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- All Subjects: Cancer
Description
Breast and other solid tumors exhibit high and varying degrees of intra-tumor heterogeneity resulting in targeted therapy resistance and other challenges that make the management and treatment of these diseases rather difficult. Due to the presence of admixtures of non-neoplastic cells with polyclonal cell populations, it is difficult to define cancer genomes in patient samples. By isolating tumor cells from normal cells, and enriching distinct clonal populations, clinically relevant genomic aberrations that drive disease can be identified in patients in vivo. An in-depth analysis of clonal architecture and tumor heterogeneity was performed in a stage II chemoradiation-naïve breast cancer from a sixty-five year old patient. DAPI-based DNA content measurements and DNA content-based flow sorting was used to to isolate nuclei from distinct clonal populations of diploid and aneuploid tumor cells in surgical tumor samples. We combined DNA content-based flow cytometry and ploidy analysis with high-definition array comparative genomic hybridization (aCGH) and next-generation sequencing technologies to interrogate the genomes of multiple biopsies from the breast cancer. The detailed profiles of ploidy, copy number aberrations and mutations were used to recreate and map the lineages present within the tumor. The clonal analysis revealed driver events for tumor progression (a heterozygous germline BRCA2 mutation converted to homozygosity within the tumor by a copy number event and the constitutive activation of Notch and Akt signaling pathways. The highlighted approach has broad implications in the study of tumor heterogeneity by providing a unique ultra-high resolution of polyclonal tumors that can advance effective therapies and clinical management of patients with this disease.
ContributorsLaughlin, Brady Scott (Author) / Ankeny, Casey (Thesis director) / Barrett, Michael (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School for the Science of Health Care Delivery (Contributor)
Created2015-05
Description
Concept mapping is a tool used in order to visually represent a person's understanding of interrelated concepts. Generally the central concept is in the center or at the top and the related concepts branch off, becoming more detailed as it continues. Additionally, links between different branches show how those concepts are related to each other. Concept mapping can be implemented in many different types of classrooms because it can be easily adjusted for the needs of the teacher and class specifically. The goal of this project is to analyze both the attitude and achievement of students using concept mapping of college students in an active learning classroom. In order to evaluate the students' concept maps we will use the expert map scoring method, which compares the students concept maps to an expertly created concept map for similarities; the more similar the two maps are, the higher the score. We will collect and record students' scores on concept maps as they continue through the one semester class. Certain chapters correspond to specific exams due to the information contained in the lectures, chapters 1-4 correspond to exam 1 and so forth. We will use this information to correlate the average concept map score across these chapters to one exam score. There was no significant correlation found between the exam grades and the corresponding scores on the concept maps (Pearson's R values of 0.27, 0.26, and -0.082 for Exam 1, 2 and 3 respectively). According to Holm et all "it was found that 85% of students found interest or attainment in the concept mapping session, only 44% thought there was a cost, and 63% thought it would help them to be successful."
ContributorsFarrell, Carilee Dawn (Author) / Ankeny, Casey (Thesis director) / Middleton, James (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Difficult to treat cancer patients, specifically those tumors that are metastatic and drug-resistant, prove to have the lowest survival rates when compared to more localized types. The commonplace combination therapies, surgery, chemotherapy, and radiation, do not usually result in remission and sometimes cannot be done with these specific patients. RNA interference therapeutics, especially those that use short-interfering RNA (siRNA), have given rise to a novel field that employs the mechanisms in the body to silence the gene expression post-transcriptionally. The main cell types used in this research were Ewing Sarcoma, Acute Myelogenous Leukemia, and Rhabdomyosarcoma cells. Initial assays involved the testing of the cells' responsiveness to a panel of siRNA compounds, to better understand the most effective ones. The siRNA UBBs1 proved to be the most cytotoxic to all cell lines tested, allowing for further investigation through transfection procedures for cellular assays and RNA purification for expression analysis. The data showed decreased cell viability for the UBBs1 treated group for both RD and RH-30 Rhabdomyosarcoma cell lines, especially at a much lower concentration than traditional chemotherapy drug dose response assays. The RNA purification and quantification of the transfected cells over time showed the biggest decrease in gene expression when treated with UBBs1. The use of siRNA in future therapeutics could be a highly-specific method to induce cytotoxicity of cancer cells, but more successful clinical testing and better manufacturing processes need to be established first.
ContributorsChilders, Robert Valente (Author) / Ankeny, Casey (Thesis director) / Azorsa, David (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12