Medicine and Health Sciences Commons^™

Novel Therapeutic Approaches To Treat Brain Cancer Combining 3d Cell Culture Models, Cold Atmospheric Plasma And Airborne Acoustic, Janith Wanigasekara

Doctoral

Glioblastoma (GBM), an adult-type diffuse grade 4 glioma (IDH wild type), is the most prevalent, aggressive, fatal, highly vascularized, malignant primary brain tumour in adults with a poor prognosis. Despite existing therapies such as surgical resection, radiation therapy and chemotherapy such as temozolomide (TMZ), patient survival remains largely unchanged over the last three decades. There is an urgent need for novel and effective therapeutic strategies that can overcome drug resistance, cross the blood brain barrier, and minimise off-target side effects that can negatively impact a patient's quality of life. The high failure rate of clinical trials is due to inefficient …

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 …

Use And Awareness Of Heated Tobacco Products In Europe, Silvano Gallus, Alessandra Lugo, Xiaoqiu Liu, Elisa Borroni, Luke Clancy, Giuseppe Gorini, Maria José Lopez, Anna Odone, Krzysztof Przewozniak, Olena Tigova, Piet A. Van Den Brandt, Constantine Vardavas, Esteve Fernandez, Tackshs Project Investigators

Articles

Background: Heated tobacco products (HTP) are new forms of tobacco consumption with limited information available on their use among the general population. Our objective was to analyze the prevalence and associations of use of HTP across 11 countries in Europe.

Methods: Within the TackSHS Project, in 2017-2018 we conducted a cross-sectional study with information on HTP use in the following countries: Bulgaria, England, France, Germany, Greece, Italy, Latvia, Poland, Portugal, Romania and Spain. In each country, face-to-face interviews were performed on a representative sample of around 1,000 subjects aged ≥15 years, for a total of 10,839 subjects.

Results: Overall, 27.8% …

Effect Of Hemolysis On Fourier Transform Infrared And Raman Spectra Of Blood Plasma, Dinesh Medipally, Daniel Cullen, Valérie Untereiner, Jane Bryant, Ganesh D. Sockalingum, Thi Nguyet Que Nguyen, Emma Noone, Shirley Bradshaw, Marie Finn, Mary Dunne, Aoife M. Shannon, John Armstrong, Aidan Meade, Fiona Lyng

Articles

Hemolysis is a very common phenomenon and is referred as the release of intracellular components from red blood cells to the extracellular fluid. Hemolyzed samples are often rejected in clinics due to the interference of hemoglobin and intracellular components in laboratory measurements. Plasma and serum based vibrational spectroscopy studies are extensively applied to generate spectral biomarkers for various diseases. However, no studies have reported the effect of hemolysis in blood based vibrational spectroscopy studies. This study was undertaken to evaluate the effect of hemolysis on infrared and Raman spectra of blood plasma. In this study, prostate cancer plasma samples (n …

Pre-Clinical Models Of Small Cell Lung Cancer And The Validation Of Therapeutic Targets, Jane S.Y. Sui, Petra Martin, Steven G. Gray

Articles

Introduction: Small-cell lung cancer (SCLC) is an aggressive form of lung cancer that has a dismal prognosis. One of the factors hindering therapeutic developments for SCLC is that most SCLC is not surgically resected resulting in a paucity of material for analysis. To address this, significant efforts have been made by investigators to develop pre-clinical models of SCLC allowing for downstream target identification in this difficult to treat cancer.

Areas covered: In this review, we describe the current pre-clinical models that have been developed to interrogate SCLC, and outline the benefits and limitations associated with each. Using examples …

Recent Advances In The Vibrational Spectroscopic Diagnosis Of Non-Small Cell Lung Cancer, Declan O'Dea, Fiona Lyng, Siobhan Nicholson, Finbar O'Connell, Aoife Maguire, Alison Malkin

Articles

Lung cancer is the leading cause of cancer deaths worldwide accounting for 1.69 million deaths in 2015. Studies have indicated a 5 year survival rate of 8%–15% in western countries, although a survival rate as low as 1% has been demonstrated for late stage diagnosis. With the advent of targeted therapies, it is imperative to accurately differentiate non-small cell lung cancer (NSCLC) subtypes in order to ensure efficacy of treatment for patients. Immunohistochemistry and molecular techniques for the diagnosis of NSCLC are increasingly part of the diagnostic algorithm and clinical work-up of lung cancer patients, however due to the limitation …

Subjective And Objective Assessment Of Taste And Smell Sensation In Advanced Cancer, Niamh Mcgettigan, Pauline Uí Dhuibhir, Michelle Barrett, Jessica Sui, Lucy Balding, Stephen Higgins, Norma O'Leary, Aileen Kennedy, Declan Walsh

Articles

Context: Taste and smell abnormalities (TSA) occur throughout the cancer trajectory regardless of cancer primary site and contribute to cancer-associated malnutrition. TSA etiology is poorly understood. Tumor-related inflammation is a possible cause. Objective: This study examined the prevalence, characteristics, and severity of TSA in advanced cancer and explored the relationship between TSA and nutritional status. No previous study combined subjective and objective measures for both taste and smell assessment in this population. Method: Consecutive advanced cancer hospice patients were recruited. A modified version of the “Taste and Smell Survey” assessed subjective TSA. Validated taste strips and “Sniffin’ …

Effect Of Neoadjuvant Chemoradiation On Preoperative Pulmonary Physiology, Postoperative Respiratory Complications And Quality Of Life In Patients With Oesophageal Cancer, J. A. Elliott, L. O'Byrne, G. Foley, C. F. Murphy, Suzanne Doyle, S. King, E. M. Guinan, N. Ravi, V. Reynolds

Articles

Background: It remains controversial whether neoadjuvant chemoradiation (nCRT) for oesophageal cancer influences operative morbidity, in particular pulmonary, and quality of life. This study combined clinical outcome data with systematic evaluation of pulmonary physiology to determine the impact of nCRT on pulmonary physiology and clinical outcomes in locally advanced oesophageal cancer.

Methods: Consecutive patients treated between 2010 and 2016 were included. Three-dimensional conformal radiation was standard, with a lung dose–volume histogram of V20 less than 25 per cent, and total radiation between 40 and 41⋅4Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity …

A Custom Radiopaque Thermoresponsive Chemotherapy-Loaded Hydrogel For Intratumoural Injection: An In Vitro And Ex Vivo Assessment Of Imaging Characteristics And Material Properties, Seóna M. Rossi, Timothy E. Murray, John Cassidy, Michael J. Lee, Helena M. Kelly

Articles

Purpose Thermoresponsive hydrogels are gels which have different properties at varying temperatures. The objective of this study was to assess the material characteristics, imaging properties and chemotherapeutic drug release profile of a novel radiopaque thermoresponsive hydrogel in vitro, which is liquid at room temperature but solidifies at body temperature, to determine potential suitability for intratumoural delivery. Materials and Methods An iodinated radiopaque thermoresponsive hydrogel was formulated using iodixanol at a range of concentrations and assessed for sol–gel transition, radiopacity and imaging using CT and US. A lead formulation containing iodixanol at a concentration of 9.22% weight by weight (w/w, g …

Patient Experiences Of A Physiotherapy-Led Multidisciplinary Rehabilitative Intervention After Successful Treatment For Oesophago-Gastric Cancer, Annemarie Bennett, L. O'Neill, D. Connolly, E. M. Guinan, L. Boland, Suzanne Doyle, J. O'Sullivan, J. V. Reynolds, J. Hussey

Articles

Purpose To qualitatively explore the perceived impact of a 12-week rehabilitative intervention for oesophago-gastric cancer survivors on their physical, mental and social wellbeing. Methods Of the 21 participants who completed the intervention, 19 took part in a semi-structured focus group interview. Four audio-taped focus groups were held, ranging in size from two to eight participants. Focus groups were transcribed and analysed using a descriptive qualitative approach. Results At recruitment, participants were 23.5 ± 15.2 months post-surgery and all had suboptimal fitness levels. Participants reported improvements in their physical capacity and ability to carry out activities of daily living during the …

Sarcopenia During Neoadjuvant Therapy For Oesophageal Cancer: Characterising The Impact On Muscle Strength And Physical Performance, E.M. Guinan, Suzanne Doyle, A.E. Bennett, L. O'Neill, J. Gannon, J.A. Elliott, J. O'Sullivan, J.V. Reynolds, J. Hussey

Articles

Purpose Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC.

Methods Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle …

Evaluation Of A Drug Delivery System Based On Cyclodextrins For Cancer Therapy, Caroline Mendes

Doctoral

Due to the side-effects caused by regular chemotherapy, the development of drug delivery systems that can specifically target cancer cells and deliver the therapeutic dose is required. In this study, a folate-derivative of β-cyclodextrin has been studied as a vehicle for targeting folate receptors (FR) and delivering the chemotherapeutic drug methotrexate (MTX). FRs can be considered key cell membrane targets since they are commonly over-expressed in cancer cells and play an important role in cancer development and progression. Cyclodextrins (CDs) are cyclic oligosaccharides with a unique structure that allows them to form inclusion complexes with guest molecules, increasing their aqueous …

Carcinogenesis In Prostate Cancer: The Role Of Long Non-Coding Rnas, John Aird, Anne-Marie Baird, Marvin C.J Lim, Ray Mcdermott, Stephen P. Finn, Steven G. Gray

Articles

LncRNAs appear to play a considerable role in tumourigenesis through regulating key processes in cancer cells such as proliferative signalling, replicative immortality, invasion and metastasis, evasion of growth suppressors, induction of angiogenesis and resistance to apoptosis. LncRNAs have been reported to play a role in prostate cancer, particularly in regulating the androgen receptor signalling pathway. In this review article, we summarise the role of 34 lncRNAs in prostate cancer with a particular focus on their role in the androgen receptor signalling pathway and the epithelial to mesenchymal transition pathway.

Biofunctionalized Capillary Flow Channel Platform Integrated With 3d Nanostructured Matrix To Capture Circulating Tumor Cells, Shashwat Banerjee, Ganesh Khutale, Vrushali Khobragade, Narendra Kale, Milind Pore, Govind Chate, Archana Jalota-Badhwar, Manoj Dongare, Jayant Khandare

Articles

Circulating tumor cells (CTCs) from peripheral blood account genetic information for cancer diagnosis and overall disease monitoring. Analysis of “liquid biopsy” holds immense promise as it may lead to new approaches for cancer treatment. The study reports effective and continuous flow microchannel system for isolating CTCs using transferrin conjugated 3D matrix synthesized by crosslinking polyethylene glycol-Fe3O4 nanostructures for rapid and efficient capturing of CTCs. The platform provides option of using multiple microchannel units in series that can influence higher cell-capture efficiency due to increasing cell-substrate contact frequency. CTCs are captured with high efficiency even at low concentration of target cells …

Advancing Vibrational Spectroscopy For Cellular And Sub Cellular Analysis: Raman Spectroscopy As An In Vitro Chemotherapeutic Screeening And Assessment Protocol, Zeineb Farhane

Doctoral

Vibrational spectroscopy, including Raman micro-spectroscopy, has attracted considerable attention over the last few years, as a powerful, non-invasive tool for clinical applications, especially in cancer diagnosis, in vivo and ex vivo. As a molecular fingerprinting technique with optical resolution, Raman micro-spectroscopy is able to monitor biochemical processes, drug uptake, efficacy and mode of action and mechanisms of interaction of chemotherapeutic drugs at a subcellular level. In vitro applications may be more strategically achievable, and can help guide drug design and discovery, and eventually evaluate To this end, different lung cell lines were used and Raman micro-spectroscopy was coupled to valuable …

The "Eyes" Have It?-Intra- And Inter-Observer Reproducibility Of The Pd-L1 Companion Diagnostic Assay, Steven G. Gray, Mark Wright, Stephen Finn

Articles

No abstract available.

The Potential Of Raman Spectroscopy For Cytological Diagnosis Of Thinprep Samples From A Cervical Cancer Screening Population, Ines Ramos

Doctoral

Cervical cancer is the second most common cancer in women worldwide. For decades, most developed countries have applied organized cytology screening programs using the Papanicolau (PAP) test to identify abnormal cases. Despite a high specificity of 95-98%, Pap test sensitivity is reported to vary greatly from 74 to 96% with constant testing needed to achieve the highest values. Semi-automated cytology screening platforms, immunocytochemistry panels and other methodologies such as human papilloma virus (HPV) testing has been developed to help reduce false negative rates. More recently, HPV testing, thus far used for triage of abnormal cytology cases and test of cure, …

Predictive Biomarkers Of Cellular Radiosensitivity For Clinical Radiotherapy Treatment, Lisa White

Doctoral

Radiotherapy is prescribed to more than 50% of cancer patients during their treatment schedule. Due to intrinsic factors, individual variation in response exists, which will result in side effects or toxicity in a number of patients. Therefore, development of an assay or biomarker for the prediction and assessment of radiosensitivity among cancer patients undergoing radiotherapy would be beneficial. Such an assay would limit toxicities and facilitate dose-escalation for those patients who require it. Assays for predicting intrinsic cellular radiosensitivity remains as the established G2 chromosomal radiosensitivity and most promising, γH2AX foci assay. They can be applied to blood samples from …

Methodologies And Considerations For Bladder Cancer Detection With Raman Based Urine Cytology, Laura T. Kerr, Thérése M. Lynn, Ivor M. Cullen, Padraig J. Daly, Nigam Shah, Shirley O'Dea, Alison Malkin, Bryan M. Hennelly

Articles

Bladder cancer has the highest recurrence rate of any cancer. The American Urological Association recommends cystoscopic surveillance every 3–6 months for 3 years, and at least once a year thereafter, particularly for high-risk patients; however, cystoscopy is invasive, expensive, and is not without insignificant morbidity for the patient. Urine cytology is often used as an adjunct to cystoscopy; however, it has a low sensitivity in detecting low grade bladder cancers. Recent studies have investigated the application of Raman micro-spectroscopy for the detection of bladder cancer via urine cytology, and it has been demonstrated to significantly improve the diagnostic sensitivity of …

Novel Therapeutic Approaches To Induce Autophagy In Brain Cancer, Gillian Conway

Doctoral

Glioblastoma Multiforme (GBM) is classified as a malignant grade IV astrocytoma, and is considered to be the most biologically aggressive brain tumour with a 5-year survival rate of ~4%. The most frequent issue arising with GBM tumours is the high level of resistance observed to conventional therapeutic methods i.e. surgery, chemotherapy and radiation, thus signifying the urgency for the development of novel therapeutic methods. This study aims to investigate and develop both a complimentary and novel method to overcome the current treatment barriers. We have investigated the use of novel technologies such as cold atmospheric plasma (CAP) as an alternative …

Parallel Profiles Of Inflammatory And Effector Memory T Cells In Visceral Fat And Liver Of Obesity-Associated Cancer Patients, Melissa Conroy, Karen Galvin, Suzanne Doyle, Maria Kavanagh, Ann-Marie Mongan, Aoife Cannon, Gillian Moore, John Reynolds, Joanne Lysaght

Articles

In the midst of a worsening obesity epidemic, the incidence of obesity-associated morbidities, including cancer, diabetes, cardiac and liver disease is increasing. Insights into mechanisms underlying pathological obesity-associated inflammation are lacking. Both the omentum, the principal component of visceral fat, and liver of obese individuals are sites of excessive inflammation, but to date the T cell profiles of both compartments have not been assessed or compared in a patient cohort with obesity-associated disease. We have previously identified that omentum is enriched with inflammatory cytokines, chemokines and T cells. Here, we compared the inflammatory profile of T cells in the omentum …

Cell Death Pathways In Directly Irradiated Cells And Cells Exposed To Medium From Irradiated Cells, K.K. Jella, Amaya Garcia, Brendan Mcclean, Hugh Byrne, Fiona Lyng

Articles

Purpose: The aim of this study was to compare levels of apoptosis, necrosis, mitotic cell death and senescence after treatment with both direct radiation and irradiated cell conditioned medium. Materials and methods: Human keratinocytes (HaCaT cell line) were irradiated (0.005, 0.05 and 0.5 Gy) using a cobalt 60 teletherapy unit. For bystander experiments, the medium was harvested from donor HaCaT cells one hour after irradiation and transferred to recipient HaCaT cells. Clonogenic assay, apoptosis, necrosis, mitotic cell death, senescence and cell cycle analysis were measured in both directly irradiated cells and bystander cells Results: A reduction in cell survival was …

The Effect Of Genetic Background And Dose On Non-Targeted Effects Of Radiation, Sarah Irons, Virginia Sierra, Deborah Bowler, Kim Chapman, Stefania Militi, Fiona Lyng, Munira Kadhim

Articles

Purpose: This work investigates the hypothesis that genetic background plays a significant role in the signalling mechanisms underlying induction and perpetuation of genomic instability following radiation exposure.

Materials and methods: Bone marrow from two strains of mice (CBA and C57) were exposed to a range of X-ray doses (0, 0.01, 0.1, 1 and 3 Gy). Different cellular signalling endpoints: Apoptosis, cytokine levels and calcium flux, were evaluated at 2 h, 24 h and 7 d post-irradiation to assess immediate and delayed effects.

Results: In CBA (radiosensitive) elevated apoptosis levels were observed at 24 h post X-irradiation, and …

Differential Genome-Wide Array–Based Methylation Profiles In Prognostic Subsets Of Chronic Lymphocytic Leukemia, Meena Kanduri, Nicola Cahill, Hanna Göransson, Camilla Enström, Fergus Ryan, Anders Isaksson, Richard Rosenquist

Articles

Global hypomethylation and regional hypermethylation are well-known epigenetic features of cancer; however, in chronic lymphocytic leukemia (CLL), studies on genome-wide epigenetic modifications are limited. Here, we analyzed the global methylation profiles in CLL, by applying high-resolution methylation microarrays (27 578 CpG sites) to 23 CLL samples, belonging to the immunoglobulin heavy-chain variable (IGHV) mutated (favorable) and IGHV unmutated/IGHV3-21 (poor-prognostic) subsets. Overall, results demonstrated significant differences in methylation patterns between these subgroups. Specifically, in IGHV unmutated CLL, we identified methylation of 7 known or candidate tumor suppressor genes (eg, VHL, ABI3, and IGSF4) as well as 8 unmethylated genes involved in …

Adenovirus E4orf4 Induces Hpv-16 Late L1 Mrna Production, Monica Somberg, Margaret Rush, Joanna Fay, Fergus Ryan, Helen Lambkin, Göran Akusjärvi, Stefan Schwartz

Articles

The adenovirus E4orf4 protein regulates the switch from early to late gene expression during the adenoviral replication cycle. Here we report that overexpression of adenovirus E4orf4 induces human papillomavirus type 16 (HPV-16) late gene expression from subgenomic expression plasmids. E4orf4 specifically overcomes the negative effects of two splicing silencers at the two late HPV-16 splice sites SD3632 and SA5639. This results in the production of HPV-16 spliced L1 mRNAs. We show that the interaction of E4orf4 with protein phosphatase 2A (PP2A) is necessary for induction of HPV-16 late gene expression. Also an E4orf4 mutant that fails to bind the cellular …

Potential Of Vibrational Spectroscopy In The Diagnosis Of Human Tumours., Eoghan O'Faolain

Doctoral

Just fewer than 20,000 people are annually diagnosed with some form of cancer in Ireland and one in three people are likely to contract some form of cancer by age 74. With the number of cases increasing at an annual rate of 2%, the early detection and treatment of cancer is becoming increasingly important. Both IR and Raman spectroscopy offer the potential for real time, quantitative detection of cancer and even precancer. This study investigates the potential of Raman and Fourier transform infrared, both benchtop and synchrotron spectroscopies for the detection of cervical cancer. The tissue was classified and its …