Cancer 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 …

Targeting The Cellular Redox Environment: A Novel Approach For The Treatment Of Hematopoietic Neoplasms, Dustin W. Carroll

Theses and Dissertations--Toxicology and Cancer Biology

Hematopoietic stem cells (HSCs) that function to maintain the hematopoietic compartment through self-renewal and differentiation capacities, as well as their downstream progeny, are susceptible to transformation resulting in the generation of the leukemic stem cell (LSC). Chief in the factors that control HSC regulation and protection of the HSC compartment is the cellular redox environment. Deregulation of the Hematopoietic Stem/Progenitor Cell (HSPC) redox environment results in loss of HSPC function and exhaustion. The characteristic developments of HSPC exhaustion via exposure to redox stress closely mirror phenotypic traits of hematopoietic malignancies, presenting the HSPC/LSC redox environment as a potential therapeutic target. …

Novel Survivin Inhibitor For Suppressing Pancreatic Cancer Cells Growth Via Downregulating Sp1 And Sp3 Transciption Factors, Myrna Hurtado, Umesh T. Sankpal, Aboubacar Kaba, Shahela Mahammad, Jaya Chhabra, Deondra T. Brown, Raj K. Gurung, Alvin A. Holder, Jamboor K. Vishwanatha, Riyaz Basha

Chemistry & Biochemistry Faculty Publications

Background/Aims: Targeting survivin, an anti-apoptotic protein and mitotic regulator, is considered as an effective therapeutic option for pancreatic cancer (PaCa). Tolfenamic acid (TA) showed anti-cancer activity in pre-clinical studies. A recent discovery demonstrated a copper(II) complex of TA (Cu-TA) can result in higher activity. In this study, the ability of Cu-TA to inhibit survivin and its transcription factors, Specificity protein (Sp) 1 and 3 in PaCa cell lines and tumor growth in mouse xenograft model were evaluated.

Methods: Cell growth inhibition was measured in MIA PaCa-2 and Panc1 cells for 2 days using CellTiter-Glo kit. Sp1, Sp3 and survivin expression …

Nanopulse Stimulation (Nps) Induces Tumor Ablation And Immunity In Orthotopic 4t1 Mouse Breast Cancer: A Review, Stephen J. Beebe, Brittany P. Lassiter, Siqi Guo

Bioelectrics Publications

Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic 4T1 mammary cancer showing that the postablation, vaccine-like effect is initiated by dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by inducing immunogenic, caspase-independent programmed cell death (PCD). With lower electric fields, like those peripheral to the primary treatment zone, NPS can activate dendritic cells (DCs). The activation of DCs by dead/dying cells leads to increases …

Determination Of The Sivmac Vif-Human Apobec3b Interaction, Oumar Sanogo

All Graduate Theses, Dissertations, and Other Capstone Projects

The APOBEC3 family of enzymes are DNA cytosine deaminases, some of which restrict replication of HIV-­‐1. This viral restriction is caused by deamination of cytosines to uracils in the viral cDNA, resulting in lethal mutation. HIV-­‐1 counteracts this deamination by producing the protein Vif, which targets the restricting APOBEC3 enzymes for proteosomal degradation. Previous studies have demonstrated that HIV-­‐1 Vif mediates degradation of APOBEC3D (A3D), APOBEC3F (A3F), APOBEC3G (A3G), and APOBEC3H (A3H). Other lentiviruses may also encode a Vif protein, however not all Vif proteins can degrade the same APOBEC3 proteins. For example, SIVmac (simian immunodeficiency virus that infects rhesus …

Altering Oligomerization Of Epha2 Via Mutations In The Intracellular Domain, Ryan W. Lingerak

Williams Honors College, Honors Research Projects

Eph receptor tyrosine kinases (RTKs) are activated by membrane-bound ligands called ephrins. Eph RTKs are divided into two subclasses, each activated by a specific classes of the ligand ephrin. The overexpression of Eph receptors is correlated to cancer cell metastasis in several different types of cancers. Studies with the EphA2 extracellular domain (ECD) and ephrinA1 ligand have shown that upon binding of ephrin to the receptor, EphA2 undergoes increased oligomerization and activation. This indicates that oligomerization is intimately connected to kinase activity. High resolution crystal structures of the EphA2 ECD have revealed some details of these ligand bound oligomers, as …

The Effect Of The Loss Of Lgl1 In Murine Neural Progenitor Cells On Mapk Signaling And Proliferation, Monique R. Lacourse

Cal Poly Humboldt theses and projects

Glioblastoma is an incurable, aggressive, and highly invasive type of brain tumor that harbors tumor initiating cells characterized by disrupted polarized cell divisions. A cell polarity gene lethal (2) giant larvae 1 (Lgl1) has been implicated in gliomas and is a tumor suppressor initially identified in Drosophila with roles in proliferation. The loss of Lgl1 in Drosophila activates the MAPK protein kinase JNK and the Ras pathway and therefore its downstream kinase ERK, a transcription factor modulator. Furthermore, when Lgl1 is knocked out in mice, a phenotype similar to glioma is seen. Loss of the human form of …

Nanoparticle Orientation To Control Rna Loading And Ligand Display On Extracellular Vesicles For Cancer Regression, Fengmei Pi, Daniel W. Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr G. Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M. Croce, Bin Guo, B. Mark Evers, Peixuan Guo

Markey Cancer Center Faculty Publications

Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for …

The Effect Of Stress Induced Premature Senescence On The Expression Of Heterogeneous Ribonucleoieoprotein, Yuriy Pechenyy

Dissertations and Theses

The role of heterogeneous nuclear ribonucleoproteins (hnRNP) in cellular senescence is yet to be defined. Cellular senescence is a terminal growth arrest in somatic cells. It is thought to be the consequence of telomeric shortening that acts as a DNA damage signal. Conversely, cells induced into premature senescence (SIPS) by oxidative stress, is independent of telomere attrition. Premature senescence has been proposed to be physiologically relevant as it can be induced by treatment with chemotherapeutic agents. In particular, we are studying the roles of hnRNP A1 and A2 in the maintenance of the senescence phenotype. hnRNPs are a family of …

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 …

Deciphering The Role Of Adrenergic Hormones In Embryonic Cardiac Calcium Signaling And Metabolism, Jessica Peoples

Electronic Theses and Dissertations

The adrenergic hormones norepinephrine (NE) and epinephrine (EPI) are critical regulators of mammalian cardiovascular physiology. NE and EPI mediate stress responses to enhance cardiovascular function, however dysregulation of adrenergic signaling leads to heart failure, congenital heart malformations, and sudden cardiac death. Adrenergic hormone-expressing cells were found in the early embryonic heart, and NE has been determined essential for embryonic cardiac development. Despite extensive work in adults, the regulatory roles and adrenergic targets of these hormones during embryonic cardiac development have not yet been fully determined. Prior transcriptomic studies from our lab showed that expression of signal transduction and metabolic genes …

Applications Of Cell-Derived Vesicles: From Single Molecule Studies To Drug Delivery, Faruk H. Moonschi

Theses and Dissertations--Chemistry

Single molecule studies can provide information of biological molecules which otherwise is lost in ensemble studies. A wide variety of fluorescence-based techniques are utilized for single molecule studies. While these tools have been widely applied for imaging soluble proteins, single molecule studies of transmembrane proteins are much more complicated. A primary reason for this is that, unlike membrane proteins, soluble proteins can be easily isolated from the cellular environment. One approach to isolate membrane proteins into single molecule level involves a very low label expression of the protein in cells. However, cells generate background fluorescence leading to a very low …

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 …

Alternative Splicing Of Cytoplasmic Polyadenylation Element Binding Protein 2 Is Modulated Via Serine Arginine Splicing Factor 3 In Cancer Metastasis, James T. Deligio, James Thomas Deligio

Theses and Dissertations

Our laboratory delineated a role for alternative pre-mRNA splicing (AS) in triple negative breast cancer (TNBC). We found the translational regulator cytosolic polyadenylation element binding protein 2 (CPEB2) which has two isoforms, CPEB2A and CPEB2B, is alternatively spliced during acquisition of anoikis resistance (AnR) and metastasis. The splicing event which determines the CPEB2 isoform is via inclusion/ exclusion of exon four in the mature mRNA transcript. The loss of CPEB2A with a concomitant increase in CPEB2B is required for TNBC cells to metastasize in vivo. We examined RNAseq profiles of TNBC cells which had CPEB2 isoforms specifically downregulated to …

Cortactin Phosphorylation By Casein Kinase 2 Regulates Actin Related Protein 2/3 Complex Activity And Invadopodia Function, Steven Michael Markwell

Graduate Theses, Dissertations, and Problem Reports (ETD)

Malregulation of the actin cytoskeleton enhances tumor cell motility and invasion. The actin-binding protein cortactin facilitates branched actin network formation through activation of the actin-related protein (Arp) 2/3 complex. Arp2/3 complex activation is responsible for driving increased migration and extracellular matrix (ECM) degradation by governing invadopodia formation and activity. While cortactin-mediated activation of Arp2/3 complex and invadopodia regulation has been well established, signaling pathways responsible for governing cortactin binding to Arp2/3 are unknown. In this dissertation we identify casein kinase (CK) 2α phosphorylation of cortactin as a negative regulator of Arp2/3 binding. CK2α directly phosphorylates cortactin at a conserved threonine …

Nuclear Spindles Pave The Way To Metastasis, Patrick J. Hensley, Natasha Kyprianou

Urology Faculty Publications

No abstract provided.

Expression Of Wnt-Signaling Pathway Genes And Their Associations With Mirnas In Colorectal Cancer, Martha L. Slattery, Lila E. Mullany, Lori C. Sakoda, Wade S. Samowitz, Roger K. Wolff, John R. Stevens, Jennifer S. Herrick

Mathematics and Statistics Faculty Publications

The Wnt-signaling pathway functions in regulating cell growth and thus is involved in the carcinogenic process of several cancers, including colorectal cancer. We tested the hypothesis that multiple genes in this signaling pathway are dysregulated and that miRNAs are associated with these dysregulated genes. We used data from 217 colorectal cancer (CRC) cases to evaluate differences in Wnt-signaling pathway gene expression between paired CRC and normal mucosa and identify miRNAs that are associated with these genes. Gene expression data from RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19.0 were analyzed. We focused on genes most strongly associated …

Potential Anticancer Effect Of Prostratin Through Sik3 Inhibition, Dalal Alotaibi, Suneetha Amara, Terrance L. Johnson, Venkataswarup Tiriveedhi

Biology Faculty Research

Prostratin, a phorbol ester natural plant compound, has been demonstrated to exert an anti‑retroviral effect through activation of latent cluster of differentiation (CD)4+T lymphocytes and inhibition of viral entry into the cell through downregulation of chemokine receptor type 4 (CXCR4) expression. However, the potential effect of prostratin on cancer is yet to be defined. As CXCR4 is well known to induce cancer migration, it was hypothesized that prostratin induces an anti‑cancer effect through inhibition of CXCR4 expression. The authors previously demonstrated that high stimulating conditions (sub‑minimal IL‑17, 0.1 ng/ml, synergized with high salt, Δ0.05 M NaCl) promote breast cancer cell …

Unseen Science: Modern Discoveries Too Far Away Or Tiny For Human Eyes, Lucy Huang

Capstones

As science has progressed, scientists have realized that evidence goes beyond the realms of physical sight. Whether it is too small or difficult to find, scientists have developed different ways to get around this problem. We see this in cancer genomics and in extrasolar planetary research. Scientists use what they know and what they measure to validate their work.

https://lucy-huang-9tge.squarespace.com/

Metabolic Dysregulation And Cancer Mortality In A National Cohort Of Blacks And Whites, Tomi Akinyemiju, Justin Xavier Moore, Suzanne Judd, Susan Lakoski, Michael Goodman, Monika M. Safford, Maria Pisu

Epidemiology and Environmental Health Faculty Publications

Background: We examined the association between metabolic dysregulation and cancer mortality in a prospective cohort of Black and White adults.

Methods: A total of 25,038 Black and White adults were included in the analysis. Metabolic dysregulation was defined in two ways: 1) using the joint harmonized criteria for metabolic syndrome (MetS) and 2) based on factor analysis of 15 variables characterizing metabolic dysregulation. We estimated hazards ratios (HRs) and 95% confidence intervals (CIs) for the association of MetS and metabolic dysregulation with cancer mortality during follow-up using Cox proportional hazards models.

Results: About 46% of Black and 39% of White …

9-Aminoacridine Inhibits Ribosome Biogenesis And Synergizes With Cytotoxic Drugs To Induce Selective Killing Of P53-Deficient Cells, Leonid Anikin, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Common cancer treatments target rapidly dividing cells and do not discriminate between cancer and normal host cells. One approach to mitigating negative side‐effects of cancer treatment is to temporarily arrest cell cycle progression and thus protect normal cells during cytotoxic treatments, a concept called cyclotherapy. We recently proposed that transient inhibition of post‐transcriptional steps of ribosome biogenesis (RBG) can be used to selectively arrest p53‐positive host cells and not p53‐null cancer cells. In this study, we investigated whether cytoprotective RBG inhibition can be achieved through small molecule treatment.

Targeting Ribosome Assembly Factors Selectively Protects P53 Positive Cells From Chemotherapeutic Agents, Russell T. Sapio, Anastasiya Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J. Manna, N. Minkovsky, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Many chemotherapeutic agents act in a nondiscriminatory fashion, targeting both cancerous and noncancerous cells in Sphase and Mphase. One approach to reduce the toxic side effects in normal tissue is to exploit the differences in p53 functionality between cancerous and noncancerous cells. For example, activating p53 signaling by nongenotoxic means can transiently arrest noncancerous p53 positive cells in G1 phase and protect them from the cytotoxic effects of chemotherapeutic drugs. However, since most cancerous cells have faulty p53 signaling, they will proceed to cycle, and continue to be affected by the drug. In this study we asked if this G1‐phase …

The Role Of Yes-Associated Protein 1 In Ovarian Physiology And Pathology, Xiangmin Lv

Theses & Dissertations

Ovarian granulosa cells are the major somatic components of the ovarian follicle. Proper proliferation and differentiation of ovarian granulosa cells are essential for successful follicle development. Accumulating evidence indicates that the Hippo-YAP signaling pathway plays critical roles in both development and tumorigenesis of several organs. The present study aims to investigate the role of Yes-associated protein 1 (YAP) in ovarian granulosa cell proliferation, differentiation, and malignant transformation. At first, we found that nuclear YAP (active) was highly expressed in proliferative granulosa cells, whereas cytoplasmic YAP (inactive) was detected mainly in terminally-differentiated luteal cells. Further studies suggested that endogenous YAP activity …

Comparative Molecular Characterization Of Typical And Exceptional Responders In Glioblastoma, Kristin Wipfler

Theses & Dissertations

Glioblastoma (GBM) is the most common and the deadliest type of primary brain tumor, with a median survival time of only 15 months despite aggressive treatment. Although most patients have an extremely poor prognosis, a small number of patients survive far beyond the median survival time. Investigation of these “exceptional responders” has sparked a great deal of interest and is becoming an important focus in the field of cancer research. To investigate the molecular differences between typical and exceptional responders in GBM, comparative analyses of copy number, methylation, gene expression, miRNA expression, and protein expression data sets from The Cancer …

Identifying The Role Of Janus Kinase 1 In Mammary Gland Development And Breast Cancer, Barbara Swenson

Theses & Dissertations

The development of the postnatal mammary gland is tightly controlled by peptide hormones and cytokines. The signaling of these extracellular ligands through their corresponding receptors rely on Janus Kinases (JAKs) that activate downstream Signal Transducers and Activators of Transcription (STATs). The JAK/STAT signaling pathway is crucial for processes such as growth, proliferation, and cell survival of the epithelial tissue, but also for the breakdown and remodeling of the mammary gland via IL-6 class inflammatory cytokines (e.g. LIF and OSM). JAK1 and JAK2, which are expressed in the mammary gland, are thought to have redundant functions. However, our previous studies demonstrated …

Evaluation Of Aminopyrazole Analogs As Cyclin-Dependent Kinase Inhibitors For Colorectal Cancer Therapy, Caroline Robb

Theses & Dissertations

Colorectal cancer (CRC) remains one of the leading causes of cancer related deaths in the United States. Currently, there are limited therapeutic options for CRC patients, none of which focus on the cell signaling mechanisms controlled by members of the cyclin dependent kinase (CDK) family. CDK5 has been implicated in a variety of cancers, and most recently as a tumor promoter in CRC.

As such, we evaluated a compound developed by Pfizer, CP-668863 (a.k.a. 20-223), that inhibits CDK5 in neurodegenerative disorders. In our CRC xenograft model, 20-223 reduced tumor growth and tumor weight, indicating its value as a potential anti-CRC …

Perturbing Anti-Apoptotic Proteins To Develop Novel Cancer Therapies, Jacob Contreras

Theses & Dissertations

The apoptotic pathway involves a tightly regulated network of proteins which respond to various stimuli. Previous studies have indicated Mcl-1 and Bcl-xL are intimately involved in determining cell fate, and if both are concurrently neutralized, it activates the apoptotic pathway. The inactivation of Bcl-xL and Mcl-1 as a mechanism to trigger the intrinsic apoptotic response can be used as a platform to develop therapeutic strategies to target cancer cells. The apoptotic pathway is largely dysregulated and often leads to therapy resistance in cancer cells. Although direct inhibitors of Bcl-xL have been developed and have advanced to clinical trials, development of …

Metabolic Reprogramming Of Pancreatic Ductal Adenocarcinoma Cells In Response To Chronic Low Ph Stress, Jaime Abrego

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of all cancers with a 5-year survival rate of only 8.2%. This is because PDAC is diagnosed in its advanced stages and is characterized by radio and chemotherapy resistance. Aggressiveness of PDAC tumors is attributed to its high metabolic phenotype, which is characterized by increased glycolysis rate and lactate secretion, while oxidative metabolism is reduced. These metabolic features are required to fulfill the biosynthetic demands of proliferating PDAC cells. However, this increase in metabolic activity results in acidification of the extracellular space because the dense fibrotic stroma of PDAC tumors limits …

Oncostatin M Promotes Breast Cancer Metastasis: Increased Expression Of Pro-Angiogenic Factors, Inflammatory Cytokine Expression, And Circulating Tumor Cell Numbers, Ken Tawara

Boise State University Theses and Dissertations

Breast cancer is the most diagnosed cancer type in women and its resultant mortality is second only to lung cancer worldwide. While breast cancer is known to have many risk factors, inflammation remains an unquantifiable risk, and it can arise from obesity, depression, poor health, autoimmune diseases, and other conditions that cause systemic chronic inflammation. Chronic inflammation is gaining recognition for its role in cancer development, the potentiation of a metastatic phenotype in cancer cells, and decreased survival in breast cancer patients. In particular, inflammatory cytokines in the interleukin-6 (IL-6) family have been shown to promote an epithelial-mesenchymal transition (EMT), …

Ecog-Acrin (E4805) Randomized Phase Ii Study To Determine The Effect Of 2 Different Doses Of Aflibercept In Patients With Metastatic Renal Cell Carcinoma, Roberto Pili, Opeyemi Jegede, Michael A. Carducci, Judith Manola, David L. Groteluschen, Leonard L. Appleman, Glenn Liu, James C. Shanks, Shaker R. Dakhil, Janice Dutcher, Robert S. Dipaola

Internal Medicine Faculty Publications

Background—Aflibercept is a recombinantly-produced fusion protein that has potent anti-VEGF activity. We tested whether aflibercept has clinical activity in clear cell renal cell carcinoma (ccRCC). The recommended Phase 2 dose was 4 mg/kg but several patients treated at 1 mg/kg demonstrated prolonged progression-free survival (PFS). We therefore tested both doses in a parallel group randomized trial.

Methods—Eligible patients (pts) had histologically confirmed advanced or metastatic ccRCC and previous treatments including prior exposure to a VEGF RTKI. Patients received aflibercept (either 1 mg/kg or 4 mg/kg) day 1 of a 14-day cycle until progression. Patients randomized to 1 mg/kg …