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Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed
Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed
Theses and Dissertations
Despite being one of the most effective chemotherapeutic agents developed to date, Anthracyclines are notorious for their cardiotoxicity. Their clinical use is frequently limited both in dosage and in prescription due to the severe cardiac damage they cause. The mechanism of anthracycline-induced cardiotoxicity is not yet fully understood. However, it is hypothesized that interactions with the myocardial membrane play an important role in imparting cardiotoxicity. In this study, we use molecular dynamics simulations and density functional theory calculations to study the anthracycline drug molecules and the interactions that they have with the myocardial membrane. We construct a myocardial membrane model …
Investigating Bmp7 Expression In Glioblastoma Multiforme, Yajaira Janett Macias
Investigating Bmp7 Expression In Glioblastoma Multiforme, Yajaira Janett Macias
Theses and Dissertations
The PI3K/AKT/mTOR pathway regulates important cell processes such as growth, survival, motility, inflammation, proliferation, and apoptosis. In Glioblastoma multiforme (GBM) the PI3K/AKT/mTOR pathway is aberrant as it is almost always active. This results in the deregulation of downstream molecules and ultimately leads to cancer progression and maintenance in GBM tumors. In this study, we used RNA-sequencing to identify differentially expressed genes (DEGs) in U87MG GBM cells treated with NVP-BEZ235, a dual inhibitory drug targeting PI3K and mTOR. A total of 7,803 differentially expressed genes were identified via RNA-seq. GEPIA2 online tool was used to assess differential gene expression …
Genetic Analysis Of Pi3k And Mtor Inhibition In U87mg Glioblastoma Cell Line, Carl G. Litif
Genetic Analysis Of Pi3k And Mtor Inhibition In U87mg Glioblastoma Cell Line, Carl G. Litif
Theses and Dissertations
NVP-BEZ235 is a Glioblastoma Multiform chemotherapeutic dual PI3K/mTOR pathway inhibitor created in 2008 and has since been proven experimentally to induce pluripotentcy in oncological cell populations. The inhibition of PI3K and mTOR has shown to coerce phenotypes associated with stem cell markers, most notably OCT4. It is necessary to understand the genetic composure of how PI3K/mTOR inhibited tumor cells are bypassing the canonical pathway for proliferation and growth and utilizing other parallel sources for tumor invasion into other neural regions. Taking a genetic approach with RNA-sequencing allowed us to gain insight into how glioblastoma interact with cytoskeleton factors MAPK4 and …
Investigating The Localization Of Foxo Transcription Factors In Glioblastoma, Leetoria Hinojosa
Investigating The Localization Of Foxo Transcription Factors In Glioblastoma, Leetoria Hinojosa
Theses and Dissertations
The Phosphatidylinositol 3 Kinase (PI3K) pathway is an essential intracellular signaling pathway that regulates cellular growth, survival, and fate. Canonically, the activation of this pathway removes forkhead box subfamily O transcription factors (FOXO -1, -3, and -4) from the nucleus. However, in cancer cells such as glioblastoma multiforme, FOXO factors are at least in part nuclear despite the activation of the PI3K pathway. Previous research indicated that FOXO3 localization was not affected when the pathway was inhibited in breast cancer cells, which challenged the conventional paradigms for FOXO factor regulation. Therefore, we were interested in investigating the nuclear localization of …
Evidence For P53-Mediated Induction Of Wrap53a In Response To Dna Damage, Anne Shelton Hucks
Evidence For P53-Mediated Induction Of Wrap53a In Response To Dna Damage, Anne Shelton Hucks
Theses and Dissertations
p53 is a powerful tumor suppressor mutated in approximately half of all cancers. Its mRNA is stabilized post-transcriptionally via complementary base pairing with the transcript of its antisense gene, WRAP53α; without this interaction, p53 protein cannot accumulate enough to carry out its many functions related to apoptosis, cell cycle arrest, and DNA damage repair. Previous studies have shown that WRAP53α is induced in response to DNA damage. The purpose of this study was to determine which transcription factors might be responsible for this induction. After identifying three putative p53 binding sites on the WRAP53α promoter, we used chromatin immunoprecipitation …
Investigating The Role Of Nuclear Foxo3 In Pten-Null Glioblastomas, Lilia Sanchez
Investigating The Role Of Nuclear Foxo3 In Pten-Null Glioblastomas, Lilia Sanchez
Theses and Dissertations
The PI3K pathway activates AKT, leading to inactivation of FOXO transcription factors. Loss of PTEN results in constitutive inactivation of tumor suppressor FOXO. There is increasing evidence that FOXO resides and promotes transcriptional activity in the nucleus despite high PI3K output within certain advanced cancers and embryonic stem cells. Here, we investigate the regulation and roles of FOXO transcription factors in glioblastoma and basal breast cancer. First, we built and published genetic models to investigate the roles of FOXO transcription factors in cancer cell lines for glioblastoma (U87MG). We examined the function of FOXO transcription factors using these genetic models …
Metabolic Dysregulation: An Investigation Of The Role Of Foxo3 In Gluconeogensis In Pten-Null Glioblastomas, Victor Fanniel
Metabolic Dysregulation: An Investigation Of The Role Of Foxo3 In Gluconeogensis In Pten-Null Glioblastomas, Victor Fanniel
Theses and Dissertations
Many processes are regulated by the Phosphatidylinositol 3 kinase (PI3K) pathway in the cell including cell survival, metabolism, and apoptosis. Increased activation of the PI3K pathway is a hallmark of many cancers which can be oftentimes attributed to the mutation of PTEN, which encodes an enzyme that performs the reverse reaction of PI3K. When PTEN is null-mutated, this creates a constitutively active PI3K pathway and constitutively active AKT. Since AKT phosphorylates conserved residues on FOXO transcription factors to mark them for nuclear export, this renders FOXO inactive. However, new research has provided evidence that FOXO is still present in …
Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie
Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie
Theses and Dissertations
Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug …
Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh
Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh
Theses and Dissertations
Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …
Identification Of Microrna Biomarkers In Her2-Positive Breast Cancer, Hossam Tashkandi
Identification Of Microrna Biomarkers In Her2-Positive Breast Cancer, Hossam Tashkandi
Theses and Dissertations
Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 30% of breast cancer patients with poor prognosis. In addition, microRNAs are small non-coding RNA that have been linked to many cancers. Here we investigate which miRNAs are differentially regulated by HER2 overexpression. Using quantitative reverse-transcription prolymerase chain reaction (QRT-PCR) and matching it with the clinical data acquired from Dvinge, we find five candidate miRNAs. When comparing the miRNAs’ effect on patient survival, only three miRNAs stand as good predictors of patient survival outcome. These miRNAs are miR-146a-5p, miR-181d, and miR-195-5p. When miR-146a-5p is up-regulated, which is the case …
The Effect Of Thymidylate Synthase Inhibitors On Bone Marrow Derived Cells In The Intestinal Tumor Microenvironment, Grishma Acharya
The Effect Of Thymidylate Synthase Inhibitors On Bone Marrow Derived Cells In The Intestinal Tumor Microenvironment, Grishma Acharya
Theses and Dissertations
Tumors have come to be known as independently functioning complex organs consisting of cancer cells coexisting with a heterogeneous mixture of host-derived non-neoplastic cells that form the tumor stroma. Tumor survival, progression, and metastasis depend on multiple close interactions between the cancer cells and the tumor stromal cells. These tumor stromal cells are mainly bone marrow derived cells (BMDCs) that are recruited to the primary tumor and sites of metastasis by a variety of signals secreted by the cancer cells. Because of the close interaction between the tumor and the tumor stroma, we propose that tumor stromal cells play an …
Antimicrobial And Anticancer Activity Of Essential Oils From Guatemalan Medicinal Plants, Andrew B. Miller
Antimicrobial And Anticancer Activity Of Essential Oils From Guatemalan Medicinal Plants, Andrew B. Miller
Theses and Dissertations
Guatemalan medicinal plants were collected and screened for the presence of essential oils using steam distillation. Oil was found in 63 species from 24 families and was tested in tube dilution assays for activity against Escherichia coli, Staphylococcus aureus, Streptococcus mutans, Lactobacillus acidophilus and Candida albicans. Several essential oils were highly active with 20 instances of oils inhibiting the microbes at an MIC of 0.31 µl/ml. Oils were also tested against cancerous and established cell lines using a 15% (v/v) agar-media which was developed to improve essential oil solubility. Assays were performed against three cancer lines: …