Cancer Biology Commons^™

Development Of Ligand Guided Selection (Ligs) To Identify Specific Dna Aptamers Against Cell Surface Proteins, Hasan Ekrem Zumrut

Dissertations, Theses, and Capstone Projects

Oligonucleotide aptamers (nucleic acid-based affinity reagents) are an emerging class of synthetic molecules that display high affinity and specificity towards their targets. Aptamer molecules for a target of interest are obtained using a combinatorial chemistry-based method termed systematic evolution of ligands by exponential enrichment (SELEX). SELEX is an in vitro selection process in which a random oligonucleotide library is subjected to repeated cycles of target incubation, separation, and amplification until target-specific evolved sequences become prevalent in the library. Typically, SELEX is used against target molecules such as small molecules and proteins, in their purified state. However, aptamers selected against purified …

Rapamycin Treatment Correlates Changes In Primary Cilia Expression With Cell Cycle Regulation In Epithelial Cells, Maha Jamal, Ane C.F. Nunes, Nosratola D. Vaziri, Ramani Ramchandran, Robert L. Bacallao, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are sensory organelles that regulate cell cycle and signaling pathways. In addition to its association with cancer, dysfunction of primary cilia is responsible for the pathogenesis of polycystic kidney disease (PKD) and other ciliopathies. Because the association between cilia formation or length and cell cycle or division is poorly understood, we here evaluated their correlation in this study. Using Spectral Karyotyping (SKY) technique, we showed that PKD and the cancer/tumorigenic epithelial cells PC3, DU145, and NL20-TA were associated with abnormal ploidy. We also showed that PKD and the cancer epithelia were highly proliferative. Importantly, the cancer epithelial cells …

Good Works: Giving Back After Cancer, Gerry Boyle

Colby Magazine

David Pulver '63 turns his experience into a primer for patients

Determining How The Human T-Cell Leukemia Virus Type-1 (Htlv-1) Latency-Maintenance Factor P30ll Modulates Antioxidant- Signaling To Promote Oncogene Activation During Retroviral Carcinogenesis, Tetiana Bowley

Biological Sciences Theses and Dissertations

The Human T-cell Leukemia Virus Type-1 (HTLV-1) is a complex oncogenic deltaretrovirus that infects and transforms CD4+ T-lymphocytes and is the etiological agent of Adult T-cell Leukemia/Lymphoma (ATL). HTLV-1 latency-maintenance factor p30^II downregulates proviral gene expression at the transcriptional and posttranscriptional levels and aids in immune escape from the host immune surveillance. HTLV-1 p30^II competes with HTLV-1 transactivator Tax for binding to CBP/p300 coactivator; this competition determines if there is Tax-mediated transcription initiation or viral gene silencing induced by p30^II. Our research group has previously demonstrated that the HTLV-1 p30^II accessory protein induces the p53 …

The Anti-Proliferative Effects Of Methotrexate And Novel Ucp1162 On Acute Myeloid Leukemia Cell Lines, Jacqueline Klepinger, Charles Giardina, Didem Ozcan

Honors Scholar Theses

Cancer cells proliferate at rapid rates due to the aberrant activity of proteins involved in regulating the cell cycle. This characteristic allows mutated cancer cells to spread and metastasize, causing lesions to form throughout the body. Two treatment conditions, one classical antifolate methotrexate (MTX) and non-classical, novel antifolate UCP1162, were tested on a panel of acute myeloid leukemia (AML) cell lines to determine if UCP1162 has higher anti-proliferative activity. High dose MTX is used as a first line chemotherapy in common childhood malignancies such as acute lymphoid leukemia (ALL). Methotrexate is excluded from acute myeloid leukemia (AML) treatments based on …

Molecular Insights Into Paf-1 Mediated Pancreatic Homeostasis, Stemness, And Cancer Progression, Saswati Karmakar

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease that has one of the lowest 5-year survival rates among cancers, at just 9%. This grim prognosis is primarily due to the extensive metastatic spread of tumor cells beyond the pancreas at diagnosis and the inability of current therapeutic modalities to treat this aggressive disease effectively. Given that the cancer cells in pancreatic tumors are heterogeneous, the major culprit for cancer initiation, progression, and metastasis remains elusive. Recent studies provide evidence for the existence of highly tumorigenic and drug-resistant cells that are capable of tumor initiation, known as the cancer stem cells …

Mitochondrial Metabolism As A Therapeutic Target For Pancreatic Cancer, Simon Shin

Theses & Dissertations

Mitochondria are biosynthetic and bioenergetic hubs that confer cancer cells the metabolic flexibility to survive and grow in harsh tumor microenvironments. Accordingly, mitochondrial metabolism represents a promising target for pancreatic ductal adenocarcinoma (PDAC), which is frequently characterized as desmoplastic and nutrient poor. The findings presented in the first set of studies highlight the importance of mitochondria-dependent metabolic flexibility in PDAC cells upon exposure to acidic conditions. An acidic tumor microenvironment is a common feature of many solid tumors and exerts a profound influence on cancer biology. Similar to previous findings, we demonstrated that low extracellular pH induces epithelial-to-mesenchymal transition (EMT) …

Dimers Of Isatin Derived Spirocyclic Nf-Κb Inhibitor Exhibit Potent Anticancer Activity By Inducing Upr Mediated Apoptosis, Smit Kour

Theses & Dissertations

Activation of NFκB pathway has been implicated in several malignancies and plays a role in many key processes including tumor initiation and progression. The NFκB pathway is activated when TNFα in the tumor microenvironment binds to its receptor, eventually leading to the phosphorylation of the kinase IKKβ. Once active, IKKβ phosphorylates IκBα, a protein that functions to sequester NFκB in the cytosol of resting cells. The phosphorylation of IκBα leads to its degradation in the proteasome and allows NFκB to translocate to the nucleus where it can drive gene transcription. The sulfhydryl groups on solvent-exposed cysteine (Cys) residues of the …

Breast Cancer Sub-Clones That Metastasize To Lung And Bone Exhibit Different Metabolic Preferences, Mollie Merrell

Honors Theses

Metastasis is responsible for the majority of cancer related deaths. In breast cancer the lungs and bones are the major sites for metastasis. Previous studies used the metastatic aggressive MDA-MB-231 breast cancer line to isolate sub-clones that preferentially invade the lungs (LM line) or bones (BoM line). While genes associated with the tissue specific metastasis have been identified, it is unknown if metabolic adaptations contribute to the growth of the LM and BoM lines in their respective organs. The goal of this study was to test the hypothesis that the LM and BoM lines exhibit differences in glucose and glutamine …

Glucose Metabolism Of Breast Cancer Sub-Clones That Preferentially Metastasize To The Lungs And Bone, Anna G. Skubiz

Honors Theses

Malignant breast cancers exhibit preferential metastasis to bone and lung (1). While changes in gene expression in lung-specific (LM) and bone-specific metastasis (BoM) lines derived from the MDA-MB-231 breast cancer line have been identified, few metabolic genes are differentially expressed; thus it is unknown if tissue-specific metabolic reprogramming occurs. Two hallmarks of cancer cells are an altered metabolic phenotype characterized by enhanced conversion of glucose to lactate in spite of adequate oxygen availability for complete mitochondrial oxidation of this substrate (referred to as aerobic glycolysis or the Warburg effect) and a greater dependence on glutamine. These changes in primary tumor …

Cell Proliferation And Viability Inhibition By Resveratrol On Breast Cancer Cell Lines, Kyle Ford Gordon Jr

Honors Theses

Antioxidants are well-known for their various health benefits. They are able to protect cells from being damaged by free radicals that are produced by vital biochemical processes. It has long been known that antioxidants are important in our everyday health, but their potential as disease preventers and potential therapeutic agents is a relatively new field of study. Resveratrol, a natural polyphenol and well-known antioxidant, is found in plants, fruits, and products derived from them, like red wine. Resveratrol has been shown to have various properties, including antiaging, anti-aggregation of platelets, anti-inflammatory, and anticancer activities. Because of their many health benefits, …

Design Of A 3d Printed Bioreactor For Bone Cancer Research, Brooklyn K. Vanderwolde, Katelyn Hillson

The Journal of Undergraduate Research

Bone cancer is an aggressive disease and has peak occurrence during physiological stimulation of growth and aging. Astronauts who undergo long-term space missions also acquire an increased risk of bone tissue degeneration and cancer. Few in-vitro models currently exist capable of reproducing the complex microenvironment of bone tissue to support multicellular activity in a three-dimensional structure. This limits the ability to understand disease progression and develop suitable treatment strategies. Therefore, developing a bone tissue model and an associated bioreactor is critical to understand the risks associated with cancer progression and improve treatment and preventions related to those risks. The goal …

Neurocognitive Risk Factors And Current Intervention Strategies For Survivors Of Pediatric Acute Lymphoblastic Leukemia, Abigail Taber

Senior Honors Theses

The improved survival rate for pediatric cancer patients is one of the greatest triumphs of recent medicine, but the late effects faced by these survivors have been uncovered through this new population of survivors. Many survivors of pediatric acute lymphoblastic leukemia (ALL) experience cognitive deficits in areas such as attention, memory, processing speed, and academic achievement following cancer treatment. Recent research has pointed to chemotherapeutic agents, host risk factors, and genetic predispositions as perpetrators of these deficits, although other factors are also under investigation. Consequently, the search for appropriate interventions for the amelioration of these deficits has dominated the literature …

Effects Of Penfluridol On Integrin-Fak Signaling And Tumor Cell Killing In Combination With Oncolytic Hsv In Glioblastoma, Mitra Nair

Dissertations and Theses (Open Access)

Integrins are known to play an important role in activating multiple intracellular pathways, one of which is focal adhesion kinase (FAK). Phosphorylation of FAK can lead to the activation of various downstream signaling pathways that can increase tumor cell growth and proliferation, making it an ideal target for cancer therapeutics. Due to the fact that many FAK inhibitors are limited in their penetration of the blood brain barrier, we investigated the use of Penfluridol, an antipsychotic drug known to attenuate integrin expression at a transcriptional level, in combination with oncolytic herpes simplex I virus (oHSV) in a glioblastoma model. We …

Preliminary Study: Leucine Supplementation Exacerbates Muscle Wasting Independent Of The Ubiquitin-Proteasome System, Katarina Bejarano

Graduate Theses and Dissertations

Cancer cachexia is the rapid, drastic loss of muscle mass associated with cancer and is not reversible by conventional nutritional means (Brown et al., 2018; Brown et al., 2017). It occurs in ~80% of cancer patients and is responsible for 20-40% of cancer-related deaths (Brown et al., 2018; Brown et al., 2017). This condition leaves patients with fatigue, functional impairment, reduced quality of life, and a decrease in survival rates. Cachexia occurs through an imbalance between protein degradation and protein synthesis (Brown et al., 2018), which is associated with inflammation and altered metabolic processes.

Several studies have investigated the effects …

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 …

Size-Dependent Inhibitory Effects Of Antibiotic Nanocarriers On Filamentation Of E. Coli, Preeyaporn Songkiatisak, Feng Ding, Pavan Kumar Cherukuri, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Multidrug membrane transporters exist in both prokaryotic and eukaryotic cells and cause multidrug resistance (MDR), which results in an urgent need for new and more effective therapeutic agents. In this study, we used three different sized antibiotic nanocarriers to study their mode of action and their size-dependent inhibitory effects against Escherichia coli (E. coli). Antibiotic nanocarriers (AgMUNH–Oflx NPs) with 8.6 × 10², 9.4 × 10³ and 6.5 × 10⁵ Oflx molecules per nanoparticle (NP) were prepared by functionalizing Ag NPs (2.4 ± 0.7, 13.0 ± 3.1 and 92.6 ± 4.4 nm) with a monolayer …

Receptor Tyrosine Kinases-Mediated Acquired Parp Inhibitor Resistance In Breast Cancer, Mei-Kuang Chen

Dissertations and Theses (Open Access)

Leveraging compromised DNA damage repair (DDR) pathways commonly found in tumor cells, a classic strategy in cancer therapy is inducing excessive DNA damage to cause cancer cell death. Small molecule poly(ADP-ribose) polymerase (PARP) inhibitors (PARP-is) have been approved for clinical use in treating breast cancer and ovarian cancer patients bearing DDR-deficient tumors with mutations in breast cancer susceptibility genes (BRCA^m). However, accumulating evidences show that both intrinsic and acquired resistances to PARP-is exist in clinic and pre-clinical animal models. Therefore, I developed panels of cells with acquired PARP-is resistance from PARP-is-sensitive triple negative breast cancer (TNBC) cell …

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). …

Effect Of Sympathetic Nervous System Mediators On The Tumor Microenvironment Via Small Extracellular Vesicles In Ovarian Cancer, Sujanitha Umamaheswaran, Sujanitha Umamaheswaran

Dissertations and Theses (Open Access)

Effect of sympathetic nervous system mediators on the tumor microenvironment via small extracellular vesicles in ovarian cancer

Sujanitha Umamaheswaran, BTech

Advisor: Anil K. Sood, MD

Background:Psychological stress can promote progression of gynecological malignancies by increasing secretion of sympathetic nervous system (SNS) mediators, namely catecholamines. However, the mechanisms underlying these effects are poorly explored. Here, we examined the effect of stress hormones on small extracellular vesicles (EVs) release in gynecological malignancies and the biological impact of these stress-conditioned EVs on the tumor microenvironment.

Methods:Supernatants were collected from epithelial ovarian cancer cell lines treated with norepinephrine, epinephrine or hydrocortisone. Small EVs were …

Impact Of Epa And Dha Supplementation And 15-Lox-1 Expression On Colitis And Colitis-Associated Colorectal Cancer, Jonathan Jaoude

Dissertations and Theses (Open Access)

Inflammatory bowel disease (IBD) patients not only suffer from colitis but also from increased morbidity and mortality of colitis-associated colorectal cancer (CAC). The enzyme 15-lipoxygenase-1 (15-LOX-1) is crucial to converting omega-3 fatty acid derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to resolvins, potent anti-inflammatory products. 15-LOX-1 effects on the conversion of EPA and DHA to resolvins that subsequently exert anti-inflammatory and anti-tumorigenic effects have received little attention. To address this knowledge gap, we hypothesize that 15-LOX-1 expression in colonic epithelial cells is essential for resolvin biosynthesis from EPA and DHA to modulate immunophenotype, limit inflammation, promote resolution, and help …

Exosomal Communication By Metastatic Osteosarcoma Cells Modulates Alveolar Macrophages To An M2 Tumor-Promoting Phenotype And Inhibits Tumoricidal Functions, Kerri Wolf

Dissertations and Theses (Open Access)

Osteosarcoma metastasizes to the lung, and there is a link between the predominance of tumor promoting immunosuppressive M2 macrophages in the metastases and poor patient survival. By contrast, M1macrophage predominance correlates with longer survival. M2 macrophages can be induced by various stimuli in the tumor microenvironment, including exosomes, which are 40- to 150-nm vesicles that are involved in intercellular communication and contribute to tumor progression and immune evasion. Recognizing that tumor cells can influence the tumor microenvironment to make it more permissive and because of the link between M2 dominance and curtailed patient survival, we evaluated the effect of …

Inhibition Of The Spectraplakin Protein Microtubule Actin Crosslinking Factor 1 Sensitizes Glioblastomas To Radiation, Kala Bonner, Danielle Borlay, Orica Kutten, Quincy A. Quick

Biology Faculty Research

Background

Microtubule actin crosslinking factor 1 (MACF1) is a spectraplakin cytoskeletal crosslinking protein whose function and role in cancer biology has lacked investigation. Recent studies have identified MACF1 as a novel target in glioblastomas expressed in tissue from tumor patient explants but not normal brain tissue and when silenced has an antitumorigenic impact on these tumors. Radiation as a single agent therapy to treat glioblastomas has been used for decades and has done little to improve survival of individuals diagnosed with this disease. However, contemporary clinical radiotherapy protocols have provided evidence that combinatorial radiotherapy approaches confer a therapeutic benefit in …

Exploring Occupational Disruption In Newly Diagnosed Individuals With Cancer With Minor (Dependent) Children, Riley S. Harrold

Student Capstone Papers

Background: According to the American Cancer Society (2019), there were more than 1.7 million new cases of cancer in 2019 alone. Individuals are being diagnosed at a young age with 22.4% of cases occurring in individuals 22-55 years old and whom are childrearing age (Shah et al., 2017). There are an estimated 2.85 million children under the age of 18 who are living with a parent who has cancer (Shah et al., 2017). Newly diagnosed individuals face changes in daily life, the threat of possible death, and fear of dying (Compas et al., 1994). Changes in shared family roles …

365— Clobetasol-Induced Quiescence In The Vulvar Carcinoma Cell Line Umscv-4 Can Be Overcome By Repeated Removal And Re-Exposure To This Ultrapotent Corticosteroid, Nolberto Jaramillo Jr., Nina Mustico

GREAT Day Posters

Vulvar cancer is rare, mostly afflicting women aged 60 and older. The cancer is often preceded by a common vulvar rash, Lichen sclerosis, that is usually treated with the ultra-potent corticosteroid, clobetasol propionate. This treatment may, in turn, be associated with vulvar carcinogenesis. Quiescence, a common characteristic of stem cells, is a reversible state of growth arrest. Our results suggest that clobetasol is causing UMSCV-4 vulvar carcinoma cells to enter quiescence, and may allow them to evade the standard treatments that target rapidly proliferating populations. Furthermore, when these cells are removed from clobetasol and re-exposed, they proliferate at higher levels. …

147— The Effect Of A Histone Deacetylase Inhibitor On Pd-L1, Hla-Abc, Hla-E, And Hla-G On Human Breast Cancer Cell Lines, Nikhil Reddy, Alec Toufexis

GREAT Day Posters

Increased expression of human leukocyte antigen (HLA) allows tumor cells to be more easily detected by the immune system. In previous research, epigenetic modifiers including the histone deacetylase inhibitor 3 (HDAC3), RGFP966, has been shown to decrease PD-L1 expression. PD-L1 expression inhibits T cell cytotoxicity, and decreasing it can enhance the immune response. We hope to elucidate whether or not HLA-ABC expression similarly decreases upon exposure to the HDAC3 inhibitor which would be detrimental to immune detection. Two breast cancer cell lines that express HLA-ABC are MCF-7 and MDA-MB-231. Our initial results show that HLA-ABC is expressed on the MDA-MB-231 …

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 …

Microrna Expression Profiling Of Normal And Malignant Human Colonic Stem Cells Identifies, Vignesh Viswanathan, Lynn Opdenaker, Shirin Modarai, Jeremy Z Fields, Gregory Gonye, Bruce M Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

MicroRNAs (miRNAs) have a critical role in regulating stem cells (SCs) during development, and because aberrant expression of miRNAs occurs in various cancers, our goal was to determine if dysregulation of miRNAs is involved in the SC origin of colorectal cancer (CRC). We previously reported that aldehyde dehydrogenase (ALDH) is a marker for normal and malignant human colonic SCs and tracks SC overpopulation during colon tumorigenesis. MicroRNA expression was studied in ALDH-positive SCs from normal and malignant human colon tissues by Nanostring miRNA profiling. Our findings show that: (1) A unique miRNA signature distinguishes ALDH-positive CRC cells from ALDH-positive normal …

Cold-Inducible Rna Binding Protein (Cirp) Impedes Proliferation And Inflammation In The Pymt Mouse Model For Breast Cancer, Daniel Albino Lujan

Biomedical Sciences ETDs

RNA binding proteins (RBPs) regulate gene expression by controlling mRNA export, translation, and stability. When altered, some RBPs allow cancer cells to grow, survive, and metastasize. Cold-inducible RNA binding protein (CIRP) is overexpressed in a subset of breast cancers, induces proliferation in breast cancer cell lines, and inhibits apoptosis. We generated a transgenic mouse model overexpressing human CIRP in the mammary epithelium to ask if it plays a role in mammary gland development. We also assessed the effects of CIRP on breast tumorigenesis using breeding crosses with the PyMT mouse model for breast cancer. CIRP decreased proliferation at the lactational …

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.