Digital Commons Network^™

Synthesis And Evaluation Of Bodipy-, Azabodipy- And Chlorin-Based Conjugates For Imaging And Photodynamic Therapy Of Egfr-Overexpressing Cancers, Simran Dhingra

LSU Doctoral Dissertations

This dissertation discusses the design of EGFR-targeted small-molecule agents that unite molecular imaging with photodynamic therapy. Chapter 1 frames the clinical need for early detection and selective treatment and surveys BODIPY, aza-BODIPY, and chlorin scaffolds as tunable chromophores for near-infrared imaging and photosensitization. It also outlines EGFR as a validated target and compares two ligand classes used throughout this work: the tyrosine kinase inhibitor erlotinib and the cyclic peptide KLARLLT.

Chapter 2 describes the synthesis of a near-IR BODIPY bearing either one or two erlotinib units. Docking and SPR show specific interactions with the EGFR kinase domain, and both conjugates …

Investigating The Role Of Prostasin In Angiogenesis: A Chorioallantoic Membrane Model Approach, Zaima Aline

Honors Undergraduate Theses

Prostasin, also known as PRSS8 or CAP1, is a glycosylphosphatidylinositol (GPI)-anchored extracellular serine protease involved in various physiological and pathophysiological processes. Prostasin expression is observed during key phases of trophoblast invasion and placental development, critical steps in embryo implantation in Rhesus monkeys. This suggests a role for prostasin in extracellular matrix remodeling and tissue invasion, both essential for a healthy pregnancy. Moreover, prostasin appears vital for development as studies in mice show that a germline knockout of the gene leads to significant placental defects and eventual embryonic death, highlighting its importance in vascular and structural development within the placenta.

Building …

Discovering Therapeutic Strategies In Colorectal Cancer Via Synthetic Lethal Genetic Screens On Patient-Derived Organoid Models, Sana Khalili

Theses and Dissertations

Precision medicine is a revolutionary approach of targeting genetic alterations that are present only in tumor cells to find vulnerabilities that can be targeted with therapy. Identifying genetic dependencies in human colon cancer could help identify effective treatment strategies. Genome-wide CRISPR-Cas9 dropout screens can reveal all genetic dependencies, some of which could be exploited as therapeutic targets using existing drugs.

In this dissertation, I comprehensively characterized genetic dependencies present in a colon cancer organoid avatar, and validated tumor-specific selectivity of select pharmacologic agents. I identified all somatic mutations, all expressed genes, and conducted a genome-wide CRISPR dropout screen to elucidate …

Direct Implantation Of Patient Brain Tumor Cells Into Matching Locations In Mouse Brains For Patient-Derived Orthotopic Xenograft Model Development, Lin Qi, Patricia Baxter, Mari Kogiso, Huiyuan Zhang, Frank K Braun, Holly Lindsay, Sibo Zhao, Sophie Xiao, Aalaa Sanad Abdallah, Milagros Suarez, Zilu Huang, Wan Yee Teo, Litian Yu, Xiumei Zhao, Zhigang Liu, Yulun Huang, Jack M Su, Tsz-Kwong Man, Ching C Lau, Laszlo Perlaky, Yuchen Du, Xiao-Nan Li

Center for Medical Ethics and Health Policy Staff Publications

Background: Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models.

Methods: We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice.

Results: Using this technique, we successfully developed 188 PDOX models from 408 brain tumor patient samples (both high-and low-grade) with a success rate of 72.3% …

Synthesis And Characterization Of Polymeric Nanoparticles To Enhance Celleullar Drug Delivery, Rahma Aly

Chemistry Theses

Medicines in the form of nanoparticles called nanomedicines, stand at the forefront of revolutionary advancements in healthcare, offering precise drug delivery and diagnostic capabilities. A recent example of nanomedicine in the clinic is the COVID-19 vaccine, which helped prevent death during the pandemic. While the potential benefits are immense, a myriad of challenges complicate their seamless integration into clinical practice. The design and fabrication of nanoparticles demand meticulous attention to biocompatibility and toxicity. Interactions with biological systems are complex, requiring a delicate balance between therapeutic efficacy and safety. The reticuloendothelial system's rapid clearance of nanoparticles, their instability in physiological environments, …

Traditional Chinese Medicine: Employing Integrative Medicine As An Approach To Treat Cancer, Jade Hudson

CMC Senior Theses

This thesis explores the history of Traditional Chinese Medicine (TCM) through its depiction in the four classics of TCM and examines the evolution of the field to date. The five categories of TCM treatments analyzed in this paper include acupuncture, dietary therapy, herbal medicine, moxibustion, and physical exercise. Research highlights significant positive outcomes in cancer patients who incorporate TCM alongside modern cancer treatments, such as reduced nausea, vomiting, fatigue, anorexia, pain, and improvements in quality of life and overall well-being. However, notable risks associated with TCM herbal medicine and moxibustion underscore the need for further research into these practices before …

Structural Surfaceomics Reveals An Aml-Specific Conformation Of Integrin Β2 As A Car T Cellular Therapy Target, Kamal Mandal, Gianina Wicaksono, Clinton Yu, Jarrett J Adams, Michael R Hoopmann, William C Temple, Adila Izgutdina, Bonell Patiño Escobar, Maryna Gorelik, Christian H Ihling, Matthew A Nix, Akul Naik, William H Xie, Juwita Hübner, Lisa A Rollins, Sandy M Reid, Emilio Ramos, Corynn Kasap, Veronica Steri, Juan Antonio Camara Serrano, Fernando Salangsang, Paul Phojanakong, Melanie Mcmillan, Victor Gavallos, Andrew D Leavitt, Aaron C Logan, Cliona M Rooney, Justin Eyquem, Andrea Sinz, Benjamin J Huang, Elliot Stieglitz, Catherine C Smith, Robert L Moritz, Sachdev S Sidhu, Lan Huang, Arun P Wiita

Faculty, Staff and Students Publications

Safely expanding indications for cellular therapies has been challenging given a lack of highly cancer-specific surface markers. Here we explore the hypothesis that tumor cells express cancer-specific surface protein conformations that are invisible to standard target discovery pipelines evaluating gene or protein expression, and these conformations can be identified and immunotherapeutically targeted. We term this strategy integrating cross-linking mass spectrometry with glycoprotein surface capture ‘structural surfaceomics’. As a proof of principle, we apply this technology to acute myeloid leukemia (AML), a hematologic malignancy with dismal outcomes and no known optimal immunotherapy target. We identify the activated conformation of integrin β2 …

Development And Biological Evaluation Of Selective Small-Molecule Inhibitors Of The Human Cytochrome P450 1b1, Austin Hachey

Theses and Dissertations--Chemistry

The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this …

Methionine Restriction And Cancer Treatment: A Systems Biology Study Of Yeast To Investigate The Possible Key Players, Esra Börklü

Turkish Journal of Biology

Background/aim: Dietary restriction, mainly carbon and/or methionine restriction are among the upcoming supporting interventions along with chemotherapy in various cancers. Although dietary restriction has been proven to be beneficial, the main cellular machineries affected by its administration lacks deeper information considerably, a notable pitfall in its use as a personalized nutritional approach. Materials and methods: In this study, cellular effects of methionine restriction on a yeast model are explored via systems biology approaches. The methionine biosynthesis network, constructed by integrating interaction data with gene ontology terms, was analysed topologically, and proved to be informative about the intertwined relationship of methionine …

Labrad : Vol 47, Issue 2 - December 2022, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• From the Editor’s Desk
• Case Quiz
• Contrast Enhanced Spectral Mammography Clinical Usefulness of Biochemical Parameters in Prenatal Diagnosis of Down Syndrome In First and Second Trimester
• The Science of Efficiency in a Clinical Laboratory
• Updates in new WHO Blue Book
• Monkeypox vs. COVID-19
• From the Diary of a Researcher- Notes on Understanding Beta-Thalassemia and Metabolic Bone Disease
• Significance of Audit in a Clinical Laboratory
• Microsatellite Instability (MSI) Testing
• Pre-Analytical Variables Affecting Coagulation Testing
• Grading of Soft Tissue Sarcomas
• Recent Updates in 2022 WHO Classification of Thyroid Neoplasms
• MMR and MSI Testing in Malignancies
• Transforming Pedagogical Framework of Pathology through Social …

Synthesis Of Bioactive Heterocycles, Shaila Akter Shetu

Theses and Dissertations

The Discovery of a variety of heterocyclic drugs for the treatment of cancer and other diseases (e.g, neglected tropical diseases) is a medical breakthrough and inspiring for the research community as a whole. A wide range of natural, semi-synthetic, and synthetic anticancer drugs are synthesized using various methods. Among them, β -lactams stand out as a novel class of antibiotics that has different types of biological as well as anti-cancer properties. β -lactam has become a premier and active research subject towards the development of revolutionary anti-cancer drugs. In recent years, a large amount of investigations have been done to …

Alkylthiocarbamate Metal Complexes With Antiproliferation Activity., Kritika Bajaj

Electronic Theses and Dissertations

Bis(thiosemicarbazones) (BTSCs) and their metal complexes have been extensively studied for various applications including catalysis for hydrogen evolution reactions, treatment of neurodegenerative diseases, hypoxia imaging, and a wide range of pharmacological purposes including antitumor, antiviral, antibacterial, and antifungal agents. The paramount property that makes BTSC metal complexes interesting for their use in these applications is the reduction potential of the coordinated metal, which can be selectively tuned by varying the substituents present on the ligand framework. Although the BTSCs have shown a great deal of success as potential cancer therapeutic agents, they lack selectivity towards cancer cells. For this matter, …

Design And Synthesis Of Curcumin Analogs For Anticancer Activity And Discovery Of Novel Hit Molecules Targeting Cxcr4., Maryam Sadat Hosseini Zare

Dissertations (2016-Present)

Curcumin as a natural compound is made of various components including protein, carbohydrate, and curcuminoid. Curcuminoid is made of curcumin, desmethoxycurcumin and bis desmethoxycurcumin. Curcumin is used for the treatment of cancer and inflammatory disorders, but it has some therapeutic problems like poor bioavailability, poor efficacy, and chemical instability. To overcome these problems, the objective of this study is (1) synthesis of pyrazole curcumin analogs, (2) synthesis of triazole curcumin analogs, and (3) in-vitro study of the anticancer activity of these curcumin analogs on head & neck, breast, pancreatic and glioblastoma cancer cells. During this part of my Ph.D. project, …

Flaxseed’S Paradoxical Role In Extending Lifespan And Reproductive Capacity In White Leghorn Laying Hens; And The Effect Of Polyunsaturated Fatty Acids (Pufas) On Lipid Metabolism, Mitochondrial Bioenergetics And E-Cadherin Expression In Laying Hen Ovarian Tumors, William Christopher Weston

Dissertations

We are the first lab to report the occurrence of a diet-induced transsulfuration (TS) blockade associating with elevated S-adenosylmethionine (i.e. SAM) synthesis, enhanced lifespan and enhanced reproductive capacity, in a vertebrate animal model. In this paradoxical study, we used LC-MS/MS-derived metabolomics data to report the effects of flaxseed (Linum Usitatissimum) on one-carbon metabolism in White Leghorn laying hens (Gallus gallus). Flaxseed contains a vitamin B6-antagonizing molecule called ‘linatine’ that is particularly effective at reducing vitamin B6 levels in small rodents and poultry. Linatine reduces TS flux through its inhibition of the vitamin B6-dependent enzymes cystathionine beta synthase (CBS) and cystathionine …

Analyzing The Effects Of E-Hook Peptides On Kinesin-1, Ashton Ward Murrah, Baylee Hope Howard

Honors Theses

Cancer is the second leading cause of death in the United States. Cancerous growth is a result of oncogenes, or mutated genes that increase the rate of cell division in an uncontrolled manner. Cell division, which consists of mitosis and cytokinesis phases, is dependent upon the active movement of kinesin motor proteins along microtubules to rearrange the cytoskeleton for equitable distribution of genetic material to daughter cells. As kinesins are vital to this process, if we could prevent kinesin from binding to the microtubules, cell division would cease.

The goal of this study is to develop a method to prevent …

Total Synthesis And Biological Evaluation Of Siderophores: Key To Develop Iron Chelators And Tackle Antibiotic Delivery To Gram-Negative Bacteria, .Pratibha Desman

Research Symposium

Siderophores are molecules that act as iron carriers in bacteria. As they sequester iron from the environment and penetrate bacterial cells through active transporters, they can bypass the porin-mediated transportation in Gram-negative bacteria. Therefore, conjugating antibiotics that lacks the ability to pass through porins to siderophores and forming “sideromycins” has been proven as a way to battle antibiotic resistance in Gram-negative bacteria. My research will focus on synthesizing two siderophores, catenulobactin B and talarazine A as well as their analogs and exploring their potential to synthesize sideromycins. These molecules will be synthesized in a modular way and their cytotoxicity, ability …

Transcriptomic Profiling Of Fibropapillomatosis In Green Sea Turtles (Chelonia Mydas) From South Texas, Nicholas B. Blackburn, Ana C. Leandro, Nina Nahvi, Mariana A. Devlin, Marcelo Leandro, Ignacio Martinez Escobedo, Juan M. Peralta, Jeff George, Thomas W. Demaar, John Blangero, Megan Keniry, Joanne E. Curran

School of Medicine Publications

Sea turtle fibropapillomatosis (FP) is a tumor promoting disease that is one of several threats globally to endangered sea turtle populations. The prevalence of FP is highest in green sea turtle (Chelonia mydas) populations, and historically has shown considerable temporal growth. FP tumors can significantly affect the ability of turtles to forage for food and avoid predation and can grow to debilitating sizes. In the current study, based in South Texas, we have applied transcriptome sequencing to FP tumors and healthy control tissue to study the gene expression profiles of FP. By identifying differentially expressed turtle genes in …

Co-Distribution Of Ambient Light At Night And Incidence Of Human Cancers And Covid-19, Yidan Meng

Public Health Theses

Introduction and BackgroundThere are increasing concerns about the effects of artificial lights on human health, including hormone-related disease and immune functions. In January 2020, the outbreak of COVID-19 disrupted everyone’s life, and people who infected have various severity. Thus, we want to analyze whether people exposed to different ambient light at night (LAN) levels make them more susceptible to COVID-19 for our summer research. Besides the effects of LAN on immune functions, we also discussed the association of LAN and multiple cancers in seven states of Northeastern U.S. We used similar statistical and geographic analysis methods and separate them into …

Design, Synthesis, And Anticancer Properties Of Ru(Ii) Complexes With Organometallic, “Expanded” Bipyridine, And O,O’-Chelating Ligands, Raphael Ryan

Theses and Dissertations--Chemistry

Cancer is a worldwide public health crisis that requires new and improved drugs to be developed to extend survival rates and improve quality of life for the patient. Platinum-based drugs are used in approximately 50% of cancer treatment regimens. These drugs are highly effective in many kinds of cancer; however, cancers can develop platinum resistance and these drugs have troubling side effects that reduced their use and efficacy. To overcome these disadvantages, many other metals have been studied for their anticancer properties. Notably, the anticancer properties of ruthenium-based agents have drawn considerable attention with multiple ruthenium complexes entering clinical trials. …

Cancer Care Annual Report 2019-2020, Children's Mercy Hospital

Cancer Center Annual Reports

Annual report of cancer care and oncology services at the Children's Mercy Hospital, Kansas City MO, a pediatric medical center. This year’s report focuses on tumors that arise in the kidney and illustrates three important areas of focus that a childhood cancer center must possess in this new age of medicine.

9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.

Engineering The Rod Of Asclepius – A Biochemical Investigation Of Snake Venom Components And Their Application As Potential Cancer Treatments, Noel Pena

Senior Honors Theses

In the wild, venom is crucial to many snakes’ success as predators. While antivenin research focuses on combatting venoms’ abilities to disrupt physiological processes, new studies are attempting to manipulate these same abilities into anticancer therapies. Given the diversity of neurotoxins, hemotoxins, cytotoxins, and others, every new discovery and development within snake venom research adds to the knowledge base and broadens applicational opportunities. Cancer-related venom research isolates various components, manipulates their interaction with target cancer cell lines, and evaluates how their natural biochemical activity counteracts mechanisms that are integral to tumor development. Several more promising components, namely disintegrins, lectins, oxidases, …

Parp Pet Imaging Agents, Brandon Carney

Dissertations, Theses, and Capstone Projects

The poly (adenosine-diphosphate (ADP) ribose) polymerase (PARP) family of enzymes has been of interest to researchers and clinicians for over fifty years, especially the first member of the family, PARP1. This enzyme has become a target for cancer therapeutics due the reliance of highly proliferating cells on PARP1 for genomic maintenance. In the coming age of individualized medicine, however, highly specific therapeutic agents like PARP inhibitors are in need of similarly highly specific companion diagnostic agents. These kind of agents have been made possible with the quickly progressing field of molecular imaging. Specifically, positron emission tomography (PET) has enabled the …

The Great Potential Of Redox Active Ligands: Applications In Cancer Research And Redox Active Catalysis, Meredith Miles

Browse all Theses and Dissertations

Metal N-heterocyclic carbene (NHC) complexes have recently gained much popularity due to their tunable, steric, and electronic properties. Applications for such versatile molecules include organocatalysis, olefin metathesis, sundry cyclization reactions, and materials chemistry. Redox active NHCs are of special interest due to their ability to alter the electronic properties of the metal centers they are ligated to. In the first chapter, Au(I)-NHC complexes were synthesized and tested for biological activity in human cancer cell lines. Increasing reactive oxygen species (ROS) in cellular systems has proven to be a successful pathway for treating cancer. The redox active group in this case …

Study Of The Mechanism Of Action For Ru(Ii) Polypyridyl Complexes As Potential Anticancer Agents, Yang Sun

Theses and Dissertations--Chemistry

Application of chemotherapeutic agents in current cancer treatment has been limited by adverse effects as poor selectivity results in systemic toxicity; most chemotherapy approaches also experience inherited or acquired drug resistance which lead to reduced treatment outcome. Research efforts have focused on the discovery of novel chemotherapies that overcome the limitations mentioned above. Ru(II) polypyridyl complexes with anti-cancer properties have been extensively studied as traditional cytotoxic agents and photodynamic therapy agents due to their photophysical and photochemical characteristics.

Most research has focused on the design of Ru(II) polypyridyl complexes that have affinities to nucleic acids as inspired by the classic …

Diverse Amide Analogs Of Sulindac For Cancer Treatment And Prevention, Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds

Pharmaceutical Sciences Faculty Publications

Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that has shown significant anticancer activity. Sulindac sulfide amide (1) possessing greatly reduced COX-related inhibition relative to sulindac displayed in vivoantitumor activity that was comparable to sulindac in a human colon tumorxenograft model. Inspired by these observations, a panel of diverse sulindac amide derivatives have been synthesized and their activity probed against three cancer cell lines (prostate, colon and breast). A neutral analog, compound 79 was identified with comparable potency relative to lead 1 and activity against a panel of lymphoblastic leukemia cell lines. Several new series also show good …

High Throughput Analysis Of The Penetration Of Iron Oxide/Polyethylene Glycol Nanoparticles Into Multicellular Breast Cancer Tumor Spheroids, Jonathan Robert Gabriel

Theses and Dissertations

The purpose of this study was to design and optimize a system for the high-throughput analysis of multicellular tumor spheroids (MCTS), and validate the system through the study of a complex biological model. The system was successfully created and optimized, allowing the histological recovery of MCTS at rates up to 90% for microarrays of 24-spheroids. Arrays of 96-spheroids were recovered at rates up to 86%. The system was used to study the penetration of 5k Da-polyethylene coated superparamagnetic iron-oxide nanoparticles (5k-PEG SPIONs) into HTB-126 breast cancer spheroids cultured to a mean diameter of 486 micrometer (± 25.2 micrometer). Results were …

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …

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, …

Fluorescent Probe Development For Fructose Specific Transporters In Cancer, Joseph Fedie

Dissertations, Master's Theses and Master's Reports

Carbohydrate transporters or GLUTs of the major facilitator superfamily (MFS) are responsible for transporting sugars into the cell and have been of research interest for decades. Disruptions, mutations, and over-activations of GLUTs have been linked to a number of major diseases including cancer, obesity, and diabetes. Differentiating between transporters is incredibly difficult due to highly conserved structures, and so specific targeting between transporters has proven a complex challenge. GLUTs are highly flexible in their conformations however exactly what will and will not pass through the transporter is ambiguous at best, and many attempt to target these transporters have failed.

In …