Cancer Biology Commons^™

The Effect Of Epigallocatechin Gallate (Egcg) And Alpha L-Mangostin On Tp53, Bax, And Vim Gene Expression And Apoptosis In Ewing Sarcoma Cells, Victoria Valdez, Terry Jo Shackleford

Cell and Molecular Methods

Ewing Sarcoma (ES) is a malignant pediatric bone tumor driven by chromosomal translocations and fusion oncogenes with limited targeted treatment options. This study investigated the chemopreventive potential of two natural compounds, Epigallocatechin Gallate (EGCG) found in green tea, and Alpha L-Mangostin from mangosteen, on apoptosis and gene expression in ES cells. We hypothesized that EGCG and Alpha L-Mangostin treatment would induce apoptosis and downregulate cancer-promoting genes. To test this, we performed tissue culture, IC50 assays, caspase-based apoptosis detection, RNA purification, cDNA synthesis, and qRT-PCR on ES cell lines treated with a high and low concentration of the two compounds. Our …

Identification Of Methylation Patterns, Associated Dna Methylating Proteins, And Methyltransferase Inhibitors On The Promoter Regions Of Dax-1, Brandon Tyler Toy

Master's Theses

The DAX-1 gene (Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X chromosome, gene 1) encodes for an orphan nuclear hormone receptor and its mutation is implicated in multiple diseases including congenital adrenal hypoplasia, adrenal cancer, and breast cancer. Previous research has linked DAX-1 downregulation to tumor initiation in breast tissue, suggesting the gene acts as a tumor suppressor with respect to breast cancer. Additional studies completed by the Tzagarakis-Foster laboratory have shown that methylation of the DAX-1 promoter region is heavily influential in breast cancer development, with release of epigenetic repression resulting in slowing of cellular proliferation …

Early Hematopoietic Differentiation Of An Inducible Pluripotent Stem Cell Model Of Infant Lymphoblastic Leukemia, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Priyanka Kumar, Jay L. Vivian, John M. Perry

Research Days

This abstract describes our work regarding the differentiation of human inducible pluripotent stem cells into hematopoietic stem and progenitor cells as the groundwork for the development of a genomics driven inducible pluripotent stem cell model of KMT2A rearranged infant acute lymphoblastic leukemia.

Minimal Anti-Cancer Effects Of Mushroom-Derived Compounds Hispidin And Chaga Extract On Ewing Sarcoma Cells, Jordan Cosgrove, Fiona Coulbourne, Iris Reyna, Giselle Serna-Flores, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is a rare and aggressive cancer of adolescents and young adults driven by the EWSR1–FLI1 gene fusion. Standard treatments include chemotherapy, surgery, and radiation, though survival rates remain low. Natural compounds such as hispidin, derived from fungi, and Chaga mushroom extract have shown potential anti-cancer effects by disrupting cell cycle progression and promoting apoptosis in other cancer models. In this study, we tested the effects of hispidin and Chaga extract on Ewing sarcoma cells to evaluate their ability to suppress cell growth and identify potential therapeutic benefits.

The Effects Of Panobinostat On Cellular Signaling Pathways And How It Relates To Antitumor Activities In Ewing Sarcoma Cancer Cells, Crystal Valenzuela, Andrew Martini, Hannah Navarro, Mario Flores, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is a rare and aggressive cancer that primarily affects the bones and surrounding soft tissues, most commonly in children and young adults. Although the exact etiology remains unclear, a well-documented cause involves a chromosomal translocation resulting in the fusion of the EWSR1 and FLI1 genes. This fusion produces abnormal proteins that disrupt normal gene expression, cell signaling, and RNA processing, contributing to tumorigenesis. Prognosis varies significantly depending on the extent of metastasis, with 5-year survival rates ranging from 82% in localized cases to 39% in metastatic cases. Standard treatments include chemotherapy typically involving vincristine, doxorubicin, etoposide, and cyclophosphamide—surgical …

The Effects Of Hispidin And Eribulin Mesylate On Cell Proliferation Of Ewing Sarcoma Cell Lines, Elena Mares, Angelina Juarrita, Sierra Munoz, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is a type of cancer that targets the cells within bones and soft tissue and is most prevalent in younger populations. It is important to look at this specific cancer because there is no cure yet, and the risks increase, even after a patient has completed their treatment. We hypothesize that if we treat Ewing sarcoma cell lines with natural compounds, specifically Hispidin and Eribulin Mesylate, then the cell lines will decrease in cell viability and there will be an increase in apoptosis of the cancerous cell lines. We performed a series of experiments, which included IC50 analysis, …

Neurodevelopmental And Environmental Mechanisms Of Invasion, Proliferation, And Tumor Cell Fate Specification In Glioblastoma, Bianca Lynn Myers

Biomedical Sciences ETDs

Glioblastomas (GBMs) are the most aggressive primary brain tumors, and despite over 50 years of research efforts, the median survival remains at 14 months post-diagnosis. The current standard of care consists of maximal surgical resection radiotherapy with concurrent chemotherapy using temozolomide. However, the highly proliferative and invasive nature of GBM cells renders total resection nearly impossible as tumor cells invade the surrounding healthy tissue. The molecular and environmental drivers of these tumorigenic phenotypes are largely unknown. Here, we demonstrate that the neurodevelopmental transcription factor ASCL1 enhances tumor cell proliferation and invasion while activating the expression of a neural stem cell …

Cholestasis And Fluid Flow Are Biomechanic Regulators Of Cholangiocarcinoma Progression, Andrew Oleksijew

Theses & Dissertations

Cholestasis, altered or absent bile flow, is associated with poor survival in patients with cholangiocarcinoma, an aggressive cancer of the biliary epithelium. Changes in bile flow often result in stricture or obstruction. Experimental cholestasis promoted tumor growth and progression. However, studies are needed that directly assess the mechanical interaction between bile flow, or bile shear stress, and cholangiocarcinoma signaling. We hypothesized that cholestasis and absent bile shear stress activated cancer signaling and increased aggressive cellular behaviors such as proliferation and migration. Fluid shear stress approximating bile flow was applied by orbital culture plate method and compared to identical static culture …

Validating The Ability Of Iag933 To Block The Interaction Of Yap1 And Tead In Ovarian Cancer Cells, Alex Sage

Theses & Dissertations

Ovarian cancer is the most common and deadliest gynecologic malignancy. Approximately 40% of ovarian cancer patients exhibit chemoresistance after receiving initial treatment in the form of neoadjuvant chemotherapy or interval debulking surgery, of which YAP1 (Yes-associated protein 1) has been implicated in enhancing the resistance of ovarian cancer to Cisplatin and Taxol.^1,2. This highlights the need to develop new therapeutic strategies that target the Hippo pathway to overcome resistance to traditional therapies.

YAP1 is a protein that acts as a transcription coregulator, promoting the transcription of genes involved in cellular proliferation and suppressing apoptotic genes. It is a …

Novel Combination Therapies For Estrogen Receptor-Positive Breast Cancer Driven By Rational Molecular Mechanisms, Anneka Lila Johnson

Dartmouth College Ph.D Dissertations

Breast cancer (BC) is the most common non-keratinocyte cancer diagnosed in women in the United States with approximately 300,000 new cases diagnosed each year. Despite a myriad of treatment options, BC remains the second-most deadly cancer. Estrogen receptor-positive (ER+) BC comprises 60-70% of BC diagnoses and is treated with endocrine therapies that limit ER signaling. Despite endocrine therapy options, ~1/3 of patients experience recurrence within 10-20 years of diagnosis. Novel therapeutic strategies are required to limit BC recurrence-related morbidity and mortality.

Radiotherapy is used as an adjuvant treatment for ER+ BC patients prior to the use of endocrine therapy. Radiation …

Unpaired Virtual Histological Staining Of Tissue From Autofluorescence Using Regularized Cycle-Consistent Adversarial Networks, Zhesi Wen

Theses and Dissertations

We present a regularized CycleGAN with a Dense Residual U-Net to virtually stain autofluorescence images of tissue into H&E-like images. Our method outperforms standard architectures, reduces artifacts, and achieves superior FID scores, enabling efficient, label-free, and accurate digital pathology for unpaired datasets using multi-channel fluorescence inputs.

Identifying Novel Molecular Targets To Induce Ferroptosis In Drug-Tolerant Cancer Cells Through Computational Modeling, Haris J. Rana

Biological Sciences Undergraduate Honors Theses

Ferroptosis is an iron-dependent, reactive oxygen species (ROS)-driven form of regulated cell death in which the cell membrane is degraded by lipid peroxidation. It is regulated by multiple enzymes, such as glutathione peroxidase 4 (GPX4), which prevents membrane degradation by reducing lipid peroxides and protecting cells from oxidative damage. When inhibitors like RSL3 target GPX4, lipid peroxides build up, and toxic ROS compromises membrane integrity. Traditional anticancer treatments, such as most chemotherapies, aim to eliminate tumor cells by damaging DNA and triggering apoptosis. However, resistance to apoptosis is a “hallmark of cancer,” often resulting in treatment failure. As a distinct …

Differential Regulation Of The Prkacaa Promoter In Zebrafish Melanoma Cell Lines, Maria Fiuk

Theses, Dissertations and Culminating Projects

The Inducible cAMP Early Repressor (ICER) comprises a group of isoforms that function as transcription factors within the cyclic AMP (cAMP) signaling pathway. These isoforms are encoded by the cAMP Response Element Modulator (CREM) gene. The cAMP signaling pathway and its associated transcriptional regulators have been implicated in the development of resistance to BRAF/MEK-targeted therapies in melanoma. Recent findings from our laboratory demonstrated that transgenic ICER expression in a zebrafish melanoma model promotes the formation of aggressive melanomas. Cell lines were established from tumors expressing ICER, as well as from control tumors expressing Green Fluorescent Protein (GFP). To begin characterizing …

Examining The Molecular Mechanisms Of Glucagon-Like Peptide-1 Receptor Agonists In Cancer Cell Biology, Oliver G. Sabet

Honors Scholar Theses

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are synthetic analogs of glucagon-like peptide-1 (GLP-1) used to treat obesity and diabetes by reducing blood glucose levels and appetite. While early rodent studies suggested a link between GLP-1RAs and thyroid cancer pathogenesis, evidence in humans remains inconclusive, with randomized controlled trials not supporting that link. Due to the rapid, widespread use of these drugs, concerns have expanded to other obesity-associated cancers, with conflicting findings on their role in cancer progression. With this contradictory evidence in a novel intersection of obesity medicine and oncology, this literature review aims to summarize current understandings between GLP-1-RAs and …

The Development Of Magmas Inhibition As A Potential Therapeutic Target In Temozolomide Resistant Glioma, Jennifer Duyen Tran

Electronic Theses, Projects, and Dissertations

Glioblastoma (GBM) is a highly aggressive brain tumor that remains a significant challenge in neuro-oncology today. Approximately 90% of GBM patients experience tumor recurrence within one to two years of diagnosis. Therefore, due to its high resistance to conventional therapies, new treatment strategies are urgently needed. The current standard of care for GBM is the chemotherapeutic Temozolomide (TMZ). TMZ is an oral alkylating agent, it functions by delivering a methyl group to purine bases. The development of resistance to TMZ is partially regulated by the DNA repair enzyme O6- methylguanine-DNA methyltransferase (MGMT). Despite the potential shown by MGMT promoter methylation …

A Nano-Scale Approach To Controlled Apoptosis In Brain Cancer Through Magneto-Mechanical Actuation, Sakura Rieck

Biological Sciences Undergraduate Honors Theses

In this study, we investigate the effects of cell therapy and magneto-mechanical actuation (MMA) to treat glioblastoma (U87). MMA approach employs super low-frequency alternating magnetic fields (AMF) to actuate intracellular PEGylated superparamagnetic iron oxide nanoparticles (PEG-SPIONs). Magnetic forces are translated into mechanical agitation on PEG-SPIONs, which can disrupt key cellular components. We explored two ways in which the MMA approach can be used to combat cancer growth. First, we investigated MMA directly in U87 cells. Preliminary observations indicate that PEG-SPIONs are intracellularly taken up by the U87 cells via micropinocytosis. Cell-counting kit-8 toxicity assays revealed a cytotoxic effect of MMA …

Which Costimulatory Domains In Chimeric Antigen Receptor T Cells Induce Cytokine Responses That Are Linked To A More Toxic Car T Cell Therapy In Acute Lymphocytic Leukemia?, Elisabeth Cohen

Longwood Senior Thesis Proposal

No abstract provided.

Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse

Dissertations and Theses (Open Access)

Acute monocytic leukemia (monocytic AML) is a subtype of AML marked by a proliferation of abnormal monoblasts. This subtype represents approximately 10% of AML cases. The prognosis of monocytic AML is poor, with a 5-year survival of ~30%. Most patients are diagnosed at an age when they are unlikely to survive first-line non-targeted cytotoxic chemotherapy as a bridge to hematopoietic stem cell transplant (HSCT). Even patients who achieve remission commonly relapse. This population of patients would greatly benefit from precision-targeted therapies but currently there are none approved for monocytic AML.

Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immune checkpoint expressed …

The Role Of Ucp2 In Pancreatic Cancer Metabolism And Its Potential As A Radiosensitizer, Emily Rieff

Dissertations and Theses (Open Access)

Uncoupling protein 2 (UCP2) is a mitochondrial protein that regulates the flow of protons down the gradient established by the electron transport chain (ETC) without generating ATP, thus uncoupling the proton gradient from ATP generation. In tumors, specifically pancreatic cancer (PDAC), the ETC is highly stimulated to generate the copious ATP needed by the tumor to grow. However, extended ETC use increases reactive oxygen species (ROS), and if left unchecked, results in cell death. To evade this, PDAC employs antioxidant strategies, including upregulating UCP2 in tumor cells. In addition to its uncoupling function, UCP2 indirectly controls ROS levels by maintaining …

Therapeutic Vulnerabilities Of Venetoclax Resistant Chronic Lymphocytic Leukemia And Novel Treatment Strategies Targeting Bcl2/Bcl-Xl, Daisy Y. Diaz-Rohena

Dissertations and Theses (Open Access)

Despite major advancements in the management of chronic lymphocytic leukemia (CLL), drug resistance remains a major challenge. CLL resistant to venetoclax (VEN) have limited available therapeutic options, especially when the leukemic cells have dysfunctional p53 and have relapsed on Bruton’s tyrosine kinase inhibitors (BTKi). The broad hypothesis of this thesis is that VEN-relapsed CLL exhibits altered dependence on BCL2 family members, which can be exploited for therapeutic benefit. I profiled 28 CLL samples collected from 15 patients either at baseline or at relapse following VEN treatment, which was administered in combination with a BTKi or sequentially as monotherapy after a …