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Theses & Dissertations: Cancer Research

Theses/dissertations from 2024 2024.

Novel Spirocyclic Dimer (SpiD3) Displays Potent Preclinical Effects in Hematological Malignancies , Alexandria Eiken

Chemotherapy-Induced Modulation of Tumor Antigen Presentation , Alaina C. Larson

Understanding the role of MASTL in colon homeostasis and colitis-associated cancer development , Kristina Pravoverov

Dying Right: Supporting Anti-Cancer Therapy Through Immunogenic Cell Death , Elizabeth Schmitz

Therapeutic Effects of BET Protein Inhibition in B-cell Malignancies and Beyond , Audrey L. Smith

Targeting KSR1 to inhibit stemness and therapy resistance , Heidi M. Vieira

Identifying the Molecular Determinants of Lung Metastatic Adaptation in Prostate Cancer , Grace M. Waldron

Identification of Mitotic Phosphatases and Cyclin K as Novel Molecular Targets in Pancreatic Cancer , Yi Xiao

Theses/Dissertations from 2023 2023

Development of Combination Therapy Strategies to Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors , Nicholas Mullen

Overcoming Resistance Mechanisms to CDK4/6 Inhibitor Treatment Using CDK6-Selective PROTAC , Sarah Truong

Theses/Dissertations from 2022 2022

Omics Analysis in Cancer and Development , Emalie J. Clement

Investigating the Role of Splenic Macrophages in Pancreatic Cancer , Daisy V. Gonzalez

Polymeric Chloroquine in Metastatic Pancreatic Cancer Therapy , Rubayat Islam Khan

Evaluating Targets and Therapeutics for the Treatment of Pancreatic Cancer , Shelby M. Knoche

Characterization of 1,1-Diarylethylene FOXM1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells , Cassie Liu

Novel Mechanisms of Protein Kinase C α Regulation and Function , Xinyue Li

SOX2 Dosage Governs Tumor Cell Identity and Proliferation , Ethan P. Metz

Post-Transcriptional Control of the Epithelial-to-Mesenchymal Transition (EMT) in Ras-Driven Colorectal Cancers , Chaitra Rao

Use of Machine Learning Algorithms and Highly Multiplexed Immunohistochemistry to Perform In-Depth Characterization of Primary Pancreatic Tumors and Metastatic Sites , Krysten Vance

Characterization of Metastatic Cutaneous Squamous Cell Carcinoma in the Immunosuppressed Patient , Megan E. Wackel

Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling , Pauline Xu

Phos-Tag-Based Screens Identify Novel Therapeutic Targets in Ovarian Cancer and Pancreatic Cancer , Renya Zeng

Theses/Dissertations from 2021 2021

Functional Characterization of Cancer-Associated DNA Polymerase ε Variants , Stephanie R. Barbari

Pancreatic Cancer: Novel Therapy, Research Tools, and Educational Outreach , Ayrianne J. Crawford

Apixaban to Prevent Thrombosis in Adult Patients Treated With Asparaginase , Krishna Gundabolu

Molecular Investigation into the Biologic and Prognostic Elements of Peripheral T-cell Lymphoma with Regulators of Tumor Microenvironment Signaling Explored in Model Systems , Tyler Herek

Utilizing Proteolysis-Targeting Chimeras to Target the Transcriptional Cyclin-Dependent Kinases 9 and 12 , Hannah King

Insights into Cutaneous Squamous Cell Carcinoma Pathogenesis and Metastasis Using a Bedside-to-Bench Approach , Marissa Lobl

Development of a MUC16-Targeted Near-Infrared Antibody Probe for Fluorescence-Guided Surgery of Pancreatic Cancer , Madeline T. Olson

FGFR4 glycosylation and processing in cholangiocarcinoma promote cancer signaling , Andrew J. Phillips

Theses/Dissertations from 2020 2020

Cooperativity of CCNE1 and FOXM1 in High-Grade Serous Ovarian Cancer , Lucy Elge

Characterizing the critical role of metabolic and redox homeostasis in colorectal cancer , Danielle Frodyma

Genomic and Transcriptomic Alterations in Metabolic Regulators and Implications for Anti-tumoral Immune Response , Ryan J. King

Dimers of Isatin Derived Spirocyclic NF-κB Inhibitor Exhibit Potent Anticancer Activity by Inducing UPR Mediated Apoptosis , Smit Kour

From Development to Therapy: A Panoramic Approach to Further Our Understanding of Cancer , Brittany Poelaert

The Cellular Origin and Molecular Drivers of Claudin-Low Mammary Cancer , Patrick D. Raedler

Mitochondrial Metabolism as a Therapeutic Target for Pancreatic Cancer , Simon Shin

Development of Fluorescent Hyaluronic Acid Nanoparticles for Intraoperative Tumor Detection , Nicholas E. Wojtynek

Theses/Dissertations from 2019 2019

The role of E3 ubiquitin ligase FBXO9 in normal and malignant hematopoiesis , R. Willow Hynes-Smith

BRCA1 & CTDP1 BRCT Domainomics in the DNA Damage Response , Kimiko L. Krieger

Targeted Inhibition of Histone Deacetyltransferases for Pancreatic Cancer Therapy , Richard Laschanzky

Human Leukocyte Antigen (HLA) Class I Molecule Components and Amyloid Precursor-Like Protein 2 (APLP2): Roles in Pancreatic Cancer Cell Migration , Bailee Sliker

Theses/Dissertations from 2018 2018

FOXM1 Expression and Contribution to Genomic Instability and Chemoresistance in High-Grade Serous Ovarian Cancer , Carter J. Barger

Overcoming TCF4-Driven BCR Signaling in Diffuse Large B-Cell Lymphoma , Keenan Hartert

Functional Role of Protein Kinase C Alpha in Endometrial Carcinogenesis , Alice Hsu

Functional Signature Ontology-Based Identification and Validation of Novel Therapeutic Targets and Natural Products for the Treatment of Cancer , Beth Neilsen

Elucidating the Roles of Lunatic Fringe in Pancreatic Ductal Adenocarcinoma , Prathamesh Patil

Theses/Dissertations from 2017 2017

Metabolic Reprogramming of Pancreatic Ductal Adenocarcinoma Cells in Response to Chronic Low pH Stress , Jaime Abrego

Understanding the Relationship between TGF-Beta and IGF-1R Signaling in Colorectal Cancer , Katie L. Bailey

The Role of EHD2 in Triple-Negative Breast Cancer Tumorigenesis and Progression , Timothy A. Bielecki

Perturbing anti-apoptotic proteins to develop novel cancer therapies , Jacob Contreras

Role of Ezrin in Colorectal Cancer Cell Survival Regulation , Premila Leiphrakpam

Evaluation of Aminopyrazole Analogs as Cyclin-Dependent Kinase Inhibitors for Colorectal Cancer Therapy , Caroline Robb

Identifying the Role of Janus Kinase 1 in Mammary Gland Development and Breast Cancer , Barbara Swenson

DNMT3A Haploinsufficiency Provokes Hematologic Malignancy of B-Lymphoid, T-Lymphoid, and Myeloid Lineage in Mice , Garland Michael Upchurch

Theses/Dissertations from 2016 2016

EHD1 As a Positive Regulator of Macrophage Colony-Stimulating Factor-1 Receptor , Luke R. Cypher

Inflammation- and Cancer-Associated Neurolymphatic Remodeling and Cachexia in Pancreatic Ductal Adenocarcinoma , Darci M. Fink

Role of CBL-family Ubiquitin Ligases as Critical Negative Regulators of T Cell Activation and Functions , Benjamin Goetz

Exploration into the Functional Impact of MUC1 on the Formation and Regulation of Transcriptional Complexes Containing AP-1 and p53 , Ryan L. Hanson

DNA Polymerase Zeta-Dependent Mutagenesis: Molecular Specificity, Extent of Error-Prone Synthesis, and the Role of dNTP Pools , Olga V. Kochenova

Defining the Role of Phosphorylation and Dephosphorylation in the Regulation of Gap Junction Proteins , Hanjun Li

Molecular Mechanisms Regulating MYC and PGC1β Expression in Colon Cancer , Jamie L. McCall

Pancreatic Cancer Invasion of the Lymphatic Vasculature and Contributions of the Tumor Microenvironment: Roles for E-selectin and CXCR4 , Maria M. Steele

Altered Levels of SOX2, and Its Associated Protein Musashi2, Disrupt Critical Cell Functions in Cancer and Embryonic Stem Cells , Erin L. Wuebben

Theses/Dissertations from 2015 2015

Characterization and target identification of non-toxic IKKβ inhibitors for anticancer therapy , Elizabeth Blowers

Effectors of Ras and KSR1 dependent colon tumorigenesis , Binita Das

Characterization of cancer-associated DNA polymerase delta variants , Tony M. Mertz

A Role for EHD Family Endocytic Regulators in Endothelial Biology , Alexandra E. J. Moffitt

Biochemical pathways regulating mammary epithelial cell homeostasis and differentiation , Chandrani Mukhopadhyay

EPACs: epigenetic regulators that affect cell survival in cancer. , Catherine Murari

Role of the C-terminus of the Catalytic Subunit of Translesion Synthesis Polymerase ζ (Zeta) in UV-induced Mutagensis , Hollie M. Siebler

LGR5 Activates TGFbeta Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

LGR5 Activates TGFβ Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

Theses/Dissertations from 2014 2014

Genetic dissection of the role of CBL-family ubiquitin ligases and their associated adapters in epidermal growth factor receptor endocytosis , Gulzar Ahmad

Strategies for the identification of chemical probes to study signaling pathways , Jamie Leigh Arnst

Defining the mechanism of signaling through the C-terminus of MUC1 , Roger B. Brown

Targeting telomerase in human pancreatic cancer cells , Katrina Burchett

The identification of KSR1-like molecules in ras-addicted colorectal cancer cells , Drew Gehring

Mechanisms of regulation of AID APOBEC deaminases activity and protection of the genome from promiscuous deamination , Artem Georgievich Lada

Characterization of the DNA-biding properties of human telomeric proteins , Amanda Lakamp-Hawley

Studies on MUC1, p120-catenin, Kaiso: coordinate role of mucins, cell adhesion molecules and cell cycle players in pancreatic cancer , Xiang Liu

Epac interaction with the TGFbeta PKA pathway to regulate cell survival in colon cancer , Meghan Lynn Mendick

Theses/Dissertations from 2013 2013

Deconvolution of the phosphorylation patterns of replication protein A by the DNA damage response to breaks , Kerry D. Brader

Modeling malignant breast cancer occurrence and survival in black and white women , Michael Gleason

The role of dna methyltransferases in myc-induced lymphomagenesis , Ryan A. Hlady

Design and development of inhibitors of CBL (TKB)-protein interactions , Eric A. Kumar

Pancreatic cancer-associated miRNAs : expression, regulation and function , Ashley M. Mohr

Mechanistic studies of mitochondrial outer membrane permeabilization (MOMP) , Xiaming Pang

Novel roles for JAK2/STAT5 signaling in mammary gland development, cancer, and immune dysregulation , Jeffrey Wayne Schmidt

Optimization of therapeutics against lethal pancreatic cancer , Joshua J. Souchek

Theses/Dissertations from 2012 2012

Immune-based novel diagnostic mechanisms for pancreatic cancer , Michael J. Baine

Sox2 associated proteins are essential for cell fate , Jesse Lee Cox

KSR2 regulates cellular proliferation, transformation, and metabolism , Mario R. Fernandez

Discovery of a novel signaling cross-talk between TPX2 and the aurora kinases during mitosis , Jyoti Iyer

Regulation of metabolism by KSR proteins , Paula Jean Klutho

The role of ERK 1/2 signaling in the dna damage-induced G2 , Ryan Kolb

Regulation of the Bcl-2 family network during apoptosis induced by different stimuli , Hernando Lopez

Studies on the role of cullin3 in mitosis , Saili Moghe

Characteristics of amyloid precursor-like protein 2 (APLP2) in pancreatic cancer and Ewing's sarcoma , Haley Louise Capek Peters

Structural and biophysical analysis of a human inosine triphosphate pyrophosphatase polymorphism , Peter David Simone

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Comprehensive Cancer Care: an outpatient treatment facility

Braden Abrams Reid , Clemson University

Date of Award

Document type, degree name.

Master of Architecture (MArch)

Legacy Department

Architecture

Committee Chair/Advisor

David Allison

Committee Member

Daniel Harding

John Jacques

Dr. Cynthia Pury

A cancer diagnosis can result in a loss of decision-making and control for patients. The majority of clinical treatments fail to adequately address corollary symptoms and needs that arise both from treatment and from the disease itself. Thus, the architectural problem identified in this thesis inquiry is how can an outpatient cancer centre treat the whole patient comprehensively, while at the same time instilling control and re-empowering the patient? This thesis project proposes a patient-centered environment designed to support the myriad and nuanced needs of the cancer patient, as well as a site-specific proposal for a comprehensive outpatient cancer treatment centre located in Spartanburg County, South Carolina. This cancer centre is designed with the notion of patient-empowerment as a design driver, and incorporates non-traditional complementary treatments in addition to those clinical treatments typically offered in the conventional North American cancer centre.

By way of supporting this topical area of inquiry, the following topics comprise the scope of inquiry undertaken in this project: Clinical Cancer Treatment Architecture: the three main facility types in which cancer treatment occurs - freestanding, aggregated, and monolithic. Complementary/Alternative Treatment Architecture: both cancer-focused and general alternative treatment centres were also investigated, in order to determine what complementary therapies might be appropriate to incorporate with a clinical cancer treatment center. Additionally, these facilities were helpful in giving cues as to what physical design drivers could help guide the subsequent thesis design proposal.

The review of many personal cancer patient blogs and video diaries (all openly available online) was important in framing the experience of the patient. What therapies were commonly feared, personal aversions that developed as a result of treatment, and similar notions written or spoken about all helped to give a sense of what it might be like to be in a patient's situation, and what design decisions might have been helpful in nurturing a more positive experience.

Design principles were developed out of the topical inquiry and architectural investigation, with the focus of patient empowerment at hand. Similarly, site selection, programmatic development, and the final design proposal were each conducted through the lens of the patient experience, and how best to instill control before, during, and after treatment is delivered (that is to say, before the patient arrives, the experience of receiving care, and what is taken away once they leave the treatment centre).

The resulting design proposal developed from this investigation is a 45,000 square foot outpatient cancer treatment centre located in Spartanburg County, South Carolina. The facility comprises a full hematology and infusion therapy suite, a radiation therapy suite, an alternative medicine suite, a physical therapy program, mind-body therapies, and a diet and nutrition area. Patients originating in the Cities of Greenville, Spartanburg, and Greer, and all surrounding areas will utilize this centre.

Recommended Citation

Reid, Braden Abrams, "Comprehensive Cancer Care: an outpatient treatment facility" (2014). All Theses . 2172. https://open.clemson.edu/all_theses/2172

Since June 16, 2015

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OPTIMIZING AND UNDERSTANDING CHECKPOINT INHIBITION THERAPY AND CHIMERIC ANTIGEN RECEPTOR THERAPY AGAINST BREAST CANCER

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thesis cancer therapy

  • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Cancer immunotherapies, which include chimeric antigen receptor therapy (CAR-T) and immune checkpoint inhibition therapy (ICI), have revolutionized the field of cancer therapy. Those therapies modulate the immune system to recognize and target cancer cells. Despite the success of immunotherapy, a large majority of cancer patients do not respond to these immunotherapies. The goal of my research is to understand the mechanisms that cause resistance to immunotherapy and utilize novel combinatorial approaches to enhance current immunotherapy. We developed strategies to enhance the activity of CAR T cells against solid tumors by utilizing a mouse model of breast cancer. We found that CAR T cells generated from Th/Tc17 cells had improved persistence in the TME. Administration of the STING agonist DMXAA greatly enhanced tumor control and was associated with Th/Tc17 CAR T cell persistence and recruitment into the TME. Additionally, DMXAA strongly modulated the immunosuppressive TME through alterations in the balance of immune-stimulatory and suppressive myeloid cells. Sustained long term tumor regression was accomplished with the addition of anti-PD-1 and anti-GR-1 mAb to Th/Tc17 CAR T cell therapy. This study provides a new understanding of the approaches needed to enhance adoptive T cell therapy in solid tumors. Another focus of my research is to further understand the mechanism by which ICI therapy boosts the anti-tumor response. To do this, we engineered a novel mammary mouse tumor that is sensitive to immune checkpoint therapy. Using this model, we uncovered that ICI therapy induced T follicular helper cell activation of B cells to facilitate the anti-tumor response. We also showed that B cell activation of T cells and the generation of antibody are key to the immunotherapy response. This work uncovers new components of the response to immune checkpoint inhibitors. In conclusion, this work has provided insight into mechanisms that can enhance the anti-tumor response of immunotherapies in breast cancer. These strategies, either through harnessing the activity of B cells or by providing STING agonists, have the potential to translate into the clinic to enhance the efficacy of current ICI therapy and CAR-T therapy.
  • breast cancer
  • Immunotherapy
  • checkpoint inhibition
  • https://doi.org/10.17615/cd9c-z255
  • Dissertation
  • Serody, Jonathan S
  • Whitmire, Jason
  • Dotti, Gianpietro
  • Tisch, Roland
  • Wan, Yisong
  • Doctor of Philosophy
  • University of North Carolina at Chapel Hill Graduate School

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