Digital Commons Network^™

Synthesis, Structure-Activity Relationships, And Antitumor Activities Of Quinoxiline-Containing Inhibitors Of The Protein-Protein Interactions Between Transcription Coactivator Af9/Enl And Dot1l/Af4, Chandra Bhushan Mishra, Xin Li, Bala Krishna Moku, Sehun Kwak, Dnyaneshwar N Garad, Yongcheng Song

Faculty, Staff and Students Publications

Mixed lineage leukemia (MLL) gene rearrangements cause ~75% of acute leukemia in infants and 5-10% in children and adults with poor clinical outcomes. Protein-protein interactions (PPI) between frequent MLL fusion partners AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Sixty-seven quinoxiline compounds were synthesized and tested for their ability to inhibit such PPIs. Compounds 16, 17, 59 and 63 were found to be potent inhibitors with IC50 values of 0.35-1.5 μM. Structure-activity relationships are discussed. Potent inhibitors can suppress expression of MLL target genes Myc and Meis1 and selectively block proliferation of MLL-r and …

Swollen Lymph Node Metastasis In Gastric Cancer: A Forgotten Prognostic Signal In Need Of Clinical Action, Keykavous Parang, Amir Nasrolahi Shirazi

Pharmacy Faculty Articles and Research

Gastric cancer (GC) remains a leading cause of cancer mortality. While the extent of nodal involvement is a well-known prognostic factor, the specific entity of swollen lymph node metastasis (SLNM), bulky nodal tumor deposits detectable radiologically or pathologically, has received little attention in staging. Recent data from a study by Cui et al demonstrated that SLNM is an independent predictor of very poor survival in GC. Through robust data and rigorous propensity-matched analyses, SLNM emerged not merely as an anatomical finding but as an independent predictor of poor prognosis, even among patients undergoing curative resection. As precision oncology advances, the …

Inflammation And Detection: Rethinking The Biomarker Landscape In Gastric Cancer, Keykavous Parang, Koosha Paydary

Pharmacy Faculty Articles and Research

Gastric carcinoma is a leading cause of cancer-related mortality worldwide, yet reliable noninvasive biomarkers for its early detection remain limited. As research continues to elucidate the inflammatory underpinnings of tumor initiation and progression, it has become increasingly clear that pro-inflammatory cytokines may hold promise as diagnostic adjuncts. Serum cytokines such as interleukin (IL)-1β, IL-6, IL-8, and interferon-gamma have been frequently reported as elevated in gastric cancer patients compared to healthy individuals. These molecules, known for their roles in modulating tumor-promoting inflammation, angiogenesis, and immune evasion, may serve as accessible indicators of disease presence or progression. Several studies have shown that …

Purulent Pericarditis: Treating A Medically-Complex Patient With Intrapericardial Antibiotics, Meryem Guler, Sudheshna Vemula, Matthew Hart, Josh Wiener, Darius Farzad, Mark Decaro, Gregary D. Marhefka, Devin Weber, John W.C. Entwistle, Jacqueline Urtecho

Division of Cardiology Faculty Papers

OBJECTIVE: Purulent pericarditis is a rare, lethal complication of a bacterial pericardial infection. This case report outlines the protocol for instilling intrapericardial antibiotics for methicillin-sensitive Staphylococcus aureus (MSSA) pericarditis without fibrinolytics in a 51-year-old man.

KEY STEPS: An appropriately sized percutaneous pericardial drain was placed. Then, a 3-day course of intrapericardial infusions of 50 mL vancomycin was begun. Drainage of all accessible fluid was performed before each infusion. The daily infusions each had an 8-hour dwell time. The prior drainage protocol continued after each infusion.

POTENTIAL PITFALLS: Strict dosage and infusion length management are required to prevent direct toxicity. Potential …

The Impact Of Myopia On Regional Visual Field Loss And Progression In Glaucoma, Anagha Lokhande, Luo Song, Yueyin Pang, Yan Luo, Louis R. Pasquale, Sarah R. Wellik, Carlos G. De Moraes, Jonathan S. Myers, Mohammad Eslami, Tobias Elze, Lucy Q. Shen, Nazlee Zebardast, David S. Friedman, Michael V. Boland, Mengyu Wang

Wills Eye Hospital Papers

PURPOSE: The purpose of this study was to investigate the impact of myopia on regional visual field (VF) loss and progression in glaucoma.

METHODS: We included 112,633 24-2 VFs; longitudinal analyses comprised patients with at least 5 reliable VFs over 4 years. The degree of myopia was measured by spherical equivalent (SE) extracted from VF testing. Linear and Cox regressions determined the impact of myopia on regional VF loss and progression, respectively. We calculated three VF progression outcomes: (1) mean deviation (MD) progression: MD slope < 0; (2) total deviation (TD) pointwise progression: at least 3 TD locations with TD slope ≤-1 decibels (dB)/year; (3) MD fast progression: MD slope ≤-1 dB/year (P value < 0.05). Longitudinal analyses were conducted for all subjects and with exclusion of patients with high myopia (SE ≤-6.00 diopters [D]).

RESULTS: More negative SE values were associated with worse TD values in the paracentral VF …

Refractory Cutaneous Symptoms In Systemic Mastocytosis, Laura Gleason, Safiyyah Bhatti, Molly Wallace, Jason B. Lee, Onder Alpdogan, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Poziotinib For Egfr Exon 20-Insertion Nsclc: Clinical Efficacy Of The Phase 2 Zenith Trial And Differential Impact Of Egfr Exon 20 Insertion Location On Sensitivity, Xiuning Le, Jacqulyne P Robichaux, Monique Nilsson, R S K Vijayan, Ashwin Ravichandran, Jia Wu, Yasir Y Elamin, Lingzhi Hong, Jun Pei, Jun He, Sonia Patel, Hibiki Udagawa, Sriramvignesh Mani, Chang Woon Jang, Jeffrey M Clarke, Nishan Tchekmedyian, Jonathan W Goldman, Mark Socinski, Gajanan Bhat, Sharon Leu, Veronica Bunn, Zhenqiang Su, Sylvie Vincent, John W Lawson, Jason B Cross, John V Heymach

Faculty, Staff and Student Publications

EGFRex20 insertions (EGFRex20ins) can be classified as near- and far-loop based on the insertion location, however, the impact of location on responses to various EGFR tyrosine kinase inhibitors (TKIs) is poorly understood. In vitro studies show that afatinib, poziotinib, and zipalertinib more potently inhibited near-loop than far-loop insertions, whereas mobocertinib has similar IC50 in both groups. Molecular dynamics simulations reveal that near-loop insertions have multiple conformational states and lower transitional energy than far-loop insertions. ZENITH20 trial cohort 1 (NCT03318939) evaluates poziotinib in EGFRex20 NSCLC patients (n = 115) and demonstrates an objective response rate of 14.8% (95% Confidence …

Associations Between Adhering To 24-Hour Movement Guidelines And Anxiety Among Adolescents Across Intersectional Identities: Kyrbs 2020-2022., Suryeon Ryu, Eun Young Lee, Zan Gao

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Identifying preventive measures for adolescent mental health is a global public health priority, as poor mental health heightens the risk of early death from related issues, including suicide. This study examined the associations between adherence to the 24-Hour Movement Guidelines and anxiety among a nationally representative sample of South Korean adolescents, using an intersectional identity framework.

METHODS: Data from the 2020-2022 Korea Youth Risk Behavior Surveys were analyzed. Adolescents aged 12-17 years were grouped based on adherence to guidelines: none, physical activity (PA), sedentary behavior (SB), sleep, two guideline combinations, and all three. Anxiety was the mental health outcome. …

Fetal Congenital Complete Heart Block: 2 Success Stories Through Multidisciplinary Care., Mohamed Aashiq Abdul Ghayum, Jenna Schermerhorn, Hayley S. Hancock, Lindsey Malloy-Walton, Steven Olsen, Laura Vricella, Kelsey Brattrud, Melanie Kathol, Rita France, Maria Kiaffas

Manuscripts, Articles, Book Chapters and Other Papers

Congenital complete heart block (CCHB) is a rare condition associated with significant fetal and neonatal mortality. It may present as an isolated conduction abnormality in association with autoimmune disease, or in conjunction with congenital heart defects including heterotaxy-polysplenia syndrome. Early prenatal diagnosis and coordinated perinatal care are critical for improving outcomes. We present 2 cases of prenatally diagnosed CCHB. The first occurred in a fetus with heterotaxy-polysplenia syndrome, and the second in the setting of maternal anti-SSA antibody exposure. Both fetuses developed progressive bradycardia, with heart rates declining to < 50 beats/min, necessitating close fetal surveillance and individualized perinatal management. Preterm delivery and prompt placement of temporary pacing wires allowed initial stabilization before eventual definitive management, resulting in survival. The successful outcomes in these neonates highlight the critical role of multidisciplinary prenatal care, timely delivery planning, and early postnatal intervention in improving survival in fetuses diagnosed with CCHB.

The Microenvironment Of Ocular Surface In Keratoconus: A Systematic Review, Sana Niazi, Farideh Doroodgar, Stephen Pflugfelder, Kia Bayat, Seyed-Farzad Mohammadi, Maedeh Mazloomi, Jorge L Alió Del Barrio, Majid Moshirfar, Jorge L Alió

Faculty, Staff and Students Publications

Purpose: Keratoconus is a progressive corneal ectatic disorder characterized by thinning and irregularity of the cornea, significantly impairing visual acuity. Recent studies have explored how non-ectatic conditions, such as dry eye and tear film instability and alteration of the ocular surface microenvironment, contribute to the development and progression of keratoconus. This comprehensive review aims to investigate the complex relationship between keratoconus and ocular surface diseases by examining the microenvironmental changes that occur on the ocular surface throughout the course of keratoconus, as well as the related clinical implications.

Methods: In this PROSPERO-registered study (ID: CRD42025643808), PubMed, Scopus, Cochrane, Embase, Web …

Pediatric Heart Failure: A Practical Guide For Primary Care Providers Supporting Families Across The Care Continuum, Shahnawaz Amdani, Kriti Puri, Julie Glickstein, Joseph A Spinner, Jonathan N Johnson, Ashraf S Harahsheh, Majd Makhoul, Susan Denfield

Faculty, Staff and Students Publications

Background/Objectives: Pediatric heart failure (HF) is a complex clinical syndrome with diverse etiologies and presentations. Primary care providers (PCPs) are critical in early recognition, family education, and coordination of ongoing care in collaboration with pediatric cardiologists. This review provides a comprehensive guide for PCPs to understand the causes, symptoms, treatments, and longitudinal considerations for children with HF.

Methods: We conducted a narrative review synthesizing published evidence and expert consensus guidelines, focusing on the clinical presentation, treatment options, and longitudinal care strategies in children with HF.

Results: HF in children most commonly results from congenital heart disease and …

Lung Nr3c1+ And Cxcr6high T Cells Distinguish Immunopathogenesis Of Human Emphysema, Yun Zhang, Maor Sauler, David B Corry, Scott A Ochsner, Sarah Perusich, Li-Zhen Song, Joshua Malo, Raul San Jose Estepar, Francesca Polverino, Farrah Kheradmand

Faculty, Staff and Students Publications

There is a significant knowledge gap in how T cells promote emphysema in smokers with chronic obstructive pulmonary disease (COPD). Single-cell RNA sequencing (scRNA seq) analysis of human samples and relevant clinical data can provide new mechanistic insights into disease pathogenesis. We generated a human lung scRNA seq dataset with extensive disease characteristic annotation and analyzed a second independent scRNA seq dataset to examine the pathophysiological role of T cells in emphysema. Comparisons of pulmonary immune landscapes in emphysematous (E)-COPD, non-emphysematous (NE)-COPD, and control showed positive enrichment of T cells in E-COPD. Pathway analyses identified upregulated inflammatory states in CD4 …

Long-Term Survival In Lung Cancer With Brain Metastases And Coronary Artery Stenosis: A Case Report, Raghad O. Alharbi, Shahad J. Alshammary, Nasser E. Alotaibi, Ruba M. Aljohani, Bader A. Alotaibi, Ihab F. Suliman

Journal of the Saudi Heart Association

Lung cancer is among the most diagnosed cancers worldwide, and its co-occurrence with coronary heart disease is life-threatening. Osimertinib is the standard treatment for epidermal growth factor receptor (EGFR) mutations in advanced non-small cell lung cancer (NSCLC). The addition of pemetrexed and carboplatin increases not only the efficacy but also the cardiotoxicity risk. We report a 59-year-old woman with NSCLC alongside brain, liver, and spleen metastases, who developed cardiovascular events following cancer therapy. With advanced imaging and multidisciplinary intervention, remarkable remission was achieved over two years. Reporting this case contributes to the understanding of its presentation and diagnostic challenges.

Monitoring The Hematologic Markers In Patients Undergoing Single-Stage Exchange Arthroplasty For Periprosthetic Joint Infection, Wenbo Mu, Juan D. Lizcano, Boyong Xu, Wentao Guo, Abudousaimi Aimaiti, Xiaogang Zhang, Javad Parvizi, Li Cao

Rothman Institute Papers

BACKGROUND: Periprosthetic joint infection (PJI) is a serious complication that necessitates a complex treatment strategy. Single-stage exchange arthroplasty, combined with intravenous and intra-articular antibiotic infusions, has shown high efficacy in treating complex PJIs. However, the impact of this approach on hematologic parameters remains underexplored. This study aims to evaluate the postoperative trends in blood platelet count, white blood cell (WBC) count, and neutrophil count in patients undergoing single-stage exchange arthroplasty.

METHODS: A retrospective analysis was conducted on 313 patients who underwent single-stage revision for PJI between June 2010 and October 2022. Hematologic parameters were monitored for the first seven postoperative …

Low Unintended Dural Puncture Rate Using A Flush-Measure-Check-Advance Technique To Perform Combined Spinal-Epidural Anesthesia In Parturients: A Quality Improvement Clinical Series, James Riopelle, Julie Gayle, Zubaer Anwar, Jeff Burton

School of Medicine Faculty Publications

Background: Reported rates of unintended dural puncture during performance of continuous epidural anesthesia (CEA) or combined spinal-epidural anesthesia (CSEA) have remained steady at approximately 0.5% to 1% since the 1970s. Methods: A modified method of inserting the Tuohy epidural catheterization needle was used during performance of CSEA in 393 parturients. A single staff/faculty anesthesiologist performed or supervised resident use of a flush-measure-check-advance Tuohy needle insertion algorithm. Results: The rate of evident Tuohy needle dural puncture during the series was 0%. One parturient experienced a post-dural puncture headache possibly because of intentional subarachnoid puncture with a very small diameter (25 gauge) …

Pediatric Sickle Cell Disease Overview And Treatment, Michael Smith, Shabnam Arsiwala

Pediatrics in Practice: A CME Podcast

In this episode, we sit down with Dr. Shabnam Arsiwala, a leading pediatric specialist in sickle cell disease, to explore the essentials of caring for children living with this complex condition. Dr. Arsiwala shares insights on early diagnosis, routine management and the role of hydroxyurea in treatment. We also discuss common complications, psychosocial support for families, and exciting innovations on the horizon. Whether you're a general pediatrician or a specialist, this conversation offers practical guidance and fresh perspectives to enhance your clinical care.

Click here to stream the podcast episode.

Practice Patterns In Management Of Low- To Intermediate-Grade Salivary Gland Carcinoma: A Multi-Institutional Study, Mirabelle Sajisevi, Kenny Nguyen, Peter Callas, Andrew Holcomb, Emre Vural, Kyle Davis, Carissa Thomas, John Stein, Ameya Asarkar, Ricardo Aulet, Rebecca Bell, Michael Blasco, Vanessa Bowmaster, Clayton Burruss, Jeffson Chung, Kimberly Chan, Brent Chang, Charles Coffey, David Cognetti, Dylan Cooper, Joehassin Cordero, John Donovan, Yue Jennifer Du, Yusuf Dundar, Rogerio Dedivitis, Heather Edwards, Boban Erovic, Antoine Eskander, Philip Feinberg, Emily Garvey, David Goldstein, Joseph Goodman, Rafael Goulart, Neerav Goyal, Stefan Grasl, Jonathan Giurintano, Nikita Gupta, Andy Habib, Trevor Hackman, Jared Hara, Christina Henson, Michael Hinni, Nadia Hua, Stephanie Johnson-Obaseki, Aditya Juloori, Noah Kalman, Alexandra Kejner, Sobia Khaja, Jamie Ku, Arnaud Lambert, Bao Luu, Kelly Magliocca, Luiz Medina Dos Santos, Cara Michael, Brett Miles, Giulianno De Melo, Michael Moore, Gregoire Morand, Kauê Moura, Hesameddin Noroozi, Rusha Patel, Joseph Paydarfar, Karolina Plonowska-Hirschfeld, Nader Sadeghi, Fabrice Savaria, Nicole Schmitt, Justin Shapiro, Timothy Shaver, Sandro Stoeckli, William Stokes, Anita Sulibhavi, Jason Tasoulas, Varun Vendra, Daniel Vinh, Celina Virgen, Neil Woody, Geoffrey Young, Kiran Kakarala, Danny Enepekides, Michael Hier, Louise Davies, William Ryan

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES: To characterize practice patterns and outcomes in the management of low- and intermediate-grade salivary gland carcinoma prior to the existence of treatment guidelines.

METHODS: Analysis of a registry of patients who underwent parotid and submandibular gland resections for low-and intermediate-grade carcinomas between 2010 and 2019.

RESULTS: Of all 786 patients included in the study, 726 (92%) had preoperative imaging and 653 (83%) had preoperative biopsy. Of the 729 patients with parotid gland cancer, the majority underwent superficial (n = 384, 53%) or total (n = 254, 35%) parotidectomy. In patients with facial nerve preservation, total parotidectomy was …

Synthetic Electrospun Fiber Matrix In The Management Of Acute Wounds Following Excision Of Hidradenitis Suppurativa Lesions: A Prospective Pilot Study, Michael Madueke, Frank Lau

School of Medicine Faculty Publications

Hurley Stage II or III hidradenitis suppurativa (HS) may necessitate surgical excision of diseased skin and subcutaneous fat for symptom control and disease management. These excisions result in open wounds in topographically challenging regions and typically cannot be primarily closed. This study evaluates the use of a synthetic electrospun fiber matrix (SEFM) as a post-resection regeneration template to accelerate re-granulation and improve subsequent skin graft incorporation. This prospective pilot study enrolled Hurley Stage II or III patients undergoing surgical resection of HS lesions. SEFM was applied to the resulting wounds in conjunction with negative pressure wound therapy (NPWT). Patients were …

“Not Today”: Overcoming Prep Hesitancy, Stigma, And Adherence Barriers With Lenacapavir, Margaret Conrad, Meredith Clement

School of Medicine Faculty Publications

No abstract provided.

Understanding Cancer Survivorship Care Needs Using Amazon Reviews: Content Analysis, Algorithm Development, And Validation Study, Liwei Wang, Qiuhao Lu, Rui Li, Taylor B. Harrison, Heling Jia, Ming Huang, Heidi Dowst, Rui Zhang, Hoda Badr, Jungwei W. Fan, Hongfang Liu

Department of Medical Oncology Faculty Papers

BACKGROUND: Complementary therapies are being increasingly used by cancer survivors. As a channel for customers to share their feelings, outcomes, and perceived knowledge about the products purchased from e-commerce platforms, Amazon consumer reviews are a valuable real-world data source for understanding cancer survivorship care needs.

OBJECTIVE: In this study, we aimed to highlight the potential of using Amazon consumer reviews as a novel source for identifying cancer survivorship care needs, particularly related to symptom self-management. Specifically, we present a publicly available, manually annotated corpus derived from Amazon reviews of health-related products and develop baseline natural language processing models using deep …

Next-Gen Tools In Cancer Neuroscience, Vera Thiel, Debpali Sur, Caroline C Picoli, Tamara Mcerlain, Katalina Couto, David J Simon, Yuan Pan, Karen Olivia Dixon, Rajan P Kulkarni, Sebastien Talbot, Alexander Birbrair

Faculty, Staff and Student Publications

The emerging field of cancer neuroscience is rapidly evolving, driven by novel technologies and tools. These include advances in single-cell and spatial transcriptomics; genetic mouse models paired with automated high-throughput; and innovative optical electrophysiological approaches, optogenetics, chemogenetics, engineered viruses, and new methods for visualizing neuronal activity. Collectively, these technologies are revolutionizing how we investigate, manipulate, and characterize distinct components that contribute to the nervous system-cancer interface. In the present review, we discuss the key technologies that are closing the gap between oncology and neuroscience, highlighting the innovations that are propelling the cancer neuroscience field forward.

Rna/Dna-Binding Protein Tdp43 Regulates Dna Mismatch Repair Genes With Implications For Genome Stability, Vincent E Provasek, Albino Bacolla, Suganya Rangaswamy, Manohar Kodavati, Joy Mitra, Issa O Yusuf, Vikas H Malojirao, Velmarini Vasquez, Gavin W Britz, Guo-Min Li, Zuoshang Xu, Sankar Mitra, Ralph M Garruto, John A Tainer, Muralidhar L Hegde

Faculty, Staff and Student Publications

TDP43 is an RNA/DNA-binding protein increasingly recognized for its role in neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As characterized by its aberrant nuclear export and cytoplasmic aggregation, TDP43 proteinopathy is a hallmark feature in over 95% of ALS/FTD cases, leading to detrimental cytosolic aggregates and a reduction in nuclear functionality in neurons. Building on our prior work linking TDP43 proteinopathy to the accumulation of DNA double-strand breaks (DSBs) in neurons, the present investigation uncovers a novel regulatory relationship between TDP43 and DNA mismatch repair (MMR) gene expression. Here, we show that TDP43 depletion or overexpression …

Understanding Cancer Survivorship Care Needs Using Amazon Reviews: Content Analysis, Algorithm Development, And Validation Study, Liwei Wang, Qiuhao Lu, Rui Li, Taylor B Harrison, Heling Jia, Ming Huang, Heidi Dowst, Rui Zhang, Hoda Badr, Jungwei W Fan, Hongfang Liu

Faculty, Staff and Students Publications

Background: Complementary therapies are being increasingly used by cancer survivors. As a channel for customers to share their feelings, outcomes, and perceived knowledge about the products purchased from e-commerce platforms, Amazon consumer reviews are a valuable real-world data source for understanding cancer survivorship care needs.

Objective: In this study, we aimed to highlight the potential of using Amazon consumer reviews as a novel source for identifying cancer survivorship care needs, particularly related to symptom self-management. Specifically, we present a publicly available, manually annotated corpus derived from Amazon reviews of health-related products and develop baseline natural language processing models using deep …

Sars-Cov-2 Nsp13 Interacts With Tead To Suppress Hippo-Yap Signaling, Fansen Meng, Jong Hwan Kim, Chang-Ru Tsai, Jeffrey D Steimle, Jun Wang, Yufeng Shi, Rich G Li, Bing Xie, Vaibhav Deshmukh, Shijie Liu, Xiao Li, James F Martin

Faculty, Staff and Students Publications

The Hippo pathway controls organ development, homeostasis, and regeneration primarily by modulating YAP/TEAD-mediated gene expression. Although emerging studies report Hippo-YAP dysfunction after viral infection, it is largely unknown in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we analyzed RNA sequencing data from human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and SARS-CoV-2-infected human lung samples, and observed a decrease in YAP target gene expression. In screening SARS-CoV-2 nonstructural proteins, we found that nonstructural protein 13 (NSP13), a conserved coronavirus helicase, inhibits YAP transcriptional activity independent of the upstream Hippo kinases LATS1/2. Consistently, introducing NSP13 into mouse cardiomyocytes suppresses …

Atrial Fibroblast-Derived Macrophage Migration Inhibitory Factor Promotes Atrial Macrophage Accumulation In Postoperative Atrial Fibrillation, Joshua A Keefe, Jose Alberto Navarro-Garcia, Shuai Zhao, Mihail G Chelu, Xander Ht Wehrens

Faculty, Staff and Students Publications

New study: Blocking MIF protein prevents irregular heartbeats after surgery by reducing harmful immune cell buildup in the atria.

Dietary Methionine Restriction Primes T Cell Metabolism For Activation And Tumor Inhibition And Enhances The Efficacy Of Immune Checkpoint Blockade, Xiaoqing Qing, Binita Chakraborty, Panpan Liu, Sandeep Artham, Patrick K Juras, Dongyin Guan, Kristen E Pauken, Ching-Yi Chang, Xia Gao

Faculty, Staff and Students Publications

The proliferation of many cancer cells is methionine dependent and dietary methionine restriction (MR) has shown anti-tumor effects in a wide variety of immunodeficiency preclinical models. Yet, whether MR exerts an anti-tumor effect in the presence of an immune-competent background remains inconclusive. Accumulating evidence has shown an essential role of methionine in immune cell differentiation and function. Thus, competition for methionine between tumor cells and immune cells in the tumor microenvironment may drive tumor growth and tumor response to therapy. Here, we aim to define the impact of MR on tumor growth and associated immunity. We first assessed the effect …

Deciphering The Mycn-Driven Metabolic Microenvironment Of Neuroblastoma, Amber Wolf, Davide Leardini, Lingzhi Li, Riccardo Masetti, Costas A Lyssiotis, Eveline Barbieri

Faculty, Staff and Students Publications

Oncogenic MYCN drives aggressive disease in many cancers including neuroblastoma (NB). Metabolic reprogramming is essential to support cancer cell homeostasis and survival under nutrient- and oxygen-deprived conditions. MYCN directly reprograms many nodes of tumor-intrinsic metabolism, which have significant repercussions on the cells of the tumor microenvironment (TME), resulting in complex intercellular metabolic circuits that contribute to the immunosuppressive microenvironment of NB. These metabolic circuits are also regulated by the organismal and cellular circadian clock and host diet to further impact the TME and NB oncogenesis. This review discusses the mechanisms by which MYCN regulates the metabolic crosstalk between tumor, TME, …

Adsl Deficiency Is A Secondary Mitochondrial Disease Affecting Organelle Homeostasis And Erk2/Akt Signaling In A Linear Genotype-Phenotype Relation, Matteo Bordi, Beatrice Testa, Claudia Compagnucci, Fiorella Colasuonno, Francesca Cipressa, Elisabetta Betterini, Andrea Mancini, Claudia Carsetti, Illari Salvatori, Caterina Ferraina, Ming Yang, Rossella De Cegli, Eugenio Del Prete, Chiara Veroni, Salvatore Rizza, Sofia Mauri, Elena Ziviani, Marina Macchiaiolo, Davide Vecchio, Filippo Maria Panfili, Teresa Rizza, Gerrit Weber, Rosalba Carrozzo, Alberto Ferri, Silvia Campello, Andrea Ballabio, Christian Frezza, Gianluca Cestra, Marco Tartaglia, Andrea Bartuli, Francesco Cecconi

Duncan NRI Faculty and Staff Publications

Adenylosuccinate lyase deficiency (ADSLd) is a rare autosomal recessive purine metabolism disorder with several clinical manifestations. While toxic substrate accumulation is a known hallmark, no additional molecular mechanisms have been established. Here, we show that ADSLd is associated with mitochondrial dysfunction, including increased fragmentation, impaired respiration, and reduced ATP production. The severity of mitochondrial impairment correlates with ADSLd pathology, especially in mitochondria-dependent tissues. We also identify defects in mitochondrial dynamics and transport linked to ERK2 and AKT suppression. Notably, overexpressing constitutively active ERK2 or supplementing purine intermediates partially rescues the mitochondrial phenotype. These findings suggest an alternative disease mechanism and …

Successful Management Of High-Risk Gestational Choriocarcinoma With Choriocarcinoma Syndrome: A Case Report, Ava R. Hansen, Hannah Daley, Priyanka Raju, Jonathan Buerger

Transformative Medicine

Introduction: Choriocarcinoma is a rare and highly malignant gestational trophoblastic neoplasia that is treatable with timely and appropriate intervention. However, choriocarcinoma may lead to life-threatening complications, such as choriocarcinoma syndrome (CCS), a rare type of tumor lysis manifesting as hemorrhage at metastatic sites of advanced tumors.

Case Description: This case involves a 30-year-old woman, gravida 3 para 0, with high-risk choriocarcinoma and a WHO score of 11, indicating high risk. Initial management comprised Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide and Vincristine (EMA/CO) chemotherapy until multisystem complications arose, including the development of CCS which resulted in an abdominal compartment syndrome. An exploratory …

Artificial Intelligence-Enhanced Electrocardiography For Hypertrophic Cardiomyopathy: Bridging The Gap Between Innovation And Clinical Implementation, Muhammad Nabeel Saddique, Alina Jamshed

Journal of the Saudi Heart Association

No abstract for this article type