Cancer Biology Commons^™

The Effects Of Cannabinoids On Migration-Related Protein Expression In Ewing’S Sarcoma, Allison Lashall

Theses

Ewing’s sarcoma is an aggressive pediatric bone cancer that has low five-year survival rates, primarily due to metastatic disease and resistance of recurring tumors to traditional treatment options; therefore, novel treatment options are needed. The compound cannabidiol (CBD) has been shown to reduce cell viability, migration, and invasion in several tumor types, though the cellular mechanism of action is not well understood. Our lab has demonstrated the ability of CBD to reduce viability, migration, and invasion of Ewing’s sarcoma cells in vitro and is investigating differential protein and cytokine expression of known mediators of migration, such as intercellular adhesion molecule …

Examination Of Oncogenic Effects Of Environmental Pollutants, Andrew Ackerman, Matthew Behling, Brock Earley, Janay Vacharasin

Journal of the South Carolina Academy of Science

Chemical byproducts produced by surrounding industrial complexes have polluted the local estuaries of Georgetown, South Carolina for several decades¹. Previous studies completed by the EPA and SCDNR showed that the estuaries contained carcinogenic pollutants released from the local manufacturing plants¹. One of the mentioned pollutants was dioxins which are produced during the paper bleaching process². Dioxins are highly toxic compounds that have various carcinogenic effects on the organisms that inhabit the area. These previous studies were conducted over thirty years ago. Therefore, a current study to determine if chemical byproducts are contaminating local estuaries …

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum …

Assessment Of Tripeptides Self-Assembly & Er Stress On Cell Viability And Exosome Secretion In Mda-Mb231, Azmat Parveen

Theses and Dissertations

This study delves into the effects of tripeptides KYpF and WYpK(NBD) on MDA-MB-231 cells, uncovering KYpF's ability to reduce cell proliferation and exosome secretion in peptide treated cells. Conversely, WYpK(NBD) demonstrated significant toxicity at 10 μM. These insights pave the way for optimizing peptide-based cellular treatments for exosome secretion purposes.

Placental Co-Transcriptional Activator Vestigial-Like 1 (Vgll1) Drives Tumorigenesis Via Increasing Transcription Of Proliferation And Invasion Genes, Heather Sonnemann

Dissertations and Theses (Open Access)

Vestigial-like 1 (VGLL1) is a co-transcriptional activator that binds to TEA domain containing transcription factors (TEADs). Its expression is upregulated in a variety of aggressive cancer types, including pancreatic and basal-like breast cancer, and increased transcription of VGLL1 is strongly correlated with poor prognosis and decreased overall patient survival. In normal tissues, VGLL1 is most highly expressed within placental trophoblast cells, which share the common attributes of rapid cellular proliferation and invasion with tumor cells. The impact of VGLL1 in cancer has not been fully elucidated and no VGLL1-targeted therapy currently exists. The aim of this study was to evaluate …

Nutrient Intake And Nutritional Status Of Blood Cancer Patients At A Tertiary Hospital In India: A Cross-Sectional Descriptive Analysis Of Leukemia, Lymphoma And Multiple Myeloma, Enock Topisia, Loise Wamahiga Wang’Ondu

Haematology and Oncology, East Africa

In 2018, there were an estimated 18 million cancer cases worldwide, with lymphoma, multiple myeloma, and leukemia contributing to a significant portion of these cases. Lymphoma accounted for 79,990 cases, multiple myeloma for 159,985 cases, and leukemia for 437,033 cases globally (AICR, 2018). In the United States alone, approximately 30,770 people are diagnosed with multiple myeloma each year. Multiple myeloma comprises about 1.8% of all cancers and around 10% of all “blood cancers,” which includes leukemia (Penn Medicine, 2020). India ranks third in the highest reported cases of blood cancer, following the United States and China, affecting more than 70,000 …

T. Boudieri Extract Potentiates The Effects Of Capecitabine Treatment In Human Colon Cancer Cells, Katia Sawaya, Mahmoud Khalil, Ghada Khawaja

BAU Journal - Science and Technology

Resistance to chemotherapy remains a major challenge for colorectal cancer patients worldwide, hence the persistent need to uncover alternative treatments as well as new adjunct therapies in the fight against cancer. Natural extracts constitute an excellent source of bioactive substances that have a promising potential in that regard, with minimal negative side effects. We have previously demonstrated that both the ethanolic as well as the water extracts of Terfezia boudieri, a black desert truffle abundant in and part of the cuisine of the Mediterranean region, have significant antiproliferative effects against colon cancer cells. Our aim in this study was …

High Mdmx (Mdm4) In Mutant P53 Expressing Breast Cancer Cells Activates The Cxcl12-Cxcr4 Metastasis Signaling Axis, Rusia H. Lee

Dissertations, Theses, and Capstone Projects

The metastasis-promoting G-protein coupled receptor (GPCR) CXCR4 is activated by the cytokine CXCL12 (also known as SDF-1) to promote metastasis through CXCR4 upregulation. High CXCR4-expressing cancer cells utilize CXCL12, the exclusive endogenous ligand of CXCR4, to intravasate into the blood as circulating tumor cells (CTCs) which then extravasate to distant metastatic sites. We previously determined the oncogenes, Mouse Double Minute 2 and 4 (MDM2 and MDM4, also known as MDMX), drive TNBC metastasis and positively correlate with high expression of CXCR4. Interestingly, this upregulation of CXCR4 was only observed in primary tumor cells grown in the tumor microenvironment …

Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales

Theses and Dissertations

Germline mutations in RUNX1 are associated with familial platelet disorder with a predisposition to myeloid malignancy (RUNX1-FPDMM), in which patients present with low platelet counts,excessive bleeding and bruising, and an increased risk of Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) development throughout their lifetime. To understand how these loss-of-function mutations in RUNX1 drive predispose to malignancy, it is important to develop a detailed understanding of the molecular basis of RUNX1 function. While RUNX1 is a transcription factor, preliminary data from our group and work from others suggests that RUNX1 also interacts with proteins that are critical for DNA damage …

Maackia Amurensis Seed Lectin (Masl) And Soluble Human Podoplanin (Shpdpn) Sequence Analysis And Effects On Human Oral Squamous Cell Carcinoma (Oscc) Cell Migration And Viability, Ariel C Yin, Cayla J Holdcraft, Eamonn J Brace, Tyler J Hellmig, Sayan Basu, Saumil Parikh, Katarzyna Jachimowska, Evelyne Kalyoussef, Dylan Roden, Soly Baredes, Eugenio M Capitle, David I Suster, Alan J Shienbaum, Caifeng Zhao, Haiyan Zheng, Kevin Balcaen, Simon Devos, Jurgen Haustraete, Mahnaz Fatahzadeh, Gary S Goldberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, …

Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …

Identifying The Molecular Determinants Of Lung Metastatic Adaptation In Prostate Cancer, Grace M. Waldron

Theses & Dissertations

Prostate cancer (PC) stands as the primary diagnosed cancer in men in the US at approximately 299,010 cases in 2024 and ranks second globally, posing a significant public health challenge. Clinical presentations vary widely, from indolent to aggressive forms, necessitating stage-specific treatment regimens. Understanding its metastatic nature is critical due to the impact of cancer cell dissemination on disease morbidity, with bone and visceral organs serving as key sites of metastasis. Despite bone metastasis being the most common site for metastasis, visceral metastases at sites such as the liver and lungs correlate with poorer survival, emphasizing the role of microenvironmental …

Identification Of Mitotic Phosphatases And Cyclin K As Novel Molecular Targets In Pancreatic Cancer, Yi Xiao

Theses & Dissertations

Pancreatic cancer is a highly lethal disease worldwide. Given the limited effectiveness of current regimens in restricting tumor progression, it is imperative that potential molecular targets be identified to offer valuable insights into alternative therapeutics. By using a phosphate-binding tag (Phos-tag) technique, previous studies have identified several Hippo pathway-related proteins and kinases required for cancer growth or paclitaxel resistance. This work has screened various phosphatases and cyclins/cyclin-dependent kinases (CDKs) as potential cancer targets, but specifically focuses on characterizing the roles of carboxy-terminal domain small phosphatase like 2 (CTDSPL2), apoptosis-stimulating protein of p53-2 (ASPP2), and Cyclin K in pancreatic cancer.

CTDSPL2 …

Mucins: Drivers Of Cancer Cell And Microenvironment Crosstalk In Pancreatic Cancer, Xiaoqi Li

Theses & Dissertations

Mucins facilitate the pancreatic cancer (PC) initiation, progression, and metastasis. Among mucins, MUC4 has been reported to inhibit lymphokine-activated cell killing and induce the apoptosis of cytotoxic T-cells. Counterintuitively, MUC4 expression is upregulated by multiple T-cell-secreted cytokines, such as IFN-γ, IL-17, and stroma-secreted factors like retinoic acid. Previously, we have identified that nuclear receptor coactivator 3 (NCOA3) regulates the MUC1 and MUC4 expression by increasing chromatin accessibility and maintaining protein stability. However, the comprehensive crosstalk mediated by MUC4 in cancer cells and T-cells and how its upstream regulator, NCOA3, modifies the cancer cell-intrinsic behavior is still elusive. Here, we show …

Investigating The Therapeutic Potential Of Soursop In Treating Hematologic Malignancies, Sabrina Marie Paparo, Rebeca Mendoza, Robert Chitren, Omar Al-Odat, Emily Nelson, Subash Jonnalagadda, Roger Strair, Manoj Pandey

Rowan-Virtua Research Day

Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM) are hematologic malignancies that originate in the bone marrow and account for approximately 1.3% and 2% of cancer cases, respectively. AML is characterized by an accumulation of myeloblasts, or immature myeloid cells, that have the potential to spread to the peripheral blood. There is an uncontrolled proliferation of plasma cells in the bone marrow in MM. While the current treatment options for both AML and MM show promise in achieving initial remission, it is unfortunately common for patients to experience relapse and develop drug resistance. There is a theory that relapse and …

Development Of Vasculature Patterns In A Mouse Model Of Supratentorial Ependymoma, Jackson Ayers

Honors Scholar Theses

Supratentorial Ependymoma (ST-EPN) is a subtype of ependymoma, a primary solid tumor found throughout the nervous system. ST-EPN are most commonly caused by an oncogenic fusion between the zinc finger gene ZFTA and the RELA, and this distinct ependymoma subtype is readily modeled in mice by conditional expression of ZFTA-RELA in radial glial cells. ST-EPN are known to have a distinctive arrangement of tumor cells and vasculature forming pseudo-rosettes in which polarized tumor cells surround blood vessels within the tumors. It is not known how these pseudo-rosettes or the tumor vasculature form and develop in ST-EPN, so in this study …

Role Of Centrosomal P4.1 Associated Protein (Cpap) In Tumor Suppression, Heena Dave

MUSC Theses and Dissertations

In eukaryotic cells, centrosomes are membrane-less organelles that function as the primary microtubules organizing center with a crucial role in cell division. For accurate bipolar spindle assembly and genetic transmission between generations, fidelity in centriolar duplication is critical. Disruption in this process can cause genomic instability, which could then lead to conditions like aneuploidy, a common feature of various cancers. Among the numerous proteins associated with mammalian centrioles, the centrosomal P4.1 associated protein (CPAP) stands out for its essential role in regulating centriole duplication. Dysfunctions in CPAP have been linked to abnormalities in centriole length that can contribute to conditions …

Deciphering The Functional Connections Between The Nuclear Paraspeckle And Rad51 Homologous Recombination Proteins Using A Yeast Protein Interaction System, Eric J. Nutz

Senior Theses

Homologous recombination (HR) is a repair pathway for DNA double-stranded breaks. Mutations in HR genes contribute to genomic instability and increase the prevalence of cancer. Exploiting HR deficiency in tumor cells has led to improved synthetic lethality outcomes. RAD51 paralogue protein complexes are known to be involved with HR. Proteomic analysis of RAD51 paralogues reveals a connection to the nuclear paraspeckle. A paraspeckle is a little-known, specialized organelle found in the interchromatin space of the nucleus in mammalian cells. Its three central protein components include SFPQ, NONO, and PSPC1. RAD51D is an HR protein shown previously to interact with SFPQ …

Honey Targets Ribosome Biogenesis Process In Human Pancreatic Cancer Cells To Inhibit Their Growth And Metastatic Phenotypes, Aun A. Bangash, Muhammad Bangash, Haider Ahsan, Shiza Khan, Mudassier Ahmad, Dae Joon Kim, Sahir Alvi, Bilal Hafeez

Research Symposium

Background: Pancreatic cancer (PanCa) is the fourth deadliest cancer worldwide and is expected to become the second deadliest cancer by 2030. In the USA, the National Cancer Institute put forth a grim prediction stating that there will be 64,050 new cases in 2023 alone and about 50,000 of these patients will die. Existing therapeutic regimens against PanCa are not that effective and show unacceptable toxicities. Therefore, developing highly effective new agents with less toxicity is urgently required, which could be used as a monotherapy or as an adjuvant to treat PanCa patients. Honey is known for its tremendous health benefits …

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner

Dissertations, Theses, and Capstone Projects

The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …

Assessing The Role Of Kmt2b Knockdown In Rhabdoid Tumorigenesis Utilizing Crispri, Karah Edmonds, Andrea Florian Phd

Science University Research Symposium (SURS)

An aggressive blood cancer commonly observed in pediatric patients, Mixed Lineage Leukemia (MLL), has a regulatory MLL complex that promotes histone methyltransferation. Modifying histones utilizing histone methyltransferases like KMT2B (MLL2), is essential for gene expression by regulating transcription. Loss of function and inhibition of KMT2B leads to dysregulation of transcription and therefore promotes MLL tumorigenesis. To improve cancer-targeted therapies, we will use CRISPR interference (CRISPRi) to knock down the expression of KMT2B and measure levels of Rhabdoid tumor cell proliferation and apoptosis. Previous research surrounding the MLL complex suggests that decreased expression of KMT2B will lead to increased levels of …

Elucidation Of Mismatch Repair Regulation By Abl1: Advantages/Disadvantages Of Tyrosine Kinase Inhibitor Treatment, Hannah Daniels

Theses and Dissertations--Toxicology and Cancer Biology

DNA mismatch repair (MMR) is a critical repair process necessary for not only repairing mispairs incorporated into the DNA during replication, but also for inducing apoptosis in response to certain types of DNA damage. MMR is required for maintaining genomic integrity and due to the importance of this pathway, any impairment of its function can lead to increased mutation frequency, which is well known to be a driving force of cancer development, progression, and resistance. Despite extensive studies involving the proteins involved in the MMR pathway, the regulation of those proteins remains relatively unknown. Regulation of MLH1, a protein necessary …

Abl1/2 And Ddr1 Cooperate To Stabilize Braf/Craf To Drive Erk1/2 Reactivation And Promote Mek Inhibitor Resistance In Nras-Mutant Melanomas, Anastasia Lyon

Theses and Dissertations--Pharmacology and Nutritional Sciences

This study addresses the escalating incidence of NRAS-mutant melanomas, a type of skin cancer lacking FDA-approved targeted therapies. Despite ongoing research targeting the RAF/MEK/ERK pathway, existing drugs fail to enhance progression-free survival due to acquired resistance. This project identifies a novel role for ABL1/2 and DDR1 kinases in driving drug resistance and proliferation of NRAS-mutant melanoma cells. ABL1/2 and DDR1 cooperate to promote RAF homodimerization and protein stability in order to reactivate MEK/ERK signaling to drive MEK1/2 inhibitor (MEKi) resistance and promote survival of resistant cells. By targeting ABL1/2 and DDR1 with nilotinib, a FDA-approved anti-leukemic inhibitor, we …

Atm-/-Ung-/- Mice Present Reduced Levels Of Switched Immunoglobulin Isotypes Igg1 And Igg3, Lyric M. Haughton

Dissertations and Theses

B cells excise and recombine the immunoglobulin heavy chain gene locus during class switch recombination (CSR). CSR is mediated by activation induced cytidine deaminase (AID) and results in a new immunoglobulin isotype that B cells will secrete and present. AID produces mutations that convert cytosines to uracils within the intronic switch regions that precede and follow the target immunoglobulin isotype coding sequence. To resolve the mutations, B cells conduct either base excision repair (BER) or mismatch repair (MMR). Inactivating genetic mutations in BER or MMR reduce CSR. For example, a knock-out of uracil DNA glycosylase (UNG) causes a 50% reduction …

Synthesis Of Novel 5-Aryl 2’-Deoxyuridine And 2’-Deoxycytidine Analogues, Kevin E. Persaud

Dissertations and Theses

Briefly, the following report details a synthetic route to prepare 5-phenyl-2’-deoxycytidine analogues. This multistep synthesis began with silyl protection of the 3’- and 5’-hydroxyl groups of 5-iodo-2’-deoxyuridine. Next, the installation of a phenyl ring at the C5 position of the nucleobase via a Suzuki-Miyaura cross-coupling reaction, yielding 5-phenyl-2’-deoxyuridine (5-PdU). After that, modification of the obtained 5-PdU at the C4 position was performed with benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP, a peptide-coupling agent) and a base (cesium carbonate) to activate the amide group of the uridine nucleobase for subsequent displacement with a variety of amines. Modification of the C4 position resulted in protected 5-phenyl-2’-deoxycytidine …

Nanotoxicology Of Cdse/Zns Quantum Dot Alternatives In Thle-2 And Hepg2 Liver Cells, Seth Harris

Graduate Theses/Dissertations

Fluorescent nanoparticles known as quantum dots (QDs) have unique properties that make them useful in biomedicine. Specifically, CdSe/ZnS QDs, while good at fluorescing, show toxicity. Due to this, safer alternatives have been developed. This study uses an XTT viability assay, ROS fluorescent imaging, and apoptosis to investigate the effect of QD alternatives InP/ZnS, CuInS₂/ZnS, and carbon dots (NCD) in liver cells. The liver is a possible destination for accumulation of QDs making it an appropriate model for testing. A cancerous liver cell line known as HepG2, and an immortalized liver cell line known as THLE-2 were used. At …

Characterization Of Trafficking And Metabolic Functions Of The Endocytic Regulator Ehd1 In Ewing Sarcoma, Sukanya Chakraborty

Theses & Dissertations

Ewing sarcoma (EWS) is the second most common bone malignancy in children and adolescents. Despite improvement in survival due to advances in multimodality treatment strategies, patients with metastatic or recurrent disease have very poor outcomes. Overexpression of the EPS15 Homology Domain containing 1 (EHD1) protein has been linked to tumorigenesis but whether its core function as a regulator of intracellular traffic of cell surface receptors plays a role in oncogenesis remains unknown.

Studies presented in this dissertation establish that EHD1 overexpression is a feature of nearly 90% EWS patient tumors with high EHD1 expression specifying shorter patient survival. ShRNA-knockdown and …

Role Of The Ganglioside Gd2 And Its Biosynthetic Enzyme Gd3 Synthase In Prostate Cancer Tumorigenesis, Aaqib Bhat

Theses & Dissertations

Despite significant advancements in managing localized prostate cancer (PC), which have notably increased survival rates, advanced PC continues to be a leading cause of cancer- related fatalities. The discovery of new pathways that can be targeted to inhibit tumor growth in PC could pave the way for innovative treatment strategies. The disialylganglioside GD2 is an FDA-approved target for antibody therapies in neuroblastoma and has not been extensively studied in the context of PC. The work done in this thesis reveals that GD2 is present on a minor subset of PC cells in certain patients and is more prevalent in metastatic …

Pcbp1 Regulates Lifr Through Fam3c To Maintain Breast Cancer Stem Cell Self-Renewal And Invasiveness, William S. Streitfeld

MUSC Theses and Dissertations

The poly(rC) binding protein 1 gene (PCBP1) encodes the heterogenous nuclear ribonucleoprotein E1 (hnRNPE1), a nucleic acid-binding protein that plays a tumor-suppressive role in mammary epithelial cells by regulating phenotypic plasticity and cell fate. Following the loss of PCBP1 function, the FAM3C gene (encoding the Interleukin-like EMT inducer, or “ILEI” protein) and the leukemia inhibitory factor receptor (LIFR) gene are upregulated. Interaction between FAM3C and LIFR in the extracellular space induces phosphorylation of signal transducer and activator of transcription 3 (pSTAT3). Overexpression and/or hyperactivity of STAT3 has been detected in 40% of breast cancer cases and is associated with a …

Tak1 And Tbk1 Are Differentially Required By Gmp- And Lmpp-Like Leukemia Stem Cells, Austin P. Runde, Joseph Michael Cannova, Ryan Mack, Kanak Joshi, Mark Sellin, Allan Youmaran, Mattias Lenz, Rohit Thalla, Wei Wei, Peter Breslin S.J., Jiwang Zhang

School of Medicine

Acute myeloid leukemia (AML) encompasses a diverse group of cancers that originate in the blood-forming tissues of the bone marrow. Aside from the M3 subtype (PML-RARA⁺), AML carries a 5-year survival rate of 28% for patients 20+ years of age. AML is the most common cancer of the hematopoietic system and is slightly more common in biological males; the average age at diagnosis is 68 years. Standard frontline treatment for AML is a 2-phase regimen of intensive chemotherapy (CTx) employing daunorubicin and cytarabine. Despite 60-70% of patients achieving complete remission (CR), at least half of CR-achieving patients …