Open Access. Powered by Scholars. Published by Universities.®
- Institution
Articles 1 - 15 of 15
Full-Text Articles in Molecular Biology
Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess
Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess
Open Access Theses & Dissertations
Anticancer drug discovery is a time and resource-consuming process for which exceedingly reliable and efficient modern approaches are needed. Phenotypic drug screenings can generate highly potent and innovative drug candidates; however, deconvolution of the drugâ??s target often presents significant barriers to drug development. To overcome this hurdle, we have originally combined in vitro and in silico analyses to uncover the molecular mechanism(s) driving the anticancer activity of the uniquely structured small molecule drug candidate, Tpz-1. Our study revealed that Tpz-1 is a multitargeted agent which induces the programmed death of HL-60 acute myeloid leukemia cells primarily through disruption of microtubule …
Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham
Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham
Legacy Theses & Dissertations (2009 - 2024)
The transcription factor, p53, plays a pivotal role in the oversight of many stimulus-dependent pathways. Its ability to respond to a wide variety of cellular stress stimuli by activating a broad range of target genes has led it to be characterized as a stress-dependent transcription factor. Our research focuses on deconvoluting the varied transcriptional response to distinct stress signals in an attempt to define the regulatory strategies leading to gene activation after cell stress. We have found that distinct stress response networks, some of which are p53-independent, are converging at activation of a common set of target genes. Our data …
The Role Of Foxd1 In Clear Cell Renal Cell Carcinoma, Kyle H. Bond
The Role Of Foxd1 In Clear Cell Renal Cell Carcinoma, Kyle H. Bond
Electronic Theses and Dissertations
Renal cell carcinoma (RCC) is the 8th most common cancer in the United States, with the clear cell variant (ccRCC) being the most prevalent. Over 14,000 people die every year to RCC, with rates continuing to increase with an aging general population. Patients suffering from metastatic RCC (mRCC) have extremely poor prognoses, with a 5-year survival of only 11.2%. Current treatment options include resection of primary lesions, tyrosine kinase inhibition (Sunitinib, Pazopanib), mTOR inhibition (Temsirolimus, Everolimus), and immune checkpoint inhibition (Nivolumab, Atezolizumab). Recent attention has been drawn to inhibition of transcription factors like HIF2α (Belzutifan). There is a need …
In Vitro Investigation Of Tumor Selective Piperidones As Therapeutic Agents Against Leukemia Cancer Cells, Lisett Contreras
In Vitro Investigation Of Tumor Selective Piperidones As Therapeutic Agents Against Leukemia Cancer Cells, Lisett Contreras
Open Access Theses & Dissertations
Cancer is a continuous global health issue. It is the second leading cause of death behind heart disease. Disparities across the emergence of cancer and resulting fatalities raise the importance of researching the disease. Treatments are available for certain types of cancers. However, these are typically accompanied by residual problems including side effects and the possibility for relapse. Some treatments attack all cells, leading to unwarranted side effects that make the possibility of living a comfortable life nearly impossible. Other treatments are specific to certain genetic alterations, making them only useful for a small percentage of patients. Not one treatment …
Examination Of Methylation Status And Occupancy Of Dna Methylation Modifying Proteins On Regulatory Regions Of The Dax-1 Gene, Caroline P. Riedstra
Examination Of Methylation Status And Occupancy Of Dna Methylation Modifying Proteins On Regulatory Regions Of The Dax-1 Gene, Caroline P. Riedstra
Master's Theses
Epigenetic modifications influence gene expression and thereby play a pivotal role in development and disease. Misregulation and mutations in the DAX-1 gene, or Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X chromosome, gene 1, have been implicated in Adrenal Hypoplasia Congenita (AHC) and Dosage Sensitive Sex Reversal (DSS). The orphan nuclear hormone receptor DAX-1 is expressed predominantly in tissues such as the testes, ovaries, breast, adrenal cortex, and lung. Critically, DAX-1 may serve as an indicator of aberrant growth in these tissues. Here we hypothesize that DAX-1 is epigenetically regulated, specifically in cancer cells, thereby reducing its …
Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde
Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde
USF Tampa Graduate Theses and Dissertations
Targeted therapies have emerged as potent treatments that lead to the remission of many tumors. However, they rarely cure cancers in advanced, metastatic settings. This is due to the evolution of resistance, which in turn can be ascribed to the survival of small subpopulations of tolerant and/or resistant cells. Here we investigated the evolution of resistance to EML4-ALK inhibitors in non-small cell lung cancer (NSCLC) and demonstrated that resistance evolves gradually, from unique pre-treatment sub-populations, as multiple resistance mechanisms accumulate in a Darwinian fashion. Despite accumulating multiple changes, cells evolved, in parallel, toward similar inhibitor specific phenotypes. Evolving cells have …
Mechanisms Of Cross-Presentation By Cdc1s, Derek James Theisen
Mechanisms Of Cross-Presentation By Cdc1s, Derek James Theisen
Arts & Sciences Electronic Theses and Dissertations
Classical dendritic cells (cDCs) are specialized antigen presenting cells that can be divided into distinct subsets based on the types of pathogens they respond to and the type of immune response they generate. The cDC1 subset is specialized in priming CD8 T cell responses through the process of cross-presentation. During cross-presentation, exogenous protein antigens are taken up by cDC1 and presented on MHCI molecules, allowing for the priming of CD8 T cells during conditions when DCs themselves are not directly infected. The ability to cross-present in vivo is unique to cDC1, and is essential for anti-viral responses and rejection of …
Mechanisms And Regulation Of Resection In Dna Damage Response, Sharad C. Paudyal
Mechanisms And Regulation Of Resection In Dna Damage Response, Sharad C. Paudyal
Arts & Sciences Electronic Theses and Dissertations
Deoxyribonucleic acid (DNA) encodes genetic information essential for cell survival and function. However, it is constantly under assault from endogenous and exogenous damaging agents that not only threaten our own survival but also affect the faithful transmission of genetic information to our offspring. Double-strand breaks (DSBs) are one of the most hazardous forms of DNA damage, which if unrepaired or improperly repaired could lead to plethora of systemic human diseases including cancer. To deal with this problem, cells have evolved with a mechanism called DNA damage response (DDR) to detect, signal, and repair the breaks by inducing multiple cellular events. …
Alternative Regulation Of Myc In Lung Cancer, Patrick N. Backman
Alternative Regulation Of Myc In Lung Cancer, Patrick N. Backman
Open Access Theses
Lung cancer is the leading cause of cancer deaths in the United States, accounting for 27% of all cancer induced deaths1. In an attempt to create a effective targeted therapy for the treatment of lung cancer, a strategy used to treat an activated KrasG12D/+;p53 R172H/+ transgenic lung cancer mouse model was to deliver a known tumor suppressive microRNA (miRNA) to stop tumor growth. The tumor suppressive miRNA let-7 was lentivirally delivered in the form of its primary transcript, pri-let-7a-1, and resulted in increased lung size and inflammation compared to lungs exposed to a control lentivirus. It was identified …
Comparative Proteomic Analysis Of Extracellular Vesicles From Prostate Cancer-Derived Cell Lines, Gloria Polanco
Comparative Proteomic Analysis Of Extracellular Vesicles From Prostate Cancer-Derived Cell Lines, Gloria Polanco
Open Access Theses & Dissertations
Prostate cancer (PCa) is the leading non-cutaneous malignancy and the second deadliest among American men. PCa mortality rates among African American men are much higher than any other ethnic group, and the same is true for men of African ancestry world-wide. There is also a lack of reliable diagnostic markers and effective treatment options. Extracellular vesicles (EVs) have been observed to play an important role in cancer processes such as promotion of tumor growth and metastasis. They are also a promising source of diagnostic markers. This study addresses these problems by studying the proteome of EVs derived from PCa cells …
Rna Aptamers For Molecular Chaperones Hsp27 And Hsp90, Sathishkumar Kumar Munusamy
Rna Aptamers For Molecular Chaperones Hsp27 And Hsp90, Sathishkumar Kumar Munusamy
Legacy Theses & Dissertations (2009 - 2024)
Hsp90 and Hsp27 are members of the heat shock protein family of chaperones that perform multiple roles in cellular maintenance through protein folding and inhibition of apoptosis. They are abundantly expressed in cells and are over-expressed during conditions of stress. Hsp90 requires ATP for its chaperone function while Hsp27 self-associates into higher order oligomers enclosing its substrate. Their ability to interact with other proteins or with themselves lies at the heart of their mechanisms. The specific consequences of each of their interactions on global cellular health have not yet been fully discovered. The sheer diversity of proteins that interact with …
Sirna Targeting Of Thymidylate Synthase, Thymidine Kinase 1 And Thymidine Kinase 2 As An Anticancer Therapy: A Combinatorial Rnai Approach, Christine Di Cresce
Sirna Targeting Of Thymidylate Synthase, Thymidine Kinase 1 And Thymidine Kinase 2 As An Anticancer Therapy: A Combinatorial Rnai Approach, Christine Di Cresce
Electronic Thesis and Dissertation Repository
Thymidylate synthase (TS) is the only de novo source of thymidylate (dTMP) for DNA synthesis and repair. Drugs targeting TS protein are a mainstay in cancer treatment but off-target effects and toxicity limit their use. Cytosolic thymidine kinase (TK1) and mitochondrial thymidine kinase (TK2) contribute to an alternative dTMP-producing pathway, by salvaging thymidine from the tumour milieu, and may modulate resistance to TS-targeting drugs. We have previously shown that TS antisense molecules (oligodeoxynucleotides, ODNs, and small interfering siRNA, siRNA) sensitize tumour cells, both in vitro and in vivo, to TS targeting drugs. As both TS and TKs contribute to cellular …
A Study On The Function Of 14-3-3sigma In Regulating Cancer Energy Metabolism, Liem M. Phan, Liem M. Phan
A Study On The Function Of 14-3-3sigma In Regulating Cancer Energy Metabolism, Liem M. Phan, Liem M. Phan
Dissertations & Theses (Open Access)
Metabolic reprogramming has been shown to be a major cancer hallmark providing tumor cells with significant advantages for survival, proliferation, growth, metastasis and resistance against anti-cancer therapies. Glycolysis, glutaminolysis and mitochondrial biogenesis are among the most essential cancer metabolic alterations because these pathways provide cancer cells with not only energy but also crucial metabolites to support large-scale biosynthesis, rapid proliferation and tumorigenesis. In this study, we find that 14-3-3σ suppresses all these three metabolic processes by promoting the degradation of their main driver, c-Myc. In fact, 14-3-3s significantly enhances c-Myc poly-ubiquitination and subsequent degradation, reduces c-Myc transcriptional activity, and down-regulates …
Matrix Metalloproteinase Genes Are Transcriptionally Regulated By E2f Transcription Factors: A Link Between Cell Cycle Control And Metastatic Progression, Jacqueline Lea Johnson
Matrix Metalloproteinase Genes Are Transcriptionally Regulated By E2f Transcription Factors: A Link Between Cell Cycle Control And Metastatic Progression, Jacqueline Lea Johnson
USF Tampa Graduate Theses and Dissertations
The RbµE2F transcriptional regulatory pathway plays a critical role in the cell cycle. Rb is inactivated through multiple waves of phosphorylation, mediated mainly by cyclin D and cyclin E associated kinases. Once Rb is inactivated, cells can enter Sµphase. Collectively, three Rb family members and ten E2F proteins coordinate every additional stage of the cell cycle, from quiescence to mitosis. However the RbµE2F pathway is frequently altered in cancer. Aside from cell proliferation, the RbµE2F pathway regulates other essential cellular processes including apoptosis, cell differentiation, angiogenesis and DNA damage repair pathways, but its role in invasion and cancer progression is …
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
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 …