The Role Of Cadherins And Ryk On Metastasis And Invasion In Triple Negative Breast Cancer Cell Model: Hs578t/Hs578ts(I)8,
2023
South Dakota State University
The Role Of Cadherins And Ryk On Metastasis And Invasion In Triple Negative Breast Cancer Cell Model: Hs578t/Hs578ts(I)8, Ibis Iser
Electronic Theses and Dissertations
Breast cancer is a major cause of death among women in European and North American countries, even with improved methods for diagnosis and therapy. The mortality of breast cancer is mainly due to the migration of the primary tumor to distinct sites in the body and is very common in triple negative breast cancer (TNBC). This type of breast cancer affects younger woman and has a high recurrence rate. Unfortunately, TNBC is extremely difficult to control because of the absence of specific targets for treatment. Therefore, our research aim is to discover new therapeutic targets and identify novel approaches for …
Modulatory Effects Of Deacetylated Sialic Acids On Breast Cancer Resistance Protein-Mediated Multidrug Resistance And Receptor Tyrosine Kinase-Targeted Therapy,
2023
South Dakota State University
Modulatory Effects Of Deacetylated Sialic Acids On Breast Cancer Resistance Protein-Mediated Multidrug Resistance And Receptor Tyrosine Kinase-Targeted Therapy, Isaac Tuffour
Electronic Theses and Dissertations
Multidrug resistance (MDR) remains a major challenge in cancer treatment, accounting for over 90% of chemotherapeutic failures. Cancers utilize sugar residues to engage in multidrug resistance. The underlying mechanism of action involving glycans, specifically the glycan sialic acid (Sia) and its various functional group alterations, has not been explored. ATP-binding cassette (ABC) transporter proteins, key proteins utilized by cancers to engage in MDR pathways, contain Sias in their extracellular domains. Modulating the expression of acetylated-Sias on Breast Cancer Resistance Protein (BCRP), a significant ABC transporter implicated in MDR, in lung and colon cancer cells directly impacted the ability of cancer …
Design Of Block Copolymer With Tunable Hydrophobic/Hydrophilic/Fluorophilic Interactions,
2023
Montclair State University
Design Of Block Copolymer With Tunable Hydrophobic/Hydrophilic/Fluorophilic Interactions, Tatiane De Fatima Dutra
Theses, Dissertations and Culminating Projects
Block copolymers (BCP) with balanced interactions and their resultant bulk-phase self-assembly have become increasingly important in advancing nanotechnology, separation, and energy applications. However, a few reports have addressed the synthesis challenge and bulk-phase self-assembly of such triblock copolymers. This thesis presents a facile route for preparing triblock copolymer via controlled radical and organocatalytic ring-opening polymerization that allows precise control over the incorporation of individual moieties in resultant polymer, responsible for balanced hydrophilic, hydrophobic/lipophilic, and fluorophilic interactions. Synthesized polymer with suggested self-assembled 2D lamellar nanostructure exhibits high-temperature stability. The long-term goal of this work is to selectively use this polymer class …
A Computational Study Of The Copper-Catalyzed Trifluoromethylation Of Boronic Acids,
2023
Montclair State University
A Computational Study Of The Copper-Catalyzed Trifluoromethylation Of Boronic Acids, Kevin Nyhuis
Theses, Dissertations and Culminating Projects
This work is a computational study of a reaction mechanism for the trifluoromethylation of boronic acids. Three steps of the proposed reaction mechanism are studied, •CF3 addition to a copper catalyst center, base promoted transmetalation between copper and aryl boronic acid, and bond forming reductive elimination in which the CF3 and aryl substituent form a bond. Limited information is known about this mechanism. This study uses computational methods to attempt to elucidate the mechanism and provide the groundwork for potential improvement. Quantum chemical methods in conjunction with tight-binding based conformational sampling methods are used to investigate the possible …
Investigating The Roles Of Active Site Residues K59, K119 And E168 In M. Tuberculosis Indole-3-Glycerol Phosphate Synthase,
2023
Montclair State University
Investigating The Roles Of Active Site Residues K59, K119 And E168 In M. Tuberculosis Indole-3-Glycerol Phosphate Synthase, Maryum M. Bhatti
Theses, Dissertations and Culminating Projects
Tuberculosis (TB) is a disease that is caused by a bacteria called Mycobacterium tuberculosis and primarily attacks the lungs but can spread to other areas of the body as well. TB can develop resistance to drugs that may be used to cure the disease. Multidrug resistant TB is especially a growing issue as it does not respond to the two most powerful anti-TB drugs, isoniazid and rifampicin. For this reason, finding new ways to target TB are critically needed. One possible way to do this is to target the enzymes in the tryptophan biosynthetic pathway of M. tuberculosis. Studies have …
Multilevel Computational Investigation Into The Catalytic Mechanisms Of Matrix Metalloproteinase-1 And Fat Mass And Obesity-Associated Enzyme,
2023
Michigan Technological University
Multilevel Computational Investigation Into The Catalytic Mechanisms Of Matrix Metalloproteinase-1 And Fat Mass And Obesity-Associated Enzyme, Ann Varghese
Dissertations, Master's Theses and Master's Reports
Enzymes are biological macromolecules, typically proteins, that efficiently accelerate the rate of chemical reactions. Their remarkable catalytic power plays a vital role in essential processes across all kingdoms of life. Nowadays, computational chemistry methods provide valuable insights into enzymatic functions aiding our understanding of biological processes and providing advancements in fields such as biomedical sciences, biomimetic catalysis, drug design and biotechnology. This dissertation employs multilevel computational chemistry methods to investigate the structure-function relationships and the catalytic mechanisms of two metalloenzymes -Zn(II)-dependent matrix metalloproteinase-1 (MMP-1) and non-heme Fe(II)/2-oxoglutarate (2OG) dependent fat-mass and obesity-associated (FTO) enzyme. Chapter 2 explores the role of …
Identification And Functional Characterization Of Myb Transcription Factors Regulating Flavonoid Biosynthesis In Durian Durio Zibethinus L. Pulps,
2023
Faculty of Science
Identification And Functional Characterization Of Myb Transcription Factors Regulating Flavonoid Biosynthesis In Durian Durio Zibethinus L. Pulps, Kamonwan Weerawanich
Chulalongkorn University Theses and Dissertations (Chula ETD)
Durian fruit possesses high nutritional value due to its enriched bioactive compounds such as phenolics, carotenoids, and vitamins. While various transcription factors (TFs) regulate the phenylpropanoid biosynthetic pathway, MYB TFs play a pivotal role in controlling key genes in this pathway. In this study, we identified candidate v-Myb myeloblastosis viral oncogene homolog, MYB TFs from our transcriptome database of the Monthong cultivar including five developmental/postharvest ripening stages. MYBs that were upregulated during the ripening stage were considered as candidate transcriptional activators, based on the positive correlation observed between flavonoid biosynthetic genes and flavonoid contents in ripe durian pulps. Conversely, MYBs …
Solubility And Anti-Cancer Efficiency Enhancement Of Phytochemicals By Complexation With Β-Cyclodextrin And Derivatives,
2023
Faculty of Science
Solubility And Anti-Cancer Efficiency Enhancement Of Phytochemicals By Complexation With Β-Cyclodextrin And Derivatives, Saba Ali
Chulalongkorn University Theses and Dissertations (Chula ETD)
Phytochemicals, abundant in plants, showcase diverse pharmacological effects, with an increasing focus on their potential as anticancer agents. Three bioactive natural compounds with pharmaceutical potential are piperine (PP), oxyresveratrol (OXY), and tanshinone IIA (Tan IIA). However, these three phytochemicals have low water solubility and susceptibility to UV light degradation. To address this problem, we explored the potential of β -cyclodextrins (βCDs), renowned for their ability to enhance the solubility and stability of lipophilic drugs by encapsulating them within their molecular structure. Our focus centered on β-cyclodextrin (βCD) and its derivatives, including hydroxypropyl-β-cyclodextrin (HPβCD), dimethyl-β-cyclodextrin (DMβCD), and sulfobutylether-β-cyclodextrin (SBEβCD). In this …
Regulation Of Cell Cycle And Apoptosis By Mirna Via Jak-Stat/Akt Pathway In White Spot Syndrom Virus-Infected Shrimp,
2023
Faculty of Science
Regulation Of Cell Cycle And Apoptosis By Mirna Via Jak-Stat/Akt Pathway In White Spot Syndrom Virus-Infected Shrimp, Waqar Ahmad
Chulalongkorn University Theses and Dissertations (Chula ETD)
WSSV infection is one of the most serious threats to the aquaculture industry. To fight against WSSV, shrimp rely on several immune effectors and pathways, i.e. the JAK/STAT pathway, which is considered an essential communication gateway for cell function. It has been reported previously that the JAK/STAT pathway interconnects with other pathways and regulates the cell cycle and apoptosis in vertebrates, but the mechanism of this pathway in the regulation of cell cycle and apoptosis in shrimps is still unclear. Thus, the purpose of this study is to investigate how the JAK/PI3K/AKT pathway controls cell cycle and cell death, as …
Functional Characterization Of Pacific White Shrimp Litopenaeus Vannamei Heat Shock Protein 90 In Response To White Spot Syndrome Virus Infection,
2023
Faculty of Science
Functional Characterization Of Pacific White Shrimp Litopenaeus Vannamei Heat Shock Protein 90 In Response To White Spot Syndrome Virus Infection, Warumporn Yingsunthonwattana
Chulalongkorn University Theses and Dissertations (Chula ETD)
Heat shock proteins (HSPs) are host chaperones that can be used by viruses to facilitate various steps of viral infections. In this study, we found that Litopenaeus vannamei heat shock protein 90 (LvHSP90) is a viral-responsive protein, due to a significant transcriptional and translational upregulation following white spot syndrome virus (WSSV) infection. Suppression of LvHSP90 significantly reduced WSSV infection which was corresponded with significantly decreased expressions of viral genes, including the immediate-early genes and viral DNA polymerase. Conversely, injecting shrimp with WSSV that had been co-incubated with a recombinant LvHSP90 (rLvHSP90) promoted WSSV infection as evidenced by an increased cumulative …
Identification And Functional Characterization Of Mads-Box Proteins And Ccos Involved In Carotenoid Metabolism In Durian Durio Zibethinus L. Pulps,
2023
Faculty of Science
Identification And Functional Characterization Of Mads-Box Proteins And Ccos Involved In Carotenoid Metabolism In Durian Durio Zibethinus L. Pulps, Kittiya Tantisuwanichkul
Chulalongkorn University Theses and Dissertations (Chula ETD)
Durian (Durio zibethinus L.), known as the "King of fruits," holds significant economic importance in Thailand. Apart from its unique odor and sweet taste, durian pulp exhibits a yellow color, which is an important aspect of fruit quality. Carotenoids are essential compounds responsible for the yellow, orange, and red coloration in many fruits and vegetables. During durian fruit development and ripening processes, its pulp changes from white to yellow due to increased carotenoid accumulation. The carotenoid biosynthetic pathway, responsible for carotenoid production, is controlled by ethylene. However, the mechanism underlying this process in durian fruit is still unknow. Notably, the …
Impact Of Sample Conditions On Dna Phosphodiester Backbone Bi/Bii Conformational Equilibrium Dynamics,
2023
Missouri State University
Impact Of Sample Conditions On Dna Phosphodiester Backbone Bi/Bii Conformational Equilibrium Dynamics, Autumn C. Pilarski
Graduate Theses/Dissertations
DNA damage, such as single base lesions and mismatches, is highly prevalent within cells. If these DNA damage events are not repaired, they could lead to mutations and thus disease and cancer. Intricate repair mechanisms are in place to fix these damage events, one such being Base Excision Repair (BER) and associated enzyme: Thymine DNA Glycosylase (TDG). The first step of this repair process, recognition of the lesion by TDG, is not well understood. The following thesis presents results to better understand the fundamental biophysical question of how a DNA lesion within a mismatch context is recognized in a million …
Engineering And Characterizing Proteins: A Dual Study On Canine P53 Protein And Cyan Thermal Protein,
2023
Missouri State University
Engineering And Characterizing Proteins: A Dual Study On Canine P53 Protein And Cyan Thermal Protein, Dhruv B. Sitapara
Graduate Theses/Dissertations
This research aims to explore protein development and characterization, focusing on a dual study of canine p53 protein and cyan thermal protein. For the canine p53 protein, the goal is to comprehend its structure to better understand a key component of canine cancers. This multi-step process involved expressing the canine p53 DNA-binding domain in E. coli and purifying it through affinity and ion-exchange chromatography. The purified protein was studied to test the binding of canine p53 protein to human DNA sequences using Surface Plasmon Resonance (SPR) experiments and an Electrophoretic Mobility Shift Assay (EMSA), visualized with a SYBR-safe stain. The …
Role Of Grb2 Intracellular Localization In Progesterone Receptor Positive Breast Cancer,
2023
Faculty of Allied Health Sciences
Role Of Grb2 Intracellular Localization In Progesterone Receptor Positive Breast Cancer, Nattamolphan Wittayavimol
Chulalongkorn University Theses and Dissertations (Chula ETD)
Progesterone receptor (PR) extranuclear signaling mediates mainly through PR polyproline domain (PPD) interaction with SH3 domain of cytoplasmic signaling molecules. PR-PPD interfered with Grb2-SOS binding through SH3 interaction resulting in decreased cell proliferation and correlates with a good prognosis in PR positive breast cancer. Grb2 is a key adaptor molecule and expressed in both nucleus and cytoplasm. We hypothesized that change in Grb2 localization alters PR transcription resulting in better clinical outcomes in PR positive breast cancer. BT-474 breast cancer cells expressing inducible Grb2-SV402x (nuclear Grb2, nuGrb2) or Grb2-MYR (membrane Grb2, memGrb2) were constructed. MemGrb2-BT-474 showed higher levels of PR …
Roles Of Progesterone Signaling On Dna Repair And Cell Survival In Ovarian Cancer Cells,
2023
Faculty of Allied Health Sciences
Roles Of Progesterone Signaling On Dna Repair And Cell Survival In Ovarian Cancer Cells, Pattarasiri Rangsrikitphoti
Chulalongkorn University Theses and Dissertations (Chula ETD)
Every year over 300,000 women worldwide are diagnosed with ovarian cancer and half of these patients die from this disease. The symptoms of ovarian cancer are very general and often confused with other common female diseases making ovarian cancer a challenging disease to diagnose and treat. Platinum-based chemotherapy, including cisplatin, stands as the first-line treatment for ovarian cancer. However, chemotherapy resistance remains a continuing problem, contributing to a high mortality rate. Progesterone receptor (PR) signaling has been implicated in various aspects of ovarian cancer biology. Clinical studies show a positive correlation between PR expression, improved patient survival and cisplatin response, …
Characterization Of The Clostridioides Difficile Glycosyl Hydrolase Ccsz,
2023
Wilfrid Laurier University
Characterization Of The Clostridioides Difficile Glycosyl Hydrolase Ccsz, Brian Lowrance
Theses and Dissertations (Comprehensive)
Bacteria inhabit many of the harshest environments on Earth; persisting and thriving in conditions thought to be unsuitable for life. One common strategy to withstand these environments is the formation of a biofilm. Biofilm composition varies greatly, depending on the underlying community that produces it. Cellulose, a polymer consistently prevalent in biofilms, has been identified as a virulence factor in many pathogens and is suspected to be involved in pathogenesis by Clostridioides difficile. C. difficile is the #1 cause of hospital acquired diarrhea, which can range from mild to life-threatening infections. Biofilm formation is hypothesized to be involved in …
Assessing The Biocatalytic Promiscuity Of Pep- Transformations For Geminal-Difluorination,
2023
Wilfrid Laurier University
Assessing The Biocatalytic Promiscuity Of Pep- Transformations For Geminal-Difluorination, Eloy Jose Torres Garcia
Theses and Dissertations (Comprehensive)
Fluorine is the most electronegative chemical element and can drastically change molecular properties, such as drug pharmacokinetics and agrochemical half-life. Although a great deal of progress is occurring in synthetic methods to access various organofluorines, these methods struggle with harsh conditions and limited substrate scope. Biocatalytic approaches offer the potential to access organofluorines that are difficult or impossible with the current methodology. Phosphoenolpyruvate (PEP) is a central metabolite and biosynthetic precursor for diverse molecules. Phosphoenol pyruvate mutase (Ppm) catalyses the interconversion of Phosphonopyruvate (PnPy) to Phosphoenolpyruvate (PEP). This research successfully expressed and …
Functional Residues Of Cjpata,
2023
Wilfrid Laurier University
Functional Residues Of Cjpata, Robert Lamont
Theses and Dissertations (Comprehensive)
Antibiotic resistance in pathogenic bacteria continues to challenge clinicians and threaten the lives of infected individuals. For this reason, new classes of antibiotics or new targets for antibiotic therapy are needed to circumvent this global health crisis. In Gram-negative bacteria, the enzymes peptidoglycan O-acetyltransferase A and B (PatA and PatB), are responsible for adding acetyl groups to the C-6 hydroxyl group of N-acetyl muramic acid (MurNAc) in peptidoglycan (PG). These acetyl groups are responsible for inhibiting the activity of lysozyme from host organisms that hydrolyze the β1-4 glycosidic linkage between MurNAc and N-acetylglucosamine (GlcNAc). The acetyl groups …
Exploring The Membrane Protein And Peptide Interactions Of Mitochondrial And Bacterial Lipid Systems,
2023
Wilfrid Laurier University
Exploring The Membrane Protein And Peptide Interactions Of Mitochondrial And Bacterial Lipid Systems, George Saudan
Theses and Dissertations (Comprehensive)
This study aims to expand the understanding of interactions between membrane lipids and proteins, and relate it to their biological functions in two experimental systems. The first system focuses on the interaction and conformation of a membrane protein Uncoupling Protein 4 (UCP4) in mitochondrial inner membrane lipids, in the absence and presence of cardiolipin; a lipid specific to mitochondrial inner membranes. The second system considers the interaction and conformation of a cell penetrating peptide, Penetratin, which can interact with both mammalian and bacterial cells. A N- and C-termini protected form of this 16-meric peptide (Pen2) was used to explore its …
Investigation Of Mechanical Regulation On Stat3 Activity And Mmp Production,
2023
University of New Hampshire, Durham
Investigation Of Mechanical Regulation On Stat3 Activity And Mmp Production, Jaxson R. Libby
Honors Theses and Capstones
Transcription factor, STAT3, is inappropriately expressed in cancer cells, and has contrasting activation in 2D versus 3D microenvironments. 2D plates are often used for drug screening and do not always recapitulate in vivo responses. To combat inaccurate 2D drug studies, a 3D hydrogel was created to support the growth of cancer cells into a tumor-like environment. The hydrogel consists of a biocompatible dextran homopolysaccharide, cell adhesion RGD sequences, and crosslinker MMP labile peptides. A pH dependent reaction couples the RGD sequences to dextran then the polymers are crosslinked into a gel. Crosslinking is accomplished using terminal cysteine peptide sequences, allowing …
