Cancer Biology Commons^™

Use Of Machine Learning Algorithms And Highly Multiplexed Immunohistochemistry To Perform In-Depth Characterization Of Primary Pancreatic Tumors And Metastatic Sites, Krysten Vance

Theses & Dissertations

Pancreatic cancer is currently the third leading cause of cancer death and projected to be the second by 2030. Metastatic pancreatic cancer, the most common form of the disease, has a dismal 3% five-year survival rate. However, understanding of the metastatic disease and particularly the metastatic tumor microenvironment (TME), which includes all non-cancerous cells in and around the tumor, has remained limited. The well-documented impact of the TME on cancer cell proliferation, chemoresistance, and patient survival in the primary tumors, indicates that the study of the microenvironment in metastatic cancer is integral to treating advanced patients. To better comprehend this …

Plant Based Polyphenols Decrease Cell Migration And Inhibit Proliferation Of Human Pancreatic Cancer Cells, Mary Gathoni

Electronic Theses & Dissertations

Pancreatic cancer is one of the most highly malignant tumors of the digestive tract. Both the incidence and death rate of pancreatic cancer have increased since 2000. The disease has a poor prognosis with a relative 5-year survival rate of 10%. Pancreatic cancer-related mortality can be mainly attributed to lack of early diagnosis, tumor metastasis, lack of effective treatment strategies and drug resistance. There has been a mounting interest on the use of plant-based compounds such as polyphenols in cancer treatment therapies. This is mainly due to their low toxicity and fewer side effects compared to the conventional chemotherapeutic options …

Sequential Illumination In A Tomographic Microendoscopic Probe For Imaging Tumor Microvasculature, Zachariah Neumeier

Biomedical Engineering Undergraduate Honors Theses

Knowledge of colorectal cancer biology is improving how we approach cancer treatment. Specifically, the tumor microenvironment and abnormal angiogenesis are of particular interest. Optical methods are a prime candidate for research of the tumor microenvironment due to their ability to quantitively assess tissue structure and perfusion in real time. Particularly, the “transport scattering regime” has been identified as a method of obtaining high-resolution images and reflectance spectroscopy data; this light scattering regime has been demonstrated compatible with endoscopic imaging systems. In this study, a proof-of-concept optical imaging system is presented, capable of resolving absorbers within scattering turbid media using a …

Colorectal Cancer Screening In The Latino Population At A Family Medicine Clinic: A Quality Improvement Project, Michael S. Vinson

The Eleanor Mann School of Nursing DNP Capstone Projects

Background: Colorectal cancer (CRC) is a preventable and curable disease that affects all genders, races, and ethnicities, and its impact on society can be reduced with early screening. The Latino population is at greater risk compared to groups or ethnicities due to social determinants and health disparities within the community. Review of Literature: Language barriers, low education levels, persistent social stressors, poor healthcare navigation, and structural barriers make it difficult for this population to be properly screened at appropriate intervals. Purpose: This quality improvement (QI) project was designed to combat reduced screening rates seen in the Latino population. The target …

Headcase Regulates Growth In Response To Nutritional Status Downstream Of Insulin Signaling, Thomas George

Honors Scholar Theses

Cancer cells are notorious for growing in an unrestricted manner without regard for environmental cues. Recently, Li et al. (2019) discovered headcase (hdc) functions by binding to the mTORC1 complex in the mTOR signaling pathway and preventing further signaling. Interestingly, under nutrient restricted (NR) conditions, cells with mutated hdc proteins proliferated more than cells with normal functioning hdc. It is well known that insulin signaling is downregulated under NR conditions, so a potential signaling pathway with insulin, PI3K, PDK1, Akt, PTEN, and hdc was created as a way to explain the link between hdc function and nutritional status. A Drosophila …

Investigating The Impact Of Hypoxia On Reactive Oxygen Species Generation Within Murine Breast Cancer Cells, Jared Mcpeake

Biomedical Engineering Undergraduate Honors Theses

When cancer metastasizes from a primary tumor site to secondary site through the bloodstream or lymph, the cancer becomes more difficult to treat. For this reason, it is vital to study what indicates the metastatic potential of a tumor. Current research has shown that cell lines with high metastatic potential display increased levels of metabolic adaptability over their nonmetastatic counterparts after undergoing hypoxic conditions. One method of assessing this adaptability is to measure the concentration of reactive oxygen species (ROS) produced by the cells while undergoing oxidative stress. In highly adaptable metastatic cells, an increase of ROS buildup within the …

Investigation Of Microbe And Host Tissue Interactions Contributing To The Pathogenesis Of Colorectal Cancer, Ryan Chapman, Dhundy Bastola

Theses/Capstones/Creative Projects

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The pathogenesis of this disease can fall under broad categories; however, the specific precursory mechanism of CRC pathogenesis is still unknown. Dysregulations of the gut microbiome have been identified in the CRC tissue environment. Additionally, CRC tissue gene expression has been observed to differ from that of healthy tissue. Despite these noticeable changes, few studies have directly compared the microorganism composition to the gene expression of CRC tissue. Doing so may identify whether the differentially abundant microorganisms influence the changes in gene expression. The goal of this …

Novel Regulators Of Cellular Secretion Alter The Tumor Microenvironment To Drive Metastasis, Rakhee Bajaj

Dissertations and Theses (Open Access)

Lung cancer is a highly aggressive disease responsible for ~25% of all cancer-related deaths, due in part to its proclivity to metastasize. Treating metastasis holds potential for improving patient survival but requires a deeper investigation into the underlying mechanisms. Some of these processes that can regulate metastasis are: (1) Oncogenic targets of epithelial micro-RNAs (miRNAs) are epigenetically de-repressed upon loss of the miRNAs during epithelial-to-mesenchymal transition (EMT) and in cancer. EMT confers plasticity and fitness to cancer cells promoting their survival through the metastatic cascade. This cascade and EMT are initiated by loss of the miRNA200 family (miR-200) and the …

The Effects Of Metronomic And Maximum-Tolerated Dose Chemotherapy In Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy And Mrna Expression, Ariel Isaac Mundo Ortiz

Graduate Theses and Dissertations

Colorectal cancer (CRC) continues to be one of the most incident and deadliest types of cancer worldwide. Chemotherapy has proven effective to reduce tumor burden for CRC patients, but there are several disadvantages associated with the use of mainstay maximtolerated dose (MTD) chemotherapeutic strategies. Metronomic chemotherapy (MET) has been developed as an alternative that addresses the shortcomings of maximum-tolerated dose chemotherapy but so far its effectiveness as a neoadjuvant strategy for CRC has not been explored.

This dissertation uses a combined optics and molecular biology approach (using diffuse reflectance spectroscopy and mRNA expression) to study the changes in angiogenesis and …

Characterization Of The Influence Of A Small Molecule Inhibitor On Ras-Related Proteins Interactions, Emilio Duverna

Graduate Theses and Dissertations

The Ras superfamily of small G proteins are involved in cell-signaling processes that, if not regulated, may lead to cell multiplication, apoptosis inhibition, and tumorigenesis. They function as molecular switches, which through GTP/GDP exchange cycle, switch on or off cellular activities. Overexpression and/or hyperactivity of these proteins have been linked to many diseases including various cancers. CDC42, a member of the Rho subfamily of the Ras superfamily of small G proteins, participates in the regulation of many cellular processes including cell adhesion, mitosis, and cytoskeletal rearrangements. CDC42 binds to and activates many effector proteins including CDC42-activated kinase (ACK). Abnormal activities …

The Roles Of Pon2 In Mitochondrial Physiology, Lung Tumor Cell Proliferation, And Lung Tumorigenesis., Aaron Whitt

Electronic Theses and Dissertations

Paraoxonase 2 (PON2) is an intracellular, multifunctional enzyme with near-ubiquitous tissue distribution. Within cells, PON2 is localized to mitochondria and endoplasmic reticulum (ER), where it mitigates the formation of reactive oxygen species (ROS). PON2’s chief enzymatic function is its lactonase activity, through which it catalyzes the hydrolysis of a bacterial quorum-sensing molecule, N-(3-oxododecanoyl)-l-homoserine lactone (C12), effectively disrupting bacterial intercellular communication and protecting against infection. C12 is produced by the opportunistic pathogen Pseudomonas aeruginosa and has been shown to disrupt various aspects of eukaryotic host cell physiology and evoke apoptotic cell death through the activity of PON2. Additionally, PON2 has garnered …

Exploiting Chemogenetic And Genetic Interactions In Human Cells As An Avenue For New Therapeutic Opportunities, Medina Colic

Dissertations and Theses (Open Access)

The advent of CRISPR technology and its adaptation to the mammalian genome made whole-genome knockout screens possible directly in human cells. Gene knockout answers how essential that gene is for cell fitness and proliferation. Genes showing moderate to severe fitness defects are called essential genes and provide insights into disease-specific candidate therapeutic targets. Additionally, CRISPR offers other applications for genome editing. Two applications this dissertation is based on are 1) combination of gene knockout and drug treatment, which enables the identification of chemogenetic interactions, or gene mutations that enhance or suppress the activity of a drug, and 2) combinatorial editing, …

An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan

Dissertations and Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and is associated with significant morbidity and mortality. To date, the majority of work in the field has focused on genomic alterations such as mutations and copy number alterations. However, the clinical success of targeted therapies that exploit known genomic alterations, such as EGFR mutations, has remained mixed. Over the past decade, the importance of epigenetic regulators has come to the forefront, with the realization that many of these genes are mutated in cancer. Despite this realization, the role of epigenetics in regulating tumorigenesis, progression and …

Modulation Of Kras Structure And Dynamics By Kras Ubiquitination And Membrane Depolarization, Vinay Nair

Dissertations and Theses (Open Access)

KRAS, a 21 kDa small GTPase protein, functions as a molecular switch playing a key role in regulating cell proliferation. Dysregulation of KRAS signaling by oncogenic mutations leads to uncontrolled cell proliferation, a hallmark of cancer cells. Attempts to therapeutically target oncogenic KRAS have led to limited success resulting in a need to identify new mechanisms to targeting KRAS. The interaction of KRAS with its regulators, effectors, and the membrane present one such avenue. In this study, we investigated how post-translational covalent and environmental modifications could modulate these interactions of KRAS. Using computational molecular dynamics simulations, nuclear magnetic resonance spectroscopy …

Integration Of Biomedical Imaging And Translational Approaches For Management Of Head And Neck Cancer, Abdallah Mohamed, Abdallah Mohamed

Dissertations and Theses (Open Access)

The aim of the clinical component of this work was to determine whether the currently available clinical imaging tools can be integrated with radiotherapy (RT) platforms for monitoring and adaptation of radiation dose, prediction of tumor response and disease outcomes, and characterization of patterns of failure and normal tissue toxicity in head and neck cancer (HNC) patients with potentially curable tumors. In Aim 1, we showed that the currently available clinical imaging modalities can be successfully used to adapt RT dose based-on dynamic tumor response, predict oncologic disease outcomes, characterize RT-induced toxicity, and identify the patterns of disease failure. We …

Development And Characterization Of B7-H3-Targeted Radioimmunotherapies For The Treatment Of Solid Tumors, Sarah Glazer

Dissertations and Theses (Open Access)

Radioimmunotherapy involves the selective targeting of therapeutic radionuclides to cancer-associated cell surface antigens using monoclonal antibodies. Radioimmunotherapy has been successful in treating hematologic cancers, such as non-Hodgkin’s Lymphoma. However, treatment of solid tumors by radioimmunotherapy remains a challenge, driven in part by a lack of high affinity antibodies against highly tumor-selective surface antigens. Herein, we characterize novel anti-B7-H3 immuno-conjugates for PET imaging and RIT of solid tumors in preclinical models.

Human B7-H3 (CD276) protein is highly expressed on solid tumor cell surfaces and endovascular surfaces in a wide variety of cancers (colon, breast, pancreatic, prostate, head and neck, glioblastoma, ovarian, …

Utilizing Pharmacology To Target Transcription Factors Involved With Cancer Onset And Development, Tristan D. Sanders

Mountaineer Undergraduate Research Review

Transcription factors (TFs) are a vital part of every living organism on earth, as they allow for the correct genes to be expressed while much of the genome is never used. They can fall victim to mutations or manipulations that lead to the deregulation of many genes within a cell. If specific genes are over/under-expressed, a cell may become cancerous and begin replicating into a tumor. It has been demonstrated that common TFs associated with cancer can be targeted using small molecule drugs, and a popular target of these drugs is the DNA binding site on the TF along with …

Identification Of Lipid Species: Potential Biomarkers For Early Detection Of Hepatocellular Carcinoma, Kit Yee Leung, Kaylee Freitas

Undergraduate Research Symposium Posters

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. HCC is associated with cirrhosis. Poor survival rate of HCC is due to diagnosis of HCC at late stage.

Jag1 Role In The Extravasation Of Metastasized Tnbc Tumor Cells, Bhavya Vegesna '23

Student Publications & Research

Breast cancer is the second leading cause of cancer death in women. Triple negative breast cancer (TNBC) is an aggressive subclass defined by its lack of hormonal receptors and HER2 amplification. Although TNBC only accounts for 15% of all invasive breast cancers, there are limited therapeutic options for patients with TNBC. Although breast cancer patients have a favorable prognosis if their tumor is detected early, patients with TNBC are prone to earlier recurrence and local/distant metastasis. Consequently, patients with metastatic TNBC have <15% relative 5-year survival rate. The development of metastasis in TNBC is a complex and poorly understood process that includes multiple steps such as genetic and epigenetic alterations, angiogenesis, epithelial-to-mesenchymal transition (EMT), intravasation, and extravasation. Expression of JAGGED-1 (JAG1), a Notch ligand, correlates with metastatic status and poor survival in clinical data. However, the exact mechanism in which JAG1 increases metastasis is unknown. We hypothesize that JAG1 increases metastasis by interacting with endothelial cells. In order to test this idea, we generated JAG1-knockout cells using CRISPR/Cas9 technologies and then modeled the extravasation of these cells compared to JAG1-positive cells. Specifically, we interrogated lung capillary extravasation after intravenous injection of TNBC cells. The lung was chosen due to the propensity of TNBC cells to invade the lung. Preliminary data demonstrates that JAG1 presented in tumor cells acts as a signaler to permit and promote extravasation and metastasis of the cancer cells. For further studies, the long term effects of tumor derived JAG1 will be studied to understand the consequences of JAG1 mediated extravasation on metastatic burden and survival.

Indispensable Role Of Immunophenotyping In Diagnosing Leukemic Phase Of Blastic Plasmacytoid Dendritic Cell Neoplasm Without Cutaneous Manifestation, Hareem Alam, Nabiha Saeed, Anila Rashid

Department of Pathology and Laboratory Medicine

Blastic plasmacytoid dendritic cell neoplasm usually presents as skin lesions. Diagnostic error occurs when it primarily presents in leukemic phase without skin involvement. Triad of CD4, CD56 and CD123 immunophenotype expression is essential to avoid misdiagnosis of this rare hematological malignancy. Here we describe a patient who presented in overt leukemic phase of BPDCN highlighting diagnostic challenges encountered that resulted in delayed diagnosis and poor outcome

Bis-Cinnamamide Derivatives As Ape/Ref-1 Inhibitors For The Treatment Of Human Melanoma, Razan Alhazmi, Shirley Tong, Shaban Darwish, Elina Khanjani, Bharti Khungar, Swati Chawla, Zhonghui Zheng, Richard Chamberlain, Keykavous Parang, Sun Yang

Pharmacy Faculty Articles and Research

Human malignant melanoma exhibits imbalances in redox status, leading to activation of many redox-sensitive signaling pathways. APE/Ref-1 is a multifunctional protein that serves as a redox chaperone that regulates many nuclear transcription factors and is an important mechanism in cancer cell survival of oxidative stress. Previous studies showed that APE/Ref-1 is a potential druggable target for melanoma therapy. In this study, we synthesized a novel APE/Ref-1 inhibitor, bis-cinnamoyl-1,12-dodecamethylenediamine (2). In a xenograft mouse model, compound 2 treatment (5 mg/kg) significantly inhibited tumor growth compared to the control group, with no significant systemic toxicity observed. We further synthesized compound …

The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez

Thinking Matters Symposium

In a clinical setting, some patients are exposed to an anti-cancer chemotherapy agent, paclitaxel. Cancerous cells undergo rapid, continuous cell division without control. Chemotherapy treatments try to slow and stop the uncontrollable cell division cycles and eliminate cancerous cells in the process. Paclitaxel serves as a treatment for some types of cancers, including lung, melanoma, bladder, and esophageal. Because it targets the cytoskeleton, paclitaxel can also influence cell migration. This project utilizes a cellular migration assay and an immunohistochemistry assay to analyze the effects of paclitaxel on the movement of cells and on the cytoskeleton of neuroglia rat cells with …

Utilization Of Bioinformatics And Immunocytochemistry To Examine Gap Junction Expression In Breast Cancers Cells, Jasmine D. Carter, Giovanni Reyes, Abeeha K. Choudhary, Eric A. Albrecht

Symposium of Student Scholars

Utilization of Bioinformatics and Immunocytochemistry to Examine Gap Junction Expression in Breast Cancers Cells.

Jasmine D. Carter¹, Giovanni Reyes¹, Abeeha Choudhary² and Eric A. Albrecht¹

Breast cancer is known for its diverse clinical classifications and expressing different levels of membrane proteins such as ion channels and gap junctions. This diversity allows more variations in cell polarization, which can lead to enhanced directional ion fluxes in certain breast cancer subtypes. We utilized the interactive web portal UALCAN to evaluate the gene expression data of gap junctions, ion exchange channels and cytoskeletal proteins in breast cancer …

Investigating The Efficacy Of Tazemetosttat For In Vitro Treatment Of Human Triple Negative Breast Cancer Cells, Harshita Indukuri

Honors Scholars Collaborative Projects

Cancer is a formidable, genetic disease that affects many people, either directly or indirectly. Breast cancer is the most commonly diagnosed cancer worldwide (31). Triple-negative breast cancer (TNBC) is a type of breast cancer that has a higher lethality compared to other breast cancers and has a poor prognosis due to its highly invasive nature and limited treatment options. Finding safe, effective, and accessible treatment for TNBC is integral to treating TNBC patients. Tazemetostat is an EZH2-inhibitor that has recently been approved for use in epithelioid sarcoma (23). EZH2 is an overexpressed protein in many cancers, including TNBC (11). However, …

Investigation Of Iron Homeostasis In Colon Tumorigenesis, Hyeoncheol Kim Ph.D.

Chemistry and Chemical Biology ETDs

Iron is essential part of the human metabolism. It is a catalytic co-factor for many proteins, but it generates harmful reactive oxygen species in human body. Also, many irons metabolic genes are changes in human cancer cells compared to normal cells, leading to iron accumulation in cancer cells especially in colorectal cancer.

Due to iron’s significant role in colorectal cancer promotion, much research is focused on its role in colorectal cancer genesis. But some important metabolic aspects are not fully addressed and researched. One key aspect of iron on colorectal cancer cell progression is hemin iron. Much research warned hemin …

Targeted Osmotic Lysis: A Novel Approach To Targeted Cancer Therapies, Harry J. Gould, Dennis Paul

School of Medicine Faculty Publications

The conventional treatment of cancer has been based on the delivery of non-selective toxins and/or ionizing energy that affect both the cancer and normal tissues in the hope of destroying the offending disease before killing the patient. Unfortunately, resistance often develops to these treatments and patients experience severe, dose-limiting adverse effects that reduce treatment efficacy and compromise quality of life. Recent advances in our knowledge of the biology of tumor cells and their microenvironment, the recognition of surface proteins that are unique to specific cancers and essential to cell growth and survival and signaling pathways associate with invasion and metastasis …

Paratesticular Solitary Fibrous Tumour Mimicking Cellular Angiofibroma: An Unusual Morphology And Rare Site, Madiha Bilal Qureshi, Muhammad Usman, Qurratulain Chundriger, Nasir Uddin

Department of Pathology and Laboratory Medicine

Solitary fibrous tumour (SFT) is a ubiquitous benign mesenchymal tumour of fibroblastic origin, which occurs most often in middle-aged adults. It usually presents as lung mass originating from pleura, but extrapleural occurrence is also common. Tumour is characterised by hypo- and hyper-cellular areas of spindle-shaped cells, arranged in haphazard manner with dispersed staghorn-shaped vessels. Surgical excision is the curative treatment. SFTs of the primary testicular or paratesticular region are extremely rare, but they exhibit histologic findings similar to SFTs originating at other body sites. Here, we report the case of a paratesticular SFT in a 37-year male, who presented with …

Analysis Of Invasion Proteins Mmp2, Mmp9, Adam12, And Adam17 In Glioblastoma U87mg Cells Treated With Anti-Cancer Compound 3,4-Dimethoxybenzaldehyde, Andras Muranyi

Honors Theses

This research tested the effectiveness of novel compound 3,4-dimethoxybenzaldehyde, demonstrated to have anti-cancer properties. U87MG Glioblastoma cells were exposed to the compound at its LC50 concentration, then processed to collect proteins from the cells. Proteins were analyzed via Western blotting for specific protein levels of matrix metalloproteinase 2 and 9 (MMP) and disintegrin and metalloprotease 12 and 17 (ADAM). Previous research indicates these proteins are involved in the invasive properties of glioblastoma cells. Westerns were quantified with ImageJ and compared using a one-way ANOVA. Results indicate the compound has minimal effect upon the expression of MMP2, MMP9, ADAM12, ADAM17 proteins.

Synthesis Of Thiol-Acrylate Hydrogels For 3d Cell Culture And Microfluidic Applications, Anowar Hossain Khan

LSU Doctoral Dissertations

Globally cell culture is an $18.98 billion industry as of 2020, with an 11.6 percent annual growth rate. Drug discovery has an estimated worth of $69.8 billion in 2020 and is predicted to grow to $110.4 billion by 2025. Three-dimensional (3D) cell culture of cancer cells is one of the rapidly growing felids since it better recapitulates in vivo conditions compared to two-dimensional (2D) models. However, it is challenging to grow 3D tumor spheroids outside the body, and some of the existing technology can generate these spheroids outside the human body but poorly mimic in vivo tumor models. Therefore, there …

Geotemporospatial And Causal Inferential Epidemiological Overview And Survey Of Usa Cannabis, Cannabidiol And Cannabinoid Genotoxicity Expressed In Cancer Incidence 2003–2017: Part 2 – Categorical Bivariate Analysis And Attributable Fractions, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Background: As the cannabis-cancer relationship remains an important open question epidemiological investigation is warranted to calculate key metrics including Rate Ratios (RR), Attributable Fractions in the Exposed (AFE) and Population Attributable Risks (PAR) to directly compare the implicated case burden between emerging cannabinoids and the established carcinogen tobacco. Methods: SEER*Stat software from Centres for Disease Control was used to access age-standardized state census incidence of 28 cancer types (including “All (non-skin) Cancer”) from National Cancer Institute in US states 2001–2017. Drug exposures taken from the National Survey of Drug Use and Health 2003–2017, response rate 74.1%. Federal seizure data provided …