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 …
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 …
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 …
Development Of Endogenous Tagging Plasmids For Characterization Of Protein Interactions, Localization, And Post-Translational Modifications Of Tetrahymena Thermophila Rad23,
2018
Missouri State University
Development Of Endogenous Tagging Plasmids For Characterization Of Protein Interactions, Localization, And Post-Translational Modifications Of Tetrahymena Thermophila Rad23, Evan Andrew Wilson
Graduate Theses/Dissertations
Rad23 is a protein involved in both nucleotide excision repair (NER) and proteasome-mediated degradation, and has been suggested to facilitate interactions between these two pathways. The model organism Tetrahymena thermophila, which has a transcriptionally silent micronucleus, provides a useful platform for studying the role of Rad23 in global genome NER (GG-NER). However, the ectopic expression systems used thus far in T. thermophila to study Rad23 are repressed by UV light and do not account for the background expression of endogenous RAD23; these phenomena prevent insightful gains to the true dynamics of Rad23. In this thesis, endogenous tagging …
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 …
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 …
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 …
Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli,
2018
CUNY Graduate Center
Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek
Dissertations, Theses, and Capstone Projects
Escherichia coli is a well-known pathogen, and importantly, a widely used model organism in all fields of biological sciences for cloning, protein purification, and as a model for Gram-negative bacterial species. And yet, researchers do not fully understand how this bacterium replicates and divides. Every year additional division proteins are discovered, which adds complexity to how we understand E. coli undergoes cell division. Due to their specific roles in cytokinesis, some of these proteins may be potential targets for development of antibacterials or bacteriostatics, which are much needed for fighting the current global antibacterial deficit. My thesis work focuses on …
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 …
The Effects Of Insulin Signaling On Follicle Development And Activation,
2018
Syracuse University
The Effects Of Insulin Signaling On Follicle Development And Activation, Ali Abdullah
Renée Crown University Honors Thesis Projects - All
Women are born with the all the germ cells they will produce in their lifetime, with the establishment of this initial pool of germ cells being critical for fertility. In the mouse model, germ cells arrive at the genital ridge around 10.5 days post coitum (dpc) and divide by mitosis, forming cysts, until 13.5 dpc. These germ cells, referred to as oocytes, enter meiosis and begin to arrest in the diplotene stage of prophase I around 17.5 dpc. Simultaneously, the cysts begin to break apart and flattened granulosa cells surround the remaining single oocytes to form primordial follicles. Most oocytes …
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 …
Low Hemodynamic Loading Alters Heart Morphogensis In E8.5 To E9.5 Mouse Embryos,
2018
Missouri State University
Low Hemodynamic Loading Alters Heart Morphogensis In E8.5 To E9.5 Mouse Embryos, Tanner Gerard Hoog
Graduate Theses/Dissertations
Hemodynamic loading, the force exerted on the cardiovascular walls as blood circulates, has been shown to alter heart morphology in chick and zebrafish embryos, but has yet to be shown to singly influence mouse heart development. Defects of heart morphology found in model organisms with physically altered hemodynamics resemble the aberrations seen in human congenital heart disease and are therefore crucial to understand in a mammalian model. In the present study, hemodynamic loading was altered by lowering the hematocrit of early stage mouse embryos. This was accomplished by injecting acrylamide and TEMED into the blood islands of cultured embryos to …
Investigation Of The Homologs Rad51 And Dmc1 Role In Cell Division And Homologous Recombination,
2018
Missouri State University
Investigation Of The Homologs Rad51 And Dmc1 Role In Cell Division And Homologous Recombination, Amaal Abulibdeh
Graduate Theses/Dissertations
RecA-like proteins homologs Rad51 and Dmc1 (disruption of meiotic control) promote recombination between homologous chromosomes by repairing programmed DNA Double-Strand Breaks (DSBs). Dmc1 is a Recombinase involved in meiosis-specific repair of DSBs, whereas Rad51 has been found to be involved in meiotic and non-meiotic DSBs repair. Previous studies showed that when RAD51 is overexpressed, interhomologous recombination still occurs even when DMC1 is knocked out. Dmc1 and Rad51 have not been fully characterized in the ciliate Tetrahymena thermophila. In order to more fully investigate the role of Rad51 and Dmc1 in Homologous Recombination Repair (HHR), this work focuses on using …
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 …
The Subcloning And Expression Of Munc18a In Escherichia Coli For Antibody Production And Analysis In Mast Cell Degranulation Reactions,
2018
University of Southern Mississippi
The Subcloning And Expression Of Munc18a In Escherichia Coli For Antibody Production And Analysis In Mast Cell Degranulation Reactions, Brandi Goble
Honors Theses
Mast cells are secretory cells responsible for fighting off infection through the early recognition of pathogens. This process is completed through the secretion of proinflammatory mediators that are stored in secretory granules within the cytoplasm of the cell. The degranulation secretion process relies on regulated fusion of secretory granules to the cell membrane via membrane-bound SNARE proteins that bridges the two opposed membranes. The intricate regulation of SNARE-mediated mast cell degranulation is not well understood. However, Sec1/Munc18 (SM) proteins, specifically the Munc18 isoforms, are known to play a critical role in the process (Brochetta, et. al., 2014). The Xu lab …
Microbiome Of Commercial Broilers Through Evisceration And Immersion Chilling,
2018
University of Arkansas, Fayetteville
Microbiome Of Commercial Broilers Through Evisceration And Immersion Chilling, John A. Handley
Graduate Theses and Dissertations
The United States poultry industry generated 38.6 billion pounds (17,500 metric ton) of meat in 2014 which averaged to 121 pounds (55 kg) per individual of the U.S that same year. Of that meat generated by the poultry industry, an estimated 1 million cases of Salmonellosis will occur. Out of the 1 million cases approximately 40, 000 to 50,000 will be confirmed cases by the CDC. Recently, the USDA has requested changes in the inspection process and are currently allowing processors more freedom to utilize innovation to drive the increase in safer and more desirable foods. The new standards set …
Combining Translational And Functional Genomic Approaches To Augment Management Strategies Of Plant Parasitic Nematodes,
2018
University of Arkansas, Fayetteville
Combining Translational And Functional Genomic Approaches To Augment Management Strategies Of Plant Parasitic Nematodes, Sandeep Sharma Khatiwada
Graduate Theses and Dissertations
Plant-parasitic nematodes pose a major threat to crop yield worldwide. Discontinued use of harmful chemicals has prompted the search for alternative management strategies that are effective yet environmentally friendly. Harpin proteins, which are derived from bacteria, and nematophagous fungi, natural predators of nematodes, are ideal for biological control of plant-parasitic nematodes. However, research on the efficacy of harpin proteins on nematodes, and biology of nematophagous fungi is minimal. Previously, a taxonomically uncharacterized nematophagous fungus designated ARF18 effectively suppressed nematode populations in soil. The overarching goal of this dissertation is to utilize applied and functional genomic approaches to augment management of …
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 …
