Biology Commons^™

Nonsurgical Approaches To Glioblastoma, Moshe Baitelman

The Science Journal of the Lander College of Arts and Sciences

Due to the sensitivity of location, brain cancer is one of the most difficult and deadly known cancers. There are various forms of cancer in the brain with many shared characteristics as well as unique manifestations in each. While cancers originating in the central nervous system present in several ways, the most common forms are high grade gliomas generally, and glioblastoma or anaplastic astrocytomas specifically. With the advent of technology, researchers have been able to propose and refine extensive profiles of these relentless tumors, enabling greater and more successful treatment profiles to be developed. Where treatments used to consist primarily …

Effects Of Diabetes On Ovarian Cancer: Data Analysis And Modeling Study, Claire Belay

Theses and Dissertations

Ovarian cancer has one of the highest mortality rates of all gynecological cancers [13]. Further knowledge of risk factors for the growth of ovarian tumors would be beneficial in both the treatment and prevention of this type of cancer. Previous research has shown a positive correlation between diabetes and prostate tumor growth [22], The first aim of this study was to determine the effect of diabetes of ovarian tumor growth. The second aim was to develop a model to predict ovarian tumor growth based on the microenvironment within a patient’s body. The hypothesis was that there would be a positive …

Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh

Theses and Dissertations

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …

Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie

Theses and Dissertations

Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug …

Ikbke Inhibits Tsc1 To Activate The Mtor/S6k Pathway For Oncogenic Transformation, Serkan İsmai̇l Göktuna

Turkish Journal of Biology

IKBKE (IKK?) has emerged as a key modulator of multiple substrates, controlling oncogenic pathways in various malignancies. mTOR signaling, required for cellular growth, proliferation, and vascular angiogenesis in cancer, is potentially one of the pathways regulated by IKK?. Upon activation by various stimuli, PI3K/AKT or similar effectors can relieve the inhibitory effect of the TSC1/TSC2 complex through their phosphorylation to favor mTOR/S6K activation in the downstream. Therefore, any activity that interferes with PI3K/AKT or their downstream targets, such as TSC1/2 or GSK3?/ß, may activate the mTOR/S6K pathway for oncogenic transformation in normal cells. Previous studies have shown that PI3K/AKT can …

The Effect Of Twist Silencing In Metastatic Chordoma Cells, Esra Aydemi̇r, Ezgi̇ Kaşikci, Burcu Coşkunçelebi̇, Ömer Faruk Bayrak, Fi̇kretti̇n Şahi̇n

Turkish Journal of Biology

Chordoma is a slowly growing and invasive bone tumor with a tendency to metastasize locally in advanced stages. It is essential to discover new therapeutics that target genes involved in the metastasis of chordoma. Epithelial-mesenchymal transition (EMT) might robustly influence the metastasis of a tumor bulk. To our knowledge, this is the first time to show that EMT might have a role in chordoma metastasis. In this study, we aim to investigate the possible role of Twist, a key player transcription factor of EMT, in chordoma metastasis. The TWIST gene was silenced by short hairpins in chordoma cell line MUG-Chor1 …

In Vitro Anticancer Effect Of Tricyclic Antidepressant Nortriptyline On Multiple Myeloma, Ayşenur Bi̇ber, İpek Zeynep Durusu, Can Özen

Turkish Journal of Biology

Drug repurposing has been proved to be an effective strategy to meet the urgent need for novel anticancer agents for multiple myeloma (MM) treatment. In this work, we aimed to investigate the anticancer effect and mechanism of tricyclic antidepressant nortriptyline (NTP) on the U266 MM cell line. The in vitro inhibitory effect of NTP at various doses and time points was studied. The combination potential of cisplatin-NTP was also investigated. Cell cycle analysis and three flow cytometric apoptosis assays were performed. NTP showed dose- and time-dependent inhibitory effects on the U266 MM cell line. NTP had greater inhibitory effect than …

Investigation Of Moringa Oleifera Leaf Extract And Its Cancer-Selective Antiproliferative Properties, Reagen H. Welch, Ashlee H. Tietje

Journal of the South Carolina Academy of Science

Moringa oleifera is a tree native to a number of Asian, African, and Central American countries and has been used in traditional medicine for an assortment of medicinal uses for centuries. Due to bioactive compounds within Moringa leaves, it is believed that Moringa leaf extract may possess cancer-selective antiproliferative properties. Previous research has been conducted in regards to this topic, but poor experimental design due to lack of necessary controls limits the legitimacy of anticancer claims. While previous research has shown that Moringa leaf extract has the potential to kill cancer cells, the research fails to demonstrate the effects of …

Mechanisms And Regulation Of Resection In Dna Damage Response, Sharad C. Paudyal

Arts & Sciences Graduate Student Theses and Dissertations

Deoxyribonucleic acid (DNA) encodes genetic information essential for cell survival and function. However, it is constantly under assault from endogenous and exogenous damaging agents that not only threaten our own survival but also affect the faithful transmission of genetic information to our offspring. Double-strand breaks (DSBs) are one of the most hazardous forms of DNA damage, which if unrepaired or improperly repaired could lead to plethora of systemic human diseases including cancer. To deal with this problem, cells have evolved with a mechanism called DNA damage response (DDR) to detect, signal, and repair the breaks by inducing multiple cellular events. …

Designing Epigenome Editing Tools To Understand The Functional Role Of Dna Methylation Changes In Cancer, James Mcdonald

Arts & Sciences Graduate Student Theses and Dissertations

DNA methylation is known to silence gene expression in the context of imprinting, X-chromosome inactivation, and retrotransposon silencing. However, the role of DNA methylation in silencing gene expression outside of these contexts is not fully understood. This is especially true in diseases such as cancer, where normal DNA methylation patterns are significantly altered. In breast cancer as well as nearly all cancer types, most of the genome loses DNA methylation while small regions of the genome gain methylation. DNA methylation generally correlates with decreased gene expression when present at a gene promoter. Therefore, these regions of hypo- and hyper-methylation may …

Dna Replication Challenges: Telomeres And R Loops, Shankar Parajuli

Arts & Sciences Graduate Student Theses and Dissertations

Faithful DNA replication and repair are essential for maintaining genome stability and preventing various diseases including cancer. Both processes are executed by numerous redundant mechanisms to ensure that these processes are uninterrupted even when a primary mechanism fails. Despite this, they are not immune to challenges and failures leading to DNA damage and genome instability. These problems are more evident at the difficult-to-replicate regions of the genome such as the telomeres that cap and protect linear chromosome ends. Additionally, topological structures such as RNA:DNA hybrids, commonly referred to as R loops, can also present severe challenges to the DNA replication …

Clinical And Therapeutic Significance Of Obesity In Melanoma, Jennifer L. Mcquade

Dissertations and Theses (Open Access)

While the FDA approval of targeted and immune therapies in metastatic melanoma (MM) have dramatically improved outcomes in this disease, de novo and/or acquired resistance can limit the clinical benefit of these agents. The IGF-1/PI3K/AKT pathway has been implicated in resistance to both targeted and immune therapy. The IGF-1/PI3K/AKT pathway has also been shown to play a key role in the pathogenesis of obesity in other malignancies. To date, the impact of energy balance on clinical outcomes and therapeutic response in MM has not been studied. I hypothesized that energy balance would impact the molecular biology, behavior, and drug sensitivity …

Basigin-2 Mediated Activation Of Erk1/2 Signaling In Human Glioblastoma Multiforme Cells, Erik R. Peterson

All NMU Master's Theses

Glioblastoma multiforme (GBM) is the most common malignant form of human brain cancer. GBM tumor cells overexpress the protein Basigin (Bsg) at the cell surface where it contributes to malignancy via stimulation of matrix metalloproteinase (MMP) expression in surrounding normal tissues, resulting in the degradation of the extracellular matrix (ECM) surrounding tumors, promoting remodeling of the tumor borders, stimulating growth. In work by Belton et al. (2008), human uterine endometrial cells treated with a recombinant form of human basigin possessing the extracellular domain of the Bsg protein (rBsg-ECD) showed activation of the Mitogen-Activated Protein Kinase (MAPK) signaling pathway proteins, ERK1/2. …

Transition From Cardiovascular Disease To Cancer As The Leading Cause Of Death In Us States, 1999-2014, Michael C. Harding, Evan Thacker

Journal of Undergraduate Research

In 1900 the three leading causes of death in the United States were pneumonia and influenza; tuberculosis; and gastritis, enteritis, and colitis.¹ However, through a combination of improved sanitation, the discovery of antibiotics, and the advent of vaccination programs, deaths from infectious diseases subsided and soon gave way to chronic diseases.² Shortly after the turn of the century, diseases of the heart became of the number one cause of death, and in the 1940s, cancer began consistently appearing at number two. Since then, heart disease and cancer have remained firmly entrenched as the number one and two causes …

Splice Site Predictor, Mark Wadsworth, Dr. Perry G. Ridge

Journal of Undergraduate Research

With the advent of nextgeneration sequencing, one of the unintended consequences is the sheer number of genomic variations requiring interpretation. Mutations in splice sites have been shown to contribute to the development of cancer [1], and dementia [2] among other potentially deadly disorders. Roughly 14 million people are diagnosed with cancer every year [3], and roughly 7 million with dementia [4]. Since these diseases cause an incredible amount of suffering, scientists in all fields are driven to search for ways to identify and treat them. These have been particularly difficult to interpret and have been largely ignored by the bioinformatics …

Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck

Arts & Sciences Graduate Student Theses and Dissertations

Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, …

Nutritional Effects On Age-Related Changes In T-Cell Differentiation And Function, Michelle Chen

Whittier Scholars Program

T-cells are a type of white blood cell that in our bodies, scanning for cellular abnormalities and infections, thus making them essential for human immunity. However, due to the effects of aging, our bodies diminish the production of T cells and as a result, elderly individuals do not respond to immune disturbance as robustly as young individuals. In this experiment, I am examining the Jurkat T-cell, a human T lymphocyte cell line, viability at different treatment concentrations of the natural compounds, resveratrol and curcumin, and two cancer treatment drugs, cisplatin and bleomycin. These natural compounds, resveratrol and curcumin, have been …

The Effect Of Nullomer-Derived Peptides 9r, 9s1r And 124r On The Nci-60 Panel And Normal Cell Lines, Abdelkrim Alileche, Greg Hampikian

Biology Faculty Publications and Presentations

Background: Nullomer peptides are the smallest sequences absent from databases of natural proteins. We first began compiling a list of absent 5-amino acid strings in 2006 (1). We report here the effects of Nullomer-derived peptides 9R, 9S1R and 124R on the NCI-60 panel, derived from human cancers of 9 organs (kidney, ovary, skin melanoma, lung, brain, lung, colon, prostate and the hematopoietic system), and four normal cell lines (endothelial HUVEC, skin fibroblasts BJ, colon epithelial FHC and normal prostate RWPE-1).

Methods: NCI-60 cancer cell panel and four normal cell lines were cultured in vitro in RPMI1640 supplemented with 10% Hyclone …

Th1 Cells In Cancer-Associated Inflammation, Güneş Di̇nç Akbulut, Di̇dem Özkazanç, Güneş Esendağli

Turkish Journal of Biology

The immune system is not only evolved to protect the body from pathogens, but it also recognizes and eliminates cancer cells. CD4+ helper T (Th) lymphocytes are central intercessors differentiated according to the character of physiological or pathological status. Generation of type 1 Th (Th1) cells is primarily associated with a pathological insult that must be removed through immune elimination. Upon interacting with other immune and transformed cells, Th1 cells can hamper cancer progression. Therefore, it is a major obstacle for tumor cells to become insensitive or resistant to Th1-oriented actions. The organism employs various mechanisms to return to a …

The Human Arf Tumor Suppressor Regulates Drosha Nucleolar Localization And Rrna Processing Activity, Sree Chandana Sridhar Yaddanapudi

Arts & Sciences Graduate Student Theses and Dissertations

Ribosomes are vital to the survival of a cell, as they are directly responsible for the synthesis of proteins, which perform critical cellular functions. As such, majority of the energy reserves in a proliferating cell are expended towards synthesis of ribosomes. Cancer cells, with their enhanced proliferation rates, tend to upregulate ribosome biogenesis in order to meet the demand for increased protein synthesis necessary to sustain rapid proliferation. Many of the oncogenes and tumor suppressors known to be deregulated in cancers are capable of positively and negatively regulating ribosome biogenesis, respectively. The ARF tumor suppressor strongly suppresses ribosome biogenesis, particularly …

The P38mapk-Mk2-Hsp27 Axis Regulates The Mrna Stability Of The Pro-Tumorigenic Senescence-Associated Secretory Phenotype, Hayley Reynolds Moore

Arts & Sciences Graduate Student Theses and Dissertations

Protecting the genome is a vital aspect of safeguarding organismal health. Inability to efficiently and effectively replicate the genome or repair damage the genome may encounter can lead to mutational accumulation or senescence, both of which are drivers of multiple diseases including cancer. Understanding the mechanisms by which the genome is maintained, as well as the consequences of repeated rounds of replication or exposure to DNA damaging agents, will allow for greater understanding of the diseases they promote as well as development of targeted therapies aimed at mitigating the detrimental effects of genomic insult. The first section of my work …

Semaphorin3a Increases Focal Adhesion Formation To Shift The Relationship Between Cell Migration And Substratum Concentration Through A Rock-Dependent Mechanism, Frances V. Compere, Scott Gehler

Celebration of Learning

Cell migration is essential for many life processes, including wound healing, embryonic development and cancer metastasis. Cells move across a surface by interacting and forming adhesions with the molecules in their environment, specifically the extracellular matrix. Past studies have shown that there is an optimal level of cell-substratum adhesive strength that allows for the most cell migration and spreading (DiMilla et al., 1993; Gaudet et al., 2003). The mechanism by which this works is not well understood, however. Semaphorin 3A (Sema3A) has been shown to increase the expression of integrin receptors, which help mediate the formation of the adhesions between …

Mechanism Of Action And Applications Of Interleukin 24 In Immunotherapy, Leah Persaud, Dayenny De Jesus, Oliver Brannigan, Maria Richiez-Paredes, Jeannette Huaman, Giselle Alvarado, Linda Riker, Gissete Mendez, Jordan Dejoie, Moira Sauane

Publications and Research

Interleukin 24 (IL-24) is an important pleiotropic immunoregulatory cytokine, whose gene is located in human chromosome 1q32-33. IL-24’s signaling pathways have diverse biological functions related to cell differentiation, proliferation, development, apoptosis, and inflammation, placing it at the center of an active area of research. IL-24 is well known for its apoptotic effect in cancer cells while having no such effect on normal cells. IL-24 can also be secreted by both immune and non-immune cells. Downstream effects of IL-24, after binding to the IL-20 receptor, can occur dependently or independently of the JAK/STAT signal transduction pathway, which is classically involved in …

The Role Of Dnmt3a In Acute Myeloid Leukemia Pathogenesis, Christopher Browning Cole

Arts & Sciences Graduate Student Theses and Dissertations

Loss of function mutations in the DNA methyltransferase DNMT3A are highly recurrent in acute myeloid leukemia (AML). DNMT3A and the highly homologous gene DNMT3B encode the two methyltransferases that are primarily responsible for mediating de novo methylation of specific DNA sequences during cellular differentiation. DNMT3A mutations are mutually exclusive of several translocations that create oncogenic fusion genes (PML-RARA, RUNX1-RUNX1T1, CBFB-MYH11, and MLL-X), suggesting that these fusions may require functional DNMT3A to initiate leukemogenesis. Using bone marrow cells from a constitutive Dnmt3a null mouse, we show that loss of Dnmt3a caused a striking loss of DNA methylation throughout the genome of …

Role Of Ecdysoneless In Erbb2/Her2 Mediated Breast Oncogenesis, Shalis A. Ammons

Theses & Dissertations

Breast cancer is the second leading cause of cancer related deaths in women in the United States. The human Epidermal Growth Factor 2 (ErbB2) gene amplification and/or receptor overexpression subtype of breast cancer accounts for 25% of all breast cancers. A crucial regulator of the ErbB2 signaling pathway is the heat shock protein 90 (Hsp90) and its interacting protein complex. One such complex is the R2TP/Prefoldin-like complex that is composed of four proteins, RUVBL1, RUVBL2, PIH1D1, and RPAP3 and seven prefoldin-like proteins. This complex has been shown to be involved in telomere elongation, ribosome biogenesis, protein stability; etc. We and …

Effects Of Arachidin-1 And Arachidin-3 On Human Colon Cancer Cells, Jessica L. Bettis

Biological Sciences Undergraduate Honors Theses

Cancer remains a leading cause of death in the state of Arkansas and across the United States. Recent research found that peanuts consumption has been correlated with a decreased risk of cancer. Although limited research has been conducted, phenolic antioxidant compounds found in peanuts, arachidin-1 and arachidin-3, are correlated to a decrease in human leukemia and lung cancer cell growth. The objective of this study was to evaluate the anti-colon cancer effects of these compounds. Experiments were conducted to examine the effects of purified arachidin-1 and arachidin-3 on Caco-2 cell proliferation. Treatment of cells with arachidin-1 (0, 1, 5, 10µM) …

A Putative Dual Role For Yorkie In Hippo Pathway Signaling, Caroline Hall

Senior Honors Projects

The Hippo pathway inactivates genes involved in organ size and when aberrant, can lead to cancer. To control organ size, the Hippo pathway inhibits Yorkie (Yki), a transcriptional coactivator that works with Scalloped (Sd), a DNA binding protein. When active, Yki translocates into the nucleus and initiates transcription. Conversely, when inactive, Yki remains in the cytoplasm. However, my work shows that cytoplasmic, inactive Yki interacts with other proteins in the Hippo pathway by recruiting them to the plasma membrane. Accordingly, this study challenges the notion that cytoplasmic Yki is inactive and instead, may play a dual role in the Hippo …

Alternative Regulation Of Myc In Lung Cancer, Patrick N. Backman

Open Access Theses

Lung cancer is the leading cause of cancer deaths in the United States, accounting for 27% of all cancer induced deaths1. In an attempt to create a effective targeted therapy for the treatment of lung cancer, a strategy used to treat an activated KrasG12D/+;p53 R172H/+ transgenic lung cancer mouse model was to deliver a known tumor suppressive microRNA (miRNA) to stop tumor growth. The tumor suppressive miRNA let-7 was lentivirally delivered in the form of its primary transcript, pri-let-7a-1, and resulted in increased lung size and inflammation compared to lungs exposed to a control lentivirus. It was identified …

Challenges Of Adoptive (T-)Cell Transfer Immunotherapy For Cancer, Aaron Volk

Biology: Student Scholarship & Creative Works

Background and significance: The rebirth of the theory of immunosurveillance in 2001 rejuvenated interest in anticancer immunotherapies. In particular, T-cell-based therapies have garnered substantial interest due to the robustness and tumor antigen-specific cytotoxicity of T-cell anticancer immune responses.

Hypothesis: The efficacy of adoptive cell transfer (ACT) T-cell immunotherapy could significantly improve and gain widespread approval if future innovations in ACT-based approaches account for the pro- and antitumoral properties of non-CD8⁺ lineages of effector T-cells, evasion of T-cell antitumor immunity, and tumor-induced suppression of antitumor immunity.

Problem Analysis: Despite numerous reports of highly successful ACT-based clinical trials, no such therapy …

Mechanisms Of Mrna Polyadenylation, Hizlan Hincal Ağuş, Ayşe Eli̇f Erson Bensan

Turkish Journal of Biology

mRNA 3'-end processing involves the addition of a poly(A) tail based on the recognition of the poly(A) signal and subsequent cleavage of the mRNA at the poly(A) site. Alternative polyadenylation (APA) is emerging as a novel mechanism of gene expression regulation in normal and in disease states. APA results from the recognition of less canonical proximal or distal poly(A) signals leading to changes in the 3' untranslated region (UTR) lengths and even in some cases changes in the coding sequence of the distal part of the transcript. Consequently, RNA-binding proteins and/or microRNAs may differentially bind to shorter or longer isoforms. …