Unraveling The Effects Of Aerobic Exercise And Erk5 Signaling In The Solid Tumor Microenvironment Using Murine Models,
2022
University of Texas MD Anderson Cancer Center
Unraveling The Effects Of Aerobic Exercise And Erk5 Signaling In The Solid Tumor Microenvironment Using Murine Models, Hannah Savage
Dissertations and Theses (Open Access)
Solid tumors are comprised of multiple cell types which communicate and work together to promote tumor progression. Advances in the treatment of solid tumors have armed clinicians with more efficacious pharmacologic agents and combinations. However, a focus on drug adjuvants in the treatment of solid cancer has left gaps in knowledge regarding non-pharmacologic treatment adjuvants, like aerobic exercise. The current dissertation investigates pharmacologic and non-pharmacologic based approaches to remodel the solid tumor microenvironment landscape and alter therapeutic efficacy. We disassemble compartments of the tumor microenvironment, including tumor vasculature and immune infiltrate, using mouse models and single cell techniques, to elucidate …
Ribonucleotide Reductase Subunit Switching In Hepatoblastoma Drug Response And Relapse,
2022
University of Tennessee Health Science Center
Ribonucleotide Reductase Subunit Switching In Hepatoblastoma Drug Response And Relapse, Anthony Brown
Theses and Dissertations (ETD)
Hepatoblastoma is the most common primary liver cancer in infants and young children. Despite being a very rare cancer that accounts for only 0.5-2% if all childhood cancer cases, HB has the largest increase in incidence among childhood cancers in the United States and worldwide. The five-year survival rate of children with the aggressive forms of HB, including those that have developed metastatic or recurrent diseases, is less than 40% due to the lack of effective treatment. We aim to identify targetable mechanisms underlying the progression and drug resistance of high-risk HB. Our recent work on HB mouse and organoid …
Cardiac Metastasis After Curative Treatment Of Hepatocellular Carcinoma: Risk Factors, Treatment Options, And Prognosis,
2022
Aurora St. Luke's Medical Center Abdominal Transplant Program, Advocate Aurora Health
Cardiac Metastasis After Curative Treatment Of Hepatocellular Carcinoma: Risk Factors, Treatment Options, And Prognosis, Gaurav Jain, Mathew Otto, Mubeen Khan Mohammed Abdul, Manpreet Chadha, Ajay Sahajpal
Journal of Patient-Centered Research and Reviews
Hepatocellular carcinoma (HCC) is primary hepatic malignancy with a high incidence of recurrence. The risk of recurrence directly correlates to patient’s overall prognosis. Management of advanced HCC involves a combination of surgical resection, locoregional therapy, and systemic treatment. Distant metastases are rare, and intraventricular cardiac metastases are even more infrequent. This brief review details an illustrative case of cardiac metastasis after curative treatment of primary HCC and then summarizes the literature on risk factors, treatment options, and patient prognosis in the setting of distant metastases from HCC. Prognosis of metastasis to the heart is generally poor, and available evidence emphasizes …
Gis Automated Delineation And Analysis Of Cancer Service Areas In The United States,
2022
Louisiana State University and Agricultural and Mechanical College
Gis Automated Delineation And Analysis Of Cancer Service Areas In The United States, Changzhen Wang
LSU Doctoral Dissertations
Delineating a meaningful and reliable geographic unit pertaining to cancer care is essential in examining geographic variations in cancer care for better analysis, management, and planning. Public health researchers have devoted great efforts to defining various service areas, which; however, lack scientific rigor or are unrepresentative of the highly specialized cancer care markets, and their methods have become obsolete in the era of big data and high geo-computation. This study develops the “Spatially Constrained Leiden (ScLeiden)” method, a network community detection algorithm in Geographic Information Systems (GIS), and applies it to delineate a series of coherent cancer service …
Synthetic Essentiality Of Tryptophan 2,3-Dioxygenase 2 In Apc-Mutated Colorectal Cancer,
2022
The Texas Medical Center Library
Synthetic Essentiality Of Tryptophan 2,3-Dioxygenase 2 In Apc-Mutated Colorectal Cancer, Rumi Lee, Jiexi Li, Jun Li, Chang-Jiun Wu, Shan Jiang, Wen-Hao Hsu, Deepavali Chakravarti, Peiwen Chen, Kyle A Labella, Jing Li, Denise J Spring, Di Zhao, Y Alan Wang, Ronald A Depinho
Faculty, Staff and Student Publications
Inactivation of adenomatous polyposis coli (APC) is common across many cancer types and serves as a critical initiating event in most sporadic colorectal cancers. APC deficiency activates WNT signaling, which remains an elusive target for cancer therapy, prompting us to apply the synthetic essentiality framework to identify druggable vulnerabilities for APC-deficient cancers. Tryptophan 2,3-dioxygenase 2 (TDO2) was identified as a synthetic essential effector of APC-deficient colorectal cancer. Mechanistically, APC deficiency results in the TCF4/β-catenin-mediated upregulation of TDO2 gene transcription. TDO2 in turn activates the Kyn-AhR pathway, which increases glycolysis to drive anabolic cancer cell growth and CXCL5 secretion to recruit …
Otulin's Novel Regulatory Mechanisms In Genotoxic And Inflammatory Nf-Kb Signaling,
2022
University of Tennessee Health Science Center
Otulin's Novel Regulatory Mechanisms In Genotoxic And Inflammatory Nf-Kb Signaling, Mingqi Li
Theses and Dissertations (ETD)
Triple negative breast cancer (TNBC) is aggressive but cannot be treated with hormone therapy or molecular therapy due to the lack of a target. Chemotherapy is a systemic treatment that works by attacking rapidly growing cells, which is initially more effective for TNBC patients than those individuals with the hormone receptor-positive breast cancer. However, patients with TNBC tend to develop resistance to chemo drugs, called chemoresistance. After years of effort, the signaling pathways involved in TNBC chemoresistance are gradually revealed, including the nuclear factor-kappa B (NF-kB) pathway. Transcription factor NF-kB is widely involved in cancer development and progression, and its …
Lysosomal Zn 2+ Release Triggers Rapid, Mitochondria-Mediated, Non-Apoptotic Cell Death In Metastatic Melanoma,
2022
University of Michigan - Ann Arbor
Lysosomal Zn 2+ Release Triggers Rapid, Mitochondria-Mediated, Non-Apoptotic Cell Death In Metastatic Melanoma, Wanlu Du, Mingxue Gu, Meiqin Hu, Timothy Nold, Prateeksunder Pinchi, Wei Chen, Michael Ryan, Ahmed Bannaga, Haoxing Xu
Medical Student Research Symposium
During tumor progression, lysosome function is often maladaptively upregulated to match the high energy demand required for cancer cell hyper-proliferation and invasion. Here, we report that mucolipin TRP channel 1 (TRPML1), a lysosomal Ca2+ and Zn2+ release channel that regulates multiple aspects of lysosome function, is dramatically upregulated in metastatic melanoma cells compared with normal cells. TRPML-specific synthetic agonists (ML-SAs) are sufficient to induce rapid (within hours) lysosomal Zn2+-dependent necrotic cell death in metastatic melanoma cells while completely sparing normal cells. ML-SA-caused mitochondria swelling and dysfunction lead to cellular ATP depletion. While pharmacological inhibition or genetic silencing of TRPML1 in …
Targeting Myeloid Protein Kinase C Signaling To Overcome Immune Suppression And Improve Immunotherapy In Cancer,
2022
University of Tennessee Health Science Center
Targeting Myeloid Protein Kinase C Signaling To Overcome Immune Suppression And Improve Immunotherapy In Cancer, Mehdi Chaib
Theses and Dissertations (ETD)
Checkpoint immunotherapy unleashes T cell antitumor potential which has revolutionized cancer treatment showing unprecedented long-term responses. However, most patients do not respond to immunotherapy which often correlates with a dysfunctional or immunosuppressive myeloid compartment. Immunosuppressive myeloid cells comprise Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) and can suppress T cells via production of immunosuppressive factors. Conversely, efficient cytotoxic T cell priming is dependent on the ability of antigen-presenting cells (APCs), mainly conventional dendritic cells (cDCs) and macrophages, to present or cross-present tumor antigens to T cells. Thus, targeting immunosuppressive myeloid cells while simultaneously enhancing APCs represents a promising strategy …
Leveraging Single Cell Technologies For The Characterization And Treatment Of Refractory Pancreatic Cancer,
2022
The Texas Medical Center Library
Leveraging Single Cell Technologies For The Characterization And Treatment Of Refractory Pancreatic Cancer, Maria Monberg
Dissertations and Theses (Open Access)
Heterogeneity is a hallmark of cancer, and the advent of multimodal single-cell technologies has helped uncover heterogeneity in a high-throughput manner in different cancers across varied contexts at an unprecedented resolution. In an effort to improve precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy with a mere 11% 5-year survival rate, this dissertation focuses on first questioning the assumptions of the most basic models used to study PDAC via multimodal single-cell characterization methods at multiple levels of biological organization (scCNVseq and snATACseq for DNA assays, scRNAseq for transcriptomics, and paired protein assays such as multiplexed immunofluorescence …
The Role And Immunogenicity Of Cbfa2t3-Glis2 In Pediatric Acute Megakaryoblastic Leukemia,
2022
University of Tennessee Health Science Center
The Role And Immunogenicity Of Cbfa2t3-Glis2 In Pediatric Acute Megakaryoblastic Leukemia, Elizabeth A. Garfinkle
Theses and Dissertations (ETD)
CBFA2T3-GLIS2 is the most prevalent fusion oncogene in pediatric acute megakaryoblastic leukemia in patients without Down syndrome (non-DS-AMKL) and is associated with an event free survival of only 8% even with high intensity chemotherapy and stem cell transplant in first remission. A cryptic inversion event on chromosome 16 joins the three nervy homology regions (NHR) of CBFA2T3 to the five zinc fingers of GLIS2. This configuration enables the encoded chimeric transcription factor to bind GLIS consensus sequences throughout the genome and recruit transcriptional activators and repressors to alter gene expression and enhance self-renewal capability. Few cooperating mutations have been identified …
A Rare Presentation Of Pericardial Tumor Presenting As Chronic Cough,
2022
Tower Health
A Rare Presentation Of Pericardial Tumor Presenting As Chronic Cough, Swarup Sharma Rijal, William H. Risher, Aakankshya Kharel, Upendra Kaphle
Advances in Clinical Medical Research and Healthcare Delivery
Chronic cough can pose various diagnostic and therapeutic dilemmas to physicians. Airway narrowing secondary to endoluminal disease or extrinsic compression are known etiologies of chronic cough. We report an extremely rare case of chronic cough due to extrinsic airway compression by a large pericardial lipoma with subsequent resolution of symptoms after the resection of the mass. This case provides insight into the rare etiology of chronic cough that is addressable with surgical intervention.
Enriching The Perioperative Enhanced Recovery After Surgery (Eras) Program For Patients Undergoing Whipple Procedure For Pancreatic Cancer,
2022
University of San Diego
Enriching The Perioperative Enhanced Recovery After Surgery (Eras) Program For Patients Undergoing Whipple Procedure For Pancreatic Cancer, Natalie E. Fisher
Doctor of Nursing Practice Final Manuscripts
Pancreatic cancer remains one of the most complex and lethal diseases worldwide with surgical resection as a major treatment choice. Although surgery may be one of the only options for advanced pancreatic cancer, it is not without a lengthy hospital stay, a long list of possible postoperative complications, and an increased risk for readmission after discharge. Enhanced recovery after surgery (ERAS) programs have been implemented for years in other surgical services for cancer care. These programs have now been extended and researched to include patients undergoing surgery for pancreatic cancer. These programs are designed to assist patients and their families …
Feasibility And Effectiveness Of A Prehabilitation Program Prior To Breast Cancer Surgery: A Critically Appraised Topic,
2022
University of Tennessee Health Science Center
Feasibility And Effectiveness Of A Prehabilitation Program Prior To Breast Cancer Surgery: A Critically Appraised Topic, Emma Choi, Alissa Lee, Kayla Woods, Morgan Mills, Carol Houston
Master of Occupational Therapy Student Critically Appraised Topics
The purpose of our project is to determine the feasibility and effectiveness of a prehabilitation (prehab) program for patients undergoing breast cancer surgery as compared to only receiving post-surgical rehabilitation. Our clinical mentor has recently obtained certification as a lymphedema specialist and is assisting with the opening of an outpatient mastectomy clinic through the Methodist University systems. Through our research process, we critically appraised two Level II articles, two Level III articles, and one Level IV article. Positive outcomes related to the feasibility were identified, however there is limited significant evidence supporting the effectiveness of the intervention. We recommend using …
Frailty And Neurocognition In Prostate Cancer,
2022
University of Nebraska Medical Center
Frailty And Neurocognition In Prostate Cancer, Lindsey Hanson
Theses & Dissertations
Prostate cancer (PCa) treatment often leads to distressing side effects ranging from muscle loss, physical inactivity, and fatigue to cancer associated cognitive decline (CACD). Evidence suggests that men treated with androgen deprivation therapy (ADT) may have a specifically high risk of CACD, partially due to increased frailty. However, the current literature on cognitive effects of ADT is equivocal. Therefore, the primary objectives of this study were to (1) compare cognitive function, physical activity (PA), and fitness in men receiving ADT, men scheduled to receive radiation, and men under active surveillance for PCa; (2) examine changes in cognitive performance and PA …
Characterization Of 1,1-Diarylethylene Foxm1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells,
2022
University of Nebraska Medical Center
Characterization Of 1,1-Diarylethylene Foxm1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells, Cassie Liu
Theses & Dissertations
Forkhead box M1 (FOXM1) is a member of the conserved forkhead box (FOX) transcription factor family. Over the last two decades, FOXM1 has emerged as a multifunctional oncoprotein and a robust biomarker of poor prognosis in many human malignancies. FOXM1 and its associated oncogenic transcriptional signature are enriched in >85% of ovarian cancer cases, and FOXM1 expression and activity can be enhanced by a plethora of genomic, transcriptional, post-transcriptional, and post-translational mechanisms. As a master transcriptional regulator, FOXM1 promotes critical oncogenic phenotypes in ovarian cancer, including: (1) cell proliferation, (2) invasion and metastasis, (3) chemotherapy resistance, (4) cancer stem cell …
Memory T Cell Populations In Human Leukemia,
2022
Children's Mercy Kansas City
Memory T Cell Populations In Human Leukemia, Sara Mcelroy
Research Days
Background: Incorporating the immune system into cancer management is an area of robust research. Treatment modalities aimed at activating cytotoxic T cells against malignancies include immune checkpoint inhibitors, bispecific T-cell engagers, and chimeric antigen receptor (CAR) tumor-specific T cells. Most anti-cancer T cell research is narrowly focused, but knowledge about the nature of diverse sub-populations of T cells in cancer, particularly memory T cells, is vital prior to potential incorporation into therapies. T memory stem cells (Tscm) are of interest due to their longevity and powerful abilities of self-renewal and creating the full spectrum of memory CD8+ T cells, including …
Extragonadal Perirectal Mature Cystic Teratoma In The Adult Male,
2022
Rowan University
Extragonadal Perirectal Mature Cystic Teratoma In The Adult Male, Pranamaya Mahankali, Liam Trimble, Diana Panciera, Hui Li, Thaer Obaid
Rowan-Virtua Research Day
A teratoma is a mass that originates from the germ cells of the three primitive embryonic layers and commonly arises from the ovaries or testicles, thereby characterized as gonadal in origin. These masses comprise different types of tissues such as fat, hair, muscle, and bone. Extragonadal teratomas are uncommon and arise from anatomical locations other than the gonads, such as the pineal gland, anterior mediastinum, retroperitoneum, and sacrococcygeal regions. The most common is the presacral region, as it contains tissue derived from all germ layers. Tumors in this specific location are far more common in neonates, infants, and children rather …
Neoadjuvant Chemotherapy As A Risk Factor For Urinary Anastomotic Leak In Patients Undergoing Radical Cystectomy,
2022
Rowan University
Neoadjuvant Chemotherapy As A Risk Factor For Urinary Anastomotic Leak In Patients Undergoing Radical Cystectomy, Young Son, Katelyn Klimowich, Joseph Flemming, Lance Earnshaw, Benjamin Fink, Brian Thomas, Thomas Mueller
Rowan-Virtua Research Day
Muscle-invasive bladder cancer (MIBC) represents approximately 25% of all bladder cancer and carries a significant risk of mortality. Neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) is the standard of care for MIBC. One complication associated with RC is ureteral anastomotic leak with a predicted rate of 3%. The objective of this National Surgical Quality Improvement Project (NSQIP) database analysis is to determine if correlations exist between radiation (RAD) and/or NAC before RC and anastomotic leak in the treatment of MIBC.
Bilateral Teratomas In Pediatric Patient With Unilateral Ovarian Torsion,
2022
Rowan University
Bilateral Teratomas In Pediatric Patient With Unilateral Ovarian Torsion, David Ho, Maya Borowczak, Archana Verma
Rowan-Virtua Research Day
Ovarian torsion is a surgical emergency found in both pediatric and adult populations. It involves the full or partial rotation of the vessels that supply the ovary, resulting in ischemia. In this report, we present the case of a pediatric patient arriving to the Pediatric Emergency Department (PED) for evaluation of right lower quadrant (RLQ) abdominal pain, who was found to have an ovarian torsion. In this particular case, the patient’s ovarian torsion was due to a teratoma, and imaging would later identify an additional smaller teratoma on the contralateral side. This case shows the importance of considering ovarian pathologies …
Case Report: Glioblastoma Tumor Presenting With Mild Changes In Memory,
2022
Rowan University
Case Report: Glioblastoma Tumor Presenting With Mild Changes In Memory, Samuel Thalathoti, Nicholas Palladino, James Espinosa, Alan Lucerna
Rowan-Virtua Research Day
We report a case of a 66-year-old female who presented to the ED with generalized headache and mild confusion, who was diagnosed with high-grade glial neoplasm. The differential diagnosis of headache is vast, but without red flags or symptoms is generally from a benign cause and easily treatable. However, even in the context of a normal neurologic physical exam, symptoms such as confusion, forgetfulness, and behavioral changes should merit imaging in the workup. Glioblastoma is the most common brain tumor, accounting for 47.7% of all cases, with an incidence of 3.21 per 100,000 population. Median age of diagnosis is 64 …
