Добірка наукової літератури з теми "060109 Proteomics and Intermolecular Interactions (excl. Medical Proteomics)"
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Дисертації з теми "060109 Proteomics and Intermolecular Interactions (excl. Medical Proteomics)"
(5930141), Minervo Perez. "HIGH-THROUGHPUT IDENTIFICATION OF ONCOGENIC TYROSINE KINASE SUBSTRATE PREFERENCES TO IMPROVE METHODS OF DETECTION." Thesis, 2021.
Знайти повний текст джерела(5930294), Mayank Srivastava. "DEVELOPMENT OF CHEMICAL PROTEOMIC APPROACHES TO STUDY VIRAL ENDOCYTOSIS AND PHOSPHOPROTEOMICS." Thesis, 2019.
Знайти повний текст джерелаA significant development in mass spectrometry instrumentation and software in the past decade has led to its application in solving complex biological problems. One of the emerging areas is Chemical Proteomics that involves design and use of chemical reagents to probe protein functions in ‘a live cell’ environment. Another aspect of Chemical Proteomics is the identification of target proteins of a drug or small molecule. This is assisted by photoreactive groups, which on exposure to UV light, covalently link the target proteins that can be purified by affinity-based enrichment followed by mass-spectrometric identification. This phenomenon of Photoaffinity labeling (PAL) has been widely used in a broad range of applications. Herein, we have designed chemical tools to study Zika endocytosis and phosphoproteomics.
Zika virus has attracted the interest of researchers globally, following its outbreak in 2016. While a significant development has been made in understanding the structure and pathogenesis, the actual mechanism of Zika entry into host cells is largely unknown. We designed a chemical probe to tag the live virus, leading to the identification of the virus receptors and other host factors involved in viral entry. We further validated neural cell adhesion molecule (NCAM1) as a host protein involved in early phase entry of Zika virus into Vero cells.
The second aspect is the development of the DIGE (Difference Gel Electrophoresis) technology for phosphoproteomics. Phosphoproteins are known to be involved in various signaling pathways and implicated in multiple diseased states. We designed chemical reagents composed of titanium (IV) ion, diazirine and a fluorophore, to covalently label the phosphoproteins. Cyanine3 and cyanine5 fluorophores were employed to reveal the difference in phosphorylation between samples for the comparative proteomics. Thus far, we have successfully demonstrated the labeling of standard phosphoproteins in both simple and complex protein mixtures, and the future efforts are towards applying the technology to identify phosphoproteins in a cell lysate.
(10731939), Pragatheiswar Giri. "ELECTROCHEMOTHERAPY WITH GALLOFLAVIN FOR EFFECTIVE TRIPLE NEGATIVE BREAST CANCER TREATMENT: AN IN VITRO MODEL STUDY." Thesis, 2021.
Знайти повний текст джерелаOne in eight woman develop breast cancer in the United States of America and is the most common type of cancer in the world. Breast cancer has the highest rate of death compared to any other form of cancer. Triple Negative Breast Cancer (TNBC) is the most lethal type of breast cancer, which is the most fatal of all breast cancer types. TNBC is onerous to treat since it lacks all the three most commonly targeted hormones and receptors. Current patients afflicted with TNBC are treated with platinum core chemotherapeutics, namely Cisplatin. Despite the anticancer effects shown by Cisplatin, TNBC attenuates its effect and develops a resistance eventually, which results in reoccurrence of TNBC after few years. Hence there is a demand for effective and alternative ways to treat TNBC. To inhibit the TNBC cell proliferation, blocking the key glycolytic enzyme Lactase Dehydrogenase B (LDHB) is studied and validated. Galloflavin (GF), a proven LDHB inhibitor is utilized in this series of studies and analysis. In addition, Electrochemotherapy, which involves the application of electrical pulses (EP) were utilized to enhance the uptake of GF. The combination of Electrochemotherapy (ECT) with LDHB is a novel way to treat TNBC to produce an alternative to traditional chemotherapy. EP+GF will be subjected onto TNBC cells at various concentrations and pulse parameters. The purpose of this study is to test the effect of alternative chemotherapeutic drug delivery methods for TNBC patients for decrease in mortality rate and improve quality of life. Results indicate TNBC cell viability is the least for EP+GF treatments and the maximum Reactive Oxygen Species (ROS) levels and a maximum decrease in Glucose and Lactate uptake for EP+GF treatments relative to control. Immunoblotting studies indicate the inhibition of LDHB is the most on EP+GF treatments, indicating that this could be a novel modality to treat TNBC.
(5930177), Vishak Raman. "INHIBITION OF METABOLISM AND INDUCTION OF APOPTOSIS IN TRIPLE NEGATIVE BREAST CANCER CELLS BY LIPPIA ORIGANOIDES PLANT EXTRACTS." Thesis, 2019.
Знайти повний текст джерелаAccording to the Global Cancer Incidence, Mortality, and Prevention (GLOBOCAN) study for 2018, 2,089,000 women will have been diagnosed with breast cancer worldwide, with 627,000 breast cancer-related mortalities. It is estimated that between 15 – 20 % of breast cancer diagnoses are of the triple-negative subtype. Triple-negative breast cancers (TNBCs) do not express the receptors for estrogen, progesterone, and human epidermal growth factor 2, and hence cannot be treated using hormone receptor-targeted therapy.
TNBCs are commonly of the basal-like phenotype, with high expression levels of proteins involved in epithelial-mesenchymal transition, extracellular-matrix (ECM) remodeling, cell cycle progression, survival and drug resistance, invasion, and metastasis. 5-year survival rates are significantly lower for TNBC patients, and the disease is characterized by poorer grade at the time of diagnosis as well as higher 5-year distant relapse rates, with a greater chance of lung and CNS metastases. Current treatments for TNBC take the form of aggressive cytotoxic chemotherapy regimens with multiple adverse side-effects. An important goal of on-going studies is to identify new compounds with significant TNBC-specificity, in order to improve patient survival outcomes while preserving a high quality of life during treatment.
For several decades, compounds originally isolated from bioactive natural extracts, such as the taxanes and vinca alkaloids, have been at the forefront of chemotherapy. However, due to their non -specific mechanisms of action, treatment with these compounds eventually leads to significant toxicity to normal cells and tissues. Modern transcriptomics, metabolomics, and proteomics tools have greatly improved our understanding of the mechanisms governing cancer initiation and progression, and revealed the considerable heterogeneity of tumor cells. This has allowed for the identification of potential vulnerabilities in multiple cancers, including TNBCs. By leveraging these new technologies and insights with the tremendous diversity of bioactive compounds from organisms that remain unstudied, new classes of onco-drugs targeting pathways specific to TNBC cells could be identified in the near future.
Here, we describe the cytotoxic effects of extracts from Lippia origanoides - a species of medicinal shrub native to Central and South America - on TNBC cells. We report that these extracts induce rapid, sustained, and irreversible apoptosis in TNBC cells in vitro, with significantly reduced cytotoxicity against normal mammary epithelial cells. The L. origanoides extracts LOE and L42 exploited two TNBC-specific characteristics to induce apoptosis in these cells: i) inhibiting the constitutively active survival and inflammatory NF-kB signaling pathway, and ii) significantly dysregulating the expression levels of mitochondrial enzymes required to maintain the TCA cycle and oxidative phosphorylation; metabolic pathways that are required for the maintenance of TNBC cell growth and proliferation.
Finally, to lay the foundations for future studies on the abilities of these extracts to prevent tumor initiation and inhibit tumor growth in vivo, we also show that the L. origanoides extract, L42, is non-toxic to immunocompetent C57BL/6 mice, and have developed an in vivo model of human TNBC in athymic nu/nu mice.
Collectively, our studies are the first to identify the anti-TNBC-specific properties of bioactive extracts from the Lippia species, and reveal that targeting NF-kB signaling and mitochondrial metabolism are potential avenues to new therapeutics against this subtype of breast cancer. Future work in our lab will focus on identifying the bioactive components (BACs) of the extract mediating its apoptotic effects, and shedding light on their protein binding partners within the cell.
(7023215), Carlie Nicole Priddy. "Mechanotransduction in Living Bone: Effects of the Keap1-Nrf2 Pathway." Thesis, 2019.
Знайти повний текст джерела(9189272), Youngwoo Lee. "NEW FUNCTIONAL LOOKS INTO THE PROTEOME USING CO-FRACTION MASS SPECTROMETRY (CF-MS)." Thesis, 2020.
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