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Advances In 3d Culture Systems For Therapeutic Discovery And Development In Brain Cancer, Janith Wanigasekara, Patrick J. Cullen, Paula Bourke, Brijesh Tiwari, James F. Curtin Nov 2022

Advances In 3d Culture Systems For Therapeutic Discovery And Development In Brain Cancer, Janith Wanigasekara, Patrick J. Cullen, Paula Bourke, Brijesh Tiwari, James F. Curtin

Articles

This review focuses on recent advances in 3D culture systems that promise more accurate therapeutic models of the glioblastoma multiforme (GBM) tumor microenvironment (TME), such as the unique anatomical, cellular, and molecular features evident in human GBM. The key components of a GBM TME are outlined, including microbiomes, vasculature, extracellular matrix (ECM), infiltrating parenchymal and peripheral immune cells and molecules, and chemical gradients. 3D culture systems are evaluated against 2D culture systems and in vivo animal models. The main 3D culture techniques available are compared, with an emphasis on identifying key gaps in knowledge for the development of suitable platforms …


Circulating Exosomal Micrornas As Predictive Biomarkers Of Neoadjuvant Chemotherapy Response In Breast Cancer, Valentina K. Todorova, Stephanie D. Byrum, Allen J. Gies, Cade Haynie, Hunter Smith, Nathan S. Reyna, Issam Makhoul Feb 2022

Circulating Exosomal Micrornas As Predictive Biomarkers Of Neoadjuvant Chemotherapy Response In Breast Cancer, Valentina K. Todorova, Stephanie D. Byrum, Allen J. Gies, Cade Haynie, Hunter Smith, Nathan S. Reyna, Issam Makhoul

Articles

Background: Neoadjuvant chemotherapy (NACT) is an increasingly used approach for treatment of breast cancer. The pathological complete response (pCR) is considered a good predictor of disease-specific survival. This study investigated whether circulating exosomal microRNAs could predict pCR in breast cancer patients treated with NACT. Method: Plasma samples of 20 breast cancer patients treated with NACT were collected prior to and after the first cycle. RNA sequencing was used to determine microRNA profiling. The Cancer Genome Atlas (TCGA) was used to explore the expression patterns and survivability of the candidate miRNAs, and their potential targets based on the expression levels and …


Ultrasound 96 Probe Device Protocol For Cancer Cell Treatment, Aisling Field, Brijesh K. Tiwari, James F. Curtin, Julie R M Mondala, Janith Wanigasekara Jan 2022

Ultrasound 96 Probe Device Protocol For Cancer Cell Treatment, Aisling Field, Brijesh K. Tiwari, James F. Curtin, Julie R M Mondala, Janith Wanigasekara

Articles

Ultrasound is a sound wave with frequencies ranging between 20 kHz and 20 MHz. Ultrasound is able to temporarily and repeatedly open the BBB safely and enhance chemotherapeutic delivery without adverse effects. This novel technique in drug delivery benefits from the powerful ability of ultrasound to produce cavitation activity. Cavitation is the generation and activity of gas-filled bubbles in a medium exposed to ultrasound. As the pressure wave passes through the media, gas bubbles expand at low pressure and contract at high pressure. This leads to oscillation which produces a circulating fluid flow known as microstreaming around the bubble with …


Plasma Induced Reactive Oxygen Species-Dependent Cytotoxicity In Glioblastoma 3d Tumourspheres, Janith Wanigasekara, Carlos Barcia, Patrick J. Cullen, Brijesh Tiwari, James F. Curtin Jan 2022

Plasma Induced Reactive Oxygen Species-Dependent Cytotoxicity In Glioblastoma 3d Tumourspheres, Janith Wanigasekara, Carlos Barcia, Patrick J. Cullen, Brijesh Tiwari, James F. Curtin

Articles

The aim of this study was to determine the effects of a pin‐to‐plate cold atmospheric plasma (CAP) on U‐251 MG three‐dimensional (3D) glioblastoma spheroids under different conditions. 3D tumorspheres showed higher resistance to the CAP treatment compared to 2D monolayer cells. A single CAP treatment was able to induce cytotoxicity, while multiple CAP treatments augmented this effect. CAP was also able to induce cytotoxicity throughout the tumoursphere, and we identified that reactive oxygen species(ROS) plays a major role, while H2O2plays a partial role in CAP‐induced cytotoxicity in tumour-spheres. We conclude that ROS‐dependent cytotoxicity is induced uniformly throughout glioblastoma and epidermoid …


U-251mg Spheroid Generation Using A Scaffold Based Method Protocol, Lara J. Carroll, Brijesh K. Tiwari, James F. Curtin, Janith Wanigasekara May 2021

U-251mg Spheroid Generation Using A Scaffold Based Method Protocol, Lara J. Carroll, Brijesh K. Tiwari, James F. Curtin, Janith Wanigasekara

Articles

3D cell culture is a technique that is used to grow cells in vitro that will mimic an in vivo environment. 3D cell models are a helpful learning tool for researchers to better understand disease mechanisms and to explore different therapeutic properties of drugs. 3D cell cultures can be developed using patient derived cancer cells. Once they have been grown, these 3D cells can be used to screen for small molecule drugs or for genetic modification in for analysis of disease pathways or to predict drug treatments toxicity or efficacy. 3D cell cultures are a big step towards the more …


U-251mg Spheroid Generation Using Low Attachment Plate Method Protocol, Lara J. Carroll, Brijesh K. Tiwari, James F. Curtin, Janith Wanigasekara May 2021

U-251mg Spheroid Generation Using Low Attachment Plate Method Protocol, Lara J. Carroll, Brijesh K. Tiwari, James F. Curtin, Janith Wanigasekara

Articles

3D cell culture is a process used to grow cells in vitro to mimic an in vivo environment. 3D cell models are very useful for understanding disease mechanisms and exploring drug therapeutics. 3D cultures can be grown from cells taken from cancer organoids in patients. Once grown, they can be used to screen for small molecule drugs or they can be genetically modified in order to analyse disease pathways or predict the toxicity or efficacy of a drug treatment. These cultures decrease the need to use animals in research and provides more reliable results as it uses human physiology. This …


U-251mg Spheroid Generation Using Hanging Drop Method Protocol, Lara J. Carroll, Brijesh K. Tiwari, James F. Curtin, Janith Wanigasekara May 2021

U-251mg Spheroid Generation Using Hanging Drop Method Protocol, Lara J. Carroll, Brijesh K. Tiwari, James F. Curtin, Janith Wanigasekara

Articles

The use of 3D cell culture has been a major step in developing cellular models that can mimic physiological tissues. Traditional 2D cell cultures are often unable to accurately represent the cellular functions and responses that are present in tissues, as a result, research findings based on 2D cultures tend to be skewed with limited predictive capability. 3D cell cultures can be grown from cells obtained from cancer organoids in patients. These models are useful for understanding disease mechanisms and exploring drug therapeutics in areas such as toxicity and efficacy. In order to gather more physiologically relevant data, a variety …


Monitoring Stem Cell Differentiation Using Raman Microspectroscopy: Chondrogenic Differentiation, Towards Cartilage Formation, Francesca Ravera, Esen Efeoglu, Hugh Byrne Jan 2021

Monitoring Stem Cell Differentiation Using Raman Microspectroscopy: Chondrogenic Differentiation, Towards Cartilage Formation, Francesca Ravera, Esen Efeoglu, Hugh Byrne

Articles

Mesenchymal Stem Cells (MSCs) have the ability to differentiate into chondrocytes, the only cellular components of cartilage and are therefore ideal candidates for cartilage and tissue repair technologies. Chondrocytes are surrounded by cartilage-like extracellular matrix (ECM), a complex network rich in glycosaminoglycans, proteoglycans, and collagen, which, together with a multitude of intracellular signalling molecules, trigger the chondrogenesis and allow the chondroprogenitor to acquire the spherical morphology of the chondrocytes. However, although the mechanisms of the differentiation of MSCs have been extensively explored, it has been difficult to provide a holistic picture of the process, in situ. Raman Micro Spectroscopy (RMS) …


Novel Role For The Golgi Membrane Protein Tmem165 In Control Of Migration And Invasion For Breast Carcinoma, Pavitra Murali, Blake P. Johnson, Zhongpeng Lu, Leslie Climer, Danielle A. Scott, Francois Foulquier, Gabriela Oprea-Ilies, Vladimir Lupashin, Richard R. Drake, Karen L. Abbott Jul 2020

Novel Role For The Golgi Membrane Protein Tmem165 In Control Of Migration And Invasion For Breast Carcinoma, Pavitra Murali, Blake P. Johnson, Zhongpeng Lu, Leslie Climer, Danielle A. Scott, Francois Foulquier, Gabriela Oprea-Ilies, Vladimir Lupashin, Richard R. Drake, Karen L. Abbott

Articles

The TMEM165 gene encodes for a multiple pass membrane protein localized in the Golgi that has been linked to congenital disorders of glycosylation. The TMEM165 protein is a putative ion transporter that regulates H+/Ca++/Mn++ homeostasis and pH in the Golgi. Previously, we identified TMEM165 as a potential biomarker for breast carcinoma in a glycoproteomic study using late stage invasive ductal carcinoma tissues with patient-matched adjacent normal tissues. The TMEM165 protein was not detected in non-malignant matched breast tissues and was detected in invasive ductal breast carcinoma tissues by mass spectrometry. Our hypothesis is that the TMEM165 protein confers a growth …


Glioma-Derived Exosomes Drive The Differentiation Of Neural Stem Cells To Astrocytes, Krishna D. Sharma, Danielle Schaal, Rajshekhar A. Kore, Rabab N. Hamzah, Sahitya Chetan Pandanaboina, Abdallah Hayar, Robert J. Griffin, Malathi Srivatsan, Nathan S. Reyna, Jennifer Yanhua Xie Jul 2020

Glioma-Derived Exosomes Drive The Differentiation Of Neural Stem Cells To Astrocytes, Krishna D. Sharma, Danielle Schaal, Rajshekhar A. Kore, Rabab N. Hamzah, Sahitya Chetan Pandanaboina, Abdallah Hayar, Robert J. Griffin, Malathi Srivatsan, Nathan S. Reyna, Jennifer Yanhua Xie

Articles

Exosomes appear to be effective inter-cellular communicators delivering several types of molecules, such as proteins and RNAs, suggesting that they could influence neural stem cell (NSC) differentiation. Our RNA sequencing studies demonstrated that the RNAs related to cell proliferation and astrocyte differentiation were upregulated in human mesenchymal stem cells (hMSC) when co-cultured with exosomes obtained from the culture medium of human glioma cells (U87). Metallothionein 3 and elastin genes, which are related to cell proliferation, increased 10 and 7.2 fold, respectively. Expression of genes for astrocyte differentiation, such as tumor growth factor alpha, induced protein 3 of the NOTCH1 family, …


3d Mammalian Cell Culture Models In Toxicology Testing, Janith Wanigasekara, Brijesh K. Tiwari, James Curtin Apr 2020

3d Mammalian Cell Culture Models In Toxicology Testing, Janith Wanigasekara, Brijesh K. Tiwari, James Curtin

Articles

3D cell culture can be successfully used as an alternative to laboratory animals, and as a cost effective and time-saving tissue culture technique, which also reduces the trial period for drug testing.


Cold Atmospheric Plasma Induces Silver Nanoparticle Uptake, Oxidative Dissolution And Enhanced Cytotoxicity In Glioblastoma Multiforme Cells, Eline Manaloto, Aoife Gowen, Anna Lesniak, Zhonglei He, Alan Casey, Patrick J. Cullen, James Curtin Jan 2020

Cold Atmospheric Plasma Induces Silver Nanoparticle Uptake, Oxidative Dissolution And Enhanced Cytotoxicity In Glioblastoma Multiforme Cells, Eline Manaloto, Aoife Gowen, Anna Lesniak, Zhonglei He, Alan Casey, Patrick J. Cullen, James Curtin

Articles

Silver nanoparticles (AgNP) emerged as a promising reagent for cancer therapy with oxidative stress implicated in the toxicity. Meanwhile, studies reported cold atmospheric plasma (CAP) generation of reactive oxygen and nitrogen species has selectivity towards cancer cells. Gold nanoparticles display synergistic cytotoxicity when combined with CAP against cancer cells but there is a paucity of information using AgNP, prompting to investigate the combined effects of CAP using dielectric barrier discharge system (voltage of 75 kV, current is 62.5 mA, duty cycle of 7.5kVA and input frequency of 50–60Hz) and 10 nm PVA-coated AgNP using U373MG Glioblastoma Multiforme cells. Cytotoxicity in …


Optimisation Of Estrogen Receptor Subtype-Selectivity Of A 4-Aryl-4h-Chromene Scaffold Previously Identified By Virtual Screening, Miriam Carr, Andrew Knox, Daniel Nevin, Niamh O'Boyle, Shu Wang, Billy Egan, Thomas Mccabe, Brendan Twamley, Daniela Zisterer, David Lloyd, Mary Meegan Jan 2020

Optimisation Of Estrogen Receptor Subtype-Selectivity Of A 4-Aryl-4h-Chromene Scaffold Previously Identified By Virtual Screening, Miriam Carr, Andrew Knox, Daniel Nevin, Niamh O'Boyle, Shu Wang, Billy Egan, Thomas Mccabe, Brendan Twamley, Daniela Zisterer, David Lloyd, Mary Meegan

Articles

4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor α and β with low nanomolar affinity and <20-fold selectivity for α over β and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERα (compound 35; 350-fold selectivity) or ERβ (compound 42; 170-fold selectivity).


Forscells: 40-Days Fixed Prepared Reagent For Detection Of Anti-Forssman Inhumans, Sofia Ferreira, Cristiana Mourato, Alyssa Corpuz, Sofia Galvão, Camilla Hesse, Clara Rocha, Carlos Jesus, Fernando Mendes Jan 2020

Forscells: 40-Days Fixed Prepared Reagent For Detection Of Anti-Forssman Inhumans, Sofia Ferreira, Cristiana Mourato, Alyssa Corpuz, Sofia Galvão, Camilla Hesse, Clara Rocha, Carlos Jesus, Fernando Mendes

Articles

In 2012, the FORS system was accepted by the International Society of Blood Transfusion as the 31st blood group system. Forssman (Fs) antigen (Ag) expression is most commonly found on sheep red blood cells (RBC) but rare in human RBC. Anti-Fs antibodies (Ab) are naturally occurring in human sera and are predominantly IgM but they can also be IgG. To this day, the global prevalence of the FORS system is unknown. Currently, there is a lack of natural FORS1-positive RBC available to use for anti-Fs screening in large populations. This study was designed to produce FORS1-positive cells viable for …


Generation Of A Fully Human Scfv That Binds Tumor-Specific Glycoforms, Zhongpeng Lu, Kalika Kamat, Blake P. Johnson, Catherin C. Yin, Nathalie Scholler, Karen L. Abbott Dec 2019

Generation Of A Fully Human Scfv That Binds Tumor-Specific Glycoforms, Zhongpeng Lu, Kalika Kamat, Blake P. Johnson, Catherin C. Yin, Nathalie Scholler, Karen L. Abbott

Articles

Tumor-specific glycosylation changes are an attractive target for the development of diagnostic and therapeutic applications. Periostin is a glycoprotein with high expression in many tumors of epithelial origin including ovarian cancer. Strategies to target the peptide portion of periostin as a diagnostic or therapeutic biomarker for cancer are limited due to increased expression of periostin in non-cancerous inflammatory conditions. Here, we have screened for antibody fragments that recognize the tumor-specific glycosylation present on glycoforms of periostin containing bisecting N-glycans in ovarian cancer using a yeast-display library of antibody fragments, while subtracting those that bind to the periostin protein with glycoforms …


Cold Atmospheric Plasma Induces Accumulation Of Lysosomes And Caspase-Independent Cell Death In U373mg Glioblastoma Multiforme Cells, Gillian Conway, Zhonglei He, Ana L. Hutanu, George P. Cribaro, Eline Manaloto, Alan Casey, Damien Traynor, Vladimir Milosavljevic, Orla Howe, Carlos Barcia, James T. Murray, Patrick Cullen, James Curtin Sep 2019

Cold Atmospheric Plasma Induces Accumulation Of Lysosomes And Caspase-Independent Cell Death In U373mg Glioblastoma Multiforme Cells, Gillian Conway, Zhonglei He, Ana L. Hutanu, George P. Cribaro, Eline Manaloto, Alan Casey, Damien Traynor, Vladimir Milosavljevic, Orla Howe, Carlos Barcia, James T. Murray, Patrick Cullen, James Curtin

Articles

Room temperature Cold Atmospheric Plasma (CAP) has shown promising efficacy for the treatment of cancer but the exact mechanisms of action remain unclear. Both apoptosis and necrosis have been implicated as the mode of cell death in various cancer cells. We have previously demonstrated a caspase-independent mechanism of cell death in p53-mutated glioblastoma multiforme (GBM) cells exposed to plasma. The purpose of this study was to elucidate the molecular mechanisms involved in caspase-independent cell death induced by plasma treatment. We demonstrate that plasma induces rapid cell death in GBM cells, independent of caspases. Accumulation of vesicles was observed in plasma …


Visceral Adipose Tissue Modulates Radiosensitivity In Oesophageal Adenocarcinoma, Ann Marie Mongan, Niamh Lynam-Lennon, Suzanne Doyle, Rory Casey, Eibhlin Carr, Aoife Cannon, Melissa J Conroy, Graham P Pidgeon, Lorraine Brennan, Joanne Lysaght, John V. Reynolds, Jacintha O’Sullivan Jan 2019

Visceral Adipose Tissue Modulates Radiosensitivity In Oesophageal Adenocarcinoma, Ann Marie Mongan, Niamh Lynam-Lennon, Suzanne Doyle, Rory Casey, Eibhlin Carr, Aoife Cannon, Melissa J Conroy, Graham P Pidgeon, Lorraine Brennan, Joanne Lysaght, John V. Reynolds, Jacintha O’Sullivan

Articles

Oesophageal adenocarcinoma (OAC) is an exemplar model of obesity-associated cancer. Response to neoadjuvant chemoradiotherapy (NA CRT) is a clinical challenge. We examined if visceral adipose tissue and obesity status alter radiosensitivity in OAC. The radioresistant (OE33R) and radioresponsive (OE33P) OAC isogenic model was cultured with adipose tissue conditioned media from three patient cohorts: non-cancer patients, surgery only OAC patients and NA CRT OAC patients. Cell survival was characterised by clonogenic assay, metabolomic profiling by nuclear magnetic resonance spectroscopy and adipokine receptor gene expression by qPCR. A retrospective in vivo study compared tumour response to NA CRT in normal weight (n=53) …


Ultrasound/Elastography Techniques, Lipidomic And Blood Markers Compared To Magnetic Resonance Imaging In Non-Alcoholic Fatty Liver Disease Adults, Irene Cantero, Mariana Elorz, Itziar Abete, Bertha Araceli Marin, Jose Ignacio Herrero, Jose Ignacio Monreal, Alberto Benito, Jorge Quiroga, Ana Martínez, Pilar Huarte, Juan Isidro Uriz-Otano, Josep Antoni Tur, John Kearney, J. Alfredo Martinez, M. Angeles Zulet Jan 2019

Ultrasound/Elastography Techniques, Lipidomic And Blood Markers Compared To Magnetic Resonance Imaging In Non-Alcoholic Fatty Liver Disease Adults, Irene Cantero, Mariana Elorz, Itziar Abete, Bertha Araceli Marin, Jose Ignacio Herrero, Jose Ignacio Monreal, Alberto Benito, Jorge Quiroga, Ana Martínez, Pilar Huarte, Juan Isidro Uriz-Otano, Josep Antoni Tur, John Kearney, J. Alfredo Martinez, M. Angeles Zulet

Articles

Introduction: Non-alcoholic fatty liver disease (NAFLD) may progress to steatohepatitis, cirrhosis and complicated hepatocellular carcinoma with defined differential symptoms and manifestations. Objective: To evaluate the fatty liver status by several validated approaches and to compare imaging techniques, lipidomic and routine blood markers with magnetic resonance imaging in adults subjects with non-alcoholic fatty liver disease. Materials and methods: A total of 127 overweight/obese with NAFLD, were parallelly assessed by Magnetic Resonance Imaging (MRI), ultrasonography, transient elastography and a validated metabolomic designed test to diagnose NAFLD in this cross-sectional study. Body composition (DXA), hepatic related biochemical measurements as well as the Fatty …


Hypoxia-Derived Exosomes Induce Putative Altered Pathways In Biosynthesis And Ion Regulatory Channels In Glioblastoma Cells, Rajshekhar A. Kore, Jacob L. Edmondson, Samir V. Jenkins, Azemat Jamshidi-Parsian, Ruud P.M. Dings, Nathan S. Reyna, Robert J. Griffin Jul 2018

Hypoxia-Derived Exosomes Induce Putative Altered Pathways In Biosynthesis And Ion Regulatory Channels In Glioblastoma Cells, Rajshekhar A. Kore, Jacob L. Edmondson, Samir V. Jenkins, Azemat Jamshidi-Parsian, Ruud P.M. Dings, Nathan S. Reyna, Robert J. Griffin

Articles

Hypoxia, a hallmark characteristic of glioblastoma (GBM) induces changes in the transcriptome and the proteome of tumor cells. We discovered that hypoxic stress produces significant qualitative and quantitative changes in the protein content of secreted exosomes from GBM cells. Among the proteins found to be selectively elevated in hypoxic exosomes were protein-lysine 6-oxidase (LOX), thrombospondin-1 (TSP1), vascular derived endothelial factor (VEGF) and a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), well studied contributors to tumor progression, metastasis and angiogenesis. Our findings demonstrate that hypoxic exosomes induce differential gene expression in recipient glioma cells. Glioma cells stimulated with hypoxic exosomes …


Cold Atmospheric Plasma Induces Atp-Dependent Endocytosis Of Nanoparticles And Synergistic U373mg Cancer Cell Death, Zhonglei He, Kangze Liu, Eline Manaloto, Alan Casey, George P. Cribaro, Hugh Byrne, Furong Tian, Carlos Barcia, Gillian Conway, Patrick Cullen, James Curtin Mar 2018

Cold Atmospheric Plasma Induces Atp-Dependent Endocytosis Of Nanoparticles And Synergistic U373mg Cancer Cell Death, Zhonglei He, Kangze Liu, Eline Manaloto, Alan Casey, George P. Cribaro, Hugh Byrne, Furong Tian, Carlos Barcia, Gillian Conway, Patrick Cullen, James Curtin

Articles

Gold nanoparticles (AuNP) have potential as both diagnostic and therapeutic vehicles. However, selective targeting and uptake in cancer cells remains challenging. Cold atmospheric plasma (CAP) can be combined with AuNP to achieve synergistic anti-cancer cytotoxicity. To explore synergistic mechanisms, we demonstrate both rate of AuNP uptake and total amount accumulated in U373MG Glioblastoma multiforme (GBM) cells are signifcantly increased when exposed to 75kV CAP generated by dielectric barrier discharge. No signifcant changes in the physical parameters of AuNP were caused by CAP but active transport mechanisms were stimulated in cells. Unlike many other biological efects of CAP, long-lived reactive species …


A Physical Biology, The Electron Neutrino Mass, And The Role Of Quantum Mechanics In Nature, Maurice Goodman Jan 2018

A Physical Biology, The Electron Neutrino Mass, And The Role Of Quantum Mechanics In Nature, Maurice Goodman

Articles

In science we need to remove physics and earth science from the fundamental sciences and treat Biology as a fundamental natural (physical) science. Attempts to keep Biology autonomous because it is holistic, from the physical sciences, are just disguised anthropocentrism. Physical sciences have holistic features also. The autonomy of Biology is at odds with a holistic, integrated, science and is preventing progress in science. For example, every cell needs a 'global' communication system to keep order and stability with rapid information transfer across cellular scales. We have yet to figure out how this is achieved. Over the last 30 years, …


The Glycosyltransferase Gnt-Iii Activates Notch Signaling And Drives Stem Cell Expansion To Promote The Growth And Invasion Of Ovarian Cancer, Heba Allam, Blake P. Johnson, Mao Zhang, Zhongpeng Lu, Martin J. Cannon, Karen L. Abbott Sep 2017

The Glycosyltransferase Gnt-Iii Activates Notch Signaling And Drives Stem Cell Expansion To Promote The Growth And Invasion Of Ovarian Cancer, Heba Allam, Blake P. Johnson, Mao Zhang, Zhongpeng Lu, Martin J. Cannon, Karen L. Abbott

Articles

Glycosylation changes associated with cellular transformation can facilitate the growth and progression of tumors. Previously we discovered that the gene Mgat3 encoding the glycosyltransferase GnT-III is elevated in epithelial ovarian carcinomas (EOCs) and leads to the production of abnormal truncated N-linked glycan structures instead of the typical bisected forms. In this study, we are interested in discovering how these abnormal glycans impact the growth and progression of ovarian cancer. We have discovered using stable shRNA gene suppression that GnT-III expression controls the expansion of side-population cells, also known as cancer stem cells. More specifically, we found that GnT-III expression regulates …


Comparative Studies Of Cellular Viability Levels On 2d And 3d In Vitro Culture Matrices, Alan Casey, Hugh Byrne, Mahmoud Gargotti, Ulises Lopez Gonzalez Sep 2017

Comparative Studies Of Cellular Viability Levels On 2d And 3d In Vitro Culture Matrices, Alan Casey, Hugh Byrne, Mahmoud Gargotti, Ulises Lopez Gonzalez

Articles

In this study, the cellular viability and function of immortalized human cervical and dermal cells are monitored and compared in conventional 2D and two commercial 3D membranes, Collagen and Geltrex, of varying working concentration and volume. Viability was monitored with the aid of the Alamar Blue assay, cellular morphology was monitored with confocal microscopy, and cell cycle studies and cell death mechanism studies were performed with flow cytometry. The viability studies showed apparent differences between the 2D and 3D culture systems, the differences attributed in part to the physical transition from 2D to 3D environment causing alterations to effective resazurin …


Non-Thermal Atmospheric Plasma Induces Ros-Independent Cell Death In U373mg Glioma Cells And Augments The Cytotoxicity Of Temozolomide, Gillian Conway, Alan Casey, Vladimir Milosavljevic, Yupeng Liu, Orla L. Howe, Patrick Cullen, James Curtin Feb 2016

Non-Thermal Atmospheric Plasma Induces Ros-Independent Cell Death In U373mg Glioma Cells And Augments The Cytotoxicity Of Temozolomide, Gillian Conway, Alan Casey, Vladimir Milosavljevic, Yupeng Liu, Orla L. Howe, Patrick Cullen, James Curtin

Articles

Non-thermal atmospheric plasma (NTAP) is an ionised gas produced under high voltage that can generate short-lived chemically active species and induce a cytotoxic insult in cancer cells. Cell-specific resistance to NTAP-mediated cytotoxicity has been reported in the literature. The aim of this study was to determine whether resistance against NTAP could be overcome using the human glioma cell line U373MG.

Methods:

Non-thermal atmospheric plasma was generated using a Dielectric Barrier Device (DBD) system with a maximum voltage output of 120 kV at 50 Hz. The viability of U373MG GBM cells and HeLa cervical carcinoma cells was determined using morphology, flow …


Comparative Genomics Of Cluster O Mycobacteriophages, Steven G. Cresawn, Nathan S. Reyna, Ruth Plymale, Welkin H. Pope, Deborah Jacobs-Sera, Charles A. Bowman, Daniel A. Russell, Rebekah M. Dedrick, Tamarah Adair, Kirk R. Anders, Sarah Ball, David Bollivar, Caroline Breitenberger, Sandra H. Burnett, Kristen Butela, Deanna Byrnes, Sarah Carzo, Kathleen A. Cornely, Trevor Cross, Richard L. Daniels, David Dunbar, Ann M. Findley, Chris R. Gissendanner, Urszula P. Golebiewska, Grant A. Hartzog, J. Robert Hatherill, Lee E. Hughes, Chernoh S. Jalloh, Carla De Los Santos, Kevin Ekanem, Sphindile L. Khambule, Rodney A. King, Christina King-Smith, Karen Klyczek, Greg P. Krukonis Mar 2015

Comparative Genomics Of Cluster O Mycobacteriophages, Steven G. Cresawn, Nathan S. Reyna, Ruth Plymale, Welkin H. Pope, Deborah Jacobs-Sera, Charles A. Bowman, Daniel A. Russell, Rebekah M. Dedrick, Tamarah Adair, Kirk R. Anders, Sarah Ball, David Bollivar, Caroline Breitenberger, Sandra H. Burnett, Kristen Butela, Deanna Byrnes, Sarah Carzo, Kathleen A. Cornely, Trevor Cross, Richard L. Daniels, David Dunbar, Ann M. Findley, Chris R. Gissendanner, Urszula P. Golebiewska, Grant A. Hartzog, J. Robert Hatherill, Lee E. Hughes, Chernoh S. Jalloh, Carla De Los Santos, Kevin Ekanem, Sphindile L. Khambule, Rodney A. King, Christina King-Smith, Karen Klyczek, Greg P. Krukonis

Articles

Mycobacteriophages - viruses of mycobacterial hosts - are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages - Corndog, Catdawg, Dylan, Firecracker, and YungJamal - designated as Cluster O with long flexible tails but with unusual prolate capsids. Proteomic analysis of phage Corndog particles, Catdawg particles, and Corndog-infected cells confirms expression of half of the predicted gene products and indicates a non-canonical mechanism for translation of the Corndog tape measure protein. Bioinformatic analysis identifies 8-9 strongly predicted SigA promoters and all five Cluster O …


Cell Viability Assessment Using The Alamar Blue Assay: A Comparison Of 2d And 3d Cell Culture Models, Franck Bonnier, Mark Keating, Tomasz P. Wrobel, Katarsyna Majzner, Malgorzata Baranska, Amaya Garcia, Alfonso Blanco, Hugh Byrne Feb 2015

Cell Viability Assessment Using The Alamar Blue Assay: A Comparison Of 2d And 3d Cell Culture Models, Franck Bonnier, Mark Keating, Tomasz P. Wrobel, Katarsyna Majzner, Malgorzata Baranska, Amaya Garcia, Alfonso Blanco, Hugh Byrne

Articles

Comparisons of 2D and 3D cell culture models in literature have indicated differences in cellular morphology and metabolism, commonly attributed the better representation of in vivo conditions of the latter cell culture environment. Thus, interest in the use of 3D collagen gels for in vitro analysis has been growing. Although comparative studies to date have indicated an enhanced resistance of cells on collagen matrices against different toxicants, in the present study it is demonstrated that non-adapted protocols can lead to misinterpretation of results obtained from classical colorometric dye-based cytotoxic assays. Using the well established Alamar Blue assay, the …


Divergent Mechanisms Of Interaction Of Helicobacter Pylori And Campylobacter Jejuni With Mucus And Mucins, Julie Ann Naughton, Karina Mariño, Brendan Dolan, Colm Reid, Ronan Gough, Mary Gallagher, Michelle Kilcoyne, Jared Gerlachscience,, Lokesh Joshi, Pauline Rudd, Stephen Carrington, Billy Bourke, Marguerite Clyne Aug 2013

Divergent Mechanisms Of Interaction Of Helicobacter Pylori And Campylobacter Jejuni With Mucus And Mucins, Julie Ann Naughton, Karina Mariño, Brendan Dolan, Colm Reid, Ronan Gough, Mary Gallagher, Michelle Kilcoyne, Jared Gerlachscience,, Lokesh Joshi, Pauline Rudd, Stephen Carrington, Billy Bourke, Marguerite Clyne

Articles

Helicobacter pylori and Campylobacter jejuni colonize the stomach and intestinal mucus, respectively. Using a combination of mucus-secreting cells, purified mucins, and a novel mucin microarray platform, we examined the interactions of these two organisms with mucus and mucins. H. pylori and C. jejuni bound to distinctly different mucins. C. jejuni displayed a striking tropism for chicken gastrointestinal mucins compared to mucins from other animals and preferentially bound mucins from specific avian intestinal sites (in order of descending preference: the large intestine, proximal small intestine, and cecum). H. pylori bound to a number of animal mucins, including porcine stomach mucin, but …


The Bio-Nano-Interface In Predicting Nanoparticle Fate And Behaviour In Living Organisms: Towards Grouping And Categorising Nanomaterials And Ensuring Nanosafety By Design, Hugh Byrne, Arti Ahluwalia, Diana Boraschi,, Bengt Fadeel, Peter Gehr, Arno C. Gutleb, Michaela Kendall, Manthos Papadopoulos, Iseult Lynch Jan 2013

The Bio-Nano-Interface In Predicting Nanoparticle Fate And Behaviour In Living Organisms: Towards Grouping And Categorising Nanomaterials And Ensuring Nanosafety By Design, Hugh Byrne, Arti Ahluwalia, Diana Boraschi,, Bengt Fadeel, Peter Gehr, Arno C. Gutleb, Michaela Kendall, Manthos Papadopoulos, Iseult Lynch

Articles

In biological media, nanoparticles acquire a coating of biomolecules (proteins, lipids, polysaccharides) from their surroundings, which reduces their surface energy and confers a biological identity to the particles. This adsorbed layer is the interface between the nanomaterial and living systems and therefore plays a significant role in determining the fate and behaviour of the nanoparticles. This review summarises the state of the art in terms of understanding the bio-nano interface and provides direction for potential future research directions and some recommendations for future priorities and strategies to support the safe implementation of nanotechnologies. The central premise is that nanomaterials must …


Reactive Oxygen Species Mediated Dna Damage In Human Lung Alveolar Epithelial (A549) Cells From Exposure To Non-Cytotoxic Mfi-Type Zeolite Nanoparticles, Kunal Bhattacharya, Pratap Naha, Izabela Naydenova, Svetlana Mintova, Hugh Byrne Dec 2012

Reactive Oxygen Species Mediated Dna Damage In Human Lung Alveolar Epithelial (A549) Cells From Exposure To Non-Cytotoxic Mfi-Type Zeolite Nanoparticles, Kunal Bhattacharya, Pratap Naha, Izabela Naydenova, Svetlana Mintova, Hugh Byrne

Articles

Increasing utilization of engineered nanoparticles in the field of electronics and biomedical applications demands an assessment of risk associated with deliberate or accidental exposure. Metal based nanoparticles are potentially most important of all the nanoparticles in terms of health risks. Microporousalumino-silicates and pure silicates named as zeolites and zeo-type materials with variety of structures, chemical compositions, particle sizes and morphologies have a significant number of industrial uses such as in catalysis, sorption and ion-exchange processes. In particular, the nanosized particles due to their unique properties are used in hybrid organic-inorganic materials for photography, photonics, electronics, labeling, imaging, and sensing. The …


Spectral Cross Correlation As A Supervised Approach For The Analysis Of Complex Raman Datasets: The Case Of Nanoparticles In Biological Cells, Mark Keating, Franck Bonnier, Hugh Byrne Oct 2012

Spectral Cross Correlation As A Supervised Approach For The Analysis Of Complex Raman Datasets: The Case Of Nanoparticles In Biological Cells, Mark Keating, Franck Bonnier, Hugh Byrne

Articles

Spectral Cross-correlation is introduced as a methodology to identify the presence and subcellular distribution of nanoparticles in cells. Raman microscopy is employed to spectroscopically image biological cells previously exposed to polystyrene nanoparticles, as a model for the study of nano-bio interactions. The limitations of previously deployed strategies of K-means clustering analysis and principal component analysis are discussed and a novel methodology of Spectral Cross Correlation Analysis is introduced and compared with the performance of Classical Least Squares Analysis, in both unsupervised and supervised modes. The previous study demonstrated the feasibility of using Raman spectroscopy to map cells and identify polystyrene …