Cancer Biology Commons^™

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 …

Exploration In Cell Growth: Rac3 And Its Effect On Ewing Sarcomas Tumorigenic Properties, Allie Woods, Samuel De La Cruz, Catherine Garcia, Terry Jo Shackleford

Cell and Molecular Methods

Multiple experiments were conducted to measure the effectiveness of certain genes on cell growth. In the exploration of this process, RAC3 acted as the target gene and was applied to both SOX18 overexpressing and normal expressing cells (control). RAC3 is a gene that typically controls the intercellular signaling pathway of a cell. This means it helps with the movement of cells and allows for migration.The purpose of these experiments were to determine how the gene RAC3 would work when introduced to carcinogenic cells, specifically Ewing Sarcoma. Typically, RAC3 acts as a messenger for the cell, but when in conjunction with …

The Effect Of Knockdown Of Gene Kit On Sox18 Gene Expression Through The Jak2/Stat3 Signaling Pathway Within An Ewing Sarcoma Cell, Samantha Aragon, Cristina Herrera, Felicity Rodriguez, Riley Smith, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is an aggressive cancer that affects children & adolescents. Common treatments include surgery, radiation, and chemotherapy, yet individuals have a poor survival rate and often develop side effects from treatment, including fertility issues, secondary cancer, heart problems, and growth abnormalities.1SOX18 is a gene identified to aid in cell proliferation and cell differentiation, leading to the development of several cancers, such as gastric, bladder, and lung cancer.2,3 SOX18 resides in the JAK2/STAT3 pathway as a regulator, along with another gene named KIT that instigates the formation of the cell signaling pathway.4KIT is a transmembrane tyrosine kinase, which instigates cell …

The Effects Of Ewing Sarcoma Through The Overexpression And Knockdown Of Transcription Factors Sox18 And Stat1, Victoria Castillo, Melany Cervantes, Nicole Robles, Terry Jo Shackleford

Cell and Molecular Methods

SOX18, a transcription factor with a DNA-binding HMG domain, plays a critical role in regulatory processes linked to cancer progression. Exhibiting oncogenic properties, SOX18 has been linked to various cancers, where it promotes tumor growth by enhancing cell invasion, uncontrolled proliferation, and resistance to apoptosis through dysregulated signaling pathways. STAT1, a protein crucial for immune system regulation, is prominently expressed in immune-associated tissues like the lymph nodes, and bone marrow, suggesting it could play a role in tumor growth. Ewing Sarcoma (EWS), an aggressive cancer that targets bone and soft tissue, carries a high mortality rate of 90% without treatment …

Mechanisms Of Extracellular Vesicle Uptake And Implications For The Design Of Cancer Therapeutics, Stephanie R Jackson Cullison, Joseph P Flemming, Kubra Karagoz, Peter J Wermuth, Mỹ G Mahoney

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue to achieve or seek approval, setbacks are often attributed to a lack of efficacy, failure to achieve clinical endpoints, and dose-limiting toxicities. Successful efforts have been characterized by the development of therapeutics designed to specifically deliver optimal and effective dosing to tumour cells while minimizing off-target toxicity. Much effort has been devoted to the rational design and application of synthetic nanoparticles to serve as targeted therapeutic delivery vehicles. Several challenges to the successful application of this modality as …

Challenges And Coping Strategies Among Caregivers Of Children With Cancer Receiving Care At A National Referral Hospital In Kenya, Doris Machaki, Albanus Kyalo Mutisya, Jostine Mutinda, Sherry Oluchina, Samwel Maina Gatimu

School of Nursing & Midwifery, East Africa

Background: The number of children diagnosed with cancer is expected to increase by 2050. The caring aspect of these children is usually left to members of the family, more so the mothers. Caregivers are usually faced with various challenges, such as financial issues, social stigma, and emotional and psychological issues. Caregivers use various coping strategies to manage the challenges they experience in the caring process, which can be positive or negative coping strategies.

Objective: To explore the challenges and coping strategies of caregivers of children with cancer receiving care at a national referral hospital in Kenya.

Methods: This study employed …

Honey: A Natural Recipe For The Management Of Pancreatic Cancer, Aun A. Bangash, Muhammad A. Bangash, Georgina Villanueva, Haider Ahsan, Shiza Khan, Rida Shareef, Mudassier Ahmad, Dae J. Kim, Sahir S. Alvi, Bilal B. Hafeez

Research Colloquium

Background: Pancreatic cancer (PanCa) is the fourth deadliest cancer worldwide and 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. The first line treatment for pancreatic cancer is Folfrinox, a three-drug regimen consisting of 5-Fluorouracil, irinotecan, and oxaliplatin. The second line treatment is gemcitabine combined with paclitaxel. Only 19% of patients who are prescribed the former regimen survive past 18 months of treatment while just 6% of patients survive …

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 …

Combination Therapy Of Ido1 Inhibition And Anti-Pd1 Mediates Anti-Tumor Immunity By Promoting Memory Immunity Development And Cytotoxicity Of Γδ T And Nk Cells Via Il-2 Signaling And By Overcoming Pro-Tumor Effects Of Tgf-Β Signaling, Hyuk Jee

Dartmouth College Master’s Theses

Cutaneous melanoma is the most aggressive form of skin cancer even though it takes only about 1% of all skin cancers. Even among all cutaneous melanomas, NRAS-mutant melanoma is more aggressive than any other, and about 10-25% of all cutaneous melanoma cases have mutations in NRAS. NRAS is a member of the RAS family of proto-oncogenic GTPase proteins, and it plays a key role in signal transduction pathways responsible for cellular survival, proliferation, and metabolism. Immunotherapy is the first line of defense against NRAS-mutant melanoma because, despite tremendous efforts made for decades, it has not been successful to develop small …

Interleukin 24 Induces Apoptosis Through Glycogen Synthase Kinase-3 Beta Inactivation In Prostate Cancer Cells, Sual J. Lopez, Moira Sauane

Theses and Dissertations

Interleukin 24 (IL-24) is a tumor-suppressing protein currently in clinical trials. IL-24 induces cancer-specific apoptosis by activating endoplasmic reticulum (ER) stress and mitochondria dysfunction. We have previously demonstrated that IL-24 leads to apoptosis in cancer cells by protein kinase A (PKA) activation in human breast cancer cells. To further understand the mechanism by which IL-24 induces apoptosis, I analyzed the role of glycogen synthase kinase-3 (GSK3), a highly conserved and normally active serine/threonine kinase in cancer cells and downstream target of PKA. The work reported here provides direct evidence that GSK3 was inhibited following IL-24 treatment in human prostate cancer …

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 …

Identifying Novel Upstream Regulators Of The Hippo Pathway: Forward Genetic Screen In Drosophila Melanogaster, Akshara Iyer

Honors Scholar Theses

The Hippo pathway is an evolutionarily conserved developmental pathway that controls organ size and tissue homeostasis in all metazoan animals. Dysregulated Hippo pathway has been implicated in a wide range of human disorders, including cancer. The physiological function of the Hippo pathway is best understood in Drosophila, where inactivation of the Hippo pathway tumor suppressors, or overexpression of the Yorkie (Yki) oncoprotein, results in tissue overgrowth characterized by excessive cell proliferation and diminished apoptosis, and increased transcription of Hippo pathway target genes such as diap1 and expanded (ex). Despite the well-established Hippo pathway core signaling cascade, the upstream regulation of …

The Transmission Of Oropharyngeal Squamous Cell Carcinoma, Kunjal Patel, Aleesha Thomas

Mako: NSU Undergraduate Student Journal

The existence of Oropharyngeal Squamous Cell Carcinoma (OPSCC) has recently been found to have correlations with the Human Papillomavirus. HPV-associated OPSCC exhibits a unique method of infection and transmission and has made this branch an emerging disease in the recent decade. This systematic review of the literature was conducted to further explore research into Oropharyngeal Squamous Cell Cancer (OPSCC). Commonly referred to as “throat cancer”, this growth originates in the oropharynx. Symptoms of this condition include sore throat, lumps in the neck, and difficulty with swallowing. OPSCC has many variants but has shown a strong association with Human Papillomavirus (HPV), …

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 …

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 …

Machine Learning As A Tool For Early Detection: A Focus On Late-Stage Colorectal Cancer Across Socioeconomic Spectrums, Hadiza Galadima, Rexford Anson-Dwamena, Ashley Johnson, Ghalib Bello, Georges Adunlin, James Blando

Community & Environmental Health Faculty Publications

Purpose: To assess the efficacy of various machine learning (ML) algorithms in predicting late-stage colorectal cancer (CRC) diagnoses against the backdrop of socio-economic and regional healthcare disparities. Methods: An innovative theoretical framework was developed to integrate individual- and census tract-level social determinants of health (SDOH) with sociodemographic factors. A comparative analysis of the ML models was conducted using key performance metrics such as AUC-ROC to evaluate their predictive accuracy. Spatio-temporal analysis was used to identify disparities in late-stage CRC diagnosis probabilities. Results: Gradient boosting emerged as the superior model, with the top predictors for late-stage CRC diagnosis being anatomic site, …

Methylene Blue-Mediated Photodynamic Therapy In Combination With Doxorubicin: A Novel Approach In The Treatment Of Ht-29 Colon Cancer Cells, Nima Rastegar-Pouyani, Jaber Zafari, Alireza Nasirpour, Hossein Vazini, Nabbaa Najjar, Seyedeh Zohreh Azarshin, Fatemeh Javani Jouni

Electrical & Computer Engineering Faculty Publications

Introduction: With an alarmingly growing number of patients diagnosed with colorectal cancer, adopting innovative anti-cancer approaches has recently garnered great attention. One interesting concept is the co-administration of cytotoxic agents and safer modalities such as photodynamic therapy (PDT), which can subsequently improve therapeutic efficacy and potentially reduce the risks of severe adverse effects and drug resistance. In the course of PDT, a locally injected photosensitizer (PS) is irradiated with a light source, which subsequently generates reactive oxygen species (ROS) and induces programmed cell death in tumor cells.

Methods: In this study, to evaluate the potential anti-cancer effects of chemotherapy combined …

A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D'Souza

Department of Medicine Faculty Publications

Introduction: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well-studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: Von Hippel-Landau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C (KDM5C). …

Near-Infrared Paired-Agent Imaging For In Vivo Quantification Of Receptor Occupancy In Tumor, Yichen Feng

Dartmouth College Ph.D Dissertations

Accurate assessment of drug receptor occupancy (RO) holds significant importance in both drug development and personalized medicine, as it facilitates quantitative characterization of dose-response relationship for a given drug. This information not only aids appropriate dose selection for clinical trials but also guides personalized dose optimization in precision medicine.

Molecular imaging, utilizing receptor-specific imaging agents for tissue visualization, has emerged as the major option for in vivo measurement of tissue RO. Nonetheless, the abnormal yet complex structure and hemodynamics of tumors often lead to substantial non-specific uptake and retention of imaging agents, thus introducing significant bias to RO measurements. To …

Desmoglein-2 As A Cancer Modulator: Friend Or Foe?, Kay Myo Min, Charlie Ffrench, Barbara Mcclure, Michael Ortiz, Emma Dorward, Michael Samuel, Lisa Ebert, Mỹ Mahoney, Claudine Bonder

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Desmoglein-2 (DSG2) is a calcium-binding single pass transmembrane glycoprotein and a member of the large cadherin family. Until recently, DSG2 was thought to only function as a cell adhesion protein embedded within desmosome junctions designed to enable cells to better tolerate mechanical stress. However, additional roles for DSG2 outside of desmosomes are continuing to emerge, particularly in cancer. Herein, we review the current literature on DSG2 in cancer and detail its impact on biological functions such as cell adhesion, proliferation, migration, invasion, intracellular signaling, extracellular vesicle release and vasculogenic mimicry. An increased understanding of the diverse repertoire of the biological …

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 …

Engineered Exosomes For The Multimodal Imaging Directed Photo-Immunotherapy Of Colorectal Cancer, Deepak S. Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

Research Symposium

Background: Rio Grande Valley experience severe cancer health disparity. A novel therapeutic modality may serve as better therapeutic option. Nanohybrids endowed with multifunctionality, longer circulation time, large surface area have emerged as an active preference for cancer research. However, rising concern of nanomaterials toxicity and scalability issues has slowed their translation to clinics. Exosomes (Exo) are endogenous endocytic origin 40-100 nm vesicles found in various body fluids, which in comparison to synthetic nanoparticles, are biodegradable, highly biocompatible as well as immunocompatible in nature. Although bulk isolation of exosomes from human body fluids is still a problem and engineering of exosomes …

Pre-Clinical Evaluation Of A Potential Ruthenium-Based Chemotherapeutic Agent For The Treatment Of Triple Negative Breast Cancer, Nazia Nayeem

Dissertations, Theses, and Capstone Projects

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that represents roughly 15% of all diagnosed breast cancers. TNBC is defined by the absence of expression of progesterone, estrogen, and human epidermal growth factor 2 receptors, and has a higher incidence rate in pre-menopausal women and women of African and of Hispanic ancestry. Due to the inability to target a receptor, treatment is limited to nonspecific chemotherapy or immunotherapy. Only one FDA approved therapy is available specifically to treat TNBC, which is antibody drug conjugate Sacitzumab-govitecan, given to patients who have already gone through two rounds of …

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 …

Understanding The Regulatory Context And Mechanism Of Hlh-25 Mediated Transcriptional Repression, Dagmawi Mamo

Masters Theses, 2020-current

The HES family of transcription factors are primarily repressors of transcription that play critical roles in mammalian embryogenesis by regulating cell differentiation and proliferation. Proper functioning of HES proteins is crucial in humans, as mutations or misexpression of HES1 is associated with lung, pancreas, colon, and other cancers. HES1 may mediate short-range or long-range repression through DNA-binding and or protein-protein interactions with other factors. However, prior genetic studies have not fully elucidated how the context-specific binding of HES1, or its C. elegans ortholog HLH-25, promotes the repression of transcription. Characterization of the cis-regulatory context and mechanism of HLH-25 mediated repression …

Development Of Combination Therapy Strategies To Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors, Nicholas Mullen

Theses & Dissertations

Cancer cells require supraphysiologic levels of nucleotide triphosphates to fuel their malignant behaviors, including uncontrolled proliferation, immune evasion, metastasis, and therapy resistance. This requirement is met by hyperactive flux through the de novo pyrimidine and de novo purine pathways. Dihydroorotate dehydrogenase (DHODH) is an essential enzyme in the de novo pyrimidine pathway that can be targeted by FDA approved and experimental drug compounds. A robust body of preclinical evidence, encompassing hundreds of independent studies over several decades, demonstrates impressive activity of DHODH inhibitors in animal models of cancer. Paradoxically, however, all clinical trials to date have failed to demonstrate efficacy …

A Dna-Peptide Crosslink (Dpc) Increases Mutagenicity In Sos-Induced Escherichia Coli, Alessandra Bassani

Honors Scholar Theses

Bacteria, such as Escherichia coli, have an inducible system in response to DNA damage termed the SOS response. This system is activated when the replicative DNA polymerase (Pol) III encounters a lesion, uncouples from DNA helicase, and single-stranded DNA (ssDNA) accumulates at the replication fork. In this study, we investigated DNA-peptide crosslink (DpC), a common lesion that results from cross-linking of proteins or peptides, UV irradiation, and alkylating agents. To increase survival following formation of a lesion, the SOS response can utilize homologous recombination, translesion synthesis (TLS), or excision repair. With TLS, the levels of DNA Pol II, IV, …

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 …

Preclinical Evaluation Of Immunomodulatory Effects Of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers, Pragya Sinha

Dissertations and Theses (Open Access)

Human papillomavirus (HPV) is the causative agent of cervical cancer and some cancers of the penis, vulva, vagina, anus, and oropharynx. Current therapies for these cancers include a combination of surgery, radiotherapy, and chemotherapy that often results in permanent, life altering adverse effects. Immunotherapy is partially effective, but with significant recurrence and lower long-term survival. Importantly, there are no few biomarker-selective targeted therapies for these cancers. To address this unmet need, our collaborators conducted a large-scale drug screen and identified Aurora Kinase (AK) inhibitors as a unique class of reagents to induce selective apoptosis in HPV+, but not HPV- human …

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 < 0.0001) in the cell cycle control and chromosomal replication pathway. CDK18 is active during the S-phase of the cell cycle and required for genomic stability. Studies were conducted to determine the epigenetic mechanisms that contributed to the repression of CDK18. Histone methylation contributes to the repression of CDK18, and histone deacetylation globally regulates expression of CDK18, while cytosine methylation was found to not contribute to CDK18 expression. Studies were performed to elucidate CDK18 functional role lung carcinogenesis and the genome-wide impact of CDK18 repression. Repression of CDK18 affects cell migration, proliferation, cell-cell signaling, and anchorage-independent growth that contribute to cancer initiation and progression.