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Articles 2671 - 2700 of 25901
Full-Text Articles in Entire DC Network
Side Effect Profiles In Immunotherapy Vs Chemotherapy In The Treatment Of Pediatric Acute Lymphoblastic Leukemia, Chloe Triolo, Mariana Sales, Amy Nguyen, Jaclyn Schultz, Melissa Crisci
Side Effect Profiles In Immunotherapy Vs Chemotherapy In The Treatment Of Pediatric Acute Lymphoblastic Leukemia, Chloe Triolo, Mariana Sales, Amy Nguyen, Jaclyn Schultz, Melissa Crisci
Rowan-Virtua Research Day
Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and also one of the most curable, with current cure rates surpassing 90%. Immunotherapy using biologics is an emerging cancer treatment approach that shows significant promise and is generally less toxic than traditional chemotherapy. Due to its lower toxicity compared to chemotherapy, standalone immunotherapy may represent a promising treatment option for pediatric ALL patients.
Hypothesis: This review aims to compare acute side effect profiles and chronic complications in chemotherapy versus immunotherapy treatment modalities for pediatric patients with ALL. Immunotherapy is hypothesized to have a more tolerable side effect …
Accelerated Tumor Growth And Lymphatic Spread Of Transplantable Melanomas In Tumor Necrosis Factor(Tnf)-Transgenic Mice, Catherine F. Alapatt, Robert Hughes, Roger Sheffmaker, Gillian Mcguire, Daniel Deegan, Igor Kuzin, Andrea Bottaro
Accelerated Tumor Growth And Lymphatic Spread Of Transplantable Melanomas In Tumor Necrosis Factor(Tnf)-Transgenic Mice, Catherine F. Alapatt, Robert Hughes, Roger Sheffmaker, Gillian Mcguire, Daniel Deegan, Igor Kuzin, Andrea Bottaro
Rowan-Virtua Research Day
Melanoma is the fifth most common cancer among American adults, with significant morbidity and mortality at 5 years remaining >60% for patients with stage IV disease. The malignancy is due to the transformation of melanocytes, with one of the major risk factors being ultraviolet light exposure. Although as many as one in five human cancers have been linked to chronic inflammation, the role of inflammatory signals in melanoma growth and metastasis remains poorly understood.
Tumor necrosis factor (TNF)-transgenic (TNFtg) mice are a well-established model of chronic systemic inflammation, with involvement of joints and other organ systems. To assess the effect …
Efficacy Of Platelet-Rich Plasma In The Management And Treatment Of Achilles Tendon Ruptures: A Literature Review, Justin Le, Savana Coraggio, Emir Shahin, Valentin Nicholas Kotlyar, Joshua Sassaman, Christopher Cherfane, Gilbert Siu
Efficacy Of Platelet-Rich Plasma In The Management And Treatment Of Achilles Tendon Ruptures: A Literature Review, Justin Le, Savana Coraggio, Emir Shahin, Valentin Nicholas Kotlyar, Joshua Sassaman, Christopher Cherfane, Gilbert Siu
Rowan-Virtua Research Day
Background
In the world of regenerative medicine, platelet-rich plasma (PRP) has gained much attention as a potential enhancer of musculoskeletal healing. However, despite promising results in many applications, the use of PRP in Achilles tendon ruptures (ATR) remains a topic of debate. While some studies suggest potential benefits in terms of pain reduction and early-phase healing, others report no significant difference in clinical or functional outcomes compared to standard treatment. This inconsistency underscores the need for further investigation into PRP’s role in tendon repair, particularly in high-stress, load-bearing structures such as the Achilles tendon.
Objective
This review aims to evaluate …
From Gut To Heart: Tmao As A Predictive Marker For Cardiovascular Risk, Jasjeet Kaur Dhaliwal, Demi Poulathas
From Gut To Heart: Tmao As A Predictive Marker For Cardiovascular Risk, Jasjeet Kaur Dhaliwal, Demi Poulathas
Rowan-Virtua Research Day
Background: Trimethylamine N-oxide (TMAO), a metabolite produced by gut microbiota from dietary nutrients such as choline and carnitine, has emerged as a potential biomarker linking the gut microbiome to cardiovascular disease (CVD). This review synthesizes findings from 31 studies examining the association between circulating TMAO levels and cardiovascular outcomes.
Objective: To evaluate the prognostic value of plasma or serum TMAO concentrations in predicting major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular mortality.
Methods: Studies were identified through a systematic search and screened based on inclusion criteria that required human populations, quantification of blood-based TMAO, and analysis of …
Mechanisms Mediating The Protective Effects Of Caffeine On Alzheimer’S Disease Progression, Jessica Ivanov, Malky Bernat, Joshua Drawbaugh, Jeremy Mehta, Namira Rahmani, Saikumar Thellapally
Mechanisms Mediating The Protective Effects Of Caffeine On Alzheimer’S Disease Progression, Jessica Ivanov, Malky Bernat, Joshua Drawbaugh, Jeremy Mehta, Namira Rahmani, Saikumar Thellapally
Rowan-Virtua Research Day
Background: This review aims to examine the molecular mechanisms through which caffeine may exert neuroprotective effects against Alzheimer’s Disease (AD).
Methods: A literature review was done across PubMed and Embase to identify studies between 2000 and 2024, exploring the mechanism behind caffeine’s effects on AD. The criteria focused on peer-reviewed articles involving human or animal models. Information was gathered on study design, participant characteristics, caffeine consumption, proposed mechanisms, and effects on cognition.
Results: The studies support caffeine's potential as a therapeutic, neuromodulator against AD through six mechanisms: inhibition of adenosine A2A receptors, decreased amyloid-beta production and aggregation, promotion of amyloid …
Systematic Review And Meta-Analysis Examining If Hyperplasia Occurs In Humans In Response To Resistance Exercise, Hitesh Gowda, Scott Dankel, Harshal Parmar, Nicholas Barton
Systematic Review And Meta-Analysis Examining If Hyperplasia Occurs In Humans In Response To Resistance Exercise, Hitesh Gowda, Scott Dankel, Harshal Parmar, Nicholas Barton
Rowan-Virtua Research Day
Background: It is commonly believed that resistance exercise in humans induces muscle growth primarily via muscle hypertrophy, but there is some debate as to whether muscle hyperplasia occurs. The purpose of this meta-analysis was to quantitively assess whether the presence of muscle hyperplasia occurs in humans performing resistance training.
Methods: Medline, Scopus, and Web of Science were searched on May 17, 2024. Studies that assessed muscle fiber number pre and post resistance training were included in a three-level random effects model to assess changes in muscle fiber number.
Results: A total of 11 studies met the search criteria, with all …
Interobserver Variability In Cardiovascular Fdg Pet/Ct Analysis In Large Vessel Vasculitis, Redemptar Kimeu, Anoop Shah, Samuel Gitau, Gemina Doolub, Jeilan Mohamed
Interobserver Variability In Cardiovascular Fdg Pet/Ct Analysis In Large Vessel Vasculitis, Redemptar Kimeu, Anoop Shah, Samuel Gitau, Gemina Doolub, Jeilan Mohamed
Imaging & Diagnostic Radiology, East Africa
Introduction: PET/CT has a synergistic value for optimal diagnosis, disease activity monitoring, and evaluation of damage progression in large vessel vasculitis. The use of standardized uptake values (SUV) as a measurement of relative tissue uptake facilitates comparisons between patients, and has been suggested as a basis for diagnosis. The SUVmean and SUVmax reproducibility in vascular structures is not widely studied.
Objective: The objective of this study was to evaluate the inter-observer variability of both qualitative visual grading of aortic 18F-FDG uptake and the quantitative aortic mean and maximum SUVs in these patients with mild to moderate covid-19 infection …
Presentation: Accuracy Of Ecg Chest Electrode Placement In Prehospital And Hospital Settings, Edwin L. Clopton, Kristiina Hyrkas Phd, Licnsc, Mnsc, Rn
Presentation: Accuracy Of Ecg Chest Electrode Placement In Prehospital And Hospital Settings, Edwin L. Clopton, Kristiina Hyrkas Phd, Licnsc, Mnsc, Rn
Costas T. Lambrew Research Retreat 2025
Recipient of the Peter W. Bates Award for Excellence in Health Professions Education Research at the 2025 Costas T. Lambrew Research Retreat.
Venlafaxine Exposure In Pregnancy And Its Association With Pre-Eclampsia Development, Jhanvi Patel
Venlafaxine Exposure In Pregnancy And Its Association With Pre-Eclampsia Development, Jhanvi Patel
Posters
Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), is widely used to manage depression and anxiety, including in pregnant women. However, its known hypertensive side effects raise concerns about a potential link to pre-eclampsia, a serious pregnancy complication characterized by new-onset hypertension and proteinuria. Pregnant women with psychiatric disorders already have an increased risk of hypertensive disorders, and while untreated depression can lead to adverse outcomes such as preterm birth and fetal cortisol elevation, the safety of venlafaxine remains uncertain. Current research lacks wellcontrolled studies assessing its association with hypertensive complications in pregnancy. This systematic review aims to evaluate whether venlafaxine use …
Comparing Spatiotemporal Gait Measures And Hip Disability And Osteoarthritis Outcome Scores-12 Through Gait Analysis Of Individuals With Hip Osteoarthritis, Collin N. Thompson
Comparing Spatiotemporal Gait Measures And Hip Disability And Osteoarthritis Outcome Scores-12 Through Gait Analysis Of Individuals With Hip Osteoarthritis, Collin N. Thompson
Biological Sciences Undergraduate Honors Theses
Hip osteoarthritis (OA) is a joint disease that leads to degenerative damage surrounding the femoroacetabular joint, which can manifest as degraded cartilage and increased inflammation at the joint site. There are several methods physician’s use to measure a patient's condition, and our study looks at one called the Hip Disability and Osteoarthritis Outcome Score-12, or HOOS-12. This is a patient-reported outcome measure where patients can self-report their pain and level of dysfunction in relation to their hip osteoarthritis. This study investigates the association between the participants’ HOOS-12 scores and objective gait characteristics measured via a portable pressure sensing walkway. At …
The Burden Of Care: Understanding Burnout Among Pediatric Healthcare Workers, Navya Khandavalli
The Burden Of Care: Understanding Burnout Among Pediatric Healthcare Workers, Navya Khandavalli
Theses/Capstones/Creative Projects
Burnout among pediatric healthcare professionals is a growing concern that impacts both employee well-being and the overall quality of patient care. The aim of this study is to analyze the definition of burnout and how healthcare organizations can implore strategies to help improve the mental and physical well-being of their staff. Analysis was done through a survey administered to healthcare employees recruited from pediatric clinics, the neonatal ICU, pediatric research, and pediatric rehabilitation facilities. Findings from the methods found that burnout is often defined as prolonged occupational stress in an individual and are often characterized by symptoms of emotional exhaustion, …
Epic Best Practice Alerts Increases Sep1 Orderset Usage, Mark Munir, Zachary Awad, Paul Bozyk, Ramin Homayouni
Epic Best Practice Alerts Increases Sep1 Orderset Usage, Mark Munir, Zachary Awad, Paul Bozyk, Ramin Homayouni
Posters
Sepsis is a massive, system-wide inflammatory response to an infection that can lead to multisystem organ failure.1 Sepsis has a very high mortality rate of 20-50% in patients with severe sepsis and is the 10th leading cause of death in the United States.2 One of the most significant ways of reducing mortality from sepsis is timely detection and initiation of treatment in septic patients.3
Electronic medical records such as Epic have implemented sepsis warning algorithms and alerts to facilitate quicker detection of sepsis and thus earlier initiation of treatment. The goal of this study is to determine if an Epic …
Global Multi-Specialty Clinician Perspectives On The Implementation Of Alzheimer's Disease Blood Biomarkers, Joanne Rodda, Lindsey A. Kuchenbecker, Wyllians V. Borelli, Mari L. Demarco, Raphael M. Castilhos, Erin E. Cawston, Tinatin Chabrashvili, Melissa M. Budelier, Claudia Duran Aniotz, Chinedu Momoh
Global Multi-Specialty Clinician Perspectives On The Implementation Of Alzheimer's Disease Blood Biomarkers, Joanne Rodda, Lindsey A. Kuchenbecker, Wyllians V. Borelli, Mari L. Demarco, Raphael M. Castilhos, Erin E. Cawston, Tinatin Chabrashvili, Melissa M. Budelier, Claudia Duran Aniotz, Chinedu Momoh
Brain and Mind Institute
Introduction: Clinicians' views on the clinical readiness of Alzheimer's disease (AD) blood biomarkers (BBMs) are not well understood.
Methods: The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment Biofluid-Based Biomarkers Professional Interest Area conducted a survey to elicit clinician opinions on AD BBM implementation, including contexts of use, assay selection, reporting, and result interpretation.
Results: Clinician respondents (n = 212) practiced in Europe (56%), North America (24%), the Caribbean and Central/South America (11%), and other continents (9%). Most respondents were medical doctors (80%) practicing in secondary or tertiary care (88%). For 56%, cerebrospinal fluid AD …
Optimum Volume Of Serious Fluid For The Detection Of Malignancy: A Systematic Review, Sarah Atieno Okech
Optimum Volume Of Serious Fluid For The Detection Of Malignancy: A Systematic Review, Sarah Atieno Okech
Master of Medicine in Anatomic Pathology
No abstract provided.
Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse
Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse
Dissertations and Theses (Open Access)
Acute monocytic leukemia (monocytic AML) is a subtype of AML marked by a proliferation of abnormal monoblasts. This subtype represents approximately 10% of AML cases. The prognosis of monocytic AML is poor, with a 5-year survival of ~30%. Most patients are diagnosed at an age when they are unlikely to survive first-line non-targeted cytotoxic chemotherapy as a bridge to hematopoietic stem cell transplant (HSCT). Even patients who achieve remission commonly relapse. This population of patients would greatly benefit from precision-targeted therapies but currently there are none approved for monocytic AML.
Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immune checkpoint expressed …
Novel Application Of Orthopedic Suture Tape For Sternal Closure After Upper Hemisternotomy, Vishal N. Shah, Joshua R. Chen, Konstadinos A. Plestis
Novel Application Of Orthopedic Suture Tape For Sternal Closure After Upper Hemisternotomy, Vishal N. Shah, Joshua R. Chen, Konstadinos A. Plestis
Department of Surgery Faculty Papers
The FiberTape (FT) System (Arthrex, Naples, FL, USA), initially developed for orthopedic surgery, is a new, nonmetallic, suture-based alternative to standard stainless-steel wires for sternal reapproximation. Publications on FT use after cardiothoracic surgery are limited. The FT System has not been used in upper hemisternotomy (UHS) closure. Consequently, we report the use of the FT System for sternal closure in a 70-year-old man after UHS aortic valve replacement and discuss several advantages of its application.
Targeting Bard1 Suppresses A Myc-Dependent Transcriptional Program And Tumor Growth In Pancreatic Ductal Adenocarcinoma, Sohum Patel, Eleanor Jenkins, Rutuj P. Kusurkar, Sherry Lee, Wei Jiang, Avinoam Nevler, Matthew Mccoy, Michael J. Pishvaian, Rosalie C. Sears, Jonathan R. Brody, Charles J. Yeo, Aditi Jain
Targeting Bard1 Suppresses A Myc-Dependent Transcriptional Program And Tumor Growth In Pancreatic Ductal Adenocarcinoma, Sohum Patel, Eleanor Jenkins, Rutuj P. Kusurkar, Sherry Lee, Wei Jiang, Avinoam Nevler, Matthew Mccoy, Michael J. Pishvaian, Rosalie C. Sears, Jonathan R. Brody, Charles J. Yeo, Aditi Jain
Department of Surgery Faculty Papers
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers demanding better and more effective therapies. BARD1 or BRCA1-Associated -Ring Domain-1 plays a pivotal role in homologous recombination repair (HRR). However, its function and the underlying molecular mechanisms in PDAC are still not fully elucidated. Here, we demonstrate that BARD1 is overexpressed in PDAC and its genetic inhibition suppresses c-Myc and disrupts c-Myc dependent transcriptional program. Mechanistically, BARD1 stabilizes c-Myc through ubiquitin-proteasome system by regulating FBXW7. Importantly, targeting BARD1 using either siRNAs or CRISPR/Cas9 deletion blocks PDAC growth in vitro and in vivo, without any signs of toxicity to mice. …
Intratumoral Fibrin As A Novel Immunomodulatory Factor In Pancreatic Ductal Adenocarcinoma, Mazharul Karim
Intratumoral Fibrin As A Novel Immunomodulatory Factor In Pancreatic Ductal Adenocarcinoma, Mazharul Karim
Open Access Theses & Dissertations
In-situ coagulation is a common clinical feature of pancreatic ductal adenocarcinoma (PDAC) that presents a highly thrombotic and crosslinked insoluble fibrin (x-fibrin)-laden tumor stroma (FibTS). However, the specific impact of FibTS on immune cells behavior remains largely unexplored in this poorly infiltrated tumor. We aimed to elucidate how FibTS in PDAC regulates immune cell infiltration, polarization, and crosstalk that favors immunosuppressive microenvironment and tumor growth. We characterized human PDAC tissues by multiplex immunostaining and checked the spatial distribution of immune cells based on the presence of x-fibrin. We investigated how FibTS influences the infiltration of tumor-associated macrophage (TAM) and T-cell …
Jak1 V658f Drives Oncogenic Transformation Via Transcriptional Reprogramming Independent Of Y598 Phosphorylation And Canonical Jak-Stat Signaling, Omar Javier Rodriguez Moncivais
Jak1 V658f Drives Oncogenic Transformation Via Transcriptional Reprogramming Independent Of Y598 Phosphorylation And Canonical Jak-Stat Signaling, Omar Javier Rodriguez Moncivais
Open Access Theses & Dissertations
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and complex malignancy that accounts for 15% of pediatric acute lymphoblastic leukemia (ALL) cases in the United States. Tyrosine kinases control critical cellular processes, including the development, survival, and activation of T cells, and are established drivers of leukemia.Tyrosine kinases involved in hematological disorders include receptor tyrosine kinases and non-receptor tyrosine kinases family members such as SRC, ABL, FAK, and Janus kinases (JAKs). This study primarily focused on JAK1 gain-of-function (GoF) mutations. These mutations are recognized as hyperactivating mutations, maintaining kinase activity of JAKs on and essentially keeping downstream signaling effectors, like …
Natural Killer T Cell-Mediated Control Of Francisella Tularensis-Induced Cytokine Storm Syndrome, Cameron M. Torres
Natural Killer T Cell-Mediated Control Of Francisella Tularensis-Induced Cytokine Storm Syndrome, Cameron M. Torres
Open Access Theses & Dissertations
Inflammation is critical for the effective clearance of viral and bacterial challenges, while simultaneously a mechanism utilized by many highly infectious pathogens to cause disease. The bacterium Francisella tularensis, the causative agent of human tularemia, elicits a cytokine storm, wherein the immune system over-responds to the presence of the bacterium causing a dysregulated release of proinflammatory and regulatory cytokines. Without treatment, tularemia mortality can be as high as 30%, with inhalation of as few as 10 CFUs inducing respiratory tularemia. Natural Killer T (NKT) cells are innate-like T lymphocytes with a diverse array of regulatory functions. Unlike conventional T cells, …
Alphamissense Predictions And Clinvar Annotations: A Deep Learning Approach To Uveal Melanoma, David J. Taylor Gonzalez, Mak B. Djulbegovic, Meghan Sharma, Michael Antonietti, Colin K. Kim, Vladimir N. Uversky, Carol L. Karp, Carol L. Shields, Matthew W. Wilson
Alphamissense Predictions And Clinvar Annotations: A Deep Learning Approach To Uveal Melanoma, David J. Taylor Gonzalez, Mak B. Djulbegovic, Meghan Sharma, Michael Antonietti, Colin K. Kim, Vladimir N. Uversky, Carol L. Karp, Carol L. Shields, Matthew W. Wilson
Wills Eye Hospital Papers
OBJECTIVE: Uveal melanoma (UM) poses significant diagnostic and prognostic challenges due to its variable genetic landscape. We explore the use of a novel deep learning tool to assess the functional impact of genetic mutations in UM.
DESIGN: A cross-sectional bioinformatics exploratory data analysis of genetic mutations from UM cases.
SUBJECTS: Genetic data from patients diagnosed with UM were analyzed, explicitly focusing on missense mutations sourced from the Catalogue of Somatic Mutations in Cancer (COSMIC) database.
METHODS: We identified missense mutations frequently observed in UM using the COSMIC database, assessed their potential pathogenicity using AlphaMissense, and visualized mutations using AlphaFold. Clinical …
Ai Model For Predicting Asthma Prognosis In Children, Elham Sagheb, Chung-Il Wi, Katherine S King, Bhavani Singh Agnikula Kshatriya, Euijung Ryu, Hongfang Liu, Miguel A Park, Hee Yun Seol, Shauna M Overgaard, Deepak K Sharma, Young J Juhn, Sunghwan Sohn
Ai Model For Predicting Asthma Prognosis In Children, Elham Sagheb, Chung-Il Wi, Katherine S King, Bhavani Singh Agnikula Kshatriya, Euijung Ryu, Hongfang Liu, Miguel A Park, Hee Yun Seol, Shauna M Overgaard, Deepak K Sharma, Young J Juhn, Sunghwan Sohn
Faculty, Staff and Student Publications
BACKGROUND: Childhood asthma often continues into adulthood, but some children experience remission. Utilizing electronic health records (EHRs) to predict asthma prognosis can aid health care providers and patients in developing effective prioritized care plans.
OBJECTIVE: We aimed to develop artificial intelligence (AI) models using various clinical variables extracted from EHRs to predict childhood asthma prognosis (remission vs no remission) in different age groups.
METHODS: We developed AI models utilizing patients' EHRs during the first 6, 9, or 12 years of their lives to predict their asthma prognosis status at ages 6 to 9, 9 to 12, or 12 to 15 …
Association Of Delayed Asthma Diagnosis With Asthma Exacerbations In Children, Chung-Il Wi, Euijung Ryu, Katherine S King, Jung Hyun Kwon, Joshua T Bublitz, Miguel Park, Sergio E Chiarella, Jason D Greenwood, Thanai Pongdee, Lynnea Myers, Björn Nordlund, Sunghwan Sohn, Elham Sagheb, Bhavani Singh Agnikula Kshatriya, Dave Watson, Hongfang Liu, Beverley J Sheares, Carla M Davis, Wade Schulz, Young J Juhn
Association Of Delayed Asthma Diagnosis With Asthma Exacerbations In Children, Chung-Il Wi, Euijung Ryu, Katherine S King, Jung Hyun Kwon, Joshua T Bublitz, Miguel Park, Sergio E Chiarella, Jason D Greenwood, Thanai Pongdee, Lynnea Myers, Björn Nordlund, Sunghwan Sohn, Elham Sagheb, Bhavani Singh Agnikula Kshatriya, Dave Watson, Hongfang Liu, Beverley J Sheares, Carla M Davis, Wade Schulz, Young J Juhn
Faculty, Staff and Student Publications
Background: There is a significant delay between symptom onset and diagnosis of childhood asthma, but the impact of this delay on asthma outcomes has not been well understood.
Objectives: We sought to study the association of delayed diagnosis of asthma with asthma exacerbations (AEs) in children.
Methods: Using the Mayo Clinic birth cohort, we identified children with a diagnosis of asthma from electronic health records. We defined onset date as the date when subjects first met predetermined asthma criteria ascertained by an electronic health records-based natural language processing algorithm. Delay in diagnosis (DD) was defined as first diagnosis >30 days …
Clinical Implications Of Mismatch Repair Deficiency In Pancreatic Ductal Adenocarcinoma, Zachary Kaplan, Elizabeth Prezioso, Aditi Jain, Harish Lavu, Charles Yeo, Wilbur Bowne, Avinoam Nevler
Clinical Implications Of Mismatch Repair Deficiency In Pancreatic Ductal Adenocarcinoma, Zachary Kaplan, Elizabeth Prezioso, Aditi Jain, Harish Lavu, Charles Yeo, Wilbur Bowne, Avinoam Nevler
Kimmel Cancer Center Faculty Papers
BACKGROUND: Pancreatic cancer is a highly aggressive and lethal disease, characterized by a limited response to chemotherapy and overall poor prognosis. Pancreatic cancers with a distinct mismatch repair deficiency, although relatively rare, have been shown to be associated with markedly better outcomes in comparison. Furthermore, whereas pancreatic cancers are generally unresponsive to current immunotherapy, this specific group of tumors has been shown to have a notable susceptibility to immune checkpoint inhibitors.
AIMS: In this review, we aim to summarize the relevant literature regarding mismatch-repair associated pancreatic cancers, the impacted biological mechanisms, and the resulting vulnerabilities for potential opportunistic immunotherapeutic treatment …
Therapeutic Applications Of A Novel Humanized Monoclonal Antibody Targeting Chemokine Receptor Ccr9 In Pancreatic Cancer, Hannah G. Mcdonald, Anna M. Reagan, Charles J. Bailey, Mei Gao, Muqiang Gao, Angelica L. Solomon, Michael J. Cavnar, Prakash Pandalai, Mautin Barry-Hundeyin, Megan Harper, Justin A. Rueckert, Ángela Turrero, Araceli Tobio, Anxo Vidal, Daniel Roca-Lema, Elia Álvarez-Coiradas, Pablo Garrido, Laureano Simón, Joseph Kim
Therapeutic Applications Of A Novel Humanized Monoclonal Antibody Targeting Chemokine Receptor Ccr9 In Pancreatic Cancer, Hannah G. Mcdonald, Anna M. Reagan, Charles J. Bailey, Mei Gao, Muqiang Gao, Angelica L. Solomon, Michael J. Cavnar, Prakash Pandalai, Mautin Barry-Hundeyin, Megan Harper, Justin A. Rueckert, Ángela Turrero, Araceli Tobio, Anxo Vidal, Daniel Roca-Lema, Elia Álvarez-Coiradas, Pablo Garrido, Laureano Simón, Joseph Kim
Markey Cancer Center Faculty Publications
The relative failure of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) despite having a dense, immunosuppressive tumor microenvironment highlights the need to target alternate/escape pathways. We have previously examined C–C chemokine receptor type 9 (CCR9) as a candidate immune checkpoint and developed a targeted, humanized monoclonal antibody (SRB2). Cytotoxicity of SRB2 was evaluated in vitro and in vivo. CCR9 expression on PDAC cells/tissues, immune components of patient-derived organoids (PDOs), and antibody-dependent cell-mediated cytotoxicity were examined. In PANC-1 and MIA PaCa-2 cell lines, we demonstrated highest CCR9 expression; however, no direct cytotoxic effect was observed with SRB2 treatment. In PANC-1 …
An Agrin-Yap/Taz Rigidity Sensing Module Drives Egfr-Addicted Lung Tumorigenesis., Reza Bayat Mokhtari, Divyaleka Sampath, Paige Eversole, Melissa Ong Yu Lin, Dmitriy A. Bosykh, Gandhi T. K. Boopathy, Aravind Sivakumar, Cheng-Chun Wang, Ramesh Kumar, Joe Yeong Poh Sheng, Ellen Karasik, Barbara A. Foster, Han Yu, Xiang Ling, Wenjie Wu, Fengzhi Li, Zoë Weaver Ohler, Christine Fillmore Brainson, David W. Goodrich, Wanjin Hong, Sayan Chakraborty
An Agrin-Yap/Taz Rigidity Sensing Module Drives Egfr-Addicted Lung Tumorigenesis., Reza Bayat Mokhtari, Divyaleka Sampath, Paige Eversole, Melissa Ong Yu Lin, Dmitriy A. Bosykh, Gandhi T. K. Boopathy, Aravind Sivakumar, Cheng-Chun Wang, Ramesh Kumar, Joe Yeong Poh Sheng, Ellen Karasik, Barbara A. Foster, Han Yu, Xiang Ling, Wenjie Wu, Fengzhi Li, Zoë Weaver Ohler, Christine Fillmore Brainson, David W. Goodrich, Wanjin Hong, Sayan Chakraborty
Markey Cancer Center Faculty Publications
Despite epidermal growth factor receptor (EGFR) is a pivotal oncogene for several cancers, including lung adenocarcinoma (LUAD), how it senses extracellular matrix (ECM) rigidity remain elusive in the context of the increasing role of tissue rigidity on various hallmarks of cancer development. Here it is shown that EGFR dictates tumorigenic agrin expression in lung cancer cell lines, genetically engineered EGFR-driven mouse models, and human specimens. Agrin expression confers substrate stiffness-dependent oncogenic attributes to EGFR-reliant cancer cells. Mechanistically, agrin mechanoactivates EGFR through epidermal growth factor (EGF)-dependent and independent modes, thereby sensitizing its activity toward localized cancer cell-ECM adherence and bulk rigidity …
Normative Variability In Retinal Nerve Fiber Layer Thickness: Does It Matter Where The Peaks Are?, Sowjanya Gowrisankaran, Ashkan Abbasi, Xubo Song, Joel Schuman, Gadi Wollstein, Bhavna Antony, Hiroshi Ishikawa
Normative Variability In Retinal Nerve Fiber Layer Thickness: Does It Matter Where The Peaks Are?, Sowjanya Gowrisankaran, Ashkan Abbasi, Xubo Song, Joel Schuman, Gadi Wollstein, Bhavna Antony, Hiroshi Ishikawa
Wills Eye Hospital Papers
PURPOSE: Retinal nerve fiber layer thickness (RNFLT), a glaucoma biomarker, has a wide normative range affecting its sensitivity and specificity for abnormality detection. The interindividual RNFLT peak location variability contribution to this wide normative range has not been directly evaluated. The purpose of this study is to assess the effect of RNFLT peak normalization (PN) on normative variability.
METHODS: Circumpapillary RNFLT profiles at 1.7 mm radius from the optic nerve head (ONH) were re-sampled from optical coherence tomography (OCT) volumes (Cirrus HD-OCT, 200 × 200) obtained from one eye of 83 healthy individuals. Fovea-ONH axis (FOA) was calculated from corresponding …
Ascl2 Positive Tumor Cells Modulate The Response Of Metastatic Colorectal Cancer To Mapk-Targeting Therapy, Oscar Eduardo Villarreal
Ascl2 Positive Tumor Cells Modulate The Response Of Metastatic Colorectal Cancer To Mapk-Targeting Therapy, Oscar Eduardo Villarreal
Dissertations and Theses (Open Access)
Colorectal cancer (CRC) is the second leading cause of cancer related deaths with nearly a quarter of patients presenting with metastatic disease at the time of their diagnosis. Therapeutic management of metastatic CRC continues to be a major challenge due to therapy resistance and disease heterogeneity. Due to its central role in tumorigenesis, CRC is commonly treated with MAPK pathway inhibitors (MAPKi). However, clinical trials repeatedly demonstrates that durability of benefit is short-lived in many patients. While genomic mechanisms of acquired resistance have been described, they explain a minority of patients, and further research is needed to determine the underlying …
Manganese-Induced Precocious Puberty Alters Mammary Epithelial Cell Proliferation In Female Rats, Alina M. Hamilton, Vinod K. Srivastava, Jill K. Hiney, William L. Dees, Robert K. Dearth
Manganese-Induced Precocious Puberty Alters Mammary Epithelial Cell Proliferation In Female Rats, Alina M. Hamilton, Vinod K. Srivastava, Jill K. Hiney, William L. Dees, Robert K. Dearth
School of Integrative Biological & Chemical Sciences Faculty Publications
Precocious puberty (PP) is an established breast cancer risk factor. In the normal mammary gland, hormone receptor-positive (HR+) cells rarely proliferate. In breast cancer, proliferating epithelial cells are often HR+. It is not known if PP can modify this population of proliferating HR+ cells. Previously, we established a manganese-induced precocious puberty (MnPP) model to study the effects of PP on mammary gland development in female rats. Here, we characterized the distribution of HR+ proliferating mammary epithelial cells in prepubertal and adult rodents, in association with precocious puberty. Female rats were exposed daily to 10 mg/kg manganese chloride or saline (control) …
Pembrolizumab In Patients With Advanced Miscellaneous Rare Cancers: Results From A Phase 2 Basket Trial, Mirella Nardo, Camila Braganca Xavier, Bettzy Stephen, Jeffrey A How, Justin Moyers, Vivek Subbiah, David S Hong, Aung Naing
Pembrolizumab In Patients With Advanced Miscellaneous Rare Cancers: Results From A Phase 2 Basket Trial, Mirella Nardo, Camila Braganca Xavier, Bettzy Stephen, Jeffrey A How, Justin Moyers, Vivek Subbiah, David S Hong, Aung Naing
Faculty, Staff and Student Publications
Introduction: Rare solid tumors account for one-quarter of cancers among adults in the United States, but few resources have been devoted to their treatment. We evaluated the efficacy of pembrolizumab, a programmed cell death-1 inhibitor, in patients with rare solid tumors.
Methods: We conducted a phase 2 basket trial that included patients with rare, advanced tumors. Patients were enrolled in the study in nine tumor-specific and a 10th cohort of miscellaneous rare histologies. Patients received pembrolizumab 200 mg intravenously every 21 days. The primary endpoint was the non-progression rate at 27 weeks per immune-related Response Evaluation Criteria in Solid Tumors …