Cancer Biology Commons^™

Apical-Out Lung Organoids: A Platform For Spaceflight And Cf Research, Valeria Jimenez, Ally Schwennesen

Discovery Day - Daytona Beach

A genetic condition known as cystic fibrosis (CF) is brought on by mutations in the CFTR gene, which results in chronic lung inflammation and impaired chloride ion transport. CF bronchial epithelial cells enable direct comparison of disease pathology, while normal human bronchial epithelial (NHBE) cells offer an essential model for researching airway physiology. Realistic modeling of respiratory tissue and its reaction to environmental stressors like microgravity is made possible by the creation of 3D lung organoids from these cells. In this project, we developed apical-out organoids, which expose the apical surface of epithelial cells to the external environment. These organoids …

Associations Between The Human Breast Microbiome And Immune Genes In Breast Cancer, Luke Pontoriero, Joan Argwings-Kodhek

Seaver College Research And Scholarly Achievement Symposium

Breast cancer (BC) affects 1 in 8 women and roughly 50% of breast cancers cannot be explained by environmental or genetic factors. There is growing evidence of the role of the human breast microbiome in breast cancer, but the mechanisms guiding this role are not well understood. The co-evolution of the human microbiome with the immune system represents an interaction between host and microbiome that is understudied with regard to breast cancer pathogenesis. We hypothesized that immune genetic variation is associated with altered abundance patterns of bacterial taxa in BC. We conducted 30X whole genome sequencing on a sample of …

Mitochondrial Transfer And Induced Ros As A Therapeutic Strategy In Idh2-Mutant Chondrosarcoma, Vegas R. Bedder, Caleb Wyckoff, Chris Osgood, Gavin A. Vasquez, Michael Stacey

Knowledge and Creativity Expo

Chondrosarcoma (CS) are common bone cancers that produce cartilaginous tumors and are extremely refractive to chemo-and-radiation therapies, leaving very limited treatment options. They contain mutations in the isocitrate dehydrogenase genes, IDH1 or IDH2. Either IDH1 or IDH2 mutations are present in individual tumors, but not both. They both convert alphaketoglutarate (αKG) into the potent oncometabolite D-2-hydroxyglutarate (D2HG). D2HG can be transported from the tumors to cells of the tumor microenvironment (TME) where it can alter metabolic and epigenetic profiles in recipient cells. The process of α-KG to D2HG conversion occurs in the cytoplasm of IDH1 mutant cells, and in the …

Exploring The Functional Role Of Neprilysin In Pi3k/Akt1 Signaling In Triple-Negative Breast Cancer, Ariadna Daniela Menjivar

Student Scholar Symposium

Our lab is investigating the protein Neprilysin (NEP) and its role in Triple-Negative Breast Cancer (TNBC). Previous bioinformatics data from Dr. Conway’s research indicated that in TNBC cells high in Neprilysin expression (HCC38), the PI3K pathway was the most active signaling pathway. This information suggests that Neprilysin is positively upregulating the PI3K pathway in this cell line. This is interesting given the fact that in the context of TNBC, Neprilysin has been shown to negatively regulate the PI3K/AKT signaling pathway. The PI3K/AKT pathway is the most commonly mutated pathway in breast cancer. AKT is the central mediator protein in this …

Impact Of Zar1l Expression On Drug Response In Breast Cancer Cells, Maryam M. Gerges, Smita Misra

Student Scholar Symposium

Breast cancer (BC) is the most common cancer in women worldwide and the second leading cause of cancer-related deaths among females. BC arises from the uncontrolled proliferation of breast epithelial cells. A crucial gene associated with BC is the Breast Cancer Susceptibility Gene 2 (BRCA2), a tumor suppressor that aids in DNA repair. Proper BRCA2 function helps prevent BC. Our lab studied the cell cycle-dependent expression of BRCA2 revealing that its promoter exhibits bi-directional activity. During cell division, forward activity transcribes BRCA2, while in the resting phase, reverse activity transcribes ZAR2 (Zygote Arrest 1 Like). ZAR2, an RNA-binding protein with …

Pediatric Glioblastoma Molecular Mechanisms, Ariana Trabachino, Joshua Owens

Student Scholar Symposium

Powerpoint presentation

Effects Of Valerobetaine In Fatty-Acid Induced Breast Cancer Cell Proliferation, Carolyn Tran, Maryam Mina, Diyar Fadhil

Student Scholar Symposium

Breast cancer is the second leading cause of cancer deaths among women with 287,500 new cases of invasive breast cancer and 43,250 deaths reported in 2022. In fact, 75% of these deaths aren’t from the initial tumor but due to the spread of breast cancer tumors to other sites, also known as metastases. Breast cancer occurs when breast tissue cells mutate and proliferate uncontrollably, resulting in a lump or mass. In breast cancer, the origin of proliferation, or the primary site, for cancer cells is mostly within the milk ducts. Then, tumor cells can start migrating away from its primary …

Investigating Carnitine-Dependent Mechanisms Of Valerobetaine In Breast Cancer Migration Inhibition, Audrey Birdwell

Student Scholar Symposium

Breast cancer accounts for approximately 297,500 cases annually in the United States, leading to over 43,000 fatalities. These deaths occur due to cancer's ability to bypass the normal cell cycle, proliferating uncontrollably and metastasizing throughout the body. Notably, over 75% of breast cancer-related deaths are attributed to metastases. The hallmark of altered cellular metabolism enables cancer cells to enhance fat metabolism alongside glycolysis, driving increased tumor aggressiveness and higher metastatic rates. Currently, no FDA-approved drugs directly target metastases or prevent migrating cancer cells. Consequently, inhibiting fat metabolism presents a potential strategy to reduce metastases and cancer cell migration; however, existing …

Her2 Amplification In Breast Cancer And Its Treatment Options, Emerald Cole, Zoe Grace Brigance

Student Scholar Symposium

Breast cancer affects approximately 2.3 million women worldwide, causing an estimated 670,000 deaths in 2022. Among its subtypes, 15-20% exhibit overexpression of Human Epidermal Growth Factor Receptor 2 (HER2), a tyrosine kinase receptor that drives tumor aggressiveness. HER2 activates the PI3K and RAS/RAF/MAPK pathways, promoting uncontrolled cell growth, proliferation, and survival. In HER2+ breast cancer, gene amplification leads to excess HER2 protein production, resulting in persistent signaling and unchecked tumor progression. However, this dependency on HER2 presents a key therapeutic opportunity. Trastuzumab, an anti-HER2 monoclonal antibody, inhibits HER2 signaling and enhances immune-mediated cancer cell destruction. When combined with Lapatinib, chemotherapy, …

Elucidating The Mechanism Of Neprilysin-Regulated Triple-Negative Breast Cancer Invasion, Kai Lam, Ellie Griner

Student Scholar Symposium

Triple-negative breast cancer (TNBC) is a highly invasive and difficult-to-target form of cancer. It is characterized by a lack of estrogen receptors, progesterone receptors, and human epidermal growth factor 2 receptors, making current targeted therapies ineffective and leaving chemotherapy as the primary treatment option. Previous studies in this lab have linked reduced expression of neprilysin (NEP), a membrane-bound protease that cleaves and inactivates mitogenic peptides, to a highly invasive phenotype in TNBC. Our data indicates that while NEP promotes phosphoinositol 3-kinase (PI3K) signaling, it simultaneously inhibits cellular invasion. Here, we begin to explain a possible mechanism behind the anti-invasive role …

Δ-Valerobetaine As A Novel Inhibitor Of Breast Cancer Cell Migration: Hinders Cellular Migration Of Mcf-7 Cells Through Reducing Atp Concentrations And Fak Activation, Braxton Ivie, Lincoln Brown, Bryson Lovorn

Student Scholar Symposium

δ-valerobetaine as a Novel Inhibitor of Breast Cancer Cell Migration: Hinders Cellular Migration of MCF-7 Cells Through Reducing ATP Concentrations and FAK Activation

Lincoln Brown, Braxton Ivie, Bryson Lovorn, Joshua Owens

Based on female breast cancer diagnoses from 2014-2020, the CDC reports that the 5-year relative survival rate for local and regional breast cancers was 98.9% and 86.3%, respectively, while the survival rate for metastasized cancers was reportedly 32.4%. These discrepancies in survival highlight an increased mortality rate when cancer metastasizes. Interestingly, aggressive tumors have been shown to metabolize fats at higher rates than low-metastatic tumors. Recently, our group has …

Mathematical Model Of Ovarian Cancer Tumor Growth In Mice, Jessica A. Hoffman

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

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.

Ks151 Synergizes With Venetoclax And Abt-737 In Aml: Efficacy In Both Flt3-Wildtype And Flt3-Mutant Models, Sahil Jethi, Arnold Rojas, Omar S. Al-Odat, Krishne Gowda, Subash C. Jonnalagadda, Manoj Pandey

Rowan-Virtua Research Day

Acute myeloid leukemia (AML) is the most common leukemia in adult patients, with a 5-year survival rate of less than 30 percent. Therefore, more effective therapeutic strategies are required to prolong the survival of AML patients. Importantly, anti-apoptotic proteins, especially B-cell lymphoma 2 (Bcl-2), overexpression in AML is associated with uncontrolled growth as well as chemoresistance. Unsurprisingly, Bruton’s tyrosine kinase (BTK) overexpresses in AML and associated with poor prognosis and chemoresistance. The FDA-approved BTK inhibitor, ibrutinib, has been successful in treating other hematologic malignancies, but a proportion of patients relapse mainly because of acquired mutations at Cys481Ser (C481S) in the …

Exploring Intracellular Signaling Responses To Ks18, A Potent Mcl-1 Inhibitor, In Multiple Myeloma, Emily Nelson, Omar S Al-Odat, Dhruti A. Brahmbhatt, Tulin Budak-Alpdogan, Subash Jonnalagadda, Manoj Kumar Pandey

Rowan-Virtua Research Day

Multiple myeloma (MM), a cancer of plasma B cells, is a hematological malignancy in which patients inevitably relapse and develop drug resistance. Mcl-1, a member of the anti-apoptotic subgroup of Bcl-2 family proteins, plays a critical role in the progression of multiple myeloma and contributes significantly to drug resistance. Elevated Mcl-1 expression is observed in approximately 52% of MM patients at diagnosis, increasing to 81% at relapse. Given its driving role in disease progression and therapy resistance, Mcl-1 inhibition has emerged as a promising therapeutic target, prompting ongoing research into the development and clinical evaluation of Mcl-1 inhibitors, particularly for …

Accelerated Tumor Growth And Lymphatic Spread Of Transplantable Melanomas In Tumor Necrosis Factor(Tnf)-Transgenic Mice, Catherine F. Alapatt, Robert Hughes, Roger Sheffmaker, Gillian Mcguire, Daniel Deegan, Igor Kuzin, Andrea Bottaro

Rowan-Virtua Research Day

Melanoma is the fifth most common cancer among American adults, with significant morbidity and mortality at 5 years remaining >60% for patients with stage IV disease. The malignancy is due to the transformation of melanocytes, with one of the major risk factors being ultraviolet light exposure. Although as many as one in five human cancers have been linked to chronic inflammation, the role of inflammatory signals in melanoma growth and metastasis remains poorly understood.

Tumor necrosis factor (TNF)-transgenic (TNFtg) mice are a well-established model of chronic systemic inflammation, with involvement of joints and other organ systems. To assess the effect …

Mcf-7 Dense Breast Cancer Cells Modulate Stress Through Senescence, Lara Donadio, Moses Alfonso, Josiah Philip, Tyler Zatarain

Molloy Multidisciplinary Undergraduate Research Conference

Breast cancer remains a leading cause of cancer-related mortality among women worldwide, with dense breast tissue being recognized as a significant risk factor for its development. This dense breast tissue, characterized by a higher concentration of mammary glandular tissue, represents additional sites for tumor development. The following study explores how the MCF-7 immortal cell line, representing dense breast cancer, modulates stress responses through cellular senescence. Cellular senescence is a defense mechanism that halts the cell cycle and acts as a tumor suppression mechanism, preventing out-of-control cell proliferation triggered by cytological stress. To simulate these stress conditions, we applied two agents: …

Dysregulation Of Cholesterol Metabolism And Sorafenib Drug Resistance In Hepatocellular Carcinoma, Veerababu Nagati, Dennis Kwabiah, Yamile Abuchard Anaya, Ana Ayala Pazzi, Manish K. Tripathi

Research Symposium

Background: Hepatocellular carcinoma (HCC) is among the most prevalent cancers and a leading cause of cancer-related deaths worldwide. Sorafenib, a multikinase inhibitor, serves as a key first-line treatment for HCC when surgical intervention is not an option. However, primary and acquired resistance to sorafenib has significantly limited its effectiveness, reducing the disease control rate. Dysregulation of numerous genes that influence cancer cell proliferation, survival, and drug resistance contributes to this challenge. Identifying the molecular drivers of sorafenib resistance remains critical to improving treatment outcomes. Several factors, including activation of oncogenic pathways (e.g., Akt/mTOR), hypoxia, cholesterol metabolism, EMT, multidrug resistance, and …

Investigating The Ability Of Foxo1 To Maintain Stem Cells, Stella A. Rios, Megan E. Keniry

Research Symposium

Background: Our group discovered that FOXO transcription factors drive stem gene expression in cancer to promote aggressiveness. Work by our group and others demonstrated that FOXO factors universally maintain stem cells including in cancer, embryonic, hematogenic and neuronal contents. Our current efforts are delineating the molecular underpinnings by which FOXO factors halt differentiation to maintain stem cells.

In this project, we are employing myoblasts as a valuable model to examine how Foxo1 maintains stem cells. Foxo1-regulated genes in myoblasts closely parallel its targets in glioblastoma and basal breast cancer stem cells, including targets such as Leukemia Inhibitory Factor, …

Uca1 As A Key Regulator Of The Warburg Effect During Anoikis Resistance In Colorectal Cancer Metastasis, Ricardo Pequeno Bracho, Salique Hassan Shaham, Yamile Abuchard Anaya, Sophia Leslie, Kyle Doxtater, Subhash Chauhan, Bilal Hafeez, Tamer Oraby, Manish K. Tripathi

Research Symposium

Colorectal carcinoma (CRC) is the second leading cause of cancer-related mortality in the United States. While localized CRC has a 90% five-year survival rate, this drops sharply to 14% upon metastasis. Metastasis occurs in approximately 40–50% of CRC cases and requires cancer cells to acquire anoikis resistance—a critical adaptation allowing survival after detachment from the extracellular matrix, enabling migration and colonization of secondary sites. Understanding the molecular mechanisms driving anoikis resistance, particularly those linked to altered glucose metabolism, is essential for developing targeted therapies for metastatic CRC.

Cancer cells frequently exhibit the Warburg Effect, a metabolic adaptation favoring glycolysis over …

Uncovering The Mechanisms Of Glioblastoma Relapse Prevention With Niclosamide And Camptothecin Treatment, Xiaoqian Fang, Araely Ruiz, Eunseo Yang, Brianna Morin, Kimberly Herrera-Toscano, Megan Szobody, Josue Fonseca, John-Beloved Osho, Raquel Lara

Research Symposium

Background: Glioblastoma multiforme (GBM) is the most common and lethal malignant primary brain tumor for which the development of efficacious chemotherapeutic agents remains an urgent need. In our previous studies, we demonstrated that niclosamide and camptothecin (CPT) synergistically suppressed the proliferation in human glioblastoma U87 MG cells. Recently, we observed that U87 MG cells failed to resume growth after the combined treatment was removed, a phenomenon not seen with either agent alone. We aimed to explore the sustained anti-tumor effects of niclosamide and CPT in GBM.

Methods: Human glioblastoma U87 MG cells were treated with 5 mM niclosamide, 5 mM …

Early Ctdna Kinetics As A Dynamic Biomarker Of Cancer Treatment Response, Aaron Li, Emil Lou, Kevin Leder, Jasmine Foo

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

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 …

A Genomics Driven Induced Pluripotent Stem Cell Model Of Infant Acute Lymphoblastic Leukemia - Early Results, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Molly Leyda, Priyanka Prem Kumar, Midhat Farooqi, Jay L. Vivian, Erin M. Guest, John M. Perry

Research Days

While the cure rates for pediatric ALL have improved over the decades, infants with ALL (iALL) have not benefitted from these advances and continue to have a devastating prognosis. Unfortunately progress in treatment has also been slowed by inadequate research models. With this project, we address this unmet need by investigating a novel model to understand the cellular and molecular changes that occur during iALL onset and progression.

Optimizing Immunotherapies For Improved Cancer Treatment, Anne Talkington, Anthony Kearsley

Biology and Medicine Through Mathematics Conference

No abstract provided.

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 …

Doxorubicin-Induced Nuclear Localization Of Scube3 Essential For Cell Survival In Tnbc, Ayooluwa Ilesanmi

Undergraduate Research Conference

Mediation of Doxorubicin-Induced SCUBE3 Nuclear Localization by A Functional NLS Involved in Pro-Tumorigenic Actions in Breast Cancer.

Signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) is a glycosylated secreted and cell membrane-associated protein considered a signature gene in cancers and known to mediate its actions in the cytoplasm where its localizes prior to its secretion. However, our study observed that SCUBE3 protein localized to the nucleus following doxorubicin (DOX) treatment. In this study, we investigated SCUBE3 nuclear localization in triple-negative breast cancer, intending to dissect the mechanism of its nuclear trafficking induced by DOX treatment. Bioinformatic analysis of the SCUBE3 protein sequence …

A Comparison Of In Vitro Studies Between Cobalt(Iii) And Copper(Ii) Complexes With Thiosemicarbazone Ligands To Treat Triple Negative Breast Cancer, Duaa R. Alajroush, Chloe B. Smith, Brittney F. Anderson, Ifeoluwa T. Oyeyemi, Stephen J. Beebe, Alvin A. Holder

Undergraduate Research Symposium

Triple negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer, and disproportionately affects African American women. TNBC cells lack the common hormone receptors that many pre-existing cancer treatments target. Fortunately, metal-based complexes with thiosemicarbazone ligands have gained significant attention for their potential as anti-cancer agents. Cobalt(III) complex ([Co(phen)2(MeATSC)](NO3)3•1.5H2O•C2H5OH]) and Copper(II) complex ([Cu(acetylethTSC)Cl]Cl•0.25C2H5OH) specifically have properties of high toxicity, which can contribute to decreased cancer cell activity. The effects of these complexes are currently being investigated on cancerous and non-cancerous breast cell lines. The cytotoxic effect of the cobalt(lll) complex and the copper(ll) complex was analyzed …

Trip13’S Crucial Role In Pancreatic Cancer Progression, Swati Dhasmana, Anupam Dhasmana, Stella Rios, Iris A. Enriquez-Perez, Sheema Khan, Farrukh Afaq, Upender Manne, Murali M. Yallapu, Subhash Chauhan

Research Symposium

Background: Pancreatic cancer, characterized by its high mortality rate, stands as one of the most aggressive cancer forms. The projected surge in pancreatic cancer-related deaths, making it the second leading cause in the United States by 2030, underscores the urgency for effective early screening tools. This study employs data mining methods to scrutinize bioinformatic data surrounding TRIP13. Examining differential expression across various cancers, correlating TRIP13 expression with pancreatic cancer stages, exploring associations with common cancer genes, and analyzing overall survival rates constitute the core investigations. Integrated with molecular biology techniques, the study further quantifies TRIP13 expression in progressive pancreatic cancer …

Human Blood Cell Isolation: The Critical First Step In Our Laboratory’S Immunobiology Experimental Protocals, Victor Rivero

UNO Student Research and Creative Activity Fair

HUMAN BLOOD CELL ISOLATION: THE CRITICAL FIRST STEP IN OUR LABORATORY’S IMMUNOBIOLOGY EXPERIMENTAL PROTOCALS

Victor Rivero1 Paul W. Denton1, [email protected]

1Department of Biology, University of Nebraska at Omaha, Omaha, NE

The Denton Immunobiology Laboratory focuses on enhancing human natural killer (NK) cell killing capabilities, particularly in the context of combating cancer. NK cells are immune cells that have the ability to kill diseased cells via two mechanisms: direct killing, and antibody-dependent cell-mediated cytotoxicity (ADCC). We recently published our novel approach to testing both methods of killing by using NK cells derived from the same human donor. Our testing approach allows …