Medical Specialties Commons^™

Knowledge And Attitude Of Lebanese Adults Towards Asthma In Beirut, Lebanon, Farah Hatem Haidar, Doaa Issa, Maha Aboul Ela, Karim Raafat

BAU Journal - Health and Wellbeing

Asthma, a serious global health problem, has been an area of interest due to its increasing prevalence, expanding treatment costs, and rising burden on patients and the community. Since asthma cannot be cured, clinical episodes can be prevented and controlled by adequate management and sufficient knowledge of the disease. Appropriate treatment may relieve asthma symptoms and improve quality of life. However, poor knowledge of asthma disease and medication use, misdiagnoses, misuse of inhalers and inadequate self-management of disease symptoms may have a greater impact on the disease process. Therefore, assessment of the population’s knowledge and attitude toward asthma is essential. …

Prolonged Ulcerative Laryngitis., Sugosh M Anur, Lauren E Melley, Robert T Sataloff

Otolaryngology (ENT) Resident Research

Ulcerative vocal fold lesions occupy the vibratory margins of the musculomembranous portion of the vocal folds and cause dysphonia. Symptoms may exist for several weeks to months before improvement occurs. Lesions observed on strobovideolaryngoscopy may resemble malignant leukoplakia and tempt physicians to obtain biopsy. Biopsy can cause permanent dysphonia and should be performed only when necessary. Therefore, it is important to identify prolonged ulcerative laryngitis and provide appropriate management.

Common Variation In A Long Non-Coding Rna Gene Modulates Variation Of Circulating Tgf-Β2 Levels In Metastatic Colorectal Cancer Patients (Alliance), Julia Quintanilha, Alexander Sibley, Yingmiao Liu, Donna Niedzwiecki, Susan Halabi, Layne Rogers, Bert O'Neil, Hedy Kindler, William Kelly, Alan Venook, Howard Mcleod, Mark Ratain, Andrew Nixon, Federico Innocenti, Kouros Owzar

Department of Medical Oncology Faculty Papers

BACKGROUND: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms. The abundance of protein markers was quantified using a multiplex enzyme-linked immunosorbent assay from plasma derived from peripheral venous …

Inchi Isotopologue And Isotopomer Specifications, Hunter N. B. Moseley, Philippe Rocca-Serra, Reza M. Salek, Masanori Arita, Emma L. Schymanski

Markey Cancer Center Faculty Publications

This work presents a proposed extension to the International Union of Pure and Applied Chemistry (IUPAC) International Chemical Identifier (InChI) standard that allows the representation of isotopically‑resolved chemi‑ cal entities at varying levels of ambiguity in isotope location. This extension includes an improved interpretation of the current isotopic layer within the InChI standard and a new isotopologue layer specification for representing chemical intensities with ambiguous isotope localization. Both improvements support the unique isotopically‑ resolved chemical identification of features detected and measured in analytical instrumentation, specifically nuclear magnetic resonance and mass spectrometry.

Scientific contribution

This new extension to the InChI standard …

Emergency Care Of An Older Adult With Complex Care Needs, Muhammad Adnan Khan, Himika Dalia, Michelle Dietz

Journal of Geriatric Emergency Medicine

In this case report, we demonstrate the application of a stepwise guiding approach for older adults with complex care needs who present to the emergency department. It also highlights the challenges encountered during the implementation of these principles, and sheds light on the factors affecting the management of complex older populations. This case report emphasizes the pressing need for the development of a standardized protocol tailored to emergency physicians, addressing the unique needs of complex-multimorbid older adults, and overcoming the system barriers in emergency care.

C-Terminal Binding Protein 2 Is A Novel Tumor Suppressor Targeting The Myc-Irf4 Axis In Multiple Myeloma, Coty Hing Yau Cheung, Chi Keung Cheng, Kam Tong Leung, Chi Zhang, Chi Yan Ho, Xi Luo, Angel Yuet Fong Kam, Tian Xia, Thomas Shek Kong Wan, Herbert Augustus Pitts, Natalie Pui Ha Chan, Joyce Sin Cheung, Raymond Siu Ming Wong, Xiao-Bing Zhang, Margaret Heung Ling Ng

Faculty, Staff and Student Publications

Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation targets IRF4 for proliferation and survival. MYC and IRF4 are still considered "undruggable," as most small-molecule inhibitors suffer from low potency, suboptimal pharmacokinetic properties, and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM. Here, we uncovered an unappreciated tumor-suppressive role of C-terminal binding protein 2 (CTBP2) in MM via strong inhibition of the MYC-IRF4 axis. In contrast to epithelial cancers, CTBP2 is frequently downregulated in MM, in association with shortened survival, hyperproliferative features, and adverse clinical outcomes. Restoration of CTBP2 exhibited potent …

Stellae-123 Gene Expression Signature Improved Risk Stratification In Taiwanese Acute Myeloid Leukemia Patients, Yu-Hung Wang, Adrián Mosquera Orgueira, Chien-Chin Lin, Chi-Yuan Yao, Min-Yen Lo, Cheng-Hong Tsai, Adolfo De La Fuente Burguera, Hsin-An Hou, Wen-Chien Chou, Hwei-Fang Tien

Faculty, Staff and Student Publications

The European Leukemia Net recommendations provide valuable guidance in treatment decisions of patients with acute myeloid leukemia (AML). However, the genetic complexity and heterogeneity of AML are not fully covered, notwithstanding that gene expression analysis is crucial in the risk stratification of AML. The Stellae-123 score, an AI-based model that captures gene expression patterns, has demonstrated robust survival predictions in AML patients across four western-population cohorts. This study aims to evaluate the applicability of Stellae-123 in a Taiwanese cohort. The Stellae-123 model was applied to 304 de novo AML patients diagnosed and treated at the National Taiwan University Hospital. We …

Novel 3d Printed Universal Conical Holder For Eye Plaque Quality Assurance, Wentao Wang, Jacqueline Emrich, Firas Mourtada

Department of Radiation Oncology Faculty Papers

PURPOSE: For the custom-built construction of eye plaques, the iodine (I-125) seeds of different source strengths are recycled in our eye plaque program. To return I-125 seeds to the correct lot, we developed a novel 3D-printed conical plaque QA holder for relative assay for eye plaques.

MATERIALS AND METHODS: A universal 3D-printed conical plaque holder was designed to accommodate six plaque sizes and fit reproducibly in a well-type dose calibrator. A reproducibility test was used to compare the plaque placement consistency in the holder versus without the holder. Plaque assays were performed for assembled plaques both before implant and after …

Third-Party Fecal Microbiota Transplantation For High-Risk Treatment-Naïve Acute Gvhd Of The Lower Gi Tract, Zachariah Defilipp, Ashish V Damania, Haesook T Kim, Chia-Chi Chang, Areej El-Jawahri, Steven L Mcafee, Aj S Bottoms, Vesselina Toncheva, Melissa M Smith, Maria Dolaher, Lindsey Perry, Meghan White, Brittany Diana, Sheila Connolly, Bimalangshu R Dey, Matthew J Frigault, Richard A Newcomb, Paul V O'Donnell, Thomas R Spitzer, Michael K Mansour, Daniela Weber, Nadim J Ajami, Elizabeth Hohmann, Robert R Jenq, Yi-Bin Chen

Faculty, Staff and Student Publications

Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract, and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study, third-party, single-donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive 1 induction dose (15 capsules per day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules per dose. The primary end point of the study was feasibility, which would be achieved if ≥80% …

Viral Meningitis And Encephalitis Update, Boris Garber, Jonathan Glauser

Faculty Scholarship

Purpose of Review: This review describes advances in the diagnosis, treatment, and prevention of non-bacterial meningitis and encephalitis, with a focus on emerging viral causes of central nervous system (CNS) infection. Recent Findings: The Infectious Diseases Society of America recently published new guidelines for the management of encephalitis. Multiple articles have been published detailing emerging etiologies in human CNS infections, including analyses of neurological complications in the ongoing COVID-19 pandemic. Finally, several novel viral detection methods have been described, which may improve the detection of the specific etiologies of CNS infections (Hongyan et al. Front Neurol 14, [1]). Summary: Meningitis …

Astrocytes Remember Inflammation, Michael R Williamson, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes respond to all forms of central nervous system maladies. In a recent issue of Nature, Lee et al. demonstrate that astrocytes encode inflammatory stimuli as epigenetic memory, which strengthens responses to subsequent stimuli and exacerbates pathology in disease models.

Mv140 Mucosal Vaccine Induces Targeted Immune Response For Enhanced Clearance Of Uropathogenic E Coli In Experimental Urinary Tract Infection, Paula Saz-Leal, Marianne Morris Ligon, Carmen María Diez-Rivero, Diego García-Ayuso, Soumitra Mohanty, Marcos Viñuela, Irene Real-Arévalo, Laura Conejero, Annelie Brauner, José Luis Subiza, Indira Uppugunduri Mysorekar

Faculty, Staff and Students Publications

MV140 is an inactivated whole-cell bacterial mucosal vaccine with proven clinical efficacy against recurrent urinary tract infections (UTIs). These infections are primarily caused by uropathogenic E. coli (UPEC) strains, which are unique in their virulence factors and remarkably diverse. MV140 contains a non-UPEC strain, suggesting that it may induce an immune response against different UPEC-induced UTIs in patients. To verify this, we experimentally evaluated the cellular and humoral responses to UTI89, a prototypical UPEC strain, in mice vaccinated with MV140, as well as the degree of protection achieved in a UPEC UTI89 model of acute cystitis. The results show that …

Real-World Treatment Patterns And Outcomes In Patients With Primary Hemophagocytic Lymphohistiocytosis Treated With Emapalumab, Shanmuganathan Chandrakasan, Michael B Jordan, Ashley Baker, Edward M Behrens, Deepika Bhatla, May Chien, Olive S Eckstein, Michael M Henry, Michelle L Hermiston, Ashley P Hinson, Jennifer W Leiding, Abiola Oladapo, Sachit A Patel, Priti Pednekar, Anish K Ray, Blachy Dávila Saldaña, Susmita N Sarangi, Kelly J Walkovich, John D Yee, Adi Zoref-Lorenz, Carl E Allen

Faculty, Staff and Students Publications

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening, hyperinflammatory syndrome. Emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon gamma, is approved in the United States to treat primary HLH (pHLH) in patients with refractory, recurrent, or progressive disease, or intolerance with conventional HLH treatments. REAL-HLH, a retrospective study, conducted across 33 US hospitals, evaluated real-world treatment patterns and outcomes in patients treated with ≥1 dose of emapalumab between 20 November 2018 and 31 October 2021. In total, 46 patients met the pHLH classification criteria. Median age at diagnosis was 1.0 year (range, 0.3-21.0). Emapalumab was initiated for …

Prognostic Impact Of Cooccurring Mutations In Flt3-Itd Pediatric Acute Myeloid Leukemia., Katherine Tarlock, Robert B. Gerbing, Rhonda E. Ries, Jenny L. Smith, Amanda Leonti, Benjamin J. Huang, Danielle Kirkey, Leila Robinson, Jack H. Peplinksi, Beverly Lange, Todd M. Cooper, Alan S. Gamis, E Anders Kolb, Richard Aplenc, Jessica A. Pollard, Todd A. Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

We sought to define the cooccurring mutational profile of FLT3-ITD-positive (ITDpos) acute myeloid leukemia (AML) in pediatric and young adult patients and to define the prognostic impact of cooperating mutations. We identified 464 patients with FLT3-ITD mutations treated on Children's Oncology Group trials with available sequencing and outcome data. Overall survival, event-free survival (EFS), and relapse risk were determined according to the presence of cooccurring risk stratifying mutations. Among the cohort, 79% of patients had cooccurring alterations across 239 different genes that were altered through mutations or fusions. Evaluation of the prognostic impact of the cooccurring mutations demonstrated that patients …

Bridging Services To Evidenced-Based Care: Implementing A Psychology Consult Check-Up Clinic, Jacqueline Pabis Phd, Sabrina Ung Ma, Angela Combs Ma, Mallory Netz Phd, Carisa Parrish Phd, Casey Lawless Phd

Research Days

This quality improvement project examines the feasibility, satisfaction, and preliminary outcomes of a hospital follow-up program for the CMH Inpatient Psychology Consultation & Liaison team.

Improving Awareness And Utilization Of Safety Net Resources After Extremity Firearm Injury, Colleen M. Moreland, Caleb W. Grote, Richard M. Schwend, Julia G. Harris

Research Days

The orthopaedic surgery department can improve follow-on care for pediatric survivors of extremity firearm injuries by creating and implementing a checklist of defined safety net resources.

A Quality Improvement Project To Improve Antibiotic Choice For Children Admitted With Urinary Tract Infections (Utis), Philip Jurasinski Do, Pgy-3, Adrienne Deporre Md, Kathleen Berg Md, Allison Hadley Md, Viktoriya Stoycheva Mha, Rn, Cpn, Rana El Feghaly Md

Research Days

This is an antibiotic stewardship quality improvement project focused on improving antibiotic choices for children with urinary tract infections who are in the Children's Mercy Kansas City system. This project aims to improve the rates of cefazolin or cephalexin for treatment from 27% to 60%. 96% of urinary tract infections in our system are caused by E. Coli that are susceptible to these first generation cephalosporins.

More Of Less: Optimizing Opioid Prescriptions For Acute Fractures In The Emergency Department At A Children’S Hospital, Colton Schwarz, Spencer Wittmeyer, Mitch Kinkor, Michelle Dephillips, Elizabeth Edmundson, Ryan Mcdonough, Warren Teachout, Nicholas Clark

Research Days

Quality improvement project that aims to improve opioid stewardship in acute fracture management.

Characterization Of Nationally Reported Pediatric Deaths Involving Fentanyl Ingestions In Missouri, Margaret Campbell, Mary Moffatt, Emily Killough, Terra Frazier

Research Days

There has been a dramatic rise in pediatric deaths associated with synthetic opioid use, with the most prominent being Fentanyl. This is a retrospective cohort study using data from the National Center for Fatality Review and Prevention with the goal of identifying risk factors that increase the vulnerability of children to Fentanyl ingestion. Ultimately this research may help lead to improved identification of at risk children with the goal of implementation of targeted prevention programming.

How Neonates Die: Mortality Trends And Associations In A Level Iv Neonatal Intensive Care Unit, Erin Bolen, Ashley K. Sherman, Julie Weiner, Jotishna Sharma

Research Days

Background

Modes of neonatal mortality include withdrawal of life-sustaining interventions, non-escalation of interventions, and secondary to a code event. Mortality trends have been examined broadly, but the impact of clinical and demographic factors on the mode of neonatal mortality has yet to be evaluated. A greater understanding of this information would help guide medical decision-making and identify potential inequities. The aim is to evaluate the impact of clinical and demographic factors on the mode of neonatal death in a level IV neonatal intensive care unit (NICU).

Study Design/Methods

Data were collected via retrospective chart review of patients who died at …

Socioeconomic Differences In Penicillin Allergy Label Rates Of Children Evaluated In Pediatric Emergency Departments And Urgent Cares, Zoya Siddiqui, Brian R. Lee, Amanda Nedved, Jennifer Mckinsey, Frances Turcotte Benedict, Brandi Missel, Aarti Pandya, Rana El Feghaly

Research Days

In this retrospective study of 183,692 patients ≤19 years evaluated in urgent cares and emergency departments of a large pediatric academic center July 2022- June 2023, we found that in addition to race, socioeconomic status reflected by insurance and area deprivation index had a large association with penicillin allergy labels.

Improving Nutritional Delivery To Pediatric Patients While Using Continuous Renal Replacement Therapy, Jennifer Ruiz-Boada, Sarah Brunner, Tara Benton, Vimal Chadha

Research Days

This quality improvement guide aims to enhance early nutritional delivery to pediatric patients with renal failure who require renal replacement therapy.ng renal replacement therapy.

Understanding Inpatient Diagnostic Imaging Use In Children’S Hospitals To Prioritize Stewardship Efforts, Megan E. Collins, Matt Hall, John Stephens, Jessica L. Markham

Research Days

We utilized the Pediatric Health Information System to perform a retrospective cohort study of hospitalized children across 45 hospitals to describe diagnostic imaging studies among hospitalized children with the highest prevalence, cost, rates of repetition, and hospital variation to help inform de-implementation efforts.

Electrical Stimulation Of The Medial Pin After Insertion Is Safe And Effective In Preventing Iatrogenic Ulnar Nerve Neuropraxias In Type Iii Supracondylar Fractures. A Case Series Of 128 Consecutive Patients., Lucas Georger B.A., Mckenna Noe B.S., Richard M. Schwend M.D.

Research Days

This case series explores the safety and efficacy of using a disposable nerve stimulator for intraoperative stimulation of both medial and lateral pins in Gartland type III supracondylar humerus fractures, revealing no instances of ulnar nerve stimulation response or postoperative iatrogenic ulnar nerve injury, thereby highlighting the potential for this cost-effective approach to ensure stable medial column pin fixation without ulnar nerve complications.

Safety And Efficacy Of Intraoperative Vectored Traction With Gardner-Wells (Gw) Tongs For Pediatric Spine Deformity Surgery - A Series Of 1000 Cases, Lucas Georger B.A., Krish Sardesai B.A., Andrew Dumas B.S., Mckenna Noe B.S., Richard M. Schwend M.D.

Research Days

Conducting an ongoing exploration, this study delves into the safety and efficacy of Gardner-Wells Tongs in pediatric spinal deformity surgery, involving a series of 418 cases, revealing a 5.5% complication rate primarily associated with facial swelling and abrasions, emphasizing the need for further investigation to validate the safety and effectiveness of this intervention.

Comprehensive Peripheral Blood Immunoprofiling Reveals Five Immunotypes With Immunotherapy Response Characteristics In Patients With Cancer, Daniiar Dyikanov, Aleksandr Zaitsev, Tatiana Vasileva, Iris Wang, Arseniy Sokolov, Evgenii Bolshakov, Alena Frank, Polina Turova, Olga Golubeva, Anna Gantseva, Anna Kamysheva, Polina Shpudeiko, Ilya Krauz, Mary Abdou, Madison Chasse, Tori Conroy, Nicholas Merriam, Julia Alesse, Noel English, Boris Shpak, Anna Shchetsova, Evgenii Tikhonov, Ivan Filatov, Anastasia Radko, Anastasiia Bolshakova, Anastasia Kachalova, Nika Lugovykh, Andrey Bulahov, Anastasiia Kilina, Syimyk Asanbekov, Irina Zheleznyak, Pavel Skoptsov, Evgenia Alekseeva, Jennifer Johnson, Joseph Curry, Alban Linnenbach, Andrew South, Enjun Yang, Kirill Morozov, Anastasiya Terenteva, Lira Nigmatullina, Dmitry Fastovetz, Anatoly Bobe, Linda Balabanian, Krystle Nomie, Sheila Yong, Christopher Davitt, Alexander Ryabykh, Olga Kudryashova, Cagdas Tazearslan, Alexander Bagaev, Nathan Fowler, Adam Luginbuhl, Ravshan Ataullakhanov, Michael Goldberg

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

The lack of comprehensive diagnostics and consensus analytical models for evaluating the status of a patient's immune system has hindered a wider adoption of immunoprofiling for treatment monitoring and response prediction in cancer patients. To address this unmet need, we developed an immunoprofiling platform that uses multiparameter flow cytometry to characterize immune cell heterogeneity in the peripheral blood of healthy donors and patients with advanced cancers. Using unsupervised clustering, we identified five immunotypes with unique distributions of different cell types and gene expression profiles. An independent analysis of 17,800 open-source transcriptomes with the same approach corroborated these findings. Continuous immunotype-based …

Mammographic Density Mediates The Protective Effect Of Early-Life Body Size On Breast Cancer Risk, Marina Vabistsevits, George Davey Smith, Tom G Richardson, Rebecca C Richmond, Weiva Sieh, Joseph H Rothstein, Laurel A Habel, Stacey E Alexeeff, Bethan Lloyd-Lewis, Eleanor Sanderson

Faculty, Staff and Student Publications

The unexplained protective effect of childhood adiposity on breast cancer risk may be mediated via mammographic density (MD). Here, we investigate a complex relationship between adiposity in childhood and adulthood, puberty onset, MD phenotypes (dense area (DA), non-dense area (NDA), percent density (PD)), and their effects on breast cancer. We use Mendelian randomization (MR) and multivariable MR to estimate the total and direct effects of adiposity and age at menarche on MD phenotypes. Childhood adiposity has a decreasing effect on DA, while adulthood adiposity increases NDA. Later menarche increases DA/PD, but when accounting for childhood adiposity, this effect is attenuated. …

High All-Cause Mortality And Increasing Proportion Of Older Adults With Tuberculosis In Texas, 2008–2020, Belinda A Medrano, Miryoung Lee, Gretchen Gemeinhardt, Lana Yamba, Blanca I Restrepo

Faculty, Staff and Student Publications

Pulmonary tuberculosis (PTB) elimination efforts must consider the global growth of the ageing population. Here we used TB surveillance data from Texas, United States (2008-2020; total n = 10656) to identify unique characteristics and outcomes in older adults (OA, ≥65 years) with PTB, compared to young adults (YA, 18-39 years) or middle-aged adults (40-64 years). We found that the proportion of OA with PTB increased from 15% in 2008 to 24% in 2020 (trend p < 0.05). Diabetes was highly prevalent in OA (32%) but not associated with adverse outcomes. Death was 13-fold higher in OA compared to YA and was 7% at the time of diagnosis which suggests diagnostic delays. However, once TB was suspected, we found no differences in culture, smear, or nucleic acid detection of mycobacteria (although less lung cavitations) in OA. During treatment, OA had less drug-resistant TB, few adverse reactions and adhered with TB treatment. We recommend training healthcare workers to 'think TB' in OA, for prompt treatment initiation to diminish deaths. Furthermore, OA should be added as a priority group to the latent TB treatment guidelines by the World Health Organization, to prevent TB disease in this highly vulnerable group.

Impact Of Renal Cell Carcinoma Molecular Subtypes On Immunotherapy And Targeted Therapy Outcomes, Renée Maria Saliby, Chris Labaki, Tejas R Jammihal, Wanling Xie, Maxine Sun, Valisha Shah, Eddy Saad, M Harry Kane, Soki Kashima, Katherine Sadak, Talal El Zarif, Deepak Poduval, Robert J Motzer, Thomas Powles, Brian I Rini, Laurence Albiges, Sumanta K Pal, Bradley A Mcgregor, Rana R Mckay, Sabina Signoretti, Eliezer M Van Allen, Sachet A Shukla, Toni K Choueiri, David A Braun

Faculty, Staff and Student Publications

Saliby et al. show that a machine learning approach can accurately classify clear cell renal cell carcinoma (RCC) into distinct molecular subtypes using transcriptomic data. When applied to tumors biospecimens from the JAVELIN Renal 101 (JR101) trial, a benefit is observed with immune checkpoint inhibitor (ICI)-based therapy across all molecular subtypes.

The Crosstalk Between Macrophages And Cancer Cells Potentiates Pancreatic Cancer Cachexia, Mingyang Liu, Yu Ren, Zhijun Zhou, Jingxuan Yang, Xiuhui Shi, Yang Cai, Alex X Arreola, Wenyi Luo, Kar-Ming Fung, Chao Xu, Ryan D Nipp, Michael S Bronze, Lei Zheng, Yi-Ping Li, Courtney W Houchen, Yuqing Zhang, Min Li

Faculty, Staff and Student Publications

With limited treatment options, cachexia remains a major challenge for patients with cancer. Characterizing the interplay between tumor cells and the immune microenvironment may help identify potential therapeutic targets for cancer cachexia. Herein, we investigate the critical role of macrophages in potentiating pancreatic cancer induced muscle wasting via promoting TWEAK (TNF-like weak inducer of apoptosis) secretion from the tumor. Specifically, depletion of macrophages reverses muscle degradation induced by tumor cells. Macrophages induce non-autonomous secretion of TWEAK through CCL5/TRAF6/NF-κB pathway. TWEAK promotes muscle atrophy by activating MuRF1 initiated muscle remodeling. Notably, tumor cells recruit and reprogram macrophages via the CCL2/CCR2 axis …