Cancer Biology Commons^™

Microglia-Neuron Interactions In A Mouse Model Of Low Grade Neuroepithelial Tumors, Veolette Hanna

Honors Scholar Theses

Microglia are the macrophages of the brain and spinal cord, playing an important role in the immune response to disease states of the nervous system. This study conducts an investigation on the activity of microglia in response to low grade neuroepithelial tumors. Using mouse models and microglial markers, a qualitative and quantitative analysis of microglia activation, migration, and invasion within the brain cortex during early stages of tumor development was conducted. It was found that the presence of a low grade neuroepithelial tumor in the cortex of one hemisphere of the brain causes significant microglia activation in comparison to the …

Heterogeneous Nuclear Ribonucleoprotein K (Hnrnp K) Overexpression And Its Interaction With Runx1 Rna In Acute Myeloid Leukemia, Marisa Aitken

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is an often devastating hematologic malignancy with 5-year overall survival lingering near 20%. Acquiring a deeper understanding of molecular underpinnings of leukemogenesis will provide a basis for developing more effective therapeutic strategies for patients with AML.

Here, we identified overexpression of hnRNP K as a recurrent abnormality in a subset (~20%) of AML patients. High levels of this RNA-binding protein associated with inferior clinical outcomes in de novo AML. Thus, to evaluate its putative oncogenic capacity in myeloid disease, we overexpressed hnRNP K in murine hematopoietic stem and progenitor cells isolated from fetal liver cells (FLCs). …

486— Cell Cycle Effect On Hla Expression In Htb-4 And Mrc-5, Nick Turnquist, Andrew Kareeparampil

GREAT Day Posters

Human Leukocyte Antigen (HLA) is a gene that codes for cell-surface proteins that are the basis of our bodies’ immune response. We observed two cell lines, HTB-4 and a non-cancerous cell line known as MRC-5. Our purpose for this experiment was to observe the effect of the cell cycle on HLA expression for these cell lines. Two flasks were prepared for each cell line: one confluent and one non-confluent. Flow cytometry analysis was performed for each of the four flasks. The flow cytometry results of the MRC-5 cells indicate increased HLA expression in the confluent flask, in the G1 phase …

3d Mammalian Cell Culture Models In Toxicology Testing, Janith Wanigasekara, Brijesh K. Tiwari, James Curtin

Articles

3D cell culture can be successfully used as an alternative to laboratory animals, and as a cost effective and time-saving tissue culture technique, which also reduces the trial period for drug testing.

Molecular Mechanisms Underlying Migratory And Immune-Evasion Properties Of Circulating Tumor Cells, Jeannette A. Huaman

Dissertations, Theses, and Capstone Projects

Metastasis is the leading cause of cancer deaths worldwide. However, there exist only limited treatment options and they are often ineffective. An important aspect of metastasis that requires study, but has previously been understudied is circulating tumor cells (CTCs). CTCs are a critical step in the metastatic cascade. They can be analyzed for the identification of key mechanisms in metastasis. To this end, we isolated CTCs from a syngeneic mouse model of hepatocellular carcinoma (HCC) and a human xenograft mouse model of castration-resistant prostate cancer (CRPC). From these mouse models, primary tumor and CTC lines were established. Functional characterization of …

Microrna And Transcription Factor Co-Regulatory Networks And Subtype Classification Of Seminoma And Non-Seminoma In Testicular Germ Cell Tumors, Guimin Qin, Saurav Mallik, Ramkrishna Mitra, Aimin Li, Peilin Jia, Christine M. Eischen, Zhongming Zhao

Department of Cancer Biology Faculty Papers

Recent studies have revealed that feed-forward loops (FFLs) as regulatory motifs have synergistic roles in cellular systems and their disruption may cause diseases including cancer. FFLs may include two regulators such as transcription factors (TFs) and microRNAs (miRNAs). In this study, we extensively investigated TF and miRNA regulation pairs, their FFLs, and TF-miRNA mediated regulatory networks in two major types of testicular germ cell tumors (TGCT): seminoma (SE) and non-seminoma (NSE). Specifically, we identified differentially expressed mRNA genes and miRNAs in 103 tumors using the transcriptomic data from The Cancer Genome Atlas. Next, we determined significantly correlated TF-gene/miRNA and miRNA-gene/TF …

The Effects Of Rolipram, A Selective Phosphodiesterase Inhibitor, On Immortalized Schwann Cell Proliferation, Kyle Kenney, Amanda Bohn, Angela Asirvatham

Student Research Poster Presentations 2020

The regulation of Schwann cell growth in vitro is facilitated by heregulin, a neuron-secreted growth factor, and an unknown mitogen that activates the cyclic adenosine monophosphate (cAMP) pathway. The quantity of cAMP available to Schwann cells can determine if they become a myelinating or proliferating phenotype. The abundance of intracellular cAMP available to the cell is widely regulated by a family of enzymes called phosphodiesterases (PDEs). PDE inhibitors such as rolipram have therapeutic potential in various disorders and function by increasing the levels of cAMP in the cell. This study was undertaken to determine the concentration of rolipram that would …

Anti-Tumor Functions Of Sphingosine Kinase 1 And Sphingosine Kinase 2 In Breast Cancer Development, Melissa A. Maczis

Theses and Dissertations

Bioactive sphingolipid metabolite sphingosine-1‐phosphate (S1P) circulating levels have been implicated in breast cancer (BC) progression. BCs usually respond to 17β-Estradiol (E2) through canonical receptor ERα66 for genomic effects, however, E2 also triggers rapid, non-genomic responses. E2 has been shown to activate sphingosine kinase 1 (SphK1), increasing S1P for S1P receptors signaling important for BC. The E2 receptor activating SphK1 has not been identified. We demonstrate triple negative BC cells, expressing only novel ERα splice variant ERα36, E2-induced SphK1 activation for S1P secretion. Tamoxifen, first-line BC endocrine therapy, an ERα66 antagonist but ERα36 agonist, activates SphK1 and increases S1P secretion in …

Identification Of Imiquimod As A Potential Combination For Anti-Cd47 Antibodies In Cancer Therapy, Nicole Brittaney Pang

Scripps Senior Theses

The avenues of targeted immunotherapy offers a promise of less toxic treatment options for those battling different forms of cancer. Specifically, the process of hijacking a patient’s own immune system to fight cancer from within versus using external treatments like chemotherapy which is extremely damaging to the patient. One such avenue includes the usage of monoclonal antibodies as an effective modality for immunotherapy. Cluster of Differentiation 47 (CD47), also known as the ‘don’t eat me signal’, aids in cell proliferation and evasion of phagocytosis and has been found to be a target for stopping tumorigenesis. Previous research has been successful …

Evidence Of Y Chromosome Long Non-Coding Rnas Involved In The Radiation Response Of Male Non-Small Cell Lung Cancer Cells, Tayvia Brownmiller

Graduate Theses, Dissertations, and Problem Reports (ETD)

Non-small cell lung cancer (NSCLC) is the number one cause of cancer related mortality in the United States and worldwide. Advanced and therapeutically resistant lung tumors contribute to the high rate of mortality from NSCLC, therefore there is a need for new methods of diagnosing and treating this disease. Long non-coding RNAs (lncRNAs) have been shown to be a crucial component of human molecular biology, regulating nearly every cellular pathway from chromatin condensation to transcription and translation. Furthermore, many lncRNAs have been classified as oncogenes or tumor suppressors, highlighting the various molecular mechanisms they are involved in regarding the formation …

Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan

Theses and Dissertations

Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …

Sphingolipids In Cancer Health Disparities And As Prospective Targets For Cancer Therapy, April E. Boyd

Theses and Dissertations

Lung cancer is the deadliest cancer both in the United States and worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. However, lung cancer disparities are not shared equally across racial groups, with large differences between African American and Caucasian populations. Advances in research have revealed roles of lipid mediators in cancer biology and disease progression, but sphingolipid alterations in tissues should be explored further. To address this, using mass spectrometry (MS), extensive sphingolipidomic characterization of NSCLC tumors and adjacent uninvolved tissues from African American and Caucasian patients were performed. This study revealed that NSCLC …

Mechanism Of Bax/Bak Activation In Apoptotic Signaling, Kai Huang

Theses & Dissertations

The Bcl-2 family proteins, including the anti-apoptotic members, pro-apoptotic effectors Bax/Bak, and the BH3-only proteins, are key components of the mitochondrial apoptotic pathway. The BH3-only protein Bid is critical for the mitochondrial pathway of apoptosis after TRAIL-induced death receptor activation. However, the mechanism of Bid activation during TRAIL-induced apoptosis is unclear. By putting back wild-type and mutants of Bid in Bid deficient (Bid KO) and Bid/Bax/Bak TKO colon cancer cells, we demonstrated that cleavage by caspase 8 and mitochondrial targeting are critical events for Bid activation. One of the biggest mysteries in apoptosis is how Bax/Bak was activated by BH3-only …

Brca1 & Ctdp1 Brct Domainomics In The Dna Damage Response, Kimiko L. Krieger

Theses & Dissertations

Genomic instability is one of the enabling characteristics of cancer. DNA damage response pathways are important for genomic integrity and cell cycle progression. Defects in DNA damage repair can often lead to cell cycle arrest, cell death, or tumorigenesis. The activation of the DNA damage response includes tightly regulated signaling cascades that involve kinase phosphorylation and modular domains that scaffold phosphorylated motifs to coordinate recruitment of DNA repair proteins. Modular domains are conserved tertiary structures of a protein that can fold, function, and evolve independently from an intact protein. One of the most common modular domains involved in DNA damage …

In Vivo Metabolic And Vascular Response To Hypoxia In Twist Knockdown Murine Breast Cancer, Brandon Sturgill

Graduate Theses and Dissertations

Twist transcription factor is often overexpressed in aggressive tumors. Although needed in early embryonic development for organogenesis, Twist is known to induce an epithelial to mesenchymal transition in cells. In cancer, epithelial to mesenchymal transitions can lead to increased motility and invasiveness. It has also been linked to metabolic reprogramming and increased metastatic risk. Furthermore, metabolic preferences can increase proliferation, enhance metastatic potential, and influence the site of metastasis. We hypothesize that Twist directly affects the metabolism of cancer cells. We expect to see in vivo what we have seen in vitro; Twist overexpression should promote a shift away from …

Uncovering The Zeb1 Interactome To Identify Novel Regulators Of Metastatic Non-Small Cell Lung Cancer, Roxsan Manshouri

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States, due in part to the robust affinity of lung cancer cells to metastasize. Understanding the processes that contribute to metastasis provides promise for the discovery of novel therapeutic targets. Epithelial-tomesenchymal transition (EMT) is a proposed model for the initiation of metastasis. During EMT cell adhesion and polarity is reduced, allowing epithelial cancer cells to dissociate from the primary tumor and invade distant organs. The transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) has been reported to uniquely correlate with NSCLC disease progression and to …

Anti-Inflammatory Effects Of Cruciferous And Apiaceous Vegetables In C57bl/6j Mice Colon, Rosa Moreno Narvaez

Graduate Theses and Dissertations

Previous studies have demonstrated chemo-preventive potential of cruciferous and apiaceous vegetables against colon cancer. Colon inflammation is one condition closely related with colon cancer initiation. Therefore, we wanted to compare if total western diet (TWD) was as pro-inflammatory as died-induced obesity (DIO) and a better dietary model for human conditions, and determine if diet supplementation with cruciferous (broccoli, watercress and cabbage) or apiaceous vegetables (celery and parsnip) could reduce dietary inflammation, and which vegetable was more effective.

Male CBL57/6J mice were fed chow for seven days, on day eight, mice were assigned to one of the following diets: American Institute …

Anti-Cancer Effects Of Oleocanthal And Extra Virgin Olive Oil, Limor Goren

Dissertations, Theses, and Capstone Projects

Oleocanthal is a phenolic compound found in varying concentrations in extra virgin olive oil. Oleocanthal has been shown to be active physiologically, benefiting several diseased states by conferring anti-inflammatory and neuroprotective benefits. Recently, we and other groups have demonstrated its specific and selective toxicity toward cancer cells; however, the mechanism leading to cancer cell death is still disputed. The current study demonstrates that oleocanthal induced damage to cancer cells’ lysosomes leading to cellular toxicity in vitro. Non-cancer cells were significantly less affected. Lysosomal membrane permeabilization following oleocanthal treatment in various cell lines was assayed via three complementary methods. Additionally, …

Towards A Mathematical Model Of Motility Using Dictyostelium Discoideum: Proteins And Geometric Features That Regulate Bleb-Based Motility, Zully Santiago

Dissertations, Theses, and Capstone Projects

A variety of biological functions depend on actin organization. The organization of actin is tightly regulated by a plethora of extracellular and intracellular signaling, scaffolding, and actin-binding proteins. Dysfunctions in this regulation lead to immune diseases, increased susceptibility to pathogens, neurodegenerative diseases, developmental disorders, and cancer metastasis. A variety of actin-dependent processes, including cell motility, are regulated by several proteins of interest: Paxillin, a scaffolding protein; WASP, an actin nucleating protein; SCAR/WAVE, another WASP family actin nucleating protein; Talin, a cortex-to-membrane binding protein; Myosin II, an F-actin contracting motor protein; and Protein Kinase C, a protein kinase. D. discoideum cells …

Modeling Cancer Using Li-Fraumeni Syndrome Patient-Derived Induced Pluripotent Stem Cells, Ruoji Zhou

Dissertations and Theses (Open Access)

Li-Fraumeni syndrome (LFS) is an autosomal dominant disease caused by germline mutations in the gene TP53, which predispose individuals to a wide range of malignancies, including osteosarcoma and breast cancer. In the previous study, our group developed a novel disease model platform by reprograming LFS patients' fibroblasts to induced pluripotent stem cells (iPSCs), and further differentiate these iPSCs into mesenchymal stem cells (MSCs) then to osteoblasts (OBs), the cells from which osteosarcomas originate. Interestingly, LFS iPSC-derived osteoblasts recapitulated the osteosarcoma phenotype, creating “a bone tumor in a dish”. This “tumor in a dish” platform proved that LFS is an …

Deubiquitinating Enzymes Promote Cancer Progression And Metastasis Via Regulating Protein Stability, Zhenna Xiao

Dissertations and Theses (Open Access)

Deubiquitinating enzymes (DUBs, also called deubiquitinases) are enzymes that remove monoubiquitin or polyubiquitin chains from target proteins. DUBs have critical roles in cell homeostasis and signal transduction, as they regulate protein degradation, subcellular localization, and protein-protein interaction. Deregulation of DUBs contributes substantially to tumor formation and progression, and therefore targeting DUBs may be a promising cancer therapy strategy. My dissertation focuses on identifying the DUBs of EZH2 and SNAI1, two proteins critical for cancer progression and metastasis, and establishing these DUBs as promising anti-cancer targets.

EZH2, the catalytic component of the PRC2 complex, silences gene transcription by histone methylation. High …

Comparison Of Nickel And Cobalt Induced Hypoxic Cell Models Using Cell Proliferation Assay, Melissa Delcasale

Seton Hall University Dissertations and Theses (ETDs)

Hypoxia is an imbalance in oxygen delivery and oxygen consumption, ultimately affecting cell survival. Low levels of oxygen diminish adenosine triphosphate synthesis resulting from a decline in oxidative phosphorylation in the mitochondria, therefore inducing apoptosis and cell death. To create a hypoxia mimicked environment, we used hypoxia mimetic compounds cobalt and nickel to treat human neuroblastoma (NMB) cells. Using hypoxic mimic human neuronal cell models, we examined and compared the effects of compound-induced hypoxia on NMB cell proliferation. The cells were treated with 100mM and 300mM concentrations of each compound at 24- and 48-hour intervals. To investigate cell proliferation, the …

Phospho Tensin Homolog In Human And Lipid Peroxides In Peripheral Blood Mononuclear Cells Following Exposure To Flavonoids, William Y. Boadi, Elbert L. Myles, Alekzander S. Garcia

Biology Faculty Research

Objectives: Studies have shown that human and peripheral blood mononuclear cells (PBMCs) are mostly used for research purposes to study several biochemical endpoints. The effects of the flavonoids, genistein, kaempferol, and quercetin on phospho tensin homolog (PTEN) levels in cancer cells (i.e., breast [BT549], lung [A549]), human embryonic kidney cells (HEK293), and the levels of lipid peroxides (LP) in PBMCs were respectively investigated.

Materials and methods: Cancer, kidney, and PBMCs from several donors were each exposed to each of the flavonoids at concentrations of 0, 5, 10, 15, 20, and 25 µM. Our hypotheses were that exposure of cancer and …

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of …

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of …

The Role Of Zyxin And Limd1 In Mitosis And Cancer, Jiuli Zhou

Theses & Dissertations

The Hippo signaling pathway, originally discovered in Drosophila, consists of a core kinase cascade and has been subsequently demonstrated to control tissue growth and tumorigenesis. The core of this pathway contains MST1/2 (Mammalian sterile 20-like kinase 1/2), LATS1/2 (large tumor suppressor 1/2) and downstream effector named Yes-associated protein (YAP) and PDZ-binding motif (TAZ). MST1/2 transduce their kinase activity mainly through directly phosphorylating LATS1/2. Once phosphorylated and activated, LATS1/2 subsequently phosphorylate and inhibit YAP/TAZ from translocating to nucleus, thereby suppressing the expression of downstream pro-growth and survival genes. While recent studies provide important insight into the tumor suppressor properties of …

Identification Of Pathways Required For The Survival Of Inversion(16) Acute Myeloid Leukemia, Yiqian Wang

Theses & Dissertations

Inversion of chromosome 16 [inv(16)] acute myeloid leukemia (AML) generates a fusion gene CBFB-MYH11. Approximately half of inv(16) AML patients eventually relapse mainly due to the existence of leukemia stem cells (LSCs). Previous work using a Cbfb-MYH11 knockin mouse model showed that the LSCs are enriched within CSF2RB^- population. Another gene upregulated by Cbfb-MYH11 encodes the cytokine receptor IL1RL1. Using Cbfb-MYH11 knockin mice, we showed that LSCs exist in multiple sub-populations defined by their immunophenotype, and IL1RL1 is expressed by cell populations with high LSC activity. We also found that treatment of IL-33, the ligand for IL1RL1, promoted …

Developing Targeted Therapy Against Pancreatic Cancer, Garima Kaushik

Theses & Dissertations

Not available.

A Dedicated Chaperone Mediates The Safe Transfer Of Mitoribosomal Proteins To Their Site Of Assembly, Gabrielle Ashley Hillman

Graduate School of Biomedical Sciences Theses and Dissertations

Mitochondrial ribosomes are functionally specialized for the synthesis of several essential inner membrane proteins of the respiratory chain. While remarkable progress has recently been made towards understanding the structure of mitoribosomes, the unique pathways and factors that facilitate their biogenesis remain largely unknown. This dissertation defines the physiological role of an evolutionarily conserved yeast protein called Mam33 in mitochondrial ribosome assembly. The biomedical relevance of this finding stems from the fact that mutations or changes in its expression of the human ortholog p32 result in mitochondrial dysfunction. In human patients, bi-allelic mutations cause severe multisystemic defects in mitochondrial energy metabolism, …

The Signaling Pathways Of Metallothionein-Mediated Chemotaxis In Breast Cancer, Jennifer Messina

University Scholar Projects

Metallothionein (MT) is a small, thiol rich protein released into the extracellular environment in response to stress. Elevated expression of MT has been linked to many inflammatory diseases including inflammatory bowel diseases, diabetes, and cancer. In breast cancer, high expression of MT has been associated with poor patient prognosis. Previous studies have shown that MT acts as a chemoattractant in lymphocytes, and that UC1MT, a monoclonal anti-MT antibody, can block this chemotactic response. In addition, it has been shown that both Cholera toxin and Pertussis toxin, which are known antagonists of G-protein coupled receptors, can inhibit MT-mediated chemotaxis. Here, I …