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Articles 1 - 23 of 23

Full-Text Articles in Cancer Biology

Host Cell Responses Modulate Oncolytic Viral Treatment Of Neuroblastoma Cells, Kritika Kedarinath Jan 2023

Host Cell Responses Modulate Oncolytic Viral Treatment Of Neuroblastoma Cells, Kritika Kedarinath

Electronic Theses and Dissertations, 2020-

Neuroblastoma is an aggressive pediatric cancer that is poorly responsive to traditional cancer therapies. Oncolytic viral (OV) vectors such as Zika virus (ZIKV) and Parainfluenza virus type 5 (P/V virus) are promising neuroblastoma therapeutics, but the role of innate immune responses in the effectiveness of OV killing is not well understood. Previous studies showed the neuroblastoma cell line SK-N-AS (expressing low CD24) had low permissivity for ZIKV infection, and this restriction was relieved by ectopic CD24 expression (CD24-high cells). Compared to permissive CD24-high cells, the non-permissive CD24-low cells had elevated basal levels of IRF-1, NF?B and phosphorylated STAT1; these cells …


Deciphering The Role And Clinical Application Of The Fgfr4-Klb-Fgf19 Axis In Colorectal Neoplastic Progression, Michael Rohr Jan 2022

Deciphering The Role And Clinical Application Of The Fgfr4-Klb-Fgf19 Axis In Colorectal Neoplastic Progression, Michael Rohr

Electronic Theses and Dissertations, 2020-

Colorectal cancer (CRC) is the third most common and third deadliest cancer worldwide with rising incidence rates attributed to environmental risk factors like diet. Investigating how these factors impact carcinogenesis requires an understanding of how transcriptional events evolve with respect to neoplastic progression. We employed meta-transcriptomics and latent trajectory modeling to establish a compendium of profiled healthy, adenoma, and CRC samples scored by their position along a pseudotemporal axis. By interpolating a continuous scale from cross-sectional data, dynamic processes occurring throughout disease progression can be analyzed more accurately. For example, smaller pseudotimes represented pre-malignant dysplasia and was characterized by cellular …


A Novel Drug To Induce Apoptosis In Advanced Prostate Cancer Cells, Parshva A. Sanghvi Jan 2022

A Novel Drug To Induce Apoptosis In Advanced Prostate Cancer Cells, Parshva A. Sanghvi

Honors Undergraduate Theses

Prostate cancer is one of the leading causes of death for men in America as approximately 1 in 41 men will have prostate cancer. In this research, we focus on enzalutamide-resistant prostate cancer cells as cell resistance to enzalutamide is a prevalent obstacle in treating prostate cancer. We tested a novel compound library at different doses and observed each compound's efficacy in inducing apoptosis in enzalutamide-resistant cells. Furthermore, we analyzed the mechanism by which apoptosis was induced in compounds that showed a high efficacy at lower doses. Overall, we found that Darapladib shows promising results in treating cells that have …


The Relationship Between Inflammatory Diet Score And Cancer Outcomes: Systematic Review And Meta-Analysis, Eric Han Jan 2022

The Relationship Between Inflammatory Diet Score And Cancer Outcomes: Systematic Review And Meta-Analysis, Eric Han

Honors Undergraduate Theses

Cancer remains one of the most prevalent diseases in the United States and a leading cause of death. Large prospective studies have found significant correlations between dietary intake and cancer. Chronic inflammation promotes pro-cancer inflammatory environments promoting the formation and growth of tumors while preventing effective anti-tumor responses. Nutrition can impact inflammation, with the intake of certain food items increasing biomarkers for systemic inflammation thus, the objective of this research was to explore the relationship between inflammatory diet score measured by the Dietary Inflammatory index and all-cause mortality, cancer-specific mortality, and cancer recurrence among cancer survivors. Web of Science, Medline, …


Evaluating Novel Combinations Of Polyamine Targeting Therapeutics In Pancreatic Ductal Adenocarcinoma, Sai Preethi Nakkina Jan 2022

Evaluating Novel Combinations Of Polyamine Targeting Therapeutics In Pancreatic Ductal Adenocarcinoma, Sai Preethi Nakkina

Electronic Theses and Dissertations, 2020-

Pancreatic cancer overall has a poor five-year survival rate of less than 8%. Well-tolerated regimens and immune cell infiltration to promote anti-cancer treatments are major challenges. Studies described herein leveraged testing different combinations/doses of polyamine targeting inhibitors to further understand the impact of targeting key polyamine pathway mediators in pancreatic ductal adenocarcinoma (PDAC). Placebo controls were compared to groups treated with difluoromethylornithine (DFMO, a polyamine biosynthesis inhibitor of ornithine decarboxylase), different polyamine transport inhibitors, and compound combinations in strategies for polyamine blockage therapy (PBT). Informatic analyses showed that the dysregulation of key polyamine pathway mediators are associated with poor patient …


Serotonin's Proliferative Effects On Lung Cancer Cell Lines, Jessy K. Ntabo Jan 2022

Serotonin's Proliferative Effects On Lung Cancer Cell Lines, Jessy K. Ntabo

Honors Undergraduate Theses

Serotonin has been widely explored in the brain. Recently, there have been new findings on how serotonin works in the periphery. Serotonin is introduced to the periphery by the enterochromaffin cells and metabolized by the liver and lung. Studies have shown that serotonin plays a role in controlling lung cancer. However, the mechanism by which it initiates tumor formation has not been fully explored. Cell viability was measured in several lung adenocarcinoma cell lines treated with serotonin to study this effect. In GFP-labelled cells, fluorescence intensity was measured for quantification of cell viability. Our data showed an overall increase in …


The Motuporamines Act Through Rho1 And Rac To Control Actin Dynamics In Drosophila, Corey Seavey Jan 2021

The Motuporamines Act Through Rho1 And Rac To Control Actin Dynamics In Drosophila, Corey Seavey

Electronic Theses and Dissertations, 2020-

Given that most cancer patients die from metastatic disease, there is an urgent need to develop drugs that inhibit the spread of tumors. Studies show that the motuporamines activate the small GTPase RhoA to prevent cancer cell migration, but little is known about the mechanism of action of dihydromotuporamine C (Motu33) and its synthetic derivative Motu-(CH2)-33. In the present study, I investigated the biomolecular processes of these compounds in Drosophila by reducing the gene dose of positive and negative regulators of actin dynamics. Consistent with previous findings, reduced gene dose of Rho1 (the Drosophila RhoA ortholog) attenuates motuporamine activity confirming …


Bacterial Association Networks From Healthy And Cancer-Associated Gut Microbiomes, Mark Loftus Jan 2021

Bacterial Association Networks From Healthy And Cancer-Associated Gut Microbiomes, Mark Loftus

Electronic Theses and Dissertations, 2020-

The human gastrointestinal tract is colonized by a diverse community of symbiotic microorganisms, mainly bacteria, that are known to play essential roles in maintaining the health of their human host. Disruption of this bacterial community has been associated with numerous diseases, including Colorectal Cancer (CRC). CRC is one of the leading causes of cancer-related deaths worldwide. As such, focus has been placed on the modulation of the bacterial community within the cancer-associated gut microbiome as the next step in possible CRC treatment and prevention strategies. To use the bacterial community for these purposes, a better understanding of the associations that …


Development Of Adjunctive Agents For Difluoromethylornithine Anti-Cancer Therapy, Aiste Dobrovolskaite Jan 2021

Development Of Adjunctive Agents For Difluoromethylornithine Anti-Cancer Therapy, Aiste Dobrovolskaite

Electronic Theses and Dissertations, 2020-

The native polyamines putrescine, spermidine, and spermine are small positively-charged molecules that can interact with negatively-charged macromolecules like DNA, RNA and proteins. These interactions aid in nucleic acid and protein conformational stability, thereby, making polyamines essential building blocks for cells. Polyamines are involved in various cellular functions including gene regulation, protein synthesis, and cell proliferation. Rapidly-proliferating cells, such as cancer cells, utilize high polyamine levels for cell growth. Targeting the polyamine addiction of cancers is a validated anti-cancer strategy. To achieve the maximal reduction of polyamine levels, polyamine blocking therapy (PBT) employs several compounds in combination. First, one can inhibit …


Evaluating Lactobacillus Acidophilus As A Model Organism For Co-Culture Cancer Studies, Samuel A. Mikhail Jan 2019

Evaluating Lactobacillus Acidophilus As A Model Organism For Co-Culture Cancer Studies, Samuel A. Mikhail

Honors Undergraduate Theses

The causality dilemma between dysbiosis and cancer has given rise to numerous studies both exploring the mechanisms behind cancer progression and the associative shifts in the microbiota upon carcinogenesis. Aside from the hallmark study of Dr. Barry Marshall in establishing the true causal relationship between Helicobacter pylori and gastric adenocarcinoma, studies have only been successful in adding associative links of carcinogenesis mediated by bacteria to the literature. The current field is limited in its ability to establish causative relationships, and further work is needed to construct a reference community whose physiological responses reflect global community responses. In this thesis, the …


Characterization Of Cytokeratin 8 In Cancer, Daniel S. Leventhal Jan 2018

Characterization Of Cytokeratin 8 In Cancer, Daniel S. Leventhal

The Pegasus Review: UCF Undergraduate Research Journal

A Cytokeratin 8 (K8)/Green Fluorescent Protein (GFP) fusion construct was created to better understand the behavior of K8 within cancer cells. This intermediate filament (IF) protein is a member of the cytoskeletal gene family, along with actin and tubulin. IFs are normally expressed in a tissue-specific and differentiation-dependent manner, in which their role is more supportive than essential to the cell. Such roles include rigidity of cellular shape, protein trafficking, cellular locomotion, and cell-signaling platforms. K8 mutation, over-expression, and aberrant post translational modifications have been observed in various carcinoma cell lines to be the cause of several phenotypes, including apoptosis …


Deciphering The Role Of Adrenergic Hormones In Embryonic Cardiac Calcium Signaling And Metabolism, Jessica Peoples Jan 2018

Deciphering The Role Of Adrenergic Hormones In Embryonic Cardiac Calcium Signaling And Metabolism, Jessica Peoples

Electronic Theses and Dissertations

The adrenergic hormones norepinephrine (NE) and epinephrine (EPI) are critical regulators of mammalian cardiovascular physiology. NE and EPI mediate stress responses to enhance cardiovascular function, however dysregulation of adrenergic signaling leads to heart failure, congenital heart malformations, and sudden cardiac death. Adrenergic hormone-expressing cells were found in the early embryonic heart, and NE has been determined essential for embryonic cardiac development. Despite extensive work in adults, the regulatory roles and adrenergic targets of these hormones during embryonic cardiac development have not yet been fully determined. Prior transcriptomic studies from our lab showed that expression of signal transduction and metabolic genes …


Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach Jan 2018

Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach

Honors Undergraduate Theses

Polyamines are a class of essential nutrients involved in many basic cellular processes such as gene expression, cell proliferation, and apoptosis. Without polyamines, cell growth is delayed or halted. Cancerous cells require an abundance of polyamines through a combination of synthesis and transport from the extracellular environment. An FDA-approved drug, D,L-α-difluoromethylornithine (DFMO), blocks polyamine synthesis but is ineffective at inhibiting cell growth due to polyamine transport. Thus, there is a need to develop drugs that inhibit polyamine transport to use in combination with DFMO. Surprisingly, little is known about the polyamine transport system in humans and other eukaryotes. Understanding the …


The Identification And Segmentation Of Astrocytoma Prior To Critical Mass, By Means Of A Volumetric/Subregion Regression Analysis Of Normal And Neoplastic Brain Tissue, Lyn Higgins Jan 2018

The Identification And Segmentation Of Astrocytoma Prior To Critical Mass, By Means Of A Volumetric/Subregion Regression Analysis Of Normal And Neoplastic Brain Tissue, Lyn Higgins

Electronic Theses and Dissertations

As the underlying cause of Glioblastoma Multiforme (GBM) is presently unclear, this research implements a new approach to identifying and segmenting plausible instances of GBM prior to critical mass. Grade-IV Astrocytoma, or GBM, is an aggressive and malignant cancer arising from star-shaped glial cells, or astrocytes, where the astrocytes, functionally, assist in the support and protection of neurons within the central nervous system and spinal cord. Subsequently, our motivation for researching the ability to recognize GBM is that the underlying cause of the mutation is presently unclear, leading to the operative that GBM is only detectable through a combination of …


Novel Cytokine Signaling And Molecular Therapeutic Strategy In Pancreatic Cancer, Sarah Gitto Jan 2017

Novel Cytokine Signaling And Molecular Therapeutic Strategy In Pancreatic Cancer, Sarah Gitto

Electronic Theses and Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is highly chemo-resistant and has a five year survival rate of < 8%. Risk factors of pancreatic cancer, such as chronic pancreatitis, help to elicit a pro-tumor immune response, and highly fibrotic environment that promotes tumorigenesis. To study how chronic pancreatitis promotes cancer initiation, traditional KRasG12D mice and double mutant Akt1Myr/KrasG12D mice were used to model microenvironment changes. Akt1Myr/KrasG12D mice were more susceptible to chronic tissue damage, accelerated tumor development and metastatic disease. These mice exhibited histological changes consistent with immune cell privilege, where M2 macrophages and non-cytotoxic eosinophils were co-localized with fibrotic regions. IL-5 expression was up regulated in pancreatic cells undergoing acinar to ductal metaplasia and then diminished in advanced lesions. Tumor cells treated with IL-5 exhibit increased migration and activation through STAT5 signaling. Collectively, the results suggest that eosinophils, which are responsive to IL-5, are key mediators in the pancreatic environment subjected to chronic inflammation and injury. Current therapeutics fall short in increasing patient survival. There remains an urgent need for innovative treatments and thus we tested difluoromethylornithine (DFMO) in combination with a novel polyamine transport inhibitor, Trimer44NMe, against Gemcitabine-resistant PDAC cells. Prior clinical failures when targeting polyamine biosynthesis with DFMO monotherapy may be due to tumor escape via an undefined polyamine transport system. In pancreatic tumor cells DFMO alone and with Trimer44NMe significantly reduced PDAC cell viability by inducing apoptosis or cell cycle arrest. In vivo orthotopic PDAC growth with DFMO treatment resulted in decreased c-Myc expression, a readout of polyamine pathway dysfunction. Moreover, dual inhibition significantly prolonged survival of tumor-bearing mice, and increased M1 macrophage infiltration and reduced FoxP3 expression. Collectively, these studies demonstrate that targeting polyamine pathways in PDAC is a promising immunomodulating therapy that increases survival.


Chaperonin Containing Tcp1 (Cct) As A Target For Cancer Therapy, Ana Carr Jan 2017

Chaperonin Containing Tcp1 (Cct) As A Target For Cancer Therapy, Ana Carr

Electronic Theses and Dissertations

Treatments for aggressive cancers like triple negative breast cancer (TNBC) and small-cell lung cancer (SCLC) have not improved and remain associated with debilitating side effects. There is an unmet medical need for better, druggable targets and improved therapeutics. To this end, we investigated the role of Chaperonin-Containing TCP1 (CCT), an evolutionarily conserved protein-folding complex composed of eight subunits (CCT1-8), in oncogenesis. Our laboratory was the first to report that the CCT2 subunit is highly expressed in breast cancer and could be therapeutically targeted. To determine whether CCT is a marker of disease progression in other cancers, we analyzed CCT2 gene …


The Effect Of K562-Il21-2 Plasma Membrane Particles On The Proliferation Of Natural Killer Cells To Fight Cancer, Michelle Prophete Jan 2017

The Effect Of K562-Il21-2 Plasma Membrane Particles On The Proliferation Of Natural Killer Cells To Fight Cancer, Michelle Prophete

Honors Undergraduate Theses

Immunotherapy has emerged as a current and future paradigm of cancer treatment, which utilizes the body’s immune system to eradicate cancer. Natural Killer (NK) cells as part of the innate immune system have immense potential in their anti-tumor cytotoxic activities and host cell surveillance properties. NK cells comprise approximately five to fifteen percent of peripheral blood lymphocytes and can be proliferated in vitro using recently developed methods with co-cultures with feeder cells (derived from engineered tumor cells) or plasma membrane (PM) particles, produced from the fore mentioned feeder cells, in combination with soluble cytokines. For efficient growth and maintenance of …


Micro-Spectroscopy Of Bio-Assemblies At The Single Cell Level, Jeslin Kera Jan 2017

Micro-Spectroscopy Of Bio-Assemblies At The Single Cell Level, Jeslin Kera

Honors Undergraduate Theses

In this thesis, we investigate biological molecules on a micron scale in the ultraviolet spectral region through the non-destructive confocal absorption microscopy. The setup involves a combination of confocal microscope with a UV light excitation beam to measure the optical absorption spectra with spatial resolution of 1.4 μm in the lateral and 3.6 μm in the axial direction. Confocal absorption microscopy has the benefits of requiring no labels and only low light intensity for excitation while providing a strong signal from the contrast generated by the attenuation of propagating light due to absorption. This enables spatially resolved measurements of single …


Screening For Anticancer Agents To Inhibit Mitotic Kinases And Proliferation Of Metastatic Prostate Cancer Cells, Khoa Nguyen Jan 2016

Screening For Anticancer Agents To Inhibit Mitotic Kinases And Proliferation Of Metastatic Prostate Cancer Cells, Khoa Nguyen

Honors Undergraduate Theses

Current treatments for prostate cancer (PCa) are marred with high relapse frequency and development of progressively aggressive cancers; developing new treatment options for PCa remains crucial. In this project, a series of synthetic compounds based on natural products will be screened to identify inhibitors for Aurora-A kinase (Aur-A). Aur-A facilitates centrosome separation and bipolar spindle formation during mitosis. Aur-A is overexpressed in metastatic PCa cells, and is a good candidate for targeted therapies. Compound libraries are designed using natural compounds that contain simple structural elements as starting points for developing drug like libraries. High-throughput screening of these libraries will be …


Prostasin Is Expressed In Benign Prostatic Hyperplasia And Regulates Cell Proliferation And Invasion Via Inos, Icam-1, And Cycli, Meghan Hatfield Jan 2008

Prostasin Is Expressed In Benign Prostatic Hyperplasia And Regulates Cell Proliferation And Invasion Via Inos, Icam-1, And Cycli, Meghan Hatfield

Electronic Theses and Dissertations

Prostasin is expressed in normal prostate epithelial cells but down-regulated in prostate cancers, while prostasin re-expression in invasive prostate cancer cells reduced invasion. We examined prostasin expression and function in benign prostatic hyperplasia (BPH). We evaluated prostasin expression in 12 BPH specimens by immunohistochemistry, and evaluated the impact of prostasin silencing by siRNA on the expression of the inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), and cyclin D1, as well as on cell proliferation and invasion, using the BPH-1 human prostate epithelial cell line model. Prostasin expression was localized in the glands of BPH tissues by immunohistochemistry, in …


Role Of Transient Receptor Potential Canonical-6 (Trpc6) Channel In Metastasis Of Glioblastoma Multiforme, Rajarajeshwari Venkataraman Jan 2008

Role Of Transient Receptor Potential Canonical-6 (Trpc6) Channel In Metastasis Of Glioblastoma Multiforme, Rajarajeshwari Venkataraman

Electronic Theses and Dissertations

Glioblastoma multiforme (GBM) is one of the extremely fatal brain tumors. The main reason that makes it so lethal is its capability to invade and spread to other parts of CNS producing secondary tumors. Among other factors hypoxia, reduced oxygen availability, is linked to higher metastatic potential of cancers. Hypoxia causes numerous changes in genome and proteome of the cell. These changes help a normal cell to adapt to nutritional deficiency, but the same changes can increase the malignancy and metastasis in tumor cells. Extensive research by a number of curious scientists reveal that various pathways involving numerous proteins cross-talk …


Mechanism Of Action And Regulation Of Membrane Serine Protease Prostasin In The Prostate And Prostate Cancer, Mengqian Chen Jan 2007

Mechanism Of Action And Regulation Of Membrane Serine Protease Prostasin In The Prostate And Prostate Cancer, Mengqian Chen

Electronic Theses and Dissertations

The glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin (PRSS8) is expressed at the apical membrane surface of epithelial cells and acts as a suppressor of tumor invasion when re-expressed in highly invasive human prostate and breast cancer cell lines. To better understand the molecular mechanisms underlying the anti-invasion phenotype associated with prostasin re-expression in prostate cancer cells, we expressed wild-type human prostasin or a serine active-site mutant prostasin in the PC-3 human prostate carcinoma cells. Molecular changes were measured at the mRNA and the protein levels. The expression of several invasion-promoting molecules is regulated by prostasin re-expression, mediated by a protein-level down-regulation …


Lim Kinase 1 Modulates Expression Of Matrix Metalloproteinases And Associates With Gamma-Tubulin: Dual Role In Invasion And Mito, Tenekua Tapia Jan 2007

Lim Kinase 1 Modulates Expression Of Matrix Metalloproteinases And Associates With Gamma-Tubulin: Dual Role In Invasion And Mito, Tenekua Tapia

Electronic Theses and Dissertations

LIM kinase 1 (LIMK1) is a unique dual specificity serine/threonine kinase containing two N-terminal LIM domains in tandem, a PDZ domain and a C-terminal catalytic domain. LIMK1 is involved in modulation of actin cytoskeleton through inactivating phosphorylation of the ADF (actin depolymerization factor) family protein cofilin. Recent studies have shown that LIMK1 is upregulated in breast and prostate cancer cells and tissues, promotes metastasis in animals and induces acquisition of an invasive phenotype when ectopically expressed in benign prostate epithelial (BPH) cells. Furthermore, overexpression of LIMK1 was associated with altered sub cellular localization of the membrane type 1 matrix metalloprotease …