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 …
Dicer1 Syndrome: Dicer1 Mutations In Rare Cancers,
2018
Boise State University
Dicer1 Syndrome: Dicer1 Mutations In Rare Cancers, Jake C. Robertson, Cheryl L. Jorcyk, Julia Thom Oxford
Biology Faculty Publications and Presentations
DICER1 syndrome is a rare genetic disorder that predisposes individuals to multiple cancer types. Through mutations of the gene encoding the endoribonuclease, Dicer, DICER1 syndrome disrupts the biogenesis and processing of miRNAs with subsequent disruption in control of gene expression. Since the first description of DICER1 syndrome, case reports have documented novel germline mutations of the DICER1 gene in patients with cancers as well as second site mutations that alter the function of the Dicer protein expressed. Here, we present a review of mutations in the DICER1 gene, the respective protein sequence changes, and clinical manifestations of DICER1 syndrome. Directions …
Wnt/Β-Catenin Signaling Components On Cancer Stem Cell Activation In Hepatocellular Carcinoma.,
2018
University of Louisville
Wnt/Β-Catenin Signaling Components On Cancer Stem Cell Activation In Hepatocellular Carcinoma., Kevin Jacob
College of Arts & Sciences Senior Theses
Hepatocellular carcinoma is the most common type of liver cancer that, when diagnosed at advanced stage, has a 5-year survival rate of less than 12%. Alarmingly, the recurrence rate of HCC after curative and palliative treatment is 70% in the first 14 months. Cancer Stem Cells are a subpopulation in the tumor mass. Accumulating evidence suggests that the CSC subpopulation can initiate cancer and drives tumor recurrence, drug resistance, and metastasis. The Wnt/β-catenin pathway is a cardinal pathway contributing to stem-cell organogenesis during embryo development. The objective of the project was to identify canonical Wnt/β-catenin pathway components and/or downstream targets …
Investigating Invasion In Ductal Carcinoma In Situ With To Pographical Single Cell Genome Sequencing,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Investigating Invasion In Ductal Carcinoma In Situ With To Pographical Single Cell Genome Sequencing, Anna Casasent, Anna Casasent
Dissertations and Theses (Open Access)
Synchronous Ductal Carcinoma in situ (DCIS-IDC) is an early stage breast cancer invasion in which it is possible to delineate genomic evolution during invasion because of the presence of both in situ and invasive regions within the same sample. While laser capture microdissection studies of DCIS-IDC examined the relationship between the paired in situ (DCIS) and invasive (IDC) regions, these studies were either confounded by bulk tissue or limited to a small set of genes or markers. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS), which combines laser-catapulting with single cell DNA sequencing to measure genomic copy …
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 …
Genetic Testing And A Real World Case Of Lynch Syndrome,
2018
University of Rhode Island
Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro
Senior Honors Projects
In recent years, advancements in genetic testing methods have revolutionized the medical field by enhancing the ability to identify persons with an inherited predisposition to cancer. According to the American Society for Clinical Oncology, individuals should undergo genetic testing when he or she meets the following criteria: the individual demonstrates familial history that indicates a predisposition to certain cancers, the test can be adequately interpreted, and the results will aid in the diagnosis, treatment, or management of the patient or additional family members at risk. Genetic testing can be done on samples of hair, skin, blood, amniotic fluid, or other …
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 and 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 …
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 and 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 …
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 and 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. …
Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Phosphorylation Impairs Dicer1 Function To Accelerate Aging And Tumorigenesis In Vivo, Neeraj Aryal
Dissertations and Theses (Open Access)
Altered DICER1 protein levels are associated with developmental disorders, infertility, macular degenerative blindness, aging, and cancer in humans. Recently, post-translational regulation of Dicer1 via phosphorylation has been described in C. elegans. Oscillation of Dicer1 phosphorylation to regulate its activity is essential for germ cell development and embryogenesis in worms. These observations led us to posit that Dicer1 protein levels and activity are under tight regulation for normal mammalian homeostasis. To test whether phosphorylation of Dicer1 regulates its activity in mammals, I generated phospho-mimetic knock-in mouse models by replacing Serines 1712 and 1836 with Aspartic acids individually or together (dual …
Sphingosine Kinase 1 Regulates Fascin Expression To Promote Metastasis In Triple Negative Breast Cancer,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Sphingosine Kinase 1 Regulates Fascin Expression To Promote Metastasis In Triple Negative Breast Cancer, Sunil Acharya
Dissertations and Theses (Open Access)
Distant metastasis is the primary cause of breast cancer–related mortality. To date, effective therapeutic drugs that target metastasis are still lacking. Triple negative breast cancer (TNBC) occurs in high frequency in young women and are more likely to recur and metastasize than are other breast cancer subtypes. Also, TNBC patients cannot benefit from currently available hormonal or targeted therapies, as they lack estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Thus, understanding the signaling pathways that promote TNBC metastasis and developing novel therapeutic approaches to target them are critical, in order to prolong the survival and improve …
Deciphering The Roles Of Δnp63 In Regulating Epithelial To Mesenchymal Transition, Cancer Progression And Metastasis,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Deciphering The Roles Of Δnp63 In Regulating Epithelial To Mesenchymal Transition, Cancer Progression And Metastasis, Ngoc Bui
Dissertations and Theses (Open Access)
p63 is a member of the p53 family, a well-known tumor suppressor which is considered the guardian of the genome. The TP63 gene encodes multiple isoforms that can be categorized into two main isoforms, TAp63 and ΔNp63, which are expressed in different cellular compartments and have distinct functions in many biological processes. While the Flores laboratory identified TAp63 as a tumor and metastasis suppressor, the precise roles of ΔNp63 isoforms in tumorigenesis and metastasis remain elusive. ΔNp63 is the predominant p63 isoform expressed in the epidermis and plays essential roles in regulating epidermal development and homeostasis. Utilizing a ΔNp63-conditional …
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 and 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. …
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 and 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 and 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 …
Mtbp Inhibits The Erk1/2-Elk-1 Signaling In Hepatocellular Carcinoma,
2018
University of Kansas
Mtbp Inhibits The Erk1/2-Elk-1 Signaling In Hepatocellular Carcinoma, Atul Ranjan, Swathi V. Iyer, Christopher Ward, Tim Link, Francisco J. Diaz, Animesh Dhar, Ossama W. Tawfik, Steven A. Weinman, Yoshiaki Azuma, Tadahide Izumi, Tomoo Iwakuma
Toxicology and Cancer Biology Faculty Publications
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the prognosis of HCC patients, especially those with metastasis, remains extremely poor. This is partly due to unclear molecular mechanisms underlying HCC metastasis. Our previous study indicates that MDM2 Binding Protein (MTBP) suppresses migration and metastasis of HCC cells. However, signaling pathways regulated by MTBP remain unknown. To identify metastasis-associated signaling pathways governed by MTBP, we have performed unbiased luciferase reporter-based signal array analyses and found that MTBP suppresses the activity of the ETS-domain transcription factor Elk-1, a downstream target of Erk1/2 MAP kinases. MTBP also inhibits phosphorylation …
Human Cancer And Platelet Interaction, A Potential Therapeutic Target,
2018
University of Kentucky
Human Cancer And Platelet Interaction, A Potential Therapeutic Target, Shike Wang, Zhenyu Li, Ren Xu
Markey Cancer Center Faculty Publications
Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft experiments and transgenic mouse models further demonstrate that platelet activation and platelet-cancer cell interaction are crucial for cancer metastasis. Direct or indirect interaction of platelets induces cancer cell plasticity and enhances survival and extravasation of circulating cancer cells during dissemination. In vivo and in vitro experiments also demonstrate that cancer cells induce platelet aggregation, suggesting that platelet-cancer interaction is bidirectional. Therefore, understanding how platelets crosstalk with cancer cells may identify potential strategies to inhibit cancer metastasis and to reduce …
Sirna Knock-Down Of Vav1 In Breast Cancer Cells: Effects On Pi3kinase And Akt,
2018
University of Lynchburg
Sirna Knock-Down Of Vav1 In Breast Cancer Cells: Effects On Pi3kinase And Akt, Tajai Sion-Milligan
Student Scholar Showcase
One in eight women in the United States will be diagnosed with breast cancer. Approximately 25-30% of these breast tumors will overexpress Human Epidermal Growth Factor Receptor 2 (HER2), associated with a worse prognosis and decreased survival rate. Stimulation of HER2 results in activation and production of many signaling molecules, ultimately resulting in increased cell division. Two of the downstream molecules activated are PI3Kinase and, further downstream, the molecule Akt. Typically, overproduction and/or overactivation of PI3Kinase can lead to oncogenesis. A molecule that may have a significant role in PI3Kinase formation is VAV1. VAV1 …
Vesicles Mimicking Normal And Cancer Cell Membranes Exhibit Differential Responses To The Cell-Penetrating Peptide Pep-1,
2018
Tennessee State University
Vesicles Mimicking Normal And Cancer Cell Membranes Exhibit Differential Responses To The Cell-Penetrating Peptide Pep-1, Bashiyar Almarwani, Esther Nzuzi Phambu, Christopher Alexander, Ha Aimee T. Nguyen, Nsoki Phambu, Anderson Sunda-Meya
Chemistry Faculty Research
The cell-penetrating peptide (CPP) Pep-1 presents a great potential in drug delivery due to its intrinsic property to cross plasma membrane. However, its mechanism of entry into the cell remains unresolved. In this study, we compare the selectivity of Pep-1 towards vesicles mimicking normal and cancer cell membranes. The interaction was performed in a wide range of peptide-to-lipid molar ratios using infrared (IR), fluorescence, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques. At low peptide concentration, fluorescence experiments show that lipid-phosphatidylserine (PS) seems to enable Pep-1 translocation into cancer cell membrane as evidenced by the …
