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Articles 1 - 6 of 6
Full-Text Articles in Life Sciences
Development Of Novel Alkaloid Derivatives For The Treatment Of Chronic Myeloid Leukemia, Lindsay Michelle Renn
Development Of Novel Alkaloid Derivatives For The Treatment Of Chronic Myeloid Leukemia, Lindsay Michelle Renn
Theses and Dissertations
The majority of chronic myeloid leukemia (CML) patients can be treated with and respond to imatinib mesylate (Gleevec). Imatinib is known to inhibit BCR-ABLl kinase activity, and is effective for the treatment of the majority of CML patients. Multiple mutations have been found in patients resistant to imatinib treatment, including many located in the BCR-ABLl tyrosine kinase domain (e.g. E255K and T315I). Matrine is a bioactive alkaloid from Sophora flavescens and has been shown to inhibit several types of cancers and is used in Chinese medicine. The goal of this study is to develop new matrine derivatives that inhibit growth …
Molecular Mechanisms Of Dna Replication Initiation In Hpvs With Genetic Variations Leading To Cellular Carcinogenesis, Gulden Yilmaz
Molecular Mechanisms Of Dna Replication Initiation In Hpvs With Genetic Variations Leading To Cellular Carcinogenesis, Gulden Yilmaz
Graduate School of Biomedical Sciences Theses and Dissertations
Human papillomaviruses are a vast family of double-stranded DNA viruses containing non-carcinogenic and carcinogenic types, whose crucial differences remain unknown, except for the difference in the frequency of DNA replication. The human papillomavirus (HPV) E2 protein regulates the initiation of viral DNA replication and transcription. Its recognition and binding to four 12 bp palindromic sequences in the viral origin is essential for its function. Little is known about the DNA binding mechanism of the E2 protein found in HPV types that have low risk for oncogenicity (low-risk) as well as the roles of various elements of the individual binding sites. …
Characterization Of E-Cadherin Regulation In Response To Zeb1 Inhibition In Endometrial Cancer Cell Lines, Chidozie Paul Chukwu
Characterization Of E-Cadherin Regulation In Response To Zeb1 Inhibition In Endometrial Cancer Cell Lines, Chidozie Paul Chukwu
Graduate School of Biomedical Sciences Theses and Dissertations
Epithelial to mesenchymal transition (EMT) is the process in which cells lose their epithelial structure during gastrulation. This process also affects the migration and movement of tumor cells and promotes invasion and metastases of endometrial carcinomas. Down-regulation of E-cadherin (CDH1) by transcription factors is the key target of EMT modulators and is achieved mainly by ZEB1 (zinc finger E-box binding homeobox 1). Current research looking at restoration of E-cadherin expression in vitro involves the use of small molecules such as histone deacetylase (HDAC) inhibitors and DNA methyltransferase inhibitors. Trichostatin A (TSA) and small interfering ribonucleic acid (siRNA) are tools that …
Mapping The Interaction Between Lrrc59 And Cip2a Oncoprotein, Tamika C. Reed
Mapping The Interaction Between Lrrc59 And Cip2a Oncoprotein, Tamika C. Reed
Graduate School of Biomedical Sciences Theses and Dissertations
The oncogene cancerous inhibitor of protein phosphatase 2A (CIP2A) has been shown to promote oncogenesis through numerous protein-protein interactions. CIP2A was initially found to be a direct inhibitor of the PP2A tumor suppressor protein; however, new research has demonstrated that CIP2A can act independently of PP2A through protein-protein interactions resulting in deregulation of the cell cycle and the development of therapeutic drug resistance, tumorigenesis, and cell proliferation. It has been shown that leucine rich repeat containing 59 protein (LRRC59) binds to and is required for the nuclear translocation of CIP2A, thereby making this interaction a target for drug therapy. Thus, …
Characterization Of Malt1 Inhibitors And Their Effect On Leukemic Cell Growth Properties, Christina Snyder
Characterization Of Malt1 Inhibitors And Their Effect On Leukemic Cell Growth Properties, Christina Snyder
Graduate School of Biomedical Sciences Theses and Dissertations
Leukemia is the most common childhood cancer, with a combined 40,000 predicted new cases in the United States in 2016 [8]. The two most common subtypes are acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) [9-11]. The commercially available inhibitor of Bruton’s tyrosine kinase (BTK) has shown promising results in clinical trials for CLL because of the importance of BCR signaling in CLL [12-15]. Recent studies suggest that the outgrowth of BTK inhibitor resistant clonal cells in some CLL patients results in a treatment-refractory phenotype [16-18]. MALT1, a protein involved in BCR activation of the NF-κB pathway that functions …
Development Of Cellular Assays To Monitor Enzymatic And Biological Activity Of Cd73: A Key Modulator Of Anti-Tumor Immune Response, Alexandra Fanuka
Development Of Cellular Assays To Monitor Enzymatic And Biological Activity Of Cd73: A Key Modulator Of Anti-Tumor Immune Response, Alexandra Fanuka
Graduate School of Biomedical Sciences Theses and Dissertations
Ecto-5’-nucleotidase, known as CD73, is an extracellular enzyme that converts adenosine monophosphate (AMP) to adenosine and has recently been identified as a potential drug target for cancer immunotherapy. Its immunosuppressive effects, mediated by the activity of adenosine, are associated with higher rates of tumor invasion and metastasis, as well as poorer prognoses overall in many cancer types. CD73 is often co-expressed with ectonucleoside triphosphate diphosphohydrolase-1 (CD39), which catalyzes the conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), and ADP to AMP on the surface of tumor cells. Dual expression further propagates immunosuppressive effects of adenosine in the tumor microenvironment. …