Cancer Biology Commons^™

Synthesis, Characterization, And Biological Activity Of Ni(Ii) And Co(Iii) Thiosemicarbazone Complexes As Potential Anticancer Agents, Jack Martin

Pitzer Senior Theses

The mechanics by which Reactive Oxygen Species work is an area of great interest given ROS’s wide range of biological applications. From cell signaling and mitochondrial regulation to pathogenesis and tumor cell death, varying concentrations of ROS in a system can lead to a whole host of positive and negative effects. In a similar vein, thiosemicarbazones are known to be equally useful for their myriad of antibacterial, antifungal, antiviral, and antitumoral effects. They have been at the core of the pharmaceutical world or the better part of the last century. The purpose of this work is to synthesize, characterize and …

Characterization Of The Overexpression Of Reca Homologs Rad51 And Dmc1 In Tetrahymena Thermophila, Jianna M. Cox

Graduate Theses/Dissertations

RecA homologs, Dmc1 and Rad51, work to repair DNA double-strand breaks (DSBs) within the cell through the recombination of homologous sections of DNA. Dmc1 works to repair programmed DSBs through meiotic recombination, while Rad51 functions to repair both meiotic and non-meiotic DSBs, the latter repaired through the process of homologous recombination repair (HHR). Chemotherapeutics, exogenous agents, work to form DSBs in cancer cells, attempting to inhibit the cell’s growth. A hyper recombinant phenotype is often seen in cancer cells due to the overexpression of RAD51, leading to drug resistance, the persistence of cancers, and an overall poor patient outcome. …

Characterization Of Cancer Cell Migration Through Brain Vascular Endothelium Model, Malak Taysser Al-Noubani

2025 Fall Honors Capstones Projects - Archive

One of the hallmarks of cancer is increased vessel growth to feed the tumor’s rapid expansion. The newly formed blood vessels are immature and often leaky due to structural and functional abnormalities. This leads to ineffective anti-cancer drug delivery and provides tumor cells with additional opportunities to metastasize. We propose to develop an in vitro vascular endothelium model and introduce aggressive triple-negative breast cancer (TNBC) cells to mimic the tumor environment, utilizing a Transwell migration assay. The impact of TNBC cells on vessel permeability will be assessed by staining for tight junction proteins, and the migratory capabilities of TNBC cells …

Determination Of Structural Factors Contributing To Protection Of Zinc Fingers In Estrogen Receptor Α Through Molecular Dynamic Simulations, Patricia B. Lutz, Wesley R. Coombs, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

The ERα transcription factor that induces tumor growth is a potential target for breast cancer treatment. Each monomer of the ERα DNA-binding domain (ERαDBD) homodimer has two conserved (Cys)₄-type zinc fingers, ZF1 (N-terminal) and ZF2 (C-terminal). Electrophilic agents release Zn²⁺ by oxidizing the coordinating Cys of the more labile ZF2 to inhibit dimerization and DNA binding. Microsecond-length molecular dynamics (MD) simulations show that greater flexibility of ZF2 in the ERαDBD monomer leaves its Cys more solvent accessible and less shielded from electrophilic attack by sulfur-centered hydrogen bonds than ZF1 which is buried in the protein. In the …

Targeting Stat3 In Tnbc Drug Resistance, Madison A. Henry

Honors Theses and Capstones

Triple negative breast cancer (TNBC) is one of the most aggressive types of breast cancer and lacks the three commonly targeted receptors in breast cancer treatments. As a result of a lack of targetable receptors, the standard of care remains to be harsh chemotherapy treatments that often are successful in early TNBC cases but often result in relapsed TNBC. In addition to high rates of recurrence, TNBC is known for its aggressive metastasis and chemoresistance. Within TNBC, the transcription factor Signal Transducer and Activator of Transcription 3 (STAT3) is constitutively active and increases proliferation, and metastasis, and plays a role …

Cardiac Injury Regulates Neuroinflammation Through Extracellular Vesicle–Mediated Heart-Brain Crosstalk, Qingxuan Li, Ramzi H. Hamdalla, Neha Dhyani, Lijun Sun, Lie Gao, Tara L. Rudebush, Irving H. Zucker, Changhai Tian

Toxicology and Cancer Biology Faculty Publications

Cognitive impairment is common in heart failure patients, contributing to morbidity and mortality. This impairment may be linked to neuroinflammation in heart failure. However, the primacy of the heart-brain axis remains to be completely understood. Here, we elucidate the potential effects of myocardial injury on pathways and inflammatory mediators responsible for cognitive impairment using a rodent myocardial injury model. The results demonstrate direct extracellular vesicle (EV)-mediated heart-brain crosstalk and the glial uptake of cardiac EVs. In addition, brain inflammation was also elicited following myocardial injury. Moreover, cardiac EVs promote brain microglial cell activation in vitro, potentially mediated by EV-enriched micro-RNAs …

Physical Ablative Methods And Cancer Cell Death: Implications For Immunity And Therapies, Alessandra Rossi, Claudia Muratori

Bioelectrics Publications

Surgery has traditionally been a cornerstone in cancer treatment, yet its feasibility can be limited by factors such as tumor location and patient health conditions. When surgery is not viable, thermal and pulsed electric field (PEF)-based ablation technologies offer valuable alternatives. Emerging evidence suggests that these approaches not only target tumors effectively but also stimulate antitumor immune responses. In this review, we begin by examining the distinctive features of hyperthermic treatments (radiofrequency and microwave ablation), cryoablation, and PEF-technologies. Subsequently, we discuss the mechanisms of cell death, stress responses, and release of danger signals triggered by these diverse ablation technologies. Finally, …

Characterization Of Actin Capping Protein Beta Isoform Specific Dynamics In Metastatic Cells, Etinosa Osamudiamen

All Graduate Theses, Dissertations, and Other Capstone Projects

To gain insight into the mechanism of cancer progression, we examined the isoform-specific roles of actin capping protein (CPβ1 and CPβ2) related to actin cytoskeletal dynamics and metastatic progression in human uterine epithelial cells (HeLa). We employed qPCR to determine the relative expression levels of CPβ1 and CPβ2 in actively growing HeLa cells. Our findings confirmed that CPβ1 and CPβ2 are differentially expressed, with CPβ2 being the predominant isoform, two-fold higher, consistent with its expression in other non-muscle tissues. To extend our expression studies, the localization and spatial distribution of the isoforms were visualized via immunolocalization studies using isoform-specific monoclonal …

Gain-Of-Function Tp53 Mutations Induce Non-Canonical Nf-Κb Transcriptional Targets To Promote Tumor Development, Kelsey A. Yutan

Scripps Senior Theses

Background: Gain-of-function TP53 mutations have previously been shown to induce chromosomal instability (CIN) in cancer cells, triggering the cGAS-STING innate immune response and subsequently activating the non-canonical NF-κB (NC-NF-κB) signaling pathway. This signaling cascade promotes cancer cell metastasis and an immunosuppressive tumor microenvironment (TME), significantly impacting tumor development and progression. However, the precise downstream mechanisms by which the mutp53-CIN-cGAS-STING-NC-NF-κB signaling pathway facilitates tumor development and progression remain poorly understood. Here, our objective was to identify direct downstream targets of mutp53-CIN-cGAS-STING-induced NC-NF-κB signaling that potentially impact the TME to promote the development and progression of oral squamous cell carcinoma.

Methods …

Exploring The Role Of Transcription Factor Nrf1 In Autophagy And Inhibiting The Nrf1 Bounce-Back Response, Madison A. Ward

Theses and Dissertations

Cells exposed to proteotoxic stress invoke adaptive responses aimed at restoring proteostasis. Our previous studies have established a firm role for the transcription factor Nuclear factor-erythroid derived-2-related factor-1 (Nrf1) in responding to proteotoxic stress elicited by inhibition of cellular proteasome. Following proteasome inhibition, Nrf1 mediates the synthesis of new proteasomes, thus enabling cells to mitigate proteotoxic stress. Here, we report that under similar circumstances, multiple components of the autophagy-lysosomal pathway (ALP) were transcriptionally upregulated in an Nrf1-dependent fashion, thus providing the cells with an additional route to cope with proteasome insufficiency. In response to proteasome inhibitors, Nrf1-deficient cells exhibited profound …

Effects Of Round-Up On The Environment, Sandra J. Marcu

Journal of Earth and Life Science

Many people around the world have used and still currently use Roundup but are unaware of the effects it has on the environment. Roundup is a spray on application weedkiller that is widely used around the world today both residentially and commercially. It enables its user to grow a garden or a field of crops with a no-tilling approach to eliminate weeds. It is a well-known and popular choice for killing weeds that has been around since the mid 1970’s (Oca, 2017). John Franz, a Monsanto scientist discovered that glyphosate (main ingredient in Roundup) was an herbicide or weedkiller, and …

Characterizing A Rad23 Dependent Ultraviolet Radiation Resistance In Tetrahymena Thermophila, Emma June Liimatta

Graduate Theses/Dissertations

In 2020, 10 million deaths were attributed to cancer, with multidrug resistance being responsible for over 90% of deaths in cancer patients receiving treatment. This study utilized the model organism Tetrahymena thermophila to study how cells become resistant to Ultraviolet Radiation (UV) radiation, a process similar to multidrug resistance, specifically focusing on the nucleotide excision repair and ubiquitin shuttle protein Rad23. The National Cancer Institute documented 30-60% of cancers tested had a mutation in RAD23. Knockdown of RAD23 in Tetrahymena thermophila demonstrated a UV resistance phenotype with decreased nucleotide excision repair and differential expression of proteins active within caspase-independent …

Comprehensive Investigation Of Proteoglycan Gene Expression In Breast Cancer: Discovery Of A Unique Proteoglycan Gene Signature Linked To The Malignant Phenotype, Simone Buraschi, Gabriel Pascal, Federico Liberatore, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Solid tumors present a formidable challenge in oncology, necessitating innovative approaches to improve therapeutic outcomes. Proteoglycans, multifaceted molecules within the tumor microenvironment, have garnered attention due to their diverse roles in cancer progression. Their unique ability to interact with specific membrane receptors, growth factors, and cytokines provides a promising avenue for the development of recombinant proteoglycan-based therapies that could enhance the precision and efficacy of cancer treatment. In this study, we performed a comprehensive analysis of the proteoglycan gene landscape in human breast carcinomas. Leveraging the available wealth of genomic and clinical data regarding gene expression in breast carcinoma and …

Impact Of Tgf-Β And Twist1 On Motility And Proliferation In Estradiol-Treated Mcf-7 Tamr Cells In-Vitro, Thomas L. Scott Iii

Honors Undergraduate Theses

Breast cancer is a highly malignant cancer and is known to be grouped into three main types: adenocarcinoma, invasive ductal carcinoma (IDC) and ductal carcinoma. Breast cancer commonly arises as adenocarcinoma, located in the milk ducts, and becomes IDC when it spreads into the surrounding tissue from the influence of cytokines and hormones. This study outlines the rate of proliferation and motility of a type of adenocarcinoma, MCF-7-TamR, to become invasive ductal carcinoma when Twist1 is downregulated and exposed to TGF- and estradiol (E2) in-vitro. We hypothesize that the downregulation of Twist1 will reduce cell adhesion and cytoskeleton proteins …

Examining The Effect Of A High Fat Diet On The Expression Of Adipokines In A Murine Model Of Barrett's Esophagus, Saagar A. Shah

Honors Undergraduate Theses

Chronic acid reflux results in injury to the esophagus and the development of Barrett’s Esophagus (BE). BE elevates the lifetime risk for a patient to develop Esophageal Adenocarcinoma (EAC). Clinically, one of the main risk factors for BE and EAC is obesity, which alters the secretion of inflammatory cytokines by adipocytes, also referred to as adipokines. Conflicting reports have been made to the expression of adipokines and their receptors in the progression to esophageal cancer. Utilizing an inflammation-based mouse model for BE, we hypothesize that alterations in the expression of adipokines and their receptors favor an inflammatory environment associated with …

Targeting The Achilles’ Heel Of Lung Cancer Induced By Oncogenic P53, Brandon G. Velasco

Theses and Dissertations

Mutations of the tumor suppressor gene, TP53, are the most prevalent oncogenic mutations in lung cancer, occurring in up to 70% of human non-small cell lung cancer (NSCLC). The majority of mutations in p53 are missense mutations that cause not only a loss of tumor suppressor function, but also gain of oncogenic functions, like tumorigenicity, immune suppression, and chemoresistance. Previous studies have shown that the depletion of gain-of-function (GOF) p53 or disruption of its ability to transactivate the expression of genes related to oncogenesis eliminates its tumorigenic properties indicating a dependency of human lung cancer cells expressing GOF p53 …

Intercellular Mitochondrial Transfer Contributes To Microenvironmental Redirection Of Cancer Cell Fate, Julie Sofie Bjerring, Yara Khodour, Emilee Anne Peterson, Patrick Christian Sachs, Robert David Bruno

School of Medical Diagnostics & Translational Sciences Publications

The mammary microenvironment has been shown to suppress tumor progression by redirecting cancer cells to adopt a normal mammary epithelial progenitor fate in vivo. However, the mechanism(s) by which this alteration occurs has yet to be defined. Here, we test the hypothesis that mitochondrial transfer from normal mammary epithelial cells to breast cancer cells plays a role in this redirection process. We evaluate mitochondrial transfer in 2D and 3D organoids using our unique 3D bioprinting system to produce chimeric organoids containing normal and cancer cells. We demonstrate that breast cancer tumoroid growth is hindered following interaction with mammary epithelial cells …

Analysis Of Differential Gene Expression In Androgen-Independent Clones Derived From The Mycap Pca Cell Line, Jessie L. Tignor, Melanie Sinanian, Richard Inho Joh, David Gewirtz, Jason Reed

UROP Posters

Androgen deprivation therapy (ADT) is a primary treatment strategy for prostate cancer (PCa), yet many tumors eventually develop androgen independence, leading to treatment resistance. To investigate the molecular changes underlying this transition, we analyzed differential gene expression in four androgen-independent (AI) clones derived from the Myc-CaP prostate cancer cell line using RNA sequencing. Gene expression profiles were compared to the parental Myc-CaP line, and differentially expressed genes (DEGs) were identified using DESeq2 and edgeR. The AI clones exhibited significant downregulation of senescence-associated genes, including Ezh2 and lamin B1, suggesting a loss of senescence-related chromatin repression. Additionally, upregulation of Wnt pathway …

The Role Of Tgf-Beta Superfamily Members In Immune Homeostasis And Disease, Natalie Eva Nieuwenhuizen, Ioannis Eleftherianos, Piotr Jan Kraj, Maria Semitekolou

Biological Sciences Faculty Publications

[Introduction] The Transforming Growth Factor beta (TGF-beta) superfamily, encompassing molecules such as TGFs, activins, Bone Morphogenetic Proteins (BMPs), Growth/Differentiation Factor (GDFs) and Nodals, represents the largest family of growth and differentiation factors, playing crucial roles in developmental and physiological processes across animal species (1). These molecules are integral to tissue homeostasis and cell fate determination. Among them, TGF-beta is particularly noted for its regulatory influence on immune responses and tissue fibrosis (2, 3). Recent research has expanded our understanding of the immune functions of other superfamily members, including activin A and BMPs (4). These molecules signal through receptor complexes composed …

Repositioning Antimalarial Drugs As Anticancer Agents: Focus On Tafenoquine, Chris Barton

Funded Scholarship

Due to the expensive and lengthy process of drug design and approval, drug repurposing (or repositioning) has become another option for identifying preexisting molecules that may be used for alternative purposes. Recently, some antimalarial compounds have been shown to display efficacy against cancer cell proliferation. In this study, we provide evidence to suggest that multiple preexisting antimalarial drugs can reduce the viability of human cancer cells in culture. Furthermore, we provide the first evidence that one antimalarial, Tafenoquine (LD50 = 9.6 μM in HCT116 cells), is capable of decreasing viability with an efficacy comparable to Etoposide (LD50 = 15.2 μM …