Matching Items (5)
Filtering by
- All Subjects: Prostate Cancer
- Creators: Rege, Kaushal
Description
The effects of specific histone deacetylase inhibitors (HDACi) on transgene expression in combination with a novel polymer as a delivery vehicle are investigated in this research. Polymer vectors, although safer than viruses, are notorious for low levels of gene expression. In this investigation, the use of an emerging chemotherapeutic anti-cancer drug molecule, HDACi, was used to enhance the polymer-mediated gene expression. HDACi are capable of inhibiting deacetylation activities of histones and other non-histone proteins in the cytoplasm and nucleus, as well as increase transcriptional activities necessary for gene expression. In a prior study, a parallel synthesis and screening of polymers yielded a lead cationic polymer with high DNA-binding properties, and even more attractive, high transgene expressions. Previous studies showed the use of this polymer in conjunction with cytoplasmic HDACi significantly enhanced gene expression in PC3-PSMA prostate cancer cells. This led to the basis for the investigation presented in this thesis, but to use nuclear HDACi to potentially achieve similar results. The HDACi, HDACi_A, was a previously discovered lead drug that had potential to significantly enhance luciferase expression in PC3-PSMA cells. The results of this study found that the 20:1 polymer:plasmid DNA weight ratio was effective with 1 uM and 2 uM HDACI_A concentrations, showing up to a 9-fold enhancement. This enhancement suggested that HDACi_A was effectively aiding transfection. While not an astounding enhancement, it is still interesting enough to investigate further. Cell viabilities need to be determined to supplement the results.
ContributorsLehrman, Jennifer (Author) / Rege, Kaushal (Thesis advisor) / Caplan, Michael (Committee member) / Pizziconi, Vincent (Committee member) / Arizona State University (Publisher)
Created2012
Description
The objective of the research presented here was to validate the use of kinetic models for the analysis of the dynamic behavior of a contrast agent in tumor tissue and evaluate the utility of such models in determining kinetic properties - in particular perfusion and molecular binding uptake associated with tissue hypoxia - of the imaged tissue, from concentration data acquired with dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) procedure. Data from two separate DCE-MRI experiments, performed in the past, using a standard contrast agent and a hypoxia-binding agent respectively, were analyzed. The results of the analysis demonstrated that the models used may provide novel characterization of the tumor tissue properties. Future research will work to further characterize the physical significance of the estimated parameters, particularly to provide quantitative oxygenation data for the imaged tissue.
ContributorsMartin, Jonathan Michael (Author) / Kodibagkar, Vikram (Thesis director) / Rege, Kaushal (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2013-12
Description
Oxygen delivery is crucial for the development of healthy, functional tissue. Low tissue oxygenation, or hypoxia, is a characteristic that is common in many tumors. Hypoxia contributes to tumor malignancy and can reduce the success of chemotherapy and radiation treatment. There is a current need to noninvasively measure tumor oxygenation or pO2 in patients to determine a personalized treatment method. This project focuses on creating and characterizing nanoemulsions using a pO2 reporter molecule hexamethyldisiloxane (HMDSO) and its longer chain variants as well as assessing their cytotoxicity. We also explored creating multi-modal (MRI/Fluorescence) nanoemulsions.
ContributorsGrucky, Marian Louise (Author) / Kodibagkar, Vikram (Thesis director) / Rege, Kaushal (Committee member) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
Description
Abstract Molecular Engineering of Novel Polymeric Agents for Targeted Cancer Gene Therapy Dana Matthews Cancer gene cell therapy is a strategy that involves the administration of genes for correcting the effect of mutated cancer cells in order to induce tumor cell death. In particular, genes that encode for pro-apoptotic proteins can result in death of tumor cells. Prostate cancer is a very common cancer among males in America, and as highly destructive chemotherapy and radiation are generally the only treatments available once the cancer has metastasized, there is a need for the development of treatments that can specifically target and kill prostate cancer cells, while demonstrating low toxicity to other tissue. This experiment will attempt to create such a treatment through gene therapy techniques. The parallel synthesis and DNA binding affinity assay utilized in these experiments have produced a polymer that surpasses pEI-25, a gene delivery polymer standard, in both transfection efficacy and low cytotoxicity and trafficking of polyplexes in the cell, and finding methods to increase the transfection efficacy and specificity of polyplexes for PC3-PSMA cells.
ContributorsMatthews, Dana (Author) / Rege, Kaushal (Thesis director) / Linton, Rebecca (Committee member) / Huang, Huang-Chial (Committee member) / Barrett, The Honors College (Contributor)
Created2008-12
Description
This research addresses the need for improvement in radiation sensors for applications of ionizing radiation such as radiotherapy. The current sensors involved are polymer gel dosimeters, MOSFETs, radio-chromic films, etc. Most of the sensors involved require expensive equipment's and processing facilities for readout. There is still a need to develop better sensors that can be clinically applied. There are numerous groups around the world trying to conceive a better dosimeter. One of the radiation sensors that was developed recently was based on fluorescence signal emitted from the sensor. To advance the field of radiation sensors, a visual indicator has been developed in-lab as a method of detect ionizing radiation. The intensity of change in color is directly dependent on the amount of incident ionizing radiation. An aqueous gold nanoparticle sensor can be used to accurately determine the incident amount of ionizing radiation1. A gold nanoparticle sensor has been developed in lab with the use of hexadecyltrimethylammonium bromide (C16TAB) as the templating molecule. In the presence of ionizing radiation, the colorless gold salt is reduced and templated, creating a dispersion within the fluid1. The formation of suspended nanoparticles leads to a color change that can be visually detected and accurately analyzed through the employment of a spectrometer. Unfortunately, the toxicity of C16TAB is high. It is expected the toxicity can be reduced by replacing C16TAB with an amino acid, as amino acids can act as templating molecules in the solution and many are naturally occuring2. The experiments included a screening of 20 natural amino acids and 12 unnatural amino acids with the gold salt solution in the presence of ionizing radiation. Stability and absorbance testing was conducted on the amino acid sensors. Additional screening of lead amino acid sensors at various concentrations of irradiation was conducted.
ContributorsGupta, Saumya (Co-author) / Rege, Kaushal (Co-author, Thesis director) / Pushpavanam, Karthik (Co-author, Committee member) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05