Matching Items (33)
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- All Subjects: Cancer
- All Subjects: Diabetes
- Creators: School of Molecular Sciences
- Creators: Kostelich, Eric
- Resource Type: Text
Description
Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into how evolutionary history has shaped mechanisms of cancer suppression by examining how life history traits impact cancer susceptibility across species. Here, we perform multi-level analysis to test how species-level life history strategies are associated with differences in neoplasia prevalence, and apply this to mammary neoplasia within mammals. We propose that the same patterns of cancer prevalence that have been reported across species will be maintained at the tissue-specific level. We used a combination of factor analysis and phylogenetic regression on 13 life history traits across 90 mammalian species to determine the correlation between a life history trait and how it relates to mammary neoplasia prevalence. The factor analysis presented ways to calculate quantifiable underlying factors that contribute to covariance of entangled life history variables. A greater risk of mammary neoplasia was found to be correlated most significantly with shorter gestation length. With this analysis, a framework is provided for how different life history modalities can influence cancer vulnerability. Additionally, statistical methods developed for this project present a framework for future comparative oncology studies and have the potential for many diverse applications.
ContributorsFox, Morgan Shane (Author) / Maley, Carlo C. (Thesis director) / Boddy, Amy (Committee member) / Compton, Zachary (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
The goal of this project was to design and create a genetic construct that would allow for <br/>tumor growth to be induced in the center of the wing imaginal disc of Drosophila larvae, the <br/>R85E08 domain, using a heat shock. The resulting transgene would be combined with other <br/>transgenes in a single fly that would allow for simultaneous expression of the oncogene and, in <br/>the surrounding cells, other genes of interest. This system would help establish Drosophila as a <br/>more versatile and reliable model organism for cancer research. Furthermore, pilot studies were <br/>performed, using elements of the final proposed system, to determine if tumor growth is possible <br/>in the center of the disc, which oncogene produces the best results, and if oncogene expression <br/>induced later in development causes tumor growth. Three different candidate genes were <br/>investigated: RasV12, PvrACT, and Avli.
ContributorsSt Peter, John Daniel (Author) / Harris, Rob (Thesis director) / Varsani, Arvind (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Current studies in Multiple Myeloma suggest that patient tumors and cell lines cluster separately based on gene expression profiles. Hyperdiploid patients are also extremely underrepresented in established human myeloma cell lines (HMCLs). This suggests that the average HMCL model system does not accurately represent the average myeloma patient. To investigate this question we performed a combined CNA and SNV evolutionary comparison between four myeloma tumors and their established HMCLs (JMW-1, VP-6, KAS-6/1-KAS-6/2 and KP-6). We identified copy number changes shared between the tumors and their cell lines (mean of 74 events - 59%), those unique to patients (mean of 21.25 events - 17%), and those only in the cell lines (mean of 30.75 events \u2014 24%). A relapse sample from the JMW-1 patient showed 58% similarity to the primary diagnostic tumor. These data suggest that, on the level of copy number abnormalities, HMCLs show equal levels of evolutionary divergence as that observed within patients. By exome sequencing, patient tumors were 71% similar to their representative HMCLs, with ~12.5% and ~16.5% of SNVs unique to the tumors and HMCLs respectively. The HMCLs studied appear highly representative of the patient from which they were derived, with most differences associated with an enrichment of sub-populations present in the primary tumor. Additionally, our analysis of the KP-6 aCGH data showed that the patient's hyperdiploid karyotype was maintained in its respective HMCL. This discovery confirms the establishment and validation of a novel and potentially clinically relevant hyperdiploid HMCL that could provide a major advance in our ability to understand the pathogenesis and progression of this prominent patient population.
ContributorsBenard, Brooks Avery (Author) / Keats, Jonathan (Thesis director) / Anderson, Karen (Committee member) / Jelinek, Diane (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique growth pattern. Consequently it is difficult for neurosurgeons to anticipate where the tumor will spread in the brain, making treatment planning difficult. Archival patient data including MRI scans depicting the progress of tumors have been helpful in developing a model to predict Glioblastoma proliferation, but limited scans per patient make the tumor growth rate difficult to determine. Furthermore, patient treatment between scan points can significantly compound the challenge of accurately predicting the tumor growth. A partnership with Barrow Neurological Institute has allowed murine studies to be conducted in order to closely observe tumor growth and potentially improve the current model to more closely resemble intermittent stages of GBM growth without treatment effects.
ContributorsSnyder, Lena Haley (Author) / Kostelich, Eric (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Over time, tumor treatment resistance inadvertently develops when androgen de-privation therapy (ADT) is applied to metastasized prostate cancer (PCa). To combat tumor resistance, while reducing the harsh side effects of hormone therapy, the clinician may opt to cyclically alternates the patient’s treatment on and off. This method,known as intermittent ADT, is an alternative to continuous ADT that improves the patient’s quality of life while testosterone levels recover between cycles. In this paper,we explore the response of intermittent ADT to metastasized prostate cancer by employing a previously clinical data validated mathematical model to new clinical data from patients undergoing Abiraterone therapy. This cell quota model, a system of ordinary differential equations constructed using Droop’s nutrient limiting theory, assumes the tumor comprises of castration-sensitive (CS) and castration-resistant (CR)cancer sub-populations. The two sub-populations rely on varying levels of intracellular androgen for growth, death and transformation. Due to the complexity of the model,we carry out sensitivity analyses to study the effect of certain parameters on their outputs, and to increase the identifiability of each patient’s unique parameter set. The model’s forecasting results show consistent accuracy for patients with sufficient data,which means the model could give useful information in practice, especially to decide whether an additional round of treatment would be effective.
ContributorsBennett, Justin Klark (Author) / Kuang, Yang (Thesis director) / Kostelich, Eric (Committee member) / Phan, Tin (Committee member) / School of Mathematical and Statistical Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Cancer is a disease that occurs in many and perhaps all multicellular organisms. Current research is looking at how different life history characteristics among species could influence cancer rates. Because somatic maintenance is an important component of a species' life history, we hypothesize the same ecological forces shaping the life history of a species should also determine its cancer susceptibility. By looking at varying life histories, potential evolutionary trends could be used to explain differing cancer rates. Life history theory could be an important framework for understanding cancer vulnerabilities with different trade-offs between life history traits and cancer defenses. Birds have diverse life history strategies that could explain differences in cancer suppression. Peto's paradox is the observation that cancer rates do not typically increase with body size and longevity despite an increased number of cell divisions over the animal's lifetime that ought to be carcinogenic. Here we show how Peto’s paradox is negatively correlated for cancer within the clade, Aves. That is, larger, long-lived birds get more cancer than smaller, short-lived birds (p=0.0001; r2= 0.024). Sexual dimorphism in both plumage color and size differ among Aves species. We hypothesized that this could lead to a difference in cancer rates due to the amount of time and energy sexual dimorphism takes away from somatic maintenance. We tested for an association between a variety of life history traits and cancer, including reproductive potential, growth rate, incubation, mating systems, and sexual dimorphism in both color and size. We found male birds get less cancer than female birds (9.8% vs. 11.1%, p=0.0058).
ContributorsDolan, Jordyn Nicole (Author) / Maley, Carlo (Thesis director) / Harris, Valerie (Committee member) / Boddy, Amy (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Tumor-stroma interactions significantly influence cancer cell metastasis and disease progression. These interactions partly comprise crosstalk between tumor and stromal fibroblasts, but the key molecular mechanisms within the crosstalk governing cancer invasion are still unclear. Here we develop a 3D in vitro organotypic microfluidic to model tumor-stroma interaction by mimicking the spatial organization of the tumor microenvironment on a chip. We co-culture breast cancer and patient-derived fibroblast cells in 3D tumor and stroma regions respectively and combine functional assessments, including cancer cell migration, with transcriptome profiling to unveil the molecular influence of tumor-stroma crosstalk on invasion. This led to the observation that cancer associated fibroblasts enhanced invasion in 3D by inducing the expression of a novel gene of interest, GPNMB, in breast cancer cells resulting in increased migration speed. Importantly, knockdown of GPNMB blunted the influence of CAFs on enhancing cancer invasion. Overall, these results demonstrate the ability of our model to recapitulate patient specific tumor microenvironment to investigate cellular and molecular consequences of tumor-stroma interactions.
ContributorsBarrientos, Eric Salvador (Author) / Nikkhah, Mehdi (Thesis director) / Veldhuizen, Jaime (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Trichoplax adhaerens (Placozoa) is the simplest multicellular animal to be described. This organism lacks nervous tissue, muscle tissue and organs, and is composed of only five cell types organized into three layers. Placozoa are gaining popularity as a model organism due to their simple make-up and completely sequenced genome. The complete sequencing of this organism’s genome has revealed the presence of important genes in cancer such as TP53 and MDM2 genes. Along with the presence of these genes, there are also additional pathways commonly deregulated in cancer that are well conserved in this organism. T. adhaerens are able to survive exposure to 160Gy and even 240Gy of X-ray radiation. Though small dark bodies form within the main body, they tend to extrude those masses, and continue to reproduce afterwards. After exposure to both grades of radiation, there was a greater increase in the apparent population size of the treated population than the control population. There was also a greater decrease in surface area of the organisms exposed to 160Gy than the control organisms. This increase in population and decrease in surface area of the treated organisms could be due to the extruded bodies. We hypothesize that the observed extrusion is a novel cancer defense mechanism for ridding the animal of damaged or mutated cells. This hypothesis should be tested through longitudinal observation and genetic analysis of the extruded bodies.
ContributorsYi, Avalon (Author) / Fortunato, Angelo (Thesis director) / Maley, Carlo (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-12
Description
Background.
Type 2 Diabetes Mellitus (T2DM) is a leading cause of health disparities, among Hispanic populations, which are disproportionately afflicted by T2DM. The growing research strongly argues that diabetes treatment interventions should be culturally sensitive to address the needs of their target populations. Nonetheless, there is little consensus regarding the necessary components of a culturally sensitive intervention. This review will examine the intervention contents and activities, and the strategies that have been implemented into culturally sensitive diabetes treatment interventions. This review will also to observe how interventions handle complex issues such as the heterogeneity of Hispanic populations and communities. The overarching research questions examined in this study were, “What are the core components of the culturally tailored diabetes interventions currently implemented with Hispanic populations in the US, and why are they needed?” and 2) “How are studies evaluating the impact of their interventions, and how can the proposed study designs be improved?”
Method.
A systematic review across 3 databases was used to identify culturally sensitive diabetes treatment interventions (CSDTI) developed for Hispanic populations. Accordingly, we searched for studies designed to treat Hispanic individuals already diagnosed with having T2DM. All identified studies provided information on the core components of these culturally sensitive interventions, while only studies that included a control or comparison group were used to assess how the studies evaluated outcomes.
Results.
First, we examined intervention effects as examined from two study designs. We examined a total of [17] interventions in this section. Our review of one study design (Design #1 Studies) includes 12 studies that developed a culturally sensitive intervention and evaluated it using a one-group pretest posttest design, or did not evaluate their intervention at all. A second study design (Design #2 Studies) includes 5 studies. These consisted of a two-group randomized controlled field study that conducted pre-post analyses of the culturally adapted intervention comparing it against a control or comparison group. The heterogeneity of all studies made a conventional meta-analysis impossible.
Second, another review section focused on examining and describing various culturally sensitive core components, we examined a total of 17 studies to describe the types of culturally sensitive components that were incorporated into the diabetes treatment intervention. This analysis resulted in a list of 11 general types of culturally sensitive components as included within these 17 interventions. Of the articles that used control or comparison groups, the manner in which interventions evaluated different outcome measures and their conclusions regarding success were examined.
Discussion.
The culturally sensitive aspects identified from these articles were used to address diverse issues that included: (a) communication barriers, (b) the inclusion of cultural relevant content, for relevance to Hispanic/Latinx patients’ lives, (c) selecting appropriate channels and settings for interventions, and (d) addressing specific cultural values, traditions, and beliefs that can either help or hinder healthy behaviors. It should be noted that the Hispanic populations are extremely heterogeneous, and so interventions that would be sensitive culturally to some sectors of a Hispanic community may not be sensitive to other Hispanic sectors of that same community. The issue of heterogeneity of Hispanic communities was addressed well by the authors of some articles and ignored by others.
Conclusions.
It was ultimately impossible draw quantitative conclusions regarding the efficacy or effectiveness of these two types of diabetes treatment interventions (CSDTIs) as delivered to their targeted sample of Hispanic participants. An emerging conclusion is that factors including ethics, cost, and lack of community acceptance, may constitute factors contributing to the higher proportion of one-group pre-test post-test designs and lower proportion of rigorous scientific designs. In the latter case, some communities oppose the use of randomized controlled studies within their community, and thus that objection may explain the low numbers of these randomized controlled studies. The use of viable and rigorous alternatives to RCTs have been proposed to address this community concern. In this review, the author sought to conduct comparative studies between culturally adapted interventions and their associated unaltered or minimally altered evidence-based interventions, although there exists various difficulties that are associated with the conduct of these analyses.
Core components of CSDTIs for Hispanic adults were identified, and their purposes were explained. Additionally, suggestions for improvement to studies were made, to aid in improving our knowledge of CSDTIs through future studies.
Type 2 Diabetes Mellitus (T2DM) is a leading cause of health disparities, among Hispanic populations, which are disproportionately afflicted by T2DM. The growing research strongly argues that diabetes treatment interventions should be culturally sensitive to address the needs of their target populations. Nonetheless, there is little consensus regarding the necessary components of a culturally sensitive intervention. This review will examine the intervention contents and activities, and the strategies that have been implemented into culturally sensitive diabetes treatment interventions. This review will also to observe how interventions handle complex issues such as the heterogeneity of Hispanic populations and communities. The overarching research questions examined in this study were, “What are the core components of the culturally tailored diabetes interventions currently implemented with Hispanic populations in the US, and why are they needed?” and 2) “How are studies evaluating the impact of their interventions, and how can the proposed study designs be improved?”
Method.
A systematic review across 3 databases was used to identify culturally sensitive diabetes treatment interventions (CSDTI) developed for Hispanic populations. Accordingly, we searched for studies designed to treat Hispanic individuals already diagnosed with having T2DM. All identified studies provided information on the core components of these culturally sensitive interventions, while only studies that included a control or comparison group were used to assess how the studies evaluated outcomes.
Results.
First, we examined intervention effects as examined from two study designs. We examined a total of [17] interventions in this section. Our review of one study design (Design #1 Studies) includes 12 studies that developed a culturally sensitive intervention and evaluated it using a one-group pretest posttest design, or did not evaluate their intervention at all. A second study design (Design #2 Studies) includes 5 studies. These consisted of a two-group randomized controlled field study that conducted pre-post analyses of the culturally adapted intervention comparing it against a control or comparison group. The heterogeneity of all studies made a conventional meta-analysis impossible.
Second, another review section focused on examining and describing various culturally sensitive core components, we examined a total of 17 studies to describe the types of culturally sensitive components that were incorporated into the diabetes treatment intervention. This analysis resulted in a list of 11 general types of culturally sensitive components as included within these 17 interventions. Of the articles that used control or comparison groups, the manner in which interventions evaluated different outcome measures and their conclusions regarding success were examined.
Discussion.
The culturally sensitive aspects identified from these articles were used to address diverse issues that included: (a) communication barriers, (b) the inclusion of cultural relevant content, for relevance to Hispanic/Latinx patients’ lives, (c) selecting appropriate channels and settings for interventions, and (d) addressing specific cultural values, traditions, and beliefs that can either help or hinder healthy behaviors. It should be noted that the Hispanic populations are extremely heterogeneous, and so interventions that would be sensitive culturally to some sectors of a Hispanic community may not be sensitive to other Hispanic sectors of that same community. The issue of heterogeneity of Hispanic communities was addressed well by the authors of some articles and ignored by others.
Conclusions.
It was ultimately impossible draw quantitative conclusions regarding the efficacy or effectiveness of these two types of diabetes treatment interventions (CSDTIs) as delivered to their targeted sample of Hispanic participants. An emerging conclusion is that factors including ethics, cost, and lack of community acceptance, may constitute factors contributing to the higher proportion of one-group pre-test post-test designs and lower proportion of rigorous scientific designs. In the latter case, some communities oppose the use of randomized controlled studies within their community, and thus that objection may explain the low numbers of these randomized controlled studies. The use of viable and rigorous alternatives to RCTs have been proposed to address this community concern. In this review, the author sought to conduct comparative studies between culturally adapted interventions and their associated unaltered or minimally altered evidence-based interventions, although there exists various difficulties that are associated with the conduct of these analyses.
Core components of CSDTIs for Hispanic adults were identified, and their purposes were explained. Additionally, suggestions for improvement to studies were made, to aid in improving our knowledge of CSDTIs through future studies.
ContributorsDilli, Christopher Joe (Author) / Castro, Felipe Gonzalez (Thesis director) / Shaibi, Gabriel (Committee member) / School of Molecular Sciences (Contributor) / School of International Letters and Cultures (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Diabesity is a global epidemic affecting millions worldwide. Diabesity is the term given to the link between obesity and Type II diabetes. It is estimated that ~90% of patients diagnosed with Type II diabetes are overweight or have struggled with excess body fat in the past. Type II diabetes is characterized by insulin resistance which is an impaired response of the body to insulin that leads to high blood glucose levels. Adipose tissue, previously thought of as an inert tissue, is now recognized as a major endocrine organ with an important role in the body's immune response and the development of chronic inflammation. It is speculated that adipose tissue inflammation is a major contributor to insulin resistance particular to Type II diabetes. This literature review explores the popular therapeutic targets and marketed drugs for the treatment of Type II diabetes and their role in decreasing adipose tissue inflammation. rAGE is currently in pre-clinical studies as a possible target to combat adipose tissue inflammation due to its relation to insulin resistance. Metformin and Pioglitazone are two drugs already being marketed that use unique chemical pathways to increase the production of insulin and/or decrease blood glucose levels. Sulfonylureas is one of the first FDA approved drugs used in the treatment of Type II diabetes, however, it has been discredited due to its life-threatening side effects. Bariatric surgery is a form of invasive surgery to rid the body of excess fat and has shown to normalize blood glucose levels. These treatments are all secondary to lifestyle changes, such as diet and exercise which can help halt the progression of Type II diabetes patients.
ContributorsRobles, Alondra Maria (Author) / Woodbury, Neal (Thesis director) / Redding, Kevin (Committee member) / Allen, James (Committee member) / Hendrickson, Kirstin (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05