Life Sciences Commons^™

Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, Javier A. Mas Rosario

Doctoral Dissertations

Macrophages are white blood cells of the innate immune system that have the ability to change phenotypically depending on the stimuli present in their surroundings through a process commonly referred to as polarization. Macrophage phenotypes broadly range from pro-inflammatory, anti-tumor (M1) to immune-suppressing (M2). Of particular interest to this work, breast cancer progression and metastasis rely on the presence of M2-like tumor-associated macrophages (TAMs). While many studies have shown the involvement of macrophages in tumor progression and metastasis, there remains a need to further explore these interactions and the polarization process, including tracking of macrophage subtypes. Toward this end, I …

Formulation And Evaluation Of Gemcitabine Plus Romidepsin + Cisplatin Combination For Controlling Tumors, Pawat Pattarawat

Doctoral Dissertations

Cancer is a deadly malignant disease that is costly to treat and still impossible to cure. Cancer treatments often come with side effects that impact the overall health of patients. Breast cancer is the most common type of cancer in the United State and bladder cancer mortality and recurrence rates are still high among cancer patients. Thus, safe and effective regimens are needed to combat these diseases.

In this study, the safe and efficacious combination of gemcitabine, cisplatin, and romidepsin (Gem plus Rom+Cis) to treat two types of cancer: bladder and breast cancer, was formulated. In vitro data from this …

Elucidating Mechanisms Of Metastasis With Implantable Biomaterial Niches, Ryan Adam Carpenter

Doctoral Dissertations

Metastasis is the leading cause of cancer related deaths, yet it remains the most poorly understood aspect of tumor biology. This can be attributed to the lack of relevant experimental models that can recapitulate the complex and lengthy progression of metastatic relapse observed in patients. Mouse models have been widely used to study cancer, however they are critically limited to study metastasis. Most models generate aggressive metastases in the lung without the use of unique cell lines or specialized injection techniques. This limits the ability to study disseminated tumor cells (DTCs) in other relevant metastasis prone tissues. Prolonged observation of …

Defining The Let-7 Microrna-Mediated Molecular Mechanisms Regulating T Cell Differentiation, Constance C. Angelou

Doctoral Dissertations

CD4⁺ and CD8⁺ T cells are lymphocytes of the adaptive immune system that play essential roles in immunity. Both T cell subsets recognize their cognate antigen through the T cell receptor (TCR), which induces the proliferation and differentiation of these antigen-specific cells into effector T cells. CD4⁺ T cells have the potential to differentiate into one of multiple lineages of helper T (Th) cells and participate indirectly in antigen clearance by orchestrating the function of other cells. CD8⁺ T cells differentiate into cytotoxic T lymphocytes (CTL), which directly contributes to the resolution of an infection by …

Engineered Nanoparticles For Site-Specific Bioorthogonal Catalysis: Imaging And Therapy, Riddha Das

Doctoral Dissertations

Bioorthogonal catalysis offers a strategy for chemical transformations complementary to bioprocesses and has proven to be a powerful tool in biochemistry and medical sciences. Transition metal catalysts (TMCs) have emerged as a powerful tool to execute selective chemical transformations, however, lack of biocompatibility and stability limits their use in biological applications. Incorporation of TMCs into nanoparticle monolayers provides a versatile strategy for the generation of bioorthogonal nanocatalysts known as “nanozymes”. We have fabricated a family of nanozymes using gold nanoparticles (AuNPs) as scaffolds featuring diverse chemical functional groups for controlled localization of nanozymes in biological environments, providing unique strategies for …

Lung And Colon Cancer Chemoprevention By Polymethoxyflavones, Mingyue Song

Doctoral Dissertations

Cancer has been a leading cause of morbidity and mortality worldwide and characterized by the uncontrolled cell proliferation and an absence of cell death. Polymethoxyflavones (PMFs) is a unique class of flavonoids that almost exclusively found in the peel of citrus fruit. Studies have shown that PMFs exhibited numerous health promoting effects, including anti-carcinogenic and anti-inflammatory ones. Nobiletin (5,6,7,8,3’,4’-hexamethyoxflavone, NBT) is a major citrus flavonoid and has been the most studied PMFs for its potential health benefits. 5-Demethylnobiletin (5-hydroxy-6,7,8,3’,4’-pentamethoxyflavone, 5DN) is a unique flavonoid found in citrus fruits with potential chemopreventive effects against human cancers. In this dissertation, we first …

Characterizing Colorectal Cancer Cells And Their Interactions With Polymethoxyflavones By Raman Microscopy, Hua Zhang

Doctoral Dissertations

Polymethoxyflavones (PMFs), especially Nobiletin (NBT) and 5-demethylnobiletin (5DN), have been widely studied and proved to have anti-cancer effects. However, their exact modes of action against cancer cells are not fully understood. Raman spectroscopy is a molecular vibrational spectroscopy can be used to measure overall biochemical function of single cells noninvasively and without adding any chemical labels. Herein, we characterized the cellular responses of human colorectal cancer HT29 and HCT116 cells, that grow on the gold coated slides, to the treatments of NBT and 5DN using Raman microscopy. Raman microscopic images obtained indicated the different modes of action of these two …

Alternative Methods For The Treatment Of Chemo-Resistant Cancers, Kaitlyn Wong

Doctoral Dissertations

Great strides have been made in cancer therapy in the past century, yet it remains one of the leading causes of death in the United States today. This work aimed to shed light on novel methods to treat a variety of aggressive and often chemo-resistant cancers both in vitro and in vivo. The first aim of this work was to evaluate the therapeutic efficacy of poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) prodrugs compared to standard chemotherapeutic agents. Conjugation of polyMPC to drugs such as doxorubicin (Dox) can result in its improved solubility, prolonged half-life and therapeutic efficacy. PolyMPC and polyMPC-Dox (at a …

Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen

Doctoral Dissertations

The tumor extracellular matrix (ECM) plays an important role in facilitating tumor growth and mediating tumor cells' resistance to drugs. However, during drug development, potential chemotherapeutics are screened in plastic plates, which lack relevant ECM physicochemical cues. In order to improve drug development process, this dissertation includes the development of relevant 2D and 3D biomaterial systems that can be used to study carcinoma cell response to drug treatment. A novel poly(ethylene glycol)-phosphorylcholine (PEG-PC) high-throughput biomaterial platform was developed to study how the ECM mechanochemical properties affect cancer cells' response to drug. The PEG-PC biomaterial is optically transparent, has a mechanical …

Engineering Novel Detection And Treatment Strategies For Bacterial Therapy Of Cancer, Jan T. Panteli

Doctoral Dissertations

Finding and treating cancer is difficult due to limited sensitivity and specificity of current detection and treatment strategies. Many chemotherapeutic drugs are small molecules that are limited by diffusion, making it difficult to reach cancer sites requiring high doses that lead to systemic toxicity and off-target effects. Tomographic detection techniques, like PET, MRI and CT, are good at identifying macroscopic lesions in the body but are limited in their ability to detect microscopic lesions. Biomarker detection strategies are extremely sensitive and able to identify ng/ml concentrations of protein, but are poor at discriminating between healthy and disease state levels due …

Characterizing The Role Of Dna Repair Proteins In Telomere Length Regulation And Maintenance: Fanconi Anemia Complementation Group C Protein And 8-Oxoguanine Dna Glycosylase, David Beomjin Rhee

Doctoral Dissertations

Telomeres are the chromosome end structures consisting of telomere-associated proteins and short tandem repeat sequences, TTAGGG, in humans and mice. Telomeres prevent chromosome termini from being recognized as broken DNA ends. The structural integrity of DNA including telomeres is constantly threatened by a variety of DNA damaging agents on a daily basis. To counteract the constant threats from DNA damage, organisms have developed a number of DNA repair pathways to ensure that the integrity of genome remains intact. A number of DNA repair proteins localize to telomeres and contribute to telomere maintenance; however, it is still unclear as to what …

Functional Analysis Of Chromodomain Helicase Dna Binding Protein 2(Chd2) Mediated Genomic Stability, Sangeetha Rajagopalan

Doctoral Dissertations

Histone modifying enzymes and chromatin remodeling complexes play an important regulatory role in chromatin dynamics that dictate the interaction of regulatory factors involved in processes such as DNA replication, recombination, repair and transcription, with DNA template. The CHD (Chromodomain Helicase DNA Binding Protein) family of proteins is known to be involved in the regulation of gene expression, recombination and chromatin remodeling via their chromatin specific interactions and activities. Phenotypic analysis of the Chd2 mutant mouse model developed by our laboratory indicates that the Chd2 protein plays a critical role in tumor suppression as the heterozygous mutant mice develop spontaneous lymphomas. …