Medicine and Health Sciences Commons^™

The Effects Of Radiation On Cancer Stem Cells In Glioblastoma And Ovarian Cancer, Aaron Keniston

Electronic Theses, Projects, and Dissertations

High grade serous ovarian cancer (HGSOC) and glioblastoma multiforme (GBM) are some of the most aggressive forms of cancer with poor patient survival. Despite successful cancer therapies, these malignancies have high recurrence rates which can be attributed to cancer stem cells (CSC) due to innate tumor initiating properties. In this study, we investigated the response of CSC populations to proton and photon radiation by quantification of core stem cell transcription factors Sox2 and Oct4. This was carried out utilizing a Sox2/Oct4 green fluorescent protein based reporter designated as SORE6-GFP measured by flow cytometry. We hypothesize that proton and photon irradiation …

Editorial: Hallmark Of Cancer: Reprogramming Of Cellular Metabolism, Baljinder Kaur, Yahya Sohrabi, Abhinav Achreja, Michael P. Lisanti, Ubaldo Emilio Martinez-Outshoorn

Department of Medical Oncology Faculty Papers

No abstract provided.

Hypoxia Regulates Vessel-Modifying Macrophages And Vice Versa In Tumors, Kayla Jo Steinberger

Graduate Theses, Dissertations, and Problem Reports

Hypoxia, or low oxygen, is a common feature of solid tumors correlating with poor survival in cancer patients. Growing tumors need a blood supply to deliver oxygen. Tumors attempt to re-acquire oxygen by forming new blood vessels from nearby, pre-existing vessels, a process known as angiogenesis. Past treatments aimed at preventing this process yielded not only disappointing results in the clinic but sometimes worsened the patient’s prognosis making the tumor more hypoxic, emphasizing the urgent need for novel targets. In tumors, angiogenesis is notoriously dysfunctional resulting in leaky, under-perfused blood vessels which cannot adequately deliver oxygen and exacerbates hypoxia. Emerging …

Msdrp: A Deep Learning Model Based On Multisource Data For Predicting Drug Response, Haochen Zhao, Xiaoyu Zhang, Qichang Zhao, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Cancer heterogeneity drastically affects cancer therapeutic outcomes. Predicting drug response in vitro is expected to help formulate personalized therapy regimens. In recent years, several computational models based on machine learning and deep learning have been proposed to predict drug response in vitro. However, most of these methods capture drug features based on a single drug description (e.g. drug structure), without considering the relationships between drugs and biological entities (e.g. target, diseases, and side effects). Moreover, most of these methods collect features separately for drugs and cell lines but fail to consider the pairwise interactions between drugs and cell …

Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter

Theses

Ewing sarcoma (ES) is an aggressive pediatric bone cancer with low five-year survival rates, particularly with recurrent disease because ES often becomes resistant to chemotherapy in these recurrences. Cannabidiol (CBD) has been identified as a potentially promising therapeutic for patients with ES. In other cancer types, CBD has demonstrated effects on two major proteins that contribute to chemotherapy resistance. The first, Poly (ADP-ribose) Polymerase I (PARP1), is a DNA damage repair enzyme that is overexpressed in recurrent ES. Though chemotherapy induces DNA damage in these cancer cells, the high levels of PARP1 facilitate repair of the DNA, allowing the mutated …

The Future Of Targeted Kinase Inhibitors In Melanoma, Signe Caksa, Usman Baqai, A E Aplin

Department of Cancer Biology Faculty Papers

Melanoma is a cancer of the pigment-producing cells of the body and its incidence is rising. Targeted inhibitors that act against kinases in the MAPK pathway are approved for BRAF-mutant metastatic cutaneous melanoma and increase patients' survival. Response to these therapies is limited by drug resistance and is less durable than with immune checkpoint inhibition. Conversely, rare melanoma subtypes have few therapeutic options for advanced disease and MAPK pathway targeting agents show minimal anti-tumor effects. Nevertheless, there is a future for targeted kinase inhibitors in melanoma: in new applications such as adjuvant or neoadjuvant therapy and in novel combinations with …

The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez

Thinking Matters Symposium

In a clinical setting, some patients are exposed to an anti-cancer chemotherapy agent, paclitaxel. Cancerous cells undergo rapid, continuous cell division without control. Chemotherapy treatments try to slow and stop the uncontrollable cell division cycles and eliminate cancerous cells in the process. Paclitaxel serves as a treatment for some types of cancers, including lung, melanoma, bladder, and esophageal. Because it targets the cytoskeleton, paclitaxel can also influence cell migration. This project utilizes a cellular migration assay and an immunohistochemistry assay to analyze the effects of paclitaxel on the movement of cells and on the cytoskeleton of neuroglia rat cells with …

Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach

Graduate School of Biomedical Sciences Theses and Dissertations

There were an estimated 20 million new cancer cases worldwide in 2020, resulting in nearly 1000 deaths per hour [1]. Oral cancer exemplifies the difficulties of treating cancer patients. The first line for oral cancer treatment is surgery and radiation that can lead to patient disfigurement and decreased quality of life in cancer survivors [2-4]. Though there have been many developments in chemotherapy in the last 30 years, the 50% mortality rate associated with oral cancer has not changed [4, 5]. Longitudinal studies that track survival rates in oral cancer patients demonstrate a 3-fold reduction in patient deaths when patients …

The Role Of Decorin And Biglycan Signaling In Tumorigenesis, Valentina Diehl, Lisa Sophie Huber, Jonel Trebicka, Malgorzata Wygrecka, Renato V. Iozzo, Liliana Schaefer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The complex and adaptive nature of malignant neoplasm constitute a major challenge for the development of effective anti-oncogenic therapies. Emerging evidence has uncovered the pivotal functions exerted by the small leucine-rich proteoglycans, decorin and biglycan, in affecting tumor growth and progression. In their soluble forms, decorin and biglycan act as powerful signaling molecules. By receptor-mediated signal transduction, both proteoglycans modulate key processes vital for tumor initiation and progression, such as autophagy, inflammation, cell-cycle, apoptosis, and angiogenesis. Despite of their structural homology, these two proteoglycans interact with distinct cell surface receptors and thus modulate distinct signaling pathways that ultimately affect cancer …

Inhibiting Fatty Acid Binding Protein Family Members Decreases Multiple Myeloma Cell Proliferation Through Effecting The Myc Pathway, Mariah Farrell, Heather Fairfield, Anastasia D'Amico, Carolyne Falank, Connor Murphy, Michaela Reagan

Costas T. Lambrew Research Retreat 2021

FABP inhibition leads to increased survival of myeloma bearing mice and decreased cell growth by inhibiting MYC signaling.

Comparative Molecular Transporter Properties Of Cyclic Peptides Containing Tryptophan And Arginine Residues Formed Through Disulfide Cyclization, Eman H. M. Mohammed, Dindyal Mandal, Saghar Mozaffari, Magdy Abdel-Hamied Zahran, Amany Mostafa Osman, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously reported cyclic cell-penetrating peptides [WR]₅ and [WR]₄ as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated their cytotoxicity as well as uptake behavior against different cancer cell lines. Thus, cyclic [C(WR)_xC] and linear counterparts (C(WR)_xC), where x = 4–5, were synthesized using Fmoc/tBu solid-phase peptide synthesis, purified, and characterized. The compounds did not show any significant cytotoxicity (at 25 µM) against ovarian (SK-OV-3), leukemia (CCRF-CEM), gastric adenocarcinoma (CRL-1739), breast …

How Can We Stop Cancer?, Joseph R. Current

The Review: A Journal of Undergraduate Student Research

Cancer is a disease that humans have been struggling to combat for centuries. It originates from the accumulation of several mutations over the life of a cell that causes it to evade cell death and multiply rapidly. It can affect any tissue in the body and can spread to other parts of the body through metastasis. Cancer comes in numerous shapes and sizes with different levels of aggression, growth speeds, and health risks. Many treatments for cancer exist today, three of the most popular being surgery, chemotherapy, and radiation therapy, which can be used in combinations with other treatments to …

Genetic Relationships And Therapeutic Options For Relapsed Acute Lymphoblastic Leukemia, Hailie Shertzer

Senior Honors Theses

Acute lymphoblastic leukemia (ALL) is the most common form of cancer among children and can be lethal to the adult population. Though 80% of patients with ALL reach complete remission after treatment, about 20% of those diagnosed fail to remain cancer-free. Genetic rearrangements are the hallmark of relapsed ALL, but the mechanism by which these rearrangements occur is still unclear. Recent research suggests these mutations may be detectable during initial diagnosis. If researchers are able to accurately assess the probability of relapse during diagnosis by analyzing the genome of the leukemic cells, the likelihood of administering effective therapy would increase. …

Interaction Of The Oncoprotein Transcription Factor Myc With Its Chromatin Cofactor Wdr5 Is Essential For Tumor Maintenance., Lance R. Thomas, Clare M. Adams, Jing Wang, April M. Weissmiller, Joy Creighton, Shelly L. Lorey, Qi Liu, Stephen W. Fesik, Christine M. Eischen, William P. Tansey

Department of Cancer Biology Faculty Papers

The oncoprotein transcription factor MYC is overexpressed in the majority of cancers. Key to its oncogenic activity is the ability of MYC to regulate gene expression patterns that drive and maintain the malignant state. MYC is also considered a validated anticancer target, but efforts to pharmacologically inhibit MYC have failed. The dependence of MYC on cofactors creates opportunities for therapeutic intervention, but for any cofactor this requires structural understanding of how the cofactor interacts with MYC, knowledge of the role it plays in MYC function, and demonstration that disrupting the cofactor interaction will cause existing cancers to regress. One cofactor …

Differential Iron Regulatory Genetics In 2d & 3d Culture Of Breast Cancer Cells, Tyler Hanna, Suzy Torti Ph. D, Frank Torti M.D., Mph, Nicole Farra Ph. D.

Honors Scholar Theses

The iron regulatory axis has consistently been shown to be perturbed in cancer cell lines relative to non-cancerous cell lines. As cancer cells rapidly divide and grow, they require iron to fuel many intracellular processes, including DNA replication and protein synthesis. Three-dimensional cell culture is an increasingly popular method of culture that purportedly more accurately mimics the in vivo microenvironment of cancers over traditional two-dimensional culture. This project was prompted by previous lab results to investigate differential iron regulatory gene expression in 2D and 3D spheroid culture models. We replicated the findings that the gene hepcidin is induced in 3D …

Tumor-Derived Extracellular Vesicles Require Β1 Integrins To Promote Anchorage-Independent Growth., Rachel M. Derita, Aejaz Sayeed, Vaughn Garcia, Shiv Ram Krishn, Christopher D. Shields, Srawasti Sarker, Andrea Friedman, Peter Mccue, Sudheer Kumar Molugu, Ulrich Rodeck, Adam P. Dicker, Lucia R. Languino

Department of Cancer Biology Faculty Papers

The β1 integrins, known to promote cancer progression, are abundant in extracellular vesicles (EVs). We investigated whether prostate cancer (PrCa) EVs affect anchorage-independent growth and whether β1 integrins are required for this effect. Specifically using a cell-line-based genetic rescue and an in vivo PrCa model, we show that gradient-purified small EVs (sEVs) from either cancer cells or blood from tumor-bearing TRAMP (transgenic adenocarcinoma of the mouse prostate) mice promote anchorage-independent growth of PrCa cells. In contrast, sEVs from cultured PrCa cells harboring a short hairpin RNA to β1, from wild-type mice or from TRAMP mice carrying a β1 conditional ablation …

Potential Applications Of Capsaicinoids In Small Cell Lung Cancer Therapy, Jamie Rae Friedman

Theses, Dissertations and Capstones

Lung cancer continues to be the leading cause of cancer related mortality worldwide. Lung cancer is not a single disease but an umbrella that encompasses two major classifications, nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC). SCLC represents about 15- 20% of all lung cancer cases and is almost exclusively diagnosed in smokers. Typically, patients will respond very well to first line treatment, but face inevitable relapse. The fact that SCLC still carries a grim 5-year survival rate of less than 5% highlights the lack of advancement in treatment options to effectively improve patient response and survival. …

Modulation Of Autophagy And Senescence To Enhance The Response To Therapy In Triple Negative Breast Cancer, Liliya Tyutyunyk-Massey

Theses and Dissertations

Abstract

Although great strides have been made over the decades in development and optimization of anti-cancer therapies, even highly effective drugs often fail to completely eliminate tumors. Residual tumor cells can enter into a state of dormancy for prolonged periods of time but eventually are able to regain proliferative capacity and reemerge as chemotherapy-resistant disease. Because recurrent disease is a leading contributor to patient’s mortality, it is paramount to identify strategies for effectively destroying residual tumor cells.

Cytotoxic drugs and ionizing radiation are used as standard therapies in a variety of cancers. These modalities induce apoptosis, autophagy and senescence. Senescence …

Targeting The Colchicine Binding Site On Tubulin To Overcome Multidrug Resistance And Anticancer Efficacy Of Selective Survivin Inhibitors, Kinsle E. Arnst

Theses and Dissertations (ETD)

Tubulin inhibitors are widely used as chemotherapeutic agents, and their successis attributed to their ability to target microtubule dynamics and disrupt critical cellular functions including cell signaling, motility, intracellular trafficking, and mitosis. Interference with microtubule dynamics consequently disrupts mitotic progression and ultimately leads to apoptosis, validating microtubule dynamics as an excellent target for anticancer agents. While this class of drug has proven to be effective against many cancer types, the clinical efficacy of current tubulin inhibitors is often limited by the development of multidrug resistance. The most common form of resistance to these agents arises from the overexpression of drug …

Roles Of Cytosolic Nucleic Acid Sensors In Cancer And Infection, Qifan Zhu

Theses and Dissertations (ETD)

Pattern recognition receptors are innate immune sensors that recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) with crucial roles in host defense against microbial infection, autoimmune diseases and cancer. Cytosolic nucleic acids including DNA and RNA originate from pathogens or self-cells, which form major groups of PAMPs and DAMPs. A range of nucleic acid sensors have evolved to sense various types of nucleic acids. How different DNA-sensing pathways regulate microbial infection and cancer is the focus of this dissertation.

Stimulator of IFN genes (STING) is a cytosolic innate immune sensor for cyclic dinucleotides that also serves a dual …

A Lin28b Tumor-Specific Transcript In Cancer, Weijie Guo, Zhixiang Hu, Yichao Bao, Yuchen Li, Shengli Li, Qiupeng Zheng, Dongbin Lyu, Di Chen, Tao Yu, Yan Li, Xiaodong Zhu, Jie Ding, Yingjun Zhao, Xianghuo He, Shenglin Huang

Markey Cancer Center Faculty Publications

The diversity and complexity of the cancer transcriptome may contain transcripts unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST, which is specifically expressed in hepatocellular carcinoma (HCC) and many other cancer types. Expression of LIN28B-TST is associated with significantly poor prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative transcription initiation site that harbors a strong promoter regulated by NFYA but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite for its transcription and transcriptional regulation. LIN28B-TST encodes a protein isoform with additional N-terminal amino acids and is critical for cancer …

The Effect Of Dna Methylation On Tp73 Expression In Tumorgenesis, Nujuma A. Moussa

Undergraduate Research Posters

Abstract: The Effect of DNA Methylation on TP73 Expression in Tumorgenesis

Nujuma Moussa, Zhixing Yao, Zaki A. Sherif

Department of Biochemistry & Molecular Biology, Howard University College of Medicine

TP73 is a member of the TP53 family of proteins that acts as a transcription factor to help regulate cellular distress. This tumor protein may play a dual role as a tumor suppressor and tumor promoter. The TP73 gene is mapped to chromosome 1p36, a frequently deleted region in neuroblastoma and other types of tumors. While mutations in the TP53 gene are commonly known to cause noxious cancers, 30% of cancers …

A Simple And Accurate Rule-Based Modeling Framework For Simulation Of Autocrine/Paracrine Stimulation Of Glioblastoma Cell Motility And Proliferation By L1cam In 2-D Culture., Justin Caccavale, David Fiumara, Michael Stapf, Liedeke Sweitzer, Hannah J. Anderson, Jonathan Gorky, Prasad Dhurjati, Deni S. Galileo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Glioblastoma multiforme (GBM) is a devastating brain cancer for which there is no known cure. Its malignancy is due to rapid cell division along with high motility and invasiveness of cells into the brain tissue. Simple 2-dimensional laboratory assays (e.g., a scratch assay) commonly are used to measure the effects of various experimental perturbations, such as treatment with chemical inhibitors. Several mathematical models have been developed to aid the understanding of the motile behavior and proliferation of GBM cells. However, many are mathematically complicated, look at multiple interdependent phenomena, and/or use modeling software not freely available to the research …

Metabolic Regulation Of Cellular Signaling, Rashid John Darbandi

Theses and Dissertations (ETD)

Using the biochemically tractable Xenopus oocyte model system, we have previously characterized a novel metabolic regulation of cell death. We found that glucose-6-phosphate (G6P) via the pentose phosphate pathway leads to increased nicotinamide adenine dinucleotide phosphate (NADPH) levels, a subsequent increase in cytosolic acetyl-coenzyme A and activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). We recently identified coenzyme A (CoA), derived from the breakdown of acetyl-CoA, as the key metabolic signal that mediates a novel mechanism of calmodulindependent activation of CaMKII. CoA binds directly to the calmodulin (CaM) binding domain (CaMBD) of CaMKII resulting in its activation and downstream inhibitory phosphorylation …

Genome-Scale Precision Proteomics Identifies Cancer Signaling Networks And Therapeutic Vulnerabilities, Hong Wang

Theses and Dissertations (ETD)

Mass spectrometry (MS) based-proteomics technology has been emerging as an indispensable tool for biomedical research. But the highly diverse physical and chemical properties of the protein building blocks and the dramatic human proteome complexity largely limited proteomic profiling depth. Moreover, there was a lack of high-throughput quantitative strategies that were both precise and parallel to in-depth proteomic techniques. To solve these grand challenges, a high resolution liquid chromatography (LC) system that coupled with an advanced mass spectrometer was developed to allow genome-scale human proteome identification. Using the combination of pre-MS peptide fractionation, MS2-based interference detection and post-MS computational interference correction, …

Dox Inducible Idh2 R140q Expression In Stem Cells Results In Cell Death, Opposite Of Cancerous Overgrowth, Reuben Hogan

Undergraduate Research Symposium Posters

Mutations in isocitrate dehydrogenase (IDH) 1 or 2 are found in about 23% of acute myeloid leukemia (AML) samples and about 90% of gliomas. Mutations result in neomorphic function of the IDH enzyme that yields the novel molecule 2-hydroxyglutarate (2HG) instead of alpha-ketoglutarate (aKG). 2HG is known to be associated with hypermethylation of DNA and histones, a phenotype seen in AML. Our lab intends to study the mechanism by which hypermethylation is achieved and how this mechanism relates to the onset of cancer. In this experiment, we utilized a line of H9 stem cells which we had developed. These cells …

Natural Killer (Nk) Cells And Their Involvement In Different Types Of Cancer. Current Status Of Clinical Research, Isadora Zaharescu, Adina D. Moldovan, Cristiana Tanase

Journal of Mind and Medical Sciences

Natural killer cells are the main agents of innate immunity. Since 1970, various studies have repeatedly confirmed their involvement in decreasing local tumor growth and also decreasing the risk of metastasis, due to their cytotoxic effects and also through the release of immunostimulatory cytokines such as IFN-gamma. In the 1990s, several studies demonstrated the existence of certain inhibiting and stimulating receptors of these cells, leading to the concept of “induced self”, thus explaining why tumors with MHC-1 are destroyed and autologous cells without it are saved out. Recognition and destruction of tumor cells by the NK cells are the result …

Yap And The Hippo Pathway In Pediatric Cancer., Atif Ahmed, Abdalla D. Mohamed, Melissa Gener, Weijie Li, Eugenio Taboada

Manuscripts, Articles, Book Chapters and Other Papers

The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis. Dysfunction of this pathway contributes to cancer development in adults and children. Emerging studies have shed light on the upregulation …

The Roles Of Nuclear Receptor Nr4a1 In Cancer Cell Proliferation And Skeletal Muscle Differentiation, Alexa Farmer

Theses and Dissertations (ETD)

Nuclear receptors (NRs) constitute a major class of drug targets in the treatment of various cancer types. NRs respond to cellular signals and become activated upon ligand binding to transcriptionally modulate expression of target genes. NR4A1 (Nur77) is a member of the NR4A family of nuclear receptors and displays an oncogenic profile in many cancer models. It is often upregulated in adult solid malignancies and is known to promote cell proliferation and survival. Knockdown studies of NR4A1 in cancer cell lines results in decreased cell growth and angiogenesis and increased apoptosis, suggesting NR4A1 is an oncogenic protein. Due to the …

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 …