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Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad Feb 2024

Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad

Dissertations, Theses, and Capstone Projects

The overexpression of HER2 accounts for 20-30% of breast cancer tumors and not only serves as a marker for poor predictive clinical outcomes but also as a target for treatment. Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutic drugs to provide targeted treatment without toxicity to normal tissue. Most of the ADCs currently in the clinic for cancer chemotherapy are based on complex organic molecules. In contrast, the conjugation of metallodrugs to mAbs has been overlooked when there is enormous potential in this area with the resurgence of metal-based drugs as prospective cancer …


Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi Oct 2023

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi

USF Tampa Graduate Theses and Dissertations

NRF2 is a redox-responsive transcription factor the directs the antioxidant program and several critical metabolic processes. Mutations in NRF2 or its negative regulator KEAP1 occur in up to one third of non-small cell lung cancers (NSCLCs) and are often associated with resistance to therapy and poor outcomes. In the present studies, murine alleles of the Keap1 and Nrf2 mutations found in human NSCLC were developed and I comprehensively investigated their impact on tumor initiation and progression. I observed that chronic Nrf2 stabilization by Keap1 loss-of-function or Nrf2 activating mutation was not sufficient to cause lung tumor initiation, even when p53 …


Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi Oct 2023

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi

USF Tampa Graduate Theses and Dissertations

NRF2 is a redox-responsive transcription factor the directs the antioxidant program and several critical metabolic processes. Mutations in NRF2 or its negative regulator KEAP1 occur in up to one third of non-small cell lung cancers (NSCLCs) and are often associated with resistance to therapy and poor outcomes. In the present studies, murine alleles of the Keap1 and Nrf2 mutations found in human NSCLC were developed and I comprehensively investigated their impact on tumor initiation and progression. I observed that chronic Nrf2 stabilization by Keap1 loss-of-function or Nrf2 activating mutation was not sufficient to cause lung tumor initiation, even when p53 …


Early Stage Or Curable Cancer Diagnoses In Minorities: A Journey Of Survivors, Lora Asberry Jul 2023

Early Stage Or Curable Cancer Diagnoses In Minorities: A Journey Of Survivors, Lora Asberry

Master of Science in Integrative Biology Theses

Patients diagnosed with early-staged or curable forms of cancer experience physical, as well as, mental challenges associated with disease progression and treatment. Previous studies have demonstrated that minorities and underrepresented communities did not receive the same level of care in comparison to their non-minority counterparts. Previous studies have also demonstrated that health disparities among minorities affected their cancer journey. This study addressed: how medical disparities varied between minorities and non-minorities, the overall effects of the cancer diagnoses in minorities compared to non-minorities, whether these perspectives differed in male vs. female participants, and whether there were any possible communication barriers between …


Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed Jun 2023

Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed

Theses and Dissertations

Despite being one of the most effective chemotherapeutic agents developed to date, Anthracyclines are notorious for their cardiotoxicity. Their clinical use is frequently limited both in dosage and in prescription due to the severe cardiac damage they cause. The mechanism of anthracycline-induced cardiotoxicity is not yet fully understood. However, it is hypothesized that interactions with the myocardial membrane play an important role in imparting cardiotoxicity. In this study, we use molecular dynamics simulations and density functional theory calculations to study the anthracycline drug molecules and the interactions that they have with the myocardial membrane. We construct a myocardial membrane model …


Characterization Of Neutrophil Extracellular Traps In Naked Mole-Rats: A Step Towards Cancer Resistance, Thomas Abraham Smith May 2023

Characterization Of Neutrophil Extracellular Traps In Naked Mole-Rats: A Step Towards Cancer Resistance, Thomas Abraham Smith

Undergraduate Honors Capstone Projects

Cancer is the second leading cause of death in the United States, exceeded only by heart disease. One of every five deaths in the United States is due to cancer. A growing area of research involves the analysis of cancer resistant traits in other species to understand their biological mechanisms and eventually make translations to human cancer research and clinical treatment. Because of their remarkable cancer resistance, the naked mole-rat (NMR) is a prime subject for this research, and various studies have already suggested that the immune mechanisms of the NMR might be harnessed for human cancer therapies1-4,7. …


Development Of A Computational Model To Investigate Pathways And The Effects Of Treatment In Fanconi Anemia, Sabrina Kellett May 2023

Development Of A Computational Model To Investigate Pathways And The Effects Of Treatment In Fanconi Anemia, Sabrina Kellett

Biological Sciences Undergraduate Honors Theses

Fanconi Anemia (FA) is a rare type of anemia that is not easily studied and can have very detrimental effects. This disease compromises the bone marrow, resulting in decreased hemopoiesis. Symptoms of FA also include abnormalities in the brain and spinal cord, incorrect formation of the kidneys, abnormal formation of the heart and lungs, and a dramatically increased risk of developing cancer. FA can be caused by various mutations in any of the 22 genes that encode for proteins involved in what is called the FA DNA repair pathway. In healthy individuals, this pathway specifically repairs interstrand cross-links (ICLs) recognized …


Computational Modeling Of The Fanconi Anemia Gene Network And Its Connection To Cancer, Alyssa Warren-Belford May 2023

Computational Modeling Of The Fanconi Anemia Gene Network And Its Connection To Cancer, Alyssa Warren-Belford

Biological Sciences Undergraduate Honors Theses

Fanconi anemia (FA) is a rare genetic condition in which the cell’s DNA repair machinery is dysregulated, significantly increasing the chances of tumorigenesis. Further research is being done in order to improve patient outcomes and incidences of cancer. Our group created a computational model of the FA DNA repair gene network, which removes interstrand crosslinks found in damaged DNA and repairs it so DNA synthesis can continue. Computer simulations show the number of DNA damage indicators decreased as the pathway continued. This was expected as the FA pathway repairs DNA damage. The goal of this project was to provide further …


Transcriptional Silencing Of Cdk18 And Its Role In Lung Carcinogenesis Of Brg1-Mutant Lung Cancers, Loryn M. Phillips Apr 2023

Transcriptional Silencing Of Cdk18 And Its Role In Lung Carcinogenesis Of Brg1-Mutant Lung Cancers, Loryn M. Phillips

Biology ETDs

BRG1 is mutated in 10% of lung cancers, making this mutation clinically relevant. The downstream effects of BRG1 included significantly affecting the cell cycle control and chromosomal replication pathway. CDK18, a cyclin-dependent kinase, was determined to be the gene with significantly decreased expression (p


Movement As Medicine: Dance/Movement Therapy For Individuals With Autism, Parkinson’S Disease, And Cancer, Alessia Zanobini Jan 2023

Movement As Medicine: Dance/Movement Therapy For Individuals With Autism, Parkinson’S Disease, And Cancer, Alessia Zanobini

CMC Senior Theses

Dance/movement therapy (D/MT) is the psychotherapeutic use of expressive, creative movement to support holistic well-being. D/MT views the human being as a single body-mind unit and movement as a manifestation of life experiences. While typically practiced as a mental health intervention, D/MT can be adapted for a variety of populations. This thesis evaluates scientific data for the non-traditional use of D/MT for three conditions: autism, Parkinson’s disease, and cancer. For individuals on the autism spectrum, D/MT can strengthen attunement skills, provide creative communication outlets, and relieve harmful physical manifestations of autism. For individuals with Parkinson’s disease, D/MT can simultaneously ease …


Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess Dec 2022

Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess

Open Access Theses & Dissertations

Anticancer drug discovery is a time and resource-consuming process for which exceedingly reliable and efficient modern approaches are needed. Phenotypic drug screenings can generate highly potent and innovative drug candidates; however, deconvolution of the drugâ??s target often presents significant barriers to drug development. To overcome this hurdle, we have originally combined in vitro and in silico analyses to uncover the molecular mechanism(s) driving the anticancer activity of the uniquely structured small molecule drug candidate, Tpz-1. Our study revealed that Tpz-1 is a multitargeted agent which induces the programmed death of HL-60 acute myeloid leukemia cells primarily through disruption of microtubule …


Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham Aug 2022

Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham

Legacy Theses & Dissertations (2009 - 2024)

The transcription factor, p53, plays a pivotal role in the oversight of many stimulus-dependent pathways. Its ability to respond to a wide variety of cellular stress stimuli by activating a broad range of target genes has led it to be characterized as a stress-dependent transcription factor. Our research focuses on deconvoluting the varied transcriptional response to distinct stress signals in an attempt to define the regulatory strategies leading to gene activation after cell stress. We have found that distinct stress response networks, some of which are p53-independent, are converging at activation of a common set of target genes. Our data …


The Role Of Foxd1 In Clear Cell Renal Cell Carcinoma, Kyle H. Bond May 2022

The Role Of Foxd1 In Clear Cell Renal Cell Carcinoma, Kyle H. Bond

Electronic Theses and Dissertations

Renal cell carcinoma (RCC) is the 8th most common cancer in the United States, with the clear cell variant (ccRCC) being the most prevalent. Over 14,000 people die every year to RCC, with rates continuing to increase with an aging general population. Patients suffering from metastatic RCC (mRCC) have extremely poor prognoses, with a 5-year survival of only 11.2%. Current treatment options include resection of primary lesions, tyrosine kinase inhibition (Sunitinib, Pazopanib), mTOR inhibition (Temsirolimus, Everolimus), and immune checkpoint inhibition (Nivolumab, Atezolizumab). Recent attention has been drawn to inhibition of transcription factors like HIF2α (Belzutifan). There is a need …


Experimental Validation Of Gene Expression Of Mybl1, Mybl2, Ubxn8, And Adrm1 Genes In Triple Negative Breast Cancer Cell Lines, Esther Jensinne Nsende May 2022

Experimental Validation Of Gene Expression Of Mybl1, Mybl2, Ubxn8, And Adrm1 Genes In Triple Negative Breast Cancer Cell Lines, Esther Jensinne Nsende

Theses (2016-Present)

A previous study conducted in our laboratory demonstrated V-Myb Avian Myeloblast Viral Oncogene Homolog Like 1 (MYBL1) gene over-expression in triple negative breast cancer (TNBC) compared to normal, some luminal, and a subpopulation of other TNBC. The MYBL1 gene belongs to the Avian myeloblastosis virus (MYB) family and is classified as proto-oncogene that functions as a strong transcription factor. The MYBL1 gene is related to cancer progression which involves dysregulation of cell cycle signaling, apoptosis and differentiation processes. A primary goal of our laboratory is to further characterize MYBL1 gene expression in TNBC samples. To achieve this goal, we performed …


Host-Pathogen Coevolution Between Tasmanian Devils (Sarcophilus Harrisii) And Devil Facial Tumor Disease, Dylan Garret Gallinson Apr 2022

Host-Pathogen Coevolution Between Tasmanian Devils (Sarcophilus Harrisii) And Devil Facial Tumor Disease, Dylan Garret Gallinson

USF Tampa Graduate Theses and Dissertations

Coevolution is a driving force of rapid evolution, yet the complexity of coevolutionary interactions has made it difficult to characterize the genomic basis of traits mediating such relationships. Coevolutionary dynamics are especially important in host-pathogen systems where the host and pathogen must constantly adapt to one another. The Tasmanian devil and its species-specific transmissible cancer, devil facial tumor disease (DFTD), provide the rare opportunity to study host-pathogen coevolution in a complex natural system. Extensive spatiotemporal devil sampling, high linkage disequilibrium in devils, and a large selective pressure imposed by DFTD facilitate a system tractable for study. Here, we characterized devil …


Analysis Of Invasion Proteins Mmp2, Mmp9, Adam12, And Adam17 In Glioblastoma U87mg Cells Treated With Anti-Cancer Compound 3,4-Dimethoxybenzaldehyde, Andras Muranyi Apr 2022

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.


Toxicity Of Indoor Dust-Derived Trace Elements And Organic Contaminants Impact On Normal Human Colon Epithelial Cells, Noura Abdulrahman Dec 2021

Toxicity Of Indoor Dust-Derived Trace Elements And Organic Contaminants Impact On Normal Human Colon Epithelial Cells, Noura Abdulrahman

Theses (2016-Present)

Indoor dust stands out as a burgeoning challenge in society due to its implication on people’s health. Exposure to toxic dust particles occurs in different ways that include inhalation, ingestion, and dermal contact. In the hindsight, many people spend most of their time indoors exposing themselves to high levels of dust. Notably, different groups of individuals present varied risk levels to the toxicity of particles with vulnerable persons being susceptible to adverse effects of these contaminants. This includes the elderly, children, and immunocompromised individuals. The study examines the impacts of two variables that are trace elements (TMD) and organic contaminants …


In Vitro Investigation Of Tumor Selective Piperidones As Therapeutic Agents Against Leukemia Cancer Cells, Lisett Contreras Dec 2021

In Vitro Investigation Of Tumor Selective Piperidones As Therapeutic Agents Against Leukemia Cancer Cells, Lisett Contreras

Open Access Theses & Dissertations

Cancer is a continuous global health issue. It is the second leading cause of death behind heart disease. Disparities across the emergence of cancer and resulting fatalities raise the importance of researching the disease. Treatments are available for certain types of cancers. However, these are typically accompanied by residual problems including side effects and the possibility for relapse. Some treatments attack all cells, leading to unwarranted side effects that make the possibility of living a comfortable life nearly impossible. Other treatments are specific to certain genetic alterations, making them only useful for a small percentage of patients. Not one treatment …


The Investigations Of Nps Modulated Immunity And Immunometabolism, Brittney Leigh Ruedlinger Dec 2021

The Investigations Of Nps Modulated Immunity And Immunometabolism, Brittney Leigh Ruedlinger

Biomedical Sciences Theses & Dissertations

Cancers remain in the top noncommunicable diseases responsible for premature mortality. The heterogeneity among cancers and within tumors makes treating them ever more challenging. Our misfortune for developing cures is mocked by cancer, with the lowest probability of success (PoS) through clinical trials and FDA approval. At the basic level, there are generally two broad gaps impeding cancer eradication: the unidentified shared mechanism(s) exploited by all cancers and the therapeutic approach to intervene. Nanosecond pulse stimulation (NPS) offers a unique approach since its broad impacts intersect those often hijacked by oncogenesis. Metabolic pathways, known for dysfunctions among cancers, share a …


Understanding The Mechanistic Roles Of Integrin Alpha 6 In Tumor Development Using A Humanized Zebrafish (Danio Rerio) Model System, Ashley B. Williams Aug 2021

Understanding The Mechanistic Roles Of Integrin Alpha 6 In Tumor Development Using A Humanized Zebrafish (Danio Rerio) Model System, Ashley B. Williams

Honors College Theses

Present day cancer incidence and mortality rates indicate the need for effective cancer diagnostic tools and targeted cancer therapeutic strategies. Recent studies have focused on the biological pathways of cells and tumor microenvironments to identify putative biomarkers and potential drug targets as diagnostic and therapeutic tools. Human integrins, adhesion receptors, have become the focal points in these studies, specifically Integrin Alpha 6 (ITGA6) which has been implicated in major tumor progression roles: metastasis and angiogenesis. These characteristics make ITGA6 an excellent candidate for potential drug or diagnostic target, however, the mechanism by which ITGA6 facilitates tumor progression remains unclear. Cell …


Examination Of Methylation Status And Occupancy Of Dna Methylation Modifying Proteins On Regulatory Regions Of The Dax-1 Gene, Caroline P. Riedstra Aug 2021

Examination Of Methylation Status And Occupancy Of Dna Methylation Modifying Proteins On Regulatory Regions Of The Dax-1 Gene, Caroline P. Riedstra

Master's Theses

Epigenetic modifications influence gene expression and thereby play a pivotal role in development and disease. Misregulation and mutations in the DAX-1 gene, or Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X chromosome, gene 1, have been implicated in Adrenal Hypoplasia Congenita (AHC) and Dosage Sensitive Sex Reversal (DSS). The orphan nuclear hormone receptor DAX-1 is expressed predominantly in tissues such as the testes, ovaries, breast, adrenal cortex, and lung. Critically, DAX-1 may serve as an indicator of aberrant growth in these tissues. Here we hypothesize that DAX-1 is epigenetically regulated, specifically in cancer cells, thereby reducing its …


Unveiling Global Roles Of G-Quadruplexes And G4-22 In Human Genetics, Ruth Barros De Paula Aug 2021

Unveiling Global Roles Of G-Quadruplexes And G4-22 In Human Genetics, Ruth Barros De Paula

Dissertations & Theses (Open Access)

G-quadruplexes are non-B DNA structures formed by four or more runs of repeated guanines that confer unique features to living organism’s genomes. These sequences are enriched in regulatory regions, such as promoters and 5’ UTRs, and have distinct regulatory roles in both health and disease states. Even though previous studies showed the impact of G4 in gene expression, none of them summarized the location-specific effect of G4. Also, there is no broad understanding about the most common G4 repeat in the human genome, named here as G4-22, and how it links to the evolution of mammals and their biology. In …


An Assessment Of Inp/Zns As Potential Anti-Cancer Therapy: Quantum Dot Treatment Induces Stress On Hela Cells, Victoria Grace Davenport Aug 2021

An Assessment Of Inp/Zns As Potential Anti-Cancer Therapy: Quantum Dot Treatment Induces Stress On Hela Cells, Victoria Grace Davenport

MSU Graduate Theses

Indium Phosphide/Zinc Sulfide (InP/ZnS) quantum dots (QDs) are an emerging option in QD technologies for uses of fluorescent imaging as well as targeted drug and anti-cancer therapies based on their customizable properties. In this study we explored effects of InP/ZnS when treated with HeLa cervical cancer cells. We employed XTT viability assays, reactive oxygen species (ROS) analysis, and apoptosis analysis to better understand cytotoxicity extents at different concentrations of InP/ZnS. In addition, we compared the transcriptome profile from the QDtreated HeLa cells with that of untreated HeLa cells to identify changes to the transcriptome in response to the QD. Intracellular …


A Comparative Study On Cannabidiol In Melanoma Migration And Invasion: Charlotte's Web Vs. Purified Cbd, 2020–2021, Ruby Thamert Jul 2021

A Comparative Study On Cannabidiol In Melanoma Migration And Invasion: Charlotte's Web Vs. Purified Cbd, 2020–2021, Ruby Thamert

Theses

Over the last decade, much attention has been focused on compounds from Cannabis sativa in treating a variety of diseases including cancer. This study examines the abilities of two different cannabidiol oils to decrease the migration and invasion of melanoma cells in vitro. Skin cancers are the most common cancers in the world. While malignant melanoma is the least common type of skin cancer, it is the deadliest. Patients diagnosed with stage IV disease have only a 15-20% five-year survival rate even with aggressive multimodal treatment, demonstrating the need for additional therapeutic options. Because melanoma is often fatal when …


Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde Jun 2021

Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde

USF Tampa Graduate Theses and Dissertations

Targeted therapies have emerged as potent treatments that lead to the remission of many tumors. However, they rarely cure cancers in advanced, metastatic settings. This is due to the evolution of resistance, which in turn can be ascribed to the survival of small subpopulations of tolerant and/or resistant cells. Here we investigated the evolution of resistance to EML4-ALK inhibitors in non-small cell lung cancer (NSCLC) and demonstrated that resistance evolves gradually, from unique pre-treatment sub-populations, as multiple resistance mechanisms accumulate in a Darwinian fashion. Despite accumulating multiple changes, cells evolved, in parallel, toward similar inhibitor specific phenotypes. Evolving cells have …


A Forward Genetic Screen To Identify Human Genes Of Interest And Their Roles In Ovarian Cancer, Susan A. Ihejirika May 2021

A Forward Genetic Screen To Identify Human Genes Of Interest And Their Roles In Ovarian Cancer, Susan A. Ihejirika

Honors College Theses

Drosophila melanogaster, fruit flies, are very important for modeling and studying human diseases. This study identifies human genes of interest and their contributions to epithelial ovarian carcinogenesis and progression as well as the roles orthologs of these genes play in Drosophila melanogaster. This is important because ovarian cancer is the most common cause of death among the gynecological cancers. This identification of genes was carried out using a forward genetic screen employing the widely used GMR-Gal4 driver/UAS-transgene system. The GMR-Gal4 driver is commonly utilized to express transgenes in the developing eye of the fruit fly. Transgenes that are expressed using …


Evaluation Of The Cytotoxyc Effects Of Lmdf5-7 On A Human T-Cell Leukemia Cell Line, Andrea F. Ibarra Chacon May 2021

Evaluation Of The Cytotoxyc Effects Of Lmdf5-7 On A Human T-Cell Leukemia Cell Line, Andrea F. Ibarra Chacon

Open Access Theses & Dissertations

According to World Health Organization (WHO), cancer is the second leading cause of death worldwide, with 9.6 million deaths in 2018 . In the United States, an estimated 434,982 people were living with cancer during 2017 . Leukemia is the most common blood cancer in children from birth to 14 years old . In particular, Hispanic children in the United States experience a higher incidence rate of leukemia . Therefore, the discovery of novel cancer therapies is necessary to help those affected survive the disease. A new compound, LMDF5-7 was investigated and found to have anticancer properties that can help …


Investigating Bmp7 Expression In Glioblastoma Multiforme, Yajaira Janett Macias May 2021

Investigating Bmp7 Expression In Glioblastoma Multiforme, Yajaira Janett Macias

Theses and Dissertations

The PI3K/AKT/mTOR pathway regulates important cell processes such as growth, survival, motility, inflammation, proliferation, and apoptosis. In Glioblastoma multiforme (GBM) the PI3K/AKT/mTOR pathway is aberrant as it is almost always active. This results in the deregulation of downstream molecules and ultimately leads to cancer progression and maintenance in GBM tumors. In this study, we used RNA-sequencing to identify differentially expressed genes (DEGs) in U87MG GBM cells treated with NVP-BEZ235, a dual inhibitory drug targeting PI3K and mTOR. A total of 7,803 differentially expressed genes were identified via RNA-seq. GEPIA2 online tool was used to assess differential gene expression …


Examining The Mechanistic Roles Of Integrin Alpha-6 In Cancer Metastasis., Chase T. Clark Mar 2021

Examining The Mechanistic Roles Of Integrin Alpha-6 In Cancer Metastasis., Chase T. Clark

Honors College Theses

Metastasis- the spread of cancer cells from the primary tumor to the surrounding tissues- is responsible for 90% of cancer deaths. Integrin alpha-6 (ITGA6) is a specific transmembrane cell surface protein that functions in cell surface adhesion and signaling. ITGA6 is upregulated in many types of cancers and promotes the migration and invasion of cancer cells to surrounding tissues. It is my objective to determine the mechanism through which ITGA6 facilitates the migration of cancer cells through the extracellular matrix (ECM). These experiments helped to establish the role of ITGA6 in tumor development and provide focus for possible chemotherapeutic treatment. …


Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant Jan 2021

Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant

Honors Theses

Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …