Cancer Biology Commons^™

Intracellular Trafficking And Distribution Of Cd And Inp Quantum Dots In Hela And Ml-1 Thyroid Cancer Cells, Min Zhang

Graduate Theses/Dissertations

The study of the interaction of engineered nanoparticles, including quantum dots (QDs), with cellular constituents and the kinetics of their localization and transport, has provided new insights into their biological consequences in cancers and for the development of effective cancer therapies. The present study aims to elucidate the toxicity and intracellular transport kinetics of CdSe/ZnS and InP/ZnS QDs in late-stage ML-1 thyroid cancer using well-tested HeLa cells as a control. The XTT viability assay showed that ML-1 cells, and non-cancerous mouse fibroblast cells, exhibit no viability defect in response to these QDs, whereas HeLa cell viability decreases. These results suggest …

Exosomal-Long Non-Coding Rnas Journey In Colorectal Cancer: Evil And Goodness Faces Of Key Players, Nehal I. Rizk, Ahmed I. Abulsoud, Mohamed M. Kamal, Dina H. Kassem, Nadia M. Hamdy

Pharmacy

Exosomes are nano-vesicles (NVs) secreted by cells and take part in cell-cell communications. Lately, these exosomes were proved to have dual faces in cancer. Actually, they can contribute to carcinogenesis through epithelial-mesenchymal transition (EMT), angiogenesis, metastasis and tumor microenvironment (TME) of various cancers, including colorectal cancer (CRC). On the other hand, they can be potential targets for cancer treatment. CRC is one of the most frequent tumors worldwide, with incidence rates rising in the recent decades. In its early stage, CRC is asymptomatic with poor treatment outcomes. Therefore, finding a non-invasive, early diagnostic biomarker tool and/or suitable defender to combat …

Alkaline Plasma-Activated Water (Paw) As An Innovative Therapeutic Avenue For Cancer Treatment, Bolun Pang, Zhijie Liu, Sitao Wang, Yuting Gao, Miao Qi, Dehui Xu, Renwu Zhou, Dingxin Liu, Michael G. Kong

Bioelectrics Publications

Plasma-activated water (PAW) is considered to be an effective anticancer agent due to the diverse aqueous reactive oxygen and nitrogen species (RONS: ROS and RNS), but the drawback of low dose and short duration of RONS in acidified PAW limits their clinical application. Herein, this Letter presents an innovative therapeutic avenue for cancer treatment with highly-effective alkaline PAW prepared by air surface plasma. This anticancer alkaline formulation is comprised of a rich mixture of highly chemical RONS and exhibited a prolonged half-life compared to acidified PAW. The H₂O₂, NO₂-, and ONOO^-/O_{2 …}

Plasmonic-Based Biosensor For The Early Diagnosis Of Prostate Cancer, Thakshila Liyanage, Bayan Alharbi, Linh Quan, Aurora Esquela-Kerscher, Gymama Slaughter

Bioelectrics Publications

A tapered optical fiber (TOF) plasmonic biosensor was fabricated and used for the sensitive detection of a panel of microRNAs (miRNAs) in human serum obtained from noncancer and prostate cancer (PCa) patients. Oncogenic and tumor suppressor miRNAs let7a, let-7c, miR-200b, miR-141, and miR-21 were tested as predictive cancer biomarkers since multianalyte detection minimizes false-positive and false-negative rates and establishes a strong foundation for early PCa diagnosis. The biosensing platform integrates metallic gold triangular nanoprisms (AuTNPs) laminated on the TOF to excite surface plasmon waves in the supporting metallic layer and enhance the evanescent mode of the fiber surface. …

The Role Of Protein Tyrosine Phosphatase Receptor Type F In Intestinal Homeostasis And Colorectal Cancer, Ashley T. Skaggs

Theses and Dissertations--Molecular and Cellular Biochemistry

Protein phosphorylation defines one of the most important regulatory mechanisms in cell signaling. PTPRF, protein tyrosine phosphatase receptor type F, belongs to the class I R2A subfamily of protein tyrosine phosphatases (PTP). The overall objective of this dissertation is to investigate the molecular mechanisms by which PTPRF regulates normal and cancer stem cells by controlling Wnt signaling.

Dysregulation of Wnt signaling promotes the initiation and progression of colorectal cancer (CRC). We first determined the functional important of PTPRF in regulating Wnt signaling in CRC. Combining cell culture, 3D tumor organoid and xenograft models, results from our study establish PTPRF as …

Extracellular Vesicles And Cancer Therapy: An Insight Into The Role Of Oxidative Stress, Jenni Ho

Theses and Dissertations--Toxicology and Cancer Biology

As a result of improvements in cancer detection and treatment methods, a growing population of cancer survivors are living with side effects associated with their cancer therapy. Oxidative stress plays a significant role in the development of cancer and as a mechanism for cancer therapy to exert its therapeutic effects, resulting in off-target tissue damage. Radiation has been long established as a means to utilize the generation of reactive oxygen species to kill cancer cells, and 50% of chemotherapy agents currently used are associated with inducing oxidative stress. One major side effect observed in cancer survivors is a decline in …

Overcoming Resistance To Sg-Aris In Castration-Resistant Prostate Cancer, Chaohao Li

Theses and Dissertations--Toxicology and Cancer Biology

Prostate cancer (PCa) ranks as the most diagnosed type of cancer and the second leading cause of death in men. Androgen receptor (AR) signaling plays a pivotal function in promoting the survival and progression of PCa. Therefore, medication for PCa mainly focuses on the inhibition of AR pathway, which is termed androgen deprivation therapy (ADT). However, the disease eventually progresses and develops to a lethal stage called castration-resistant prostate cancer (CRPC) that is characterized by resistance to canonical ADT. To deal with this situation, several second-generation AR inhibitors (SG-ARIs) have been created that have better efficacy against AR, including Enzalutamide …

Assessment Of Combined Modality Therapy For Non-Small-Cell Lung Carcinoma: A Simulation Study Concerning Concurrent Chemo-Brachytherapy, Hadi Rezaei, Hesameddin Mostaghimi, Ali Reza Mehdizadeh

Electrical & Computer Engineering Faculty Publications

Although surgery is the treatment of choice for early-stage non-small-cell lung carcinoma, almost two-thirds of patients do not have acceptable pulmonary function for extensive surgeries. The alternative approach for this large group of patients is sublobar resection along with low-dose-rate (LDR) brachytherapy (BT). However, patients with resected lungs have a high risk of recurrence and are often treated with platinum-based (Pt-based) chemotherapy (CT). In this study, we aimed to evaluate the absorbed doses of lung and other thoracic organs, considering concurrent chemo-BT with LDR sources in two modalities: conventional vs. unconventional Pt-based CT. We used the MCNPX code for simulations …

Cell-Engineered Vesicles For Therapeutic Delivery And Immunomodulatory Applications, Khaga Neupane

Theses and Dissertations--Chemistry

Development of a new kind of drug delivery system (DDS) that could efficiently deliver therapeutics to the cell of interest would allow us to accomplish cell-specific drug delivery while eliminating systemic toxicity. Although nanocarriers including endogenously released extracellular vesicles (EEVs), liposomes, and small molecules seem to be promising drug delivery systems, biological challenges persist for their use in clinical applications. Here, we demonstrate nanovesicles engineered by fragmenting cellular membranes can be exploited as versatile DDSs for therapeutics delivery as well as immunomodulatory functions. Cell-engineered vesicles were produced by cavitating cells using nitrogen gas at high pressure followed by serial centrifugation. …

Tumor-Targeted Ph-Sensitive Manganese Oxide Nanoparticle For Enhanced Detection Of Breast Cancer Using Mri, Celia Martinez De La Torre

Graduate Theses, Dissertations, and Problem Reports (ETD)

In the United States, approximately 287,850 new cases of invasive breast cancer will be diagnosed, and over 43,000 women will die because of it in 2022. Currently, mammography is the gold standard for breast cancer surveillance. Although this detection technique is relatively cheap and fast, it misses about 1 in 5 breast cancers in younger women with dense breast tissue, causing a delay in treatment. Compared to mammography, magnetic resonance imaging (MRI) has superior soft-tissue contrast that elucidates structural differences within soft tissue to detect more breast cancers. However, MRI still misses

NEMO particles were produced by synthesizing manganese oxide …

Ero1Α Promotes Tumorigenesis In Egfr Driven Nsclc, Brennan D. Johnson

Graduate Theses, Dissertations, and Problem Reports (ETD)

Non-Small Cell Lung Cancer (NSCLC) is a pulmonary malignancy most commonly associated with smoking, or exposure to asbestos or Radon. Approximately, 1.6 Million deaths occur each year due to lung cancer. Lung Cancer is categorized by two main types, Small Cell Lung Cancer (SCLC) and NSCLC. NSCLC accounts for approximately 85% of all lung cancer cases and is subdivided into three sub-categories: Adenocarcinoma, the most common and leading cause of death in the United States; Squamous Cell Carcinoma (SCC), and Large Cell Carcinoma. Though NSCLC treatment regimens have shown increasing clinical benefit over the last two decades with targeted therapies. …

Actin Cytoskeletal Regulation And Matrix Metalloproteinase Targeting In Head And Neck Squamous Cell Carcinoma (Hnscc) Progression, Jessica Lea Allen

Graduate Theses, Dissertations, and Problem Reports (ETD)

Head and neck squamous cell carcinoma (HNSCC) is a cancer originating from the epithelial lining of the oral cavity, larynx, and pharynx. HNSCC is associated with extensive locoregional invasion and tissue destruction. Invasive processes underlying HNSCC contribute to poor prognosis and decreased quality of life. Amplification of chromosome 11q13 is the most common DNA aberration in human papilloma virus negative (HPV^-) HNSCC. This region includes various genes known to drive tumor progression. CORO1B (coronin 1B) flanks the core 11q13 region and is amplified in 7-14% of HNSCC. Coronin 1B is essential for mesenchymal cell motility by promoting turnover …

Development Of A Muc16-Targeted Near-Infrared Antibody Probe For Fluorescence-Guided Surgery Of Pancreatic Cancer, Madeline T. Olson

Theses & Dissertations

Pancreatic cancer (PDAC) is an extremely lethal disease with an overall survival rate of 10%. Surgery remains the only potentially curative treatment option, but resections are complicated by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Surgeons are limited to tactile and visual cues to differentiate cancerous tissue from normal tissue. Furthermore, translating preoperative images to the intraoperative setting poses additional challenges for tumor detection, and can result in undetected and unresected lesions. Thus, PDAC has high rates of incomplete resections, and subsequently, disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection …

A Pkcα-Mediated Growth Suppressive Mek-Erk Signaling Axis In Intestinal Epithelial Cells, Navneet Kaur

Theses & Dissertations

Members of the protein kinase C (PKC) family of serine/threonine kinases are involved in regulation of fundamental cellular functions, including proliferation, differentiation, survival, migration, and transformation. Increasing evidence points to anti-proliferative and tumor suppressive role of PKCs. Our laboratory and others have reported that the classical PKC isozyme, PKCαnegatively regulates proliferation and tumorigenesis in the intestinal epithelium. Our laboratory has further determined that PKCα signaling induces a program of cell cycle withdrawal in intestinal epithelial cells that involves downregulation of the pro-proliferative proteins, cyclin D1 and Id1, and upregulation of the cyclin dependent kinase (CDK) inhibitor, p21^Cip1. Unexpectedly, …

Nuclear Receptor Coactivator 3 In Endoplasmic Reticulum Stress And Stress Granule Dynamics In Pancreatic Cancer, Andrew Kisling

Theses & Dissertations

Pancreatic cancer is predicted to be the second-leading cause of cancer-related deaths within the next decade. Nuclear receptor coactivator 3 (NCOA3/SRC3/AIB1) regulates an array of metabolic and signaling pathways and has been established by our group and others as a critical regulator pancreatic cancer progression and metastasis. A recent study demonstrated NCOA3 regulation by the IRE1α-XBP1 axis of the unfolded protein response (UPR), suggesting a link between NCOA3 and cellular stress management. Furthermore, NCOA3 has been shown to directly bind to a scaffolding protein of stress granules (SGs). Since SG assembly is regulated by the UPR, we hypothesized that NCOA3 …

Functional Characterization Of Cancer-Associated Dna Polymerase Ε Variants, Stephanie R. Barbari

Theses & Dissertations

Replicative DNA polymerases ε (Polε) and δ (Polδ) achieve high fidelity DNA synthesis through a precise balance of polymerization and exonucleolytic proofreading. Errors that escape proofreading are corrected by DNA mismatch repair (MMR). Ultramutated human cancers with proficient MMR carry alterations in the exonuclease domain of Polε, which were initially predicted to abolish proofreading. However, functional studies in yeast of the most recurrent Polε-P286R variant suggested defects beyond a loss of exonuclease activity. Indeed, biochemical analysis of the yeast Polε-P286R analog revealed increased polymerization capacity in addition to decreased proofreading, which enables efficient mismatch extension and bypass of replication-blocking non-B …

Molecular Investigation Into The Biologic And Prognostic Elements Of Peripheral T-Cell Lymphoma With Regulators Of Tumor Microenvironment Signaling Explored In Model Systems, Tyler Herek

Theses & Dissertations

Peripheral T-cell lymphoma (PTCL) is heterogenous group of mature T-cell neoplasms characterized by distinctive transcriptional and genetic lesions. Herein, we investigated DNMT3A mutations in angioimmunoblastic T-cell lymphoma (AITL, n = 176) and novel molecular subtypes (i.e., PTCL-GATA3, n = 61 and PTCL-TBX21, n = 80) within PTCL- NOS and observed significant biological and prognostic differences associated with DNMT3A mutations. DNMT3A-mutated PTCL-TBX21 cases showed inferior overall survival (OS; p < 0.005), with DNMT3A mutations (DNMT3A-MT) skewed toward the methyltransferase domain and in the dimerization domain (S881-R887). Transcriptional profiling demonstrated significant enrichment of activated CD8⁺ T-cell cytotoxic gene signatures in the tumor microenvironment of DNMT3A-MT PTCL-TBX21 cases. Genome-wide methylation analysis of DNMT3A-R882/Q886 versus wild-type in PTCL-TBX21 cases demonstrated hypomethylation in target genes regulating T-cytotoxic genes, TCR …

Molecular Mechanisms Of Aberrant Protein Glycosylation In Pancreatic Cancer Stemness And Metastasis, Frank Leon

Theses & Dissertations

A myriad of genetic and other abnormal changes underlies the aggressiveness and dissemination properties observed in pancreatic cancer (PC). Aberrant protein glycosylation is a commonly observed feature in PC. The modification of protein O-glycosylation is mediated by glycosyltransferases, which attach and sequentially elongate monosaccharides on Serine/Threonine (Ser/Thr) motifs. Aberrant glycosylation is recognized as an emerging hallmark of cancer where a disruption in normal glycosylation results in irregular O-glycans.

This dissertation research has investigated the consequences of aberrant protein glycosylation on stemness and enhancement of metastatic properties in pancreatic ductal adenocarcinoma (PDAC). Several publications have reported aberrant O-glycosylation increases in oncogenic …

Clinical Diagnosis Support With Convolutional Neural Network By Transfer Learning, Spencer Fogleman, Jeremy Otsap, Sangrae Cho

SMU Data Science Review

Breast cancer is prevalent among women in the United States. Breast cancer screening is standard but requires a radiologist to review screening images to make a diagnosis. Diagnosis through the traditional screening method of mammography currently has an accuracy of about 78% for women of all ages and demographics. A more recent and precise technique called Digital Breast Tomosynthesis (DBT) has shown to be more promising but is less well studied. A machine learning model trained on DBT images has the potential to increase the success of identifying breast cancer and reduce the time it takes to diagnose a patient, …

Role Of Sox18 In Promoting Tumorigenesis In Pediatric Cancer Cell Lines, Cherubina S. Rubannelsonkumar

Honors Program Theses and Research Projects

Sarcomas constitute a high percentage (∼13%) of cancer-related deaths among pediatric patients between 0-19 years of age, with Rhabdomyosarcoma (RMS) being the most common pediatric soft tissue sarcoma and Ewing Sarcoma being the second most common malignant bone tumor in children. Yet, survival for those who develop such metastatic sarcomas remains below 20-30%. Interestingly, SOX family proteins are known to be up regulated in various cancer types and play a role in cancer progression (tumorigenesis, metastasis, etc.). More specifically, targeted knockdown of SOX18 has been shown to suppress various tumorigenic properties in cancer cell lines including osteosarcoma cells, hepatocellular carcinoma …

Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach

Graduate School of Biomedical Sciences Theses and Dissertations

There were an estimated 20 million new cancer cases worldwide in 2020, resulting in nearly 1000 deaths per hour [1]. Oral cancer exemplifies the difficulties of treating cancer patients. The first line for oral cancer treatment is surgery and radiation that can lead to patient disfigurement and decreased quality of life in cancer survivors [2-4]. Though there have been many developments in chemotherapy in the last 30 years, the 50% mortality rate associated with oral cancer has not changed [4, 5]. Longitudinal studies that track survival rates in oral cancer patients demonstrate a 3-fold reduction in patient deaths when patients …

4d Ex Vivo Crispr/Cas9 Whole-Genome Screen To Identify Genes Regulating Lung Cancer Metastasis, Alexandria Plumer

Dissertations and Theses (Open Access)

Metastatic lung cancer has a 5-year survival rate of 5%. Lung cancers tend to be asymptomatic until late stages, and almost 90% are not diagnosed until they are advanced. Metastases are very rare events, often initiated by a single cell from a primary tumor into a new niche at a distant location. Investigation of the early metastatic process is of urgent need for the development of early diagnostics and targeted therapeutics. We performed a proof-of-concept CRISPR/Cas9 whole genome knockout screen in the A549 lung adenocarcinoma cell line and utilized a novel ex vivo 4D lung metastasis model to find gene …

Lgr5 Regulation Of Stat3 Signaling And Drug Resistance In Colorectal Cancer, Tressie Posey, Tressie Alexandra Posey

Dissertations and Theses (Open Access)

LGR5 Regulation of STAT3 Signaling and Drug Resistance in Colorectal Cancer

Tressie Alexandra Capri Posey B.S.

Advisory Professor: Kendra Carmon, Ph.D.

The greatest difficulty in treating colorectal cancer (CRC) is the development of drug resistance which leads to relapse after treatment and progression to metastasis. Cancer stem cells (CSCs) are believed to drive relapse because of their capacity to self-renew, acquire resistance mechanisms, and differentiate promoting tumor growth and heterogeneity. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is a bona-fide marker of CSCs and has been considered a viable target for CSC specific therapeutic development. While we showed targeting LGR5 …

Longitudinal Monitoring Of Tumor Response To Immune Checkpoint Inhibitors Using Diffuse Optical Spectroscopy, Joel Isaac Rodriguez Troncoso

Graduate Theses and Dissertations

Immune checkpoint drugs have completely changed the way people treat metastatic melanoma and non-small-cell lung cancer. While the impacts of these immunological checkpoints and their suppression on T cell function are well characterized, their consequences on the tumor microenvironment are not. In a CT26 mouse colorectal cancer model, we employed diffuse reflectance spectroscopy to track in vivo tumor microenvironmental alterations in response to immune checkpoint inhibitors. On three separate days, animals bearing CT26 tumor xenografts were given anti-PD-L1, anti-CTLA-4, a combination of both inhibitors, and isotype control. Within the first 6 days, monotherapy with either anti-PD-L1 or anti-CTLA-4 resulted in …

Investigating Therapeutic Strategies To Target Metabolic Vulnerabilities Of Nsclc Tumors With Mutant Keap1 Gene, Pranavi Koppula

Dissertations and Theses (Open Access)

The metabolic vulnerability of cancers has long been envisaged as an attractive window to develop novel therapeutic strategies. Metabolic flexibility at the cellular level encompasses the efficient rerouting of anabolic and catabolic pathways in response to varying environmental stimuli to maintain cellular homeostasis and sustain proliferation. The primary objective of this study is to identify metabolic vulnerabilities bestowed by KEAP1/NRF2 signaling axis through SLC7A11. SLC7A11 is a transcriptional target of NRF2, an essential regulator of cellular anti-oxidant response. Under unstressed basal conditions, NRF2 interacts with KEAP1, a tumor suppressor gene and a substrate adaptor protein of the Cullin3-dependent ubiquitin ligase …

Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells, Taylor Chrisikos

Dissertations and Theses (Open Access)

Conventional dendritic cells (cDCs) are an essential immune population, responsible for controlling adaptive immunity and tolerance. Recently, type I cDCs (cDC1s) have been delineated as a distinct cDC subset, uniquely responsible for coordinating T cell-mediated immunity against pathogens and tumors. Although the importance of cDC1s is now well established, the mechanisms that regulate cDC1 function remain largely unknown. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of interleukin 10 (IL-10), an immunosuppressive cytokine. Therefore, we hypothesized that STAT3 and IL-10 inhibit cDC1 function and induction of T cell-mediated immunity. Herein, we show that IL-10 inhibits polyinosinic:polycytidylic …

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Atrx Inactivation And Idh1-R132h Drive Preferential Sensitivity To Proton Vs. X-Ray Radiotherapy In Glioma Stem Cells, Ángel Adrián Garcés

Dissertations and Theses (Open Access)

Background: Glioma Stem Cells (GSCs) are self-renewable, treatment resistant cells in the glioma tumor mass known to promote tumor development. In contrast to traditional photon-based radiation therapy (XRT), proton radiation therapy (PRT) may induce more complex DNA damage and therefore might have the potential to eliminate GSCs. Although previous studies have individually linked IDH mutations, specifically IDH1^R132H, and ATRX inactivating mutations to improved patient outcomes and suppressed DNA damage repair compared to their respective wild-types, the mechanisms by which these two genetic alterations interact in GSCs treated with PRT compared to XRT are currently unknown. We hypothesize that …

Role Of Sex Differences On Cancer Cachexia Progression And Fibrosis During Cancer Cachexia Development, Wesley Haynie

Graduate Theses and Dissertations

Cancer cachexia is a multifactorial wasting syndrome characterized by losses in bodymass >5% and occurs in approximately 80% of all cancer patients. Chronic inflammation and fibrosis play roles in cancer cachexia and a greater understanding of these contributing pathways to this pathology will pave the way for potential therapeutic avenues. While inflammation and fibrosis have been researched in various models of cancer cachexia, little to no studies have been performed in both sexes as most previous studies focus on males. PURPOSE The purpose of these studies is to investigate the role of fibrosis on cancer cachexia development as well as …

Oligomerization Of Mutant P53 R273h Is Not Required For Gain-Of-Function Chromatin Associated Activities, George K. Annor, Nour Elshabassy, Devon Lundine, Don-Gerard Conde, Gu Xiao, Viola Ellison, Jill Bargonetti

Publications and Research

The TP53 gene is often mutated in cancer, with missense mutations found in the central DNA binding domain, and less often in the C-terminal oligomerization domain (OD). These types of mutations are found in patients with the rare inherited cancer predisposition disorder called Li-Fraumeni syndrome. We previously found that mutant p53 (mtp53) R273H associates with replicating DNA and promotes the chromatin association of replication-associated proteins mini-chromosome maintenance 2 (MCM2), and poly ADP-ribose polymerase 1(PARP1). Herein, we created dual mutants in order to test if the oligomerization state of mtp53 R273H played a role in chromatin binding oncogenic gain-of-function (GOF) activities. …