma And Plasma Cell Myeloma: Report Of Two Cases, Ahmed A Ahmed, Muhammad Hassaan Khalid, Asad Ur Rehman, Nghia D Nguyen, Xinhai Robert Zhang

Faculty, Staff and Student Publications

Synchronous coexistence of plasma cell neoplasms (PCNs) and metastatic carcinoma is not a common phenomenon and poses a significant diagnostic challenge requiring meticulous histopathological and immunophenotypic analysis for accurate lineage assignment. We report two cases of collision tumors comprising PCN and metastatic lung carcinoma. Case 1 involved a 68-year-old male with metastatic non-small cell lung adenocarcinoma who developed intracranial lesions; resection revealed metastatic adenocarcinoma intermingled with clonal plasma cells. Case 2 was a 73-year-old woman with a lytic iliac crest lesion whose bone marrow and lesion biopsies showed diffuse infiltration by both carcinoma and atypical plasma cells. Comprehensive immunohistochemical profiling, …

Functional, Pharmacogenomic, And Immune Landscapes Of Long Non-Coding Rnas In Cancer, Runhao Wang, Mei Luo, Yuan Liu, Jingwen Yang, Yamei Chen, Chengxuan Chen, Lifei Ma, Stephanie Ding, James Wengler, Yong Zang, Bora Lim, Wenbo Li, Liuqing Yang, Chunru Lin, Lixia Diao, Leng Han

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) are emerging as key regulators in cancer, with significant potential as diagnostic, prognostic, and therapeutic targets. Here, this work systematically analyzes lncRNA associations with targeted therapies and immunotherapies across 33 cancer types using The Cancer Genome Atlas (TCGA) and real-world datasets. This work identifies 53,173 lncRNA-pathway associations, millions of lncRNA-drug response associations (via CancerRxTissue and VAEN), and extensive correlations with immune checkpoints and infiltration. This work further identifies 69 lncRNAs associated with immunotherapy response and 2,611 differentially expressed lncRNAs between low and high objective response rate (ORR) groups. Additionally, two lncRNAs are correlated with immune-related adverse …

Contemporary Opportunities And Potential Of Auger Electron-Emitting Theranostics, Seok-Yong Lee, H Charles Manning

Faculty, Staff and Student Publications

Recent breakthroughs in radiopharmaceutical (RP) therapy have emerged interest in employing Auger electron (AE)-emitting radionuclides as potential agents for precise theranostics. AE provides energy with exceptional localization due to their short tissue penetration range (TPR, < 10 nm), rendering them particularly effective for targeting nuclear DNA in tumor cells. In this context, AE-emitting radionuclide therapy (AE-emitting RLT) enables the targeted destruction of tumor cells while reducing harm to adjacent healthy tissue, a significant challenge in this field. Preclinical and early clinical investigations reveal the efficacy of AE-emitting RLTs in the theranostics of diverse malignancies, such as glioblastoma, prostate cancer, and neuroendocrine tumors. Notwithstanding these developments, challenges and limitations persist regarding dosimetry, delivery efficiency, and the treatment of radiotoxicity. A new paradigm is being developed to tackle the obstacles encountered by integrating molecular target markers (e.g., PARP) that function near the nucleus to improve the intranuclear delivery efficiency of AE-emitting radionuclides. Novel radiochemical methods such as these have facilitated the more stable and efficient labeling of biomolecules with AE-emitting radionuclides. Also, recent advances in DNA-molecular targeting, nanoparticles, nucleic acid/protein engineering, click- or bioorthogonal conjugation chemistry, and artificial intelligence (AI)-based structure modeling present concrete opportunities to overcome these limitations. Moreover, the integration of diagnostic imaging companion platforms employing theranostic radioisotope pairings facilitates real-time assessment of therapeutic efficacy and biodistribution, resulting in the formulation of enhanced treatment regimens. This review summarizes the prior development, recent advancements, barriers in clinical implementation, and future perspective of AE-emitting RLTs.

Nsd2 Inhibitors Rewire Chromatin To Treat Lung And Pancreatic Cancers, Jinho Jeong, Simone Hausmann, Hanyang Dong, Kacper Szczepski, Natasha M Flores, Andy Garcia Gonzalez, Liyang Shi, Xiaoyin Lu, Joanna Lempiäinen, Moritz Jakab, Liyong Zeng, Tourkian Chasan, Eric Bareke, Rui Dong, Emma Carlson, Reinnier Padilla, Dylan Husmann, Julia Thompson, Gerry A Shipman, Emily Zahn, Courtney A Barnes, Laiba F Khan, Liz Marie Albertorio-Sáez, Eva Brill, Vishnu Udayakumar Sunita Kumary, Matthew R Marunde, Danielle N Maryanski, Cheryl C Szany, Bryan J Venters, Carolina Lin Windham, Michal Eligiusz Nowakowski, Iwona Czaban, Mariusz Jaremko, Michael-Christopher Keogh, Kang Le, Michael J Soth, Benjamin A Garcia, Łukasz Jaremko, Jacek Majewski, Pawel K Mazur, Or Gozani

Faculty, Staff and Student Publications

NSD2 catalyses the epigenetic modification H3K36me2 (refs. 1,2) and is a candidate convergent downstream effector of oncogenic signalling in diverse malignancies3–5. However, it remains unclear whether the enzymatic activity of NSD2 is therapeutically targetable. Here we characterize a series of clinical-grade small-molecule catalytic NSD2 inhibitors (NSD2i) and show that the pharmacological targeting of NSD2 constitutes an epigenetic dependency with broad therapeutic efficacy in KRAS-driven preclinical cancer models. NSD2i inhibits NSD2 with single-digit nanomolar half-maximal inhibitory concentration potency and high selectivity over related methyltransferases. Structural analyses reveal that the specificity of NSD2i for NSD2 …

Proliferation And Apoptosis Adaptor Protein 15 (Pea15), A Potential Oncogenic Regulator Of Vhl And Hif1a Identified Through Proteomic Analysis In Hepatocellular Carcinoma, Yun Seong Jeong, Ji-Hyun Shin, Soo Mi Kim, Bo Hwa Sohn, Sun Young Yim, Ji Hoon Kim, Jae Jun Shim, Sung Hwan Lee, Yun Shin Chun, Sunyoung S Lee, Hui Dai, Ahmed Kaseb, Koo Jeong Kang, Holger K Eltzschig, A Robert Macleod, Xiaolin Luo, Alexey Revenko, Youngsoo Kim, Ju-Seog Lee

Faculty, Staff and Student Publications

No abstract provided.

Hyperglycemia In Combination With Excess Fat Intake Promotes Renal Pyroptosis And Fibrosis Through Gα12-Dependent Endoplasmic Reticulum Stress, Muhammad Sohaib Khan, Boram Kim, Yerim Jeon, Jihoon Tak, Yun Seok Kim, Sang Gil Lee, Eun Byul Lee, Chang-Hoon Lee, Cheol Bin Eom, Hyun Sook Lee, Hyeon-Ki Jang, Nakyeom Lee, Jeong Hae Kie, Jee Myung Yang, Yoon Mee Yang, Sang Geon Kim

Faculty, Staff and Student Publications

Background: Chronic exposure to free fatty acids (FFAs) and glucose may disrupt metabolic homeostasis and initiate pathological processes. This study investigated the effects of hyperglycemia and fat overload on renal endoplasmic reticulum (ER) stress, pyroptosis and fibrogenesis in mice and the underlying basis. We hypothesized that the combined insult would more severely induce Gα12-dependent ER stress and renal complications.

Methods: Mice were subjected to either high fat diet (HFD)+streptozotocin (STZ), or STZ treatment, and AZ2 was used as an anti-diabetic agent. Blood sera were used for blood biochemistry, and tissues were employed for RNA sequencing, immunoblottings, TEM, histology and immunohistochemistry. …

Nampt Inhibition Uncovers Therapeutic Vulnerabilities To Venetoclax And Chemotherapy In Acute Myelogenous Leukemia, John R Sanchez, Chaomei Liu, Vishakha Pawar, Yanqing Huang, Daisy Diaz-Rohena, Jyotsana Singh, Priya Koppikar, Tzung-Huei Lai, Lisa St John, Vinay Puduvalli, Jeffrey Molldrem, Palaniraja Thandapani, Nitin Jain, Rosa Lapalombella, Deepa Sampath

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) cells depend on nicotinamide adenine dinucleotide (NAD

Freeze-Dried, Not Frozen: Lyophilized Mesenchymal Stromal Cell-Derived Extracellular Vesicles And Therapeutic Function In Neuroinflammatory Models, Janet R Ashley, Aidan M Collier, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

Background: Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) offer a promising acellular therapy for immune modulation, but clinical translation is hindered by variability and storage constraints. Lyophilization (freeze-drying) could enable shelf-stable EV therapeutics, although its effects on biological activity remain incompletely defined.

Study design: We compared the immunomodulatory effects of frozen and lyophilized EVs from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) MSCs using lipopolysaccharide-stimulated rodent splenocytes and microglial models and human peripheral blood mononuclear cells (PBMCs). Variables included batch scale (small vs large), cytokine priming, and MSC source. Tumor necrosis factor alpha (TNF-α) secretion was measured …

Rendering Knowledge Graphs From Aerospace Dentistry Processes For Clinical Decision Support Systems, Muhammad Tuan Amith, Jessica Vu, Serena Hou, Vinu Sista, Yang Gong, Ronak Shah, Ana C Neumann

Faculty, Staff and Student Publications

NASA and commercial space flight companies expect to make long-term missions into deep space with the Artemis project and Mars mission. Health care in deep space is a priority as the missions require limited crew and equipment to accommodate astronauts' needs. Analyzing the probable clinical procedures and workflows for this setting is needed to ensure quality care and safety. This paper introduces Business Process Modeling and Notation (BPMN) and OWL2-based modeling to represent aerospace dental workflows for low-earth orbit and potential deep space missions. We developed BPMN process models and created ontology-based knowledge graph representations for individual dental procedures using …

Provgen: A Privacy-Preserving Approach For Outcome Validation In Genomic Research, Yuzhou Jiang, Tianxi Ji, Erman Ayday

Faculty, Staff and Student Publications

As genomic research has grown increasingly popular in recent years, dataset sharing has remained limited due to privacy concerns. This limitation hinders the reproducibility and validation of research outcomes, both of which are essential for identifying computational errors during the research process. In this paper, we introduce PROVGEN, a privacy-preserving method for sharing genomic datasets that facilitates reproducibility and outcome validation in genome-wide association studies (GWAS). Our approach encodes genomic data into binary space and applies a two-stage process. First, we generate a differentially private version of the dataset using an XOR-based mechanism tailored to biological characteristics. Second, we restore …

Management Of Retropharyngeal Lymph Node Metastases In Thyroid Cancer, Isabelle Fournier, Ashwini Venkata Bandi, Sarah Hamidi, Priyanka Iyer, Naifa L Busaidy, Maria E Cabanillas, Ramona Dadu, Mimi I Hu, Steven G Waguespack, Ugur Nur Basmaci, Michelle D Williams, Mena Mansour, Maria Gule Monroe, Neil D Gross, Ryan P Goepfert, Nancy D Perrier, Victoria Banuchi, Jennifer R Wang, Anastasios Maniakas, Mark E Zafereo

Faculty, Staff and Student Publications

Background: Retropharyngeal lymph node (RPLN) metastases in thyroid cancer are rare, with optimal management underreported.

Methods: Retrospective study of consecutive thyroid cancer patients with RPLN metastases treated at MD Anderson Cancer Center between 2000 and 2024.

Results: One hundred and sixty-seven patients (75% differentiated, 21% medullary, 4% poorly differentiated thyroid cancer) were divided into three groups: active surveillance (AS) (13%), surgery (56%), and nonsurgical treatment (31%). In the AS group (median follow-up 2.3 years), RPLN metastases grew a median 3% (range: 0-56) or 0.02 cm (range: 0-0.7) per year. Surgical therapy included transcervical (73%), transoral robotic (14%), transoral (12%), and …

Risk Factors And Outcomes Of Reintubation Following Combined Heart-Lung Transplantation, Ye In Christopher Kwon, Michael Keller, Alan Lai, Brian Bao, Joshua Pei, Matthew Ambrosio, Jay Patel, Motaz Al-Yafi, Zachary Fitch, Josue Chery, Patricia Nicolato, Vigneshwar Kasirajan, Zubair A Hashmi

Faculty, Staff and Student Publications

Background: Unplanned reintubation after combined heart-lung transplantation (HLT) significantly affects morbidity and mortality, yet national data are limited. We evaluated the incidence, predictors, timing, and outcomes associated with reintubation after HLT.

Methods: We retrospectively reviewed adults undergoing primary HLT in the UNOS registry from January 2004 to September 2024. Patients were stratified by reintubation status (defined as re-established mechanical ventilation (MV) after initial extubation). Propensity matching (1:1) balanced recipient and donor characteristics. Multivariable logistic regression models identified independent risk factors.

Results: Among 609 adult HLT recipients, 165 (27.1%) required postoperative reintubation. After 1:1 propensity score matching, 146 patients who were …

Physical Activity, Telomere Length, And Cardiometabolic Syndrome In Older Women: The Cardiovascular Health Study, Jeni Page, Melissa Richard, Elizabeth Lyons, Elizabeth Baumler, M Terese Verklan, Michelle C Odden, Elizabeth Lorenzo

Faculty, Staff and Student Publications

Background: Cardiometabolic syndrome (CMS) affects approximately 39% of US women and increases risk for cardiovascular disease, diabetes, and stroke. Telomere length, a biomarker of cellular aging, is associated with CMS and may be influenced by physical activity (PA), potentially mitigating telomere shortening. Black women have higher CMS prevalence compared to white women and may exhibit distinct telomere length dynamics influenced by interactions between CMS and PA.

Methods: Data were drawn from the Cardiovascular Health Study and included black and white women who provided data on PA, CMS risk factors, and telomere length (N = 417). Linear regression models examined the …

Evaluation Of Organ-Specific Relative Biological Effectiveness Of Proton Therapy Using Radiation-Induced Pneumonitis As An Endpoint, Li Liao, Ting Xu, Mei Chen, Tingshi Su, Narayan Sahoo, Xiaorong Zhu, Steven J Frank, Quynh-Nhu Nguyen, Zhongxing Liao, Xiaodong Zhang

Faculty, Staff and Student Publications

Background and purpose: Proton therapy has become widely used for non-small cell lung cancer (NSCLC) due to its ability to spare normal tissue. However, the commonly assumed relative biological effectiveness (RBE) of 1.1 may underestimate the therapy's true biological effects on lung, potentially leading to a higher than expected incidence of radiation-induced pneumonitis (RP). In this retrospective study, we evaluated the variability of organ-specific RBE of proton therapy using RP grade 2 or higher (RP2+) as an endpoint.

Materials and methods: Data from 270 NSCLC patients across two clinical trials were analyzed, with 134 given photon therapy and 136 given …

Applications And Challenges Of Utilizing Digital Pathology And Ai-Enabled Workflows In Clinical Trials, Manu Sebastian, Harsh Batra, Monika Lamba Saini, Staci Kearney, Lorcan Sherry, Serge Alexanian, Michael Cohen, William Weber, Joe Lennerz, Anil V Parwani

Faculty, Staff and Student Publications

This is a comprehensive review on current utilization and challenges of digital pathology adoption in clinical trials and aims to provide a broad view on its impact on pathology review processes in clinical trials. It provides an overview of current pathology review practices in clinical trials and unique advantages digital pathology adoption can offer. The key areas including existing workflows, use case scenarios in different disease areas in clinical trials, including but not limited to patient identification and pre-screening, and regulatory aspects have been described with relevance. In addition, the review delves into the integration of genomics, AI, image analysis, …

Reconsidering The Definition Of Triple-Negative Breast Cancer In The Immune Checkpoint Inhibitor Era: An Optimal Cut-Off Value For Hormone Receptor Percentage Of Her2-Negative Invasive Breast Cancer, Takeo Fujii, Toshiaki Iwase, Yu Shen, Jami Fukui, Naoto T Ueno

Faculty, Staff and Student Publications

The optimal cut-off values of estrogen receptor (ER) and progesterone receptor (PgR) expression to define the positivity of ER and PgR have been under discussion for over a decade but remain controversial. The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) and the St. Gallen International Expert Consensus recommended that breast cancers with ≥1% of ER or PgR expression should be considered hormone receptor (HR)-positive tumors but ER/PR expression of 1% to 10% should be reported as HR-low positive; however, among HER2-negative disease, data on the overall benefit of adjuvant endocrine therapies for patients with HR-low positive disease is …

T Cells Modulate The Development And Maintenance Of Painful Paclitaxel-Induced Peripheral Neuropathy In Rnu Rats, Ahmed Olalekan Bakare, Gerard Limerick, Vasudha Goel, Ratan K Banik, Lei Zheng, Andrew J Shepherd, Kristine Glunde, Qin Zheng, Eellan Sivanesan

Faculty, Staff and Student Publications

The role of T cells in chemotherapy-induced peripheral neuropathy (CIPN) is complex and shaped by biological and experimental factors, including sex, hormonal status, genetic background, and cancer model. This complexity has contributed to inconsistent findings among studies, limiting therapeutic progress. In this study, we investigate how T cells contribute to painful paclitaxel (PTX)-induced peripheral neuropathy (PIPN). Adult male T cell-competent (RNU+/−) and T cell-deficient (RNU−/−) rats were subcutaneously inoculated with tumor cells and subsequently treated with intraperitoneal PTX (8 mg/kg total dose). Reflexive (mechanical, heat, cold) and non-reflexive (burrowing, gait) pain behaviors were assessed from baseline through week 6. Immunohistochemistry …

The Lysine Demethylase Kdm4c Is An Oncogenic Driver And Regulates Erk Activity In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Menna-T-Allah Shaheen, Sarah Dhebat, Kimal I Rajapakshe, Bidyut Ghosh, Benson Chellakkan Selvanesan, Shariq S Ansari, Cara L Haymaker, Dorsay Sadeghian, Huamin Wang, Ching-Fei Li, Haoqiang Ying, Anirban Maitra

Faculty, Staff and Student Publications

Deregulation of proteins involved in chromatin regulation is common in pancreatic ductal adenocarcinoma (PDAC). Lysine demethylase 4C (KDM4C) is one of the chromatin-modifying proteins frequently overexpressed across multiple solid cancers and is linked to chromatin instability, increased cell proliferation, and enhanced stem cell–like behavior. We observed upregulation of KDM4C protein in a panel of human PDAC cell lines and patient samples compared with nonneoplastic controls. CRISPR/Cas9-mediated deletion of KDM4C in human and murine PDAC cells reduced proliferation, clonogenicity, and increased survival of orthotopically implanted murine PDAC allografts. Transcriptomic and proteomic analyses revealed that loss of KDM4C in both human and …

Clinical And Molecular Characteristics Of Patients With Young-Onset And Average-Onset Pancreatic Adenocarcinoma, Adriana C Gamboa, Kever A Lewis, Laura R Prakash, Zhouxuan Li, Wei Qiao, Dan Zhao, Mark W Hurd, Mahmoud Yousef, Naruhiko Ikoma, Michael P Kim, Jeffrey E Lee, Jessica E Maxwell, Ching-Wei D Tzeng, Matthew H G Katz, Rebecca A Snyder

Faculty, Staff and Student Publications

Purpose: The incidence of young-onset pancreatic cancer (YO-PC) has risen over the past two decades, yet its molecular characteristics and long-term outcomes remain poorly defined.

Methods: We retrospectively evaluated patients with PC treated at a tertiary referral center from 2016 to 2022 who had available molecular data. Patients were classified as YO-PC (≤50 years) or average-onset PC (AO-PC, >50 years). A subset analysis examined outcomes in those who underwent curative-intent pancreatectomy. Primary end points included overall survival (OS) and recurrence-free survival (RFS).

Results: Among 511 patients, 10.9% had YO-PC (n = 56; median age 44 years). Patients with YO-PC more …

Case Report: Management Of A Challenging Case Presenting With Dysphagia After Thyroidectomy Requiring Administration Of Liquid 131i Via Mic-Key Low-Profile Tube—A Multidisciplinary Approach, Ahmed Ebada Salem, Sandra Ramirez, Brian R Weston, Akram Hussein, Simone Krebs

Faculty, Staff and Student Publications

Radioactive iodine (RAI) therapy with 131-iodine (131I) remains a cornerstone in the postoperative management of differentiated thyroid carcinoma (DTC). The standard route of administration is oral, typically in capsule form and less commonly as a liquid. However, in patients with severe dysphagia and compromised airway, traditional oral 131I delivery may be contraindicated due to the risk of aspiration and radioactivity contamination. These scenarios present unique clinical challenges that necessitate deviation from conventional protocols. While liquid 131I may be administered through the mouth or via nasogastric or percutaneous gastrostomy tubes, there is currently no standardized approach, and potential risks, such as …

Preliminary Examination Of Orexin Receptor Antagonism With Suvorexant In Individuals With Methamphetamine Use Disorder: A Case Series Study, Heather Webber, Jessica Badawi, Douglas Calvillo, Jin Yoon, Michael Weaver, Scott Lane, Joy Schmitz

Faculty, Staff and Student Publications

No abstract provided.

Evolving Molecular Subtypes Of Gastric Cancer: From Past Classifications To Present Consensus And Future Directions For Precision Therapy, Ju-Seog Lee

Faculty, Staff and Student Publications

Gastric cancer is a biologically heterogeneous disease. The advent of high-throughput multi-omic technologies has revolutionized our understanding of gastric cancer by deconstructing this heterogeneous entity into distinct and more homogeneous molecular subtypes. Early classifications based on gene expression, methylation, and histology have laid the groundwork for multi-omic frameworks proposed by The Cancer Genome Atlas and Asian Cancer Research Group, which established the foundation of modern molecular taxonomy. Subsequent integrative efforts, particularly the Consensus Genomic Subtypes (Super 6) model, have unified this collected information into clinically relevant subtypes that bridge prognostic stratification with treatment strategies. Established biomarkers such as human epidermal …

Bop2-Te: Bayesian Optimal Phase 2 Design For Jointly Monitoring Efficacy And Toxicity With Application To Dose Optimization, Kai Chen, Heng Zhou, J Jack Lee, Ying Yuan

Faculty, Staff and Student Publications

We propose a Bayesian optimal phase 2 design for jointly monitoring efficacy and toxicity, referred to as BOP2-TE, to improve the operating characteristics of the BOP2 design proposed by Zhou et al. (2017). BOP2-TE utilizes a Dirichlet-multinomial model to jointly model the distribution of toxicity and efficacy endpoints, making go/no-go decisions based on the posterior probability of toxicity and futility. In comparison to the original BOP2 and other existing designs, BOP2-TE offers the advantage of providing rigorous type I error control in cases where the treatment is toxic and futile, effective but toxic, or safe but futile, while optimizing …

Prickle4 Drives Microenvironmental Remodeling And Resistance To Parp Inhibition In Idh-Mutant Glioma, Ju Yang, Hua Yang, Yifan Yuan, Chenyang Zhang, Ziwei Fu, Yanyan Chen, Yinghong Xiong, Shuyu Chen, Kexin Ling, Ying Liu, Jason T Huse, Bo Chen, Timothy A Chan, Zengxin Qi, Zhao Zhang, Xiuping Liu, Yuxiang Wang

Faculty, Staff and Student Publications

Mutations in isocitrate dehydrogenase (IDH) genes sensitize gliomas to PARP inhibition (PARPi) by inducing epigenetic reprogramming of DNA damage repair circuits. However, tumors treated with PARPi eventually relapse despite initial responsiveness. In this study, it is demonstrated that the anti-angiogenic agent lenvatinib synergizes effectively with PARPi, resulting in substantial tumor regression and significantly extended survival. Genomic analysis of tumors reveals that PARPi induces widespread transcriptomic changes that are predominantly pro-inflammatory, thereby promoting tumor angiogenesis. Prickle4, a planar cell polarity protein, is identified as a critical mediator of PARPi-induced neovascularization. Targeting Prickle4 effectively overcomes PARPi resistance in these tumors. Collectively, these …