Ketone Bodies And Signaling In Pancreatic Cancer Cell Lines,
2018
University of Nebraska at Omaha
Ketone Bodies And Signaling In Pancreatic Cancer Cell Lines, Kyla B. Buettner, Pankaj K. Singh, Surendra K. Shukla
Theses/Capstones/Creative Projects
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, and 95% of these cases are caused by PDAC (pancreatic ductal adenocarcinoma). Ketone bodies have previously been shown to decrease cell proliferation and cancer-induced cachexia. The molecular mechanism of ketone body-mediated growth inhibition of pancreatic cancer cells is not well understood. Research conducted thus far has not explored which molecular pathways are affected by ketone body treatment in pancreatic cancer cells. In the current study, the effect of the ketone body sodium hydroxybutyrate on the JAK-STAT and mTOR pathways and cell migration was explored. A decrease …
Functional Heterogeneity Of Fibroblasts In Dermal Wound Healing,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Functional Heterogeneity Of Fibroblasts In Dermal Wound Healing, Ehsan Ehsanipour
Dissertations & Theses (Open Access)
Impaired wound healing can lead to excessive scarring, dehiscence, chronic ulcers, and infection, which have adverse impact on the quality of life and pose a significant economic burden on the health care system. Thus, new therapeutic approaches are critically important. Dermal fibroblasts are critical players in cutaneous wound healing, possibly lending their contractile properties and extracellular matrix (ECM) remodeling functions to promote effective tissue repair. Dermal fibroblasts are also postulated to orchestrate tissue repair by interacting with and controlling other cell types in the wound microenvironment. It has become increasingly clear that the generic term “fibroblast” encompasses a diverse cell …
Trim24 As An Oncogene In The Mammary Gland,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Trim24 As An Oncogene In The Mammary Gland, Aundrietta Duncan
Dissertations & Theses (Open Access)
Despite the many advances made in breast cancer research and treatments, breast cancer remains one of the deadliest diseases plaguing women worldwide. While many findings on genetic mutations and their role in predisposing people to breast cancer have been uncovered, we are just beginning to understand the extent to which epigenetic regulators promote tumorigenic phenotypes, metastasis, and chemotherapeutic resistance. Moreover, new experimental tools offer the ability to address questions we were previously unable to assess. My project takes advantage of a new mouse model to understand the role of a proto-oncogenic, transcriptional co-regulator, TRIM24, in mammary gland development and disease. …
Mice Harbouring An Oculodentodigital Dysplasia-Linked Cx43 G60s Mutation Have Severe Hearing Loss,
2018
University of Western Ontario, Department of Anatomy and Cell Biology
Mice Harbouring An Oculodentodigital Dysplasia-Linked Cx43 G60s Mutation Have Severe Hearing Loss, Julia M. Abitbol, John J. Kelly, Kevin J. Barr, Brian L. Allman, Dale W. Laird
Anatomy and Cell Biology Publications
Given the importance of connexin43 (Cx43, encoded by GJA1) function in the central nervous system and sensory organ processing, we proposed that it would also be crucial in auditory function. To that end, hearing was examined in two mouse models of oculodentodigital dysplasia that globally express GJA1 mutations resulting in mild or severe loss of Cx43 function. Although Cx43(I130T/+) mutant mice, with similar to 50% Cx43 channel function, did not have any hearing loss, Cx43(G60S/+) mutant mice, with similar to 20% Cx43 channel function, had severe hearing loss. There was no evidence of inner ear sensory hair cell loss, suggesting …
Circulating Tumor Cell Analysis In Preclinical Mouse Models Of Metastasis,
2018
London Regional Cancer Program, London Health Sciences Centre, Department of Anatomy & Cell Biology,Western University
Circulating Tumor Cell Analysis In Preclinical Mouse Models Of Metastasis, Jenna Kitz, Lori E. Lowes, David Goodale, Alison L. Allan
Anatomy and Cell Biology Publications
The majority of cancer deaths occur because of metastasis since current therapies are largely non-curative in the metastatic setting. The use of in vivo preclinical mouse models for assessing metastasis is, therefore, critical for developing effective new cancer biomarkers and therapies. Although a number of quantitative tools have been previously developed to study in vivo metastasis, the detection and quantification of rare metastatic events has remained challenging. This review will discuss the use of circulating tumor cell (CTC) analysis as an effective means of tracking and characterizing metastatic disease progression in preclinical mouse models of breast and prostate cancer and …
Effect Of Silk-Based Hydrogel Topography On Intestinal Epithelial Cell Morphology And Wound Healing In Vitro,
2018
University of Connecticut
Effect Of Silk-Based Hydrogel Topography On Intestinal Epithelial Cell Morphology And Wound Healing In Vitro, Marisa E. Boch
University Scholar Projects
Recent advances in the field of biomaterials have suggested that cells cultured on substrates resembling the native tissue mechanical properties, matrix and growth factor composition, and topography can adopt phenotypes that more closely resemble the in vivo tissue compared to cells cultured on non-mimetic constructs. Understanding the effect of culture substrate on in vitro tissue formation is important for bioengineering applications that include mechanistic studies of healthy tissue function and development of disease models. In this work, Caco-2 adenocarcinoma cells were seeded on flat and crypt-like topographies of 3D-printed cytocompatible hydrogels derived from silk fibroin protein. Silk hydrogels were selected …
Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells,
2018
University of Connecticut
Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells, Matthew Lin
University Scholar Projects
Hepatocellular carcinoma (HCC) is the most common form of liver cancer that affects ~14 million people in the world. Like all cancers, HCC is a disease that arises from unstinted cellular growth initiated by genetic alterations, metabolic changes, and dysregulation in key cellular pathways. Of interest is the relationship between metabolism and cell proliferation/degradation for therapeutic targeting. Pyruvate kinase M2 is a dimeric, glycolytically inactive isoform of the final enzyme involved in glycolysis, that is often upregulated in cancerous tissue. It is thought that the enzymatic function of PKM2 outside of glycolysis contributes to the biosynthesis of anabolic intermediates used …
Effect Of Silk-Based Hydrogel Topography On Intestinal Epithelial Cell Morphology And Wound Healing In Vitro,
2018
University of Connecticut
Effect Of Silk-Based Hydrogel Topography On Intestinal Epithelial Cell Morphology And Wound Healing In Vitro, Marisa E. Boch
Honors Scholar Theses
Recent advances in the field of biomaterials have suggested that cells cultured on substrates resembling the native tissue mechanical properties, matrix and growth factor composition, and topography can adopt phenotypes that more closely resemble the in vivo tissue compared to cells cultured on non-mimetic constructs. Understanding the effect of culture substrate on in vitro tissue formation is important for bioengineering applications that include mechanistic studies of healthy tissue function and development of disease models. In this work, Caco-2 adenocarcinoma cells were seeded on flat and crypt-like topographies of 3D-printed cytocompatible hydrogels derived from silk fibroin protein. Silk hydrogels were selected …
Investigation Of P-Glycoprotein (Pgp) Induction By Pgp Substrates To Induce Paclitaxel Resistance In Ovarian Cancer Cells,
2018
University of the Incarnate Word
Investigation Of P-Glycoprotein (Pgp) Induction By Pgp Substrates To Induce Paclitaxel Resistance In Ovarian Cancer Cells, Ryker Penn
Theses & Dissertations
The purpose of this study was to investigate the development of chemotherapeutic resistance to paclitaxel in ovarian cancer cells after treatment with drugs that are substrates for P-glycoprotein (PGP). A core concept of this experiment was to identify if PGP substrate drugs could also act as PGP inducers after prolonged treatment in SKOV-3 ovarian cancer cells. In order to test this, SKOV-3 cells were exposed to either fexofenadine, a PGP substrate used as an antihistamine, or the chemotherapeutic drug vinblastine. After 42 days of drug treatment, ABCB1 gene expression was measured by qRT-PCR. Analysis of ABCB1 expression in treated cells …
Functional Studies Of The E. Coli Proc And A Putative Ortholog Mrub_1345,
2018
Augustana College, Rock Island Illinois
Functional Studies Of The E. Coli Proc And A Putative Ortholog Mrub_1345, Maureen Azar, Dr. Lori Scott
Meiothermus ruber Genome Analysis Project
This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation –Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of Escherichia coli and Meiothermus ruber proC genes using the complementation assay. In this research project, mutants of varying severity to the functional state of the protein were developed. The results showed that two or more amino acid deletions reduced or eliminated ProC function. Amino acid substitutions, on the other hand, were not severe enough to impact ProC function. Double and triple mutants …
Expression Of Androgen Receptor And Cancer Stem Cell Markers (Cd44 +/Cd24 - And Aldh1 +): Prognostic Implications In Invasive Breast Cancer,
2018
Aga Khan University
Expression Of Androgen Receptor And Cancer Stem Cell Markers (Cd44 +/Cd24 - And Aldh1 +): Prognostic Implications In Invasive Breast Cancer, Nazia Riaz, Romana Idress, Sadia Habib, Iqbal Azam Syed, El Nasir Lalani
Section of General Surgery
Background: Androgen receptor (AR) has emerged as a significant prognostic marker in early breast cancer (BCa). Association of AR with cancer stem cell (CSC) markers in BCa is unknown. Aim of the present study was to evaluate the immunohistochemical expression of AR, CD44, CD24 and ALDH1 in a cohort of Pakistani patients diagnosed with invasive BCa and to correlate the expression with 5- year disease free survival.
Patients and methods: We evaluated immunohistochemical expression AR, CD44, CD24 and ALDH1 in formalin fixed paraffin embedded archival blocks of 166 cases of primary invasive BCa (stage I-III) and correlated the expression with …
Trim24 In Normal & Malignant Hematopoiesis,
2018
The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Trim24 In Normal & Malignant Hematopoiesis, Justin Shaw
Dissertations & Theses (Open Access)
Treatment for acute myeloid leukemia (AML) has changed little in the past four decades. For the majority of AML patients, current treatment options include chemotherapy and allogeneic stem cell transplants, which also involves high-dose chemotherapy or radiation treatment. These options have little success in the long-run, as only an estimated 26% of patients survive five years post-diagnosis. In efforts to address this low survival rate, interest has increased for targeting epigenetic pathways in AML. This focus stems from the discovery that AML is frequently driven by blockades on hematopoietic stem cell differentiation, which involves a series of coordinated epigenetic changes. …
Targeting Mitochondrial Proline Dehydrogenase (Prodh) With A Suicide Inhibitor As A Novel Anticancer Strategy,
2018
Dominican University of California
Targeting Mitochondrial Proline Dehydrogenase (Prodh) With A Suicide Inhibitor As A Novel Anticancer Strategy, Beatrice Becker
Dissertations, Masters Theses, Capstones, and Culminating Projects
Proline dehydrogenase (PRODH) is a p53-inducible inner mitochondrial membrane protein linked to electron transport and capable of generating mitochondrial glutamate and intracellular ATP, especially under cellular stress conditions. Among a panel of 51 human breast cancer cell lines, PRODH and glutaminase (GLS1) expression levels were found to be inversely correlated (1) implicating two independent and alternative mitochondrial pathways supplying anaplerotic glutamate for cancer cell energy production and macromolecular synthesis. Proposing PRODH to be a promising cancer therapeutic target, we compared the in vitro cellular effects of PRODH knockdown by siRNA as well as competitive (L-tetrahydrofuroic acid, THFA; or 5-oxo-2-tetrahydrofurancarboxylic acid, …
Identification Of Substrate-Selective Histone Deacetylases And Their Inhibitors That Mediate Her2 Transcript Stability,
2018
Dominican University of California
Identification Of Substrate-Selective Histone Deacetylases And Their Inhibitors That Mediate Her2 Transcript Stability, Mariah Alejo
Dissertations, Masters Theses, Capstones, and Culminating Projects
Breast cancer is the most common malignancy diagnosed in women. 15-20% of these cancers overexpress the HER2 (ERRB2) oncoprotein. HER2-positive breast cancers are generally aggressive and are associated with poor prognosis. Unfortunately, only a mere 30% of HER2-positve patients respond to therapies when they are used as a single agent. Combining therapeutics can potentially lead to synergy and improved anticancer efficacy, and there is clearly a need for the development of new HER2-directed therapeutics. Newer approaches include the utilization of histone deacetylase (HDAC) inhibitors. It has been observed that HDAC inhibitors can induce the rapid decay of oncogenic transcripts such …
Mechanisms And Targeting Of Neurodevelopmental Regulator Rest In Medulloblastoma Dissemination,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Mechanisms And Targeting Of Neurodevelopmental Regulator Rest In Medulloblastoma Dissemination, Keri Callegari
Dissertations & Theses (Open Access)
Molecular subgrouping of medulloblastoma (MB) has produced four subgroups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4. While patients with WNT tumors have the best prognosis, patients with SHH tumors have a more variable prognosis concurrent with metastatic disease. This subset of SHH patients have elevated levels of the neurogenic regulator, RE1 Silencing Transcription factor (REST). To understand the role of REST in MB, we utilized a novel transgenic mouse model wherein REST expression can be conditionally elevated during postnatal development in the cells of origin of SHH MB, cerebellar granule neural progenitors (GNPs). While these mice did …
Disentangling The Subalpine Marshmarigold Species Complex: The Cytogeography, Phylogeography, And Systematics Of Caltha Biflora Dc., C. Chionophila Greene, And C. Leptosepala Dc. (Ranunculaceae),
2018
University of Wisconsin-Milwaukee
Disentangling The Subalpine Marshmarigold Species Complex: The Cytogeography, Phylogeography, And Systematics Of Caltha Biflora Dc., C. Chionophila Greene, And C. Leptosepala Dc. (Ranunculaceae), Keir Wefferling
Theses and Dissertations
Subalpine marshmarigolds (Caltha biflora DC., C. chionophila DC., and C. leptosepala Greene, Ranunculaceae) are herbaceous perennials that grow in western North American mountainous and subarctic regions, from Alaska and Yukon in the north to California, Arizona, and New Mexico in the south. Variation in morphology across the range has generally led to recognition of a single species, though some have described up to nine species in the complex. In this dissertation, I describe our approaches to disentangling reticulate evolution across the geographical range of the subalpine marshmarigold complex, including chromosome counts (Chapter II), genome size estimates (Chapter III), morphology (Chapters …
Identification And Utility Of Dna In Exosomes,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Identification And Utility Of Dna In Exosomes, Paul Kurywchak
Dissertations & Theses (Open Access)
Cancer-associated mortality has been declining for two decades but remains a significant public health problem, especially when patients initially present with advanced disease. Early detection methods have improved survival rates but remain unavailable for a majority of cancers due to a lack of sensitive biomarkers or numerous limitations associated with current diagnosis strategies. Approaches to develop “liquid biopsies” by detecting tumor cells or DNA in the blood have led to several breakthroughs and create the potential for non-invasive, routine assessment of diseases status. However, these biomarkers are rare and currently difficult to isolate, especially in the early stages of disease. …
The Regulation Of Dna Methylation In Mammalian Development And Cancer,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland
Dissertations & Theses (Open Access)
DNA methylation is an essential epigenetic modification in mammals, as it plays important regulatory roles in multiple biological processes, such as gene transcription, maintenance of chromosomal structure and genomic stability, genomic imprinting, retrotransposon silencing, and X-chromosome inactivation. Dysregulation of DNA methylation is associated with various human diseases. For example, cancer cells usually show global hypomethylation and regional hypermenthylation, which have been implicated in genomic instability and tumor suppressor silencing, respectively. Although great progress has been made in elucidating the biological functions of DNA methylation over the last several decades, how DNA methylation patterns and levels are regulated and dysregulated is …
Epithelial To Mesenchymal Transition As A Predictor Of Response To Polo-Like Kinase 1 Inhibition-Induced Apoptosis In Non-Small Cell Lung Carcinoma,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Epithelial To Mesenchymal Transition As A Predictor Of Response To Polo-Like Kinase 1 Inhibition-Induced Apoptosis In Non-Small Cell Lung Carcinoma, Pavitra Viswanath
Dissertations & Theses (Open Access)
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Outcomes are poor for patients with recurrent, advanced or metastatic NSCLC. Polo-like kinase 1 (PLK1), involved in the regulation of mitotic processes and the response to DNA damage, is overexpressed in NSCLC. Inhibiting PLK1 may be an effective treatment for NSCLC patients as it is involved in the mechanisms of resistance to several chemotherapy drugs. PLK1 inhibition or knock-down has various effects in cancer cells, including mitotic arrest, apoptosis, and senescence. Predictive biomarkers have not been identified to select those patients who are likely to respond to …
Cancer-Induced Muscle Wasting,
2018
University of Arkansas, Fayetteville
Cancer-Induced Muscle Wasting, Jacob Levi Brown
Graduate Theses and Dissertations
Cancer-induced muscle wasting, otherwise known as cancer-cachexia, is a wasting syndrome that occurs in approximately 80% of cancer patients that is the primary cause of death for 22%-30% of cancer cases. Cancer-cachexia may be metabolically induced; therefore, the central hypothesis of this dissertation is mitochondrial degeneration occurs before cancer-cachexia, and increased oxidative stress because of mitochondrial degeneration in muscle may instigate cancer-cachexia. Lewis Lung Carcinoma cells (LLC) or PBS (control) were injected into the hind-flank of C57Bl6/J mice at 8 wks age, and tumor allowed to develop for 1, 2, 3 or 4 wks. Mitochondrial quality, function, ROS emission, protein …
