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Bcl2 Mediated Targeted Drug Delivery For The Treatment Of Kidney Fibrosis And Stomach Cancer, Humayra Afrin
Bcl2 Mediated Targeted Drug Delivery For The Treatment Of Kidney Fibrosis And Stomach Cancer, Humayra Afrin
Open Access Theses & Dissertations
Apoptosis, the programmed death of cells, is primarily regulated by a delicate balance between pro-apoptotic and anti-apoptotic signals. The Bcl-2 (B-cell lymphoma 2) family of proteins acts as anti-apoptotic agents, promoting cell survival. Dysregulation of these proteins is a common occurrence in conditions such as cancer and fibrosis, where overexpression of anti-apoptotic members can foster tumor cell survival and fibroblast activation. In this study, our aim was to explore the therapeutic potential of Bcl-2 inhibitors, both as a small molecule (specifically Navitoclax (Navi)), inhibitor and as Bcl-2 siRNA, for targeted treatment. Intravenous administration of Navi often leads to thrombocytopenia, necessitating …
Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad
Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad
Dissertations, Theses, and Capstone Projects
The overexpression of HER2 accounts for 20-30% of breast cancer tumors and not only serves as a marker for poor predictive clinical outcomes but also as a target for treatment. Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutic drugs to provide targeted treatment without toxicity to normal tissue. Most of the ADCs currently in the clinic for cancer chemotherapy are based on complex organic molecules. In contrast, the conjugation of metallodrugs to mAbs has been overlooked when there is enormous potential in this area with the resurgence of metal-based drugs as prospective cancer …
Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner
Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner
Dissertations, Theses, and Capstone Projects
The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …
The Role Of The Cdk8 Kinase Module In Maintaining Proteostasis, Stephen Willis
The Role Of The Cdk8 Kinase Module In Maintaining Proteostasis, Stephen Willis
Theses and Dissertations
The underlying etiology of numerous disease states results from perturbations in the maintenance of cellular proteostasis. Carcinogenesis relies on these perturbations to foster uncontrolled cell growth and eventual metastases, while neurodegenerative diseases are a consequence of such perturbations. Control of these processes occurs at numerous molecular levels, commonly starting with transcription. A key transcriptional complex that is involved is the CDK8 Kinase Module (CKM). The CKM is conserved from yeast to man, forming a tetrameric complex consisting of MED12, MED13, CDK8, and CCNC. The CKM has not only been implicated in a variety of cancers but also in a spectrum …
"Hunter-Killer" Peptoid-Peptide Conjugate To Target And Eliminate Cancer Stem Cells, Breanne F. Mcelderry
"Hunter-Killer" Peptoid-Peptide Conjugate To Target And Eliminate Cancer Stem Cells, Breanne F. Mcelderry
Chemistry Theses
In the contemporary paradigm concerning the emergence of therapy-resistant recurrent cancer, recent studies posit the existence of a limited population of self-renewing malignant progenitors known as cancer stem cells (CSCs). The presence of CSCs explains why tumors often relapse despite clinical remission with initial therapeutic interventions. Consequently, the development of innovative therapeutic modalities specifically tailored to target and eliminate CSCs represents a highly promising strategy for eradicating cancer without the risk of recurrence. In previous research, we successfully developed a synthetic peptoid-based ligand CL-1-19-1 that selectively binds to CSC over non-CSC. However, CL-1-19-1 did not exhibit any significant inhibitory effect …
Csn-5: A Tumor's Friend Or Foe In The C. Elegans Germline?, Kellie C. Kuch
Csn-5: A Tumor's Friend Or Foe In The C. Elegans Germline?, Kellie C. Kuch
Graduate Student Theses, Dissertations, & Professional Papers
The COP9 signalosome is a highly conserved eukaryotic complex regulating protein degradation via deneddylation of Cullin-RING E3 ligases. CSN5, the COP9’s fifth component, contains the catalytically active domain for CSN deneddylation. The complex is inactive without CSN5; however, CSN5 engages in COP9-independent binding with several other proteins, typically promoting either destruction or stabilization of its partners. Many of its confirmed interaction partners are also implicated in tumorigenesis (prominent examples being p27 and p53) and a complex cancer interactome has been established for CSN5. Additionally, CSN5 overexpression has been documented in a staggering array of cancers of diverse origins. This discovery …