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December 2002 - present
September 2008 - present
Publications
Publications (84)
Research in applying various atmospheric plasma discharges to cancer treatment has progressed significantly in recent years. Atmospheric plasma discharges (DC and AC discharges or RF jets) can initiate cell death via the production of reactive nitrogen and oxygen species (RONS) in the intercellular medium. However, there remains a need to find prop...
For many years, there has been increasing concern about the effects of the presence of hazardous substances in the environment. The chemical and biological effect (BE) monitoring of these pollutants has proven difficult due to low environmental concentrations, variable bioavailability, and the generalised nature of ecological responses to these sub...
Although significant advances in understanding the molecular drivers of acquired and inherited radiosensitivity have occurred in recent decades, a single analytical method which can detect and classify radiosensitivity remains elusive. Raman microspectroscopy has demonstrated capabilities in the objective classification of various diseases, and mor...
Predicting long-term recurrence of disease in breast cancer (BC) patients remains a significant challenge for patients with early stage disease who are at low to intermediate risk of relapse as determined using current clinical tools. Prognostic assays which utilize bulk transcriptomics ignore the spatial context of the cellular material and are, t...
Vibrational spectroscopic techniques, such as Fourier transform infrared (FTIR) absorption and Raman spectroscopy (RS), offer unique and detailed biochemical fingerprints by detecting specific molecular vibrations within samples. These techniques provide profound insights into the molecular alterations induced by ionising radiation, which are both...
The use of Fourier transform infrared (FTIR) and Raman spectroscopy (RS) for the analysis of lymphocytes in clinical applications is increasing in the field of biomedicine. The pre-analytical phase, which is the most vulnerable stage of the testing process, is where most errors and sample variance occur; however, it is unclear how pre-analytical va...
Aidan D. Meade, Fiona M. Lyng and Hugh J. Byrne introduce the Analyst themed issue on SPEC 2022: International Conference on Clinical Spectroscopy.
In recent years, scientific understanding of the changes radiation makes to the various tissues of the body has vastly increased. Identification of biological markers of radiation exposure and response has become a wide field with an increasing interest across the radiation research community. This chapter introduces the concepts of individual radi...
The ultimate aim of radiobiological research is to establish a quantitative relationship between the radiation dose absorbed by biological samples (being this a cell, a tissue, an organ, or a body) and the effect caused. Therefore, radiobiological investigations need to be supported by accurate and precise dosimetric measurements. A rigorous standa...
This chapter is focused on radiobiological aspects at the molecular, cellular, and tissue level which are relevant for the clinical use of ionizing radiation (IR) in cancer therapy. For radiation oncology, it is critical to find a balance, i.e., the therapeutic window, between the probability of tumor control and the probability of side effects cau...
Radiation biology is the study of the effects of ionizing radiation on biological tissues and living organisms. It combines radiation physics and biology. The purpose of this chapter is to introduce the terminology and basic concepts of radiobiology to create a better understanding of the ionizing radiation interactions with a living organism. This...
Severe radiation toxicity can continue years after the completion of radiotherapy for prostate cancer patients. Currently, it is impossible to predict before treatment which patients will experience these long-term side effects. New approaches based on vibrational spectroscopy have advantages over lymphocyte and genomic assays in terms of minimal s...
Irradiation of the tumour site during treatment for cancer with external-beam ionising radiation results in a complex and dynamic series of effects in both the tumour itself and the normal tissue which surrounds it. The development of a spectral model of the effect of each exposure and interaction mode between these tissues would enable label free...
Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 5%. Carbohydrate antigen 19-9 (CA19-9) is the most commonly used blood-based biomarker for PDAC in current clinical practice, despite having been shown repeatedly to be inaccurate and have poor diagnostic performance. This review aims to assess the reported diagnostic accuracy...
Recent reports have shown a link between radiation exposure and non-cancer diseases such as radiation-induced heart disease (RIHD). Radiation exposures are often inhomogeneous, and out-of-target effects have been studied in terms of cancer risk, but very few studies have been carried out for non-cancer diseases. Here, the role of miRNAs in the path...
This poster presents our current progress towards plasmon mapping of SERS-active nanostructures using SPELS. NP have been produced on silicon substrates by dewetting of thin silver films. The morphology of these films has been characterised by atomic force microscopy (AFM), preliminary SPELS measurements have been performed and their SERS enhanceme...
Thermal dewetting of silver thin film can lead to SERS-active Ag nanoparticles. Here, we report our progress towards using scanning probe energy loss spectroscopy (SPELS) to map the plasmonic behaviour of SERS-active Ag nanoparticles (NP) by investigating NPs produced through the dewetting study of Ag thin films on SiO2/Si and Ti/SiO2/Si substrates...
Background: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal form of pancreatic cancer, being responsible for ~90% of all pancreatic cancers and having a 5-year survival rate of ~8.5%. The current clinical gold-standard for diagnosis of PDAC is the blood-based biomarker CA19-9. However, many studies have highlighted the limitations of CA1...
Molecular communication between irradiated and unirradiated neighbouring cells initiates radiation-induced bystander effects (RIBE) and out-of-field (abscopal) effects which are both an example of the non-targeted effects (NTE) of ionising radiation (IR). Exosomes are small membrane vesicles of endosomal origin and newly identified mediators of NTE...
The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1 and PCNA previously reported to be radiation-respo...
Fourier Transform Infrared (FTIR) based chemical imaging is a powerful, non‐destructive, label‐free biophotonic technique which spatially acquires bio‐molecularly relevant information in histopathology. Cancer detection with objective chemical imaging techniques is relatively well established, though detection of pre‐cancer stages within a continuu...
The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detri...
Rheumatoid arthritis (RA) possess not only a substantial degree of clinical heterogeneity but is diagnosed on a diverse array of clinical criteria. The lack of a single marker predictive methodology means that the timely diagnosis and treatment of these patients proves challenging. With the advent of targeted therapies, it is becoming increasingly...
Surface-enhanced Raman spectroscopy (SERS) relies on adsorbing target molecules onto metal nanostructures where the light can resonantly couple with localised surface plasmon resonances. These plasmons can be tuned by changing the nanostructure size, shape, spacing and composition, but this is a complex process. Therefore, having an experimental me...
The exquisite sensitivity of Raman spectroscopy to the molecular composition of biological samples has been a particular strength in its development towards clinical applicates. Its strength in this regard also presents challenges in the development of its diagnostic capabilities owing to its sensitivity, not only to the sample biochemistry, but al...
Molecular communication between irradiated and unirradiated neighbouring cells initiates radiation-induced bystander effects (RIBE) and out-of-field (abscopal) effects which are both an example of the non-targeted effects (NTE) of ionising radiation (IR). Exosomes are small membrane vesicles of endosomal origin and newly identified mediators of NTE...
Activation and proliferation of immune cells such as lymphocytes and monocytes are appropriate inflammatory responses to invading pathogens and are key to overcoming an infection. In contrast, uncontrolled and prolonged activation of these cellular signalling pathways can be deleterious to the body and result in the development of autoimmune condit...
In oesophageal cancer (OC) neo‐adjuvant chemoradiotherapy (neoCRT) is used to debulk tumour size prior to surgery, with a complete pathological response (pCR) observed in approximately ~30% of patients. Presently no predictive quantitative methodology exists which can predict response, in particular a pCR or major response (MR), in patients prior t...
The poster outlined the proposed research of my PhD project which was to investigate the plasmonic behaviour of SERS-active substrates, produced using nanosphere and soft lithography, as a function of the nanostructure shape, size, spacing and composition using scanning probe energy loss spectroscopy (SPELS).
Preliminary SPELS measurements report...
Background
Screening for prostate cancer with prostate specific antigen and digital rectal examination allows early diagnosis of prostate malignancy but has been associated with poor sensitivity and specificity. There is also a considerable risk of over-diagnosis and over-treatment, which highlights the need for better tools for diagnosis of prosta...
The success of radiotherapy in tumour control depends on the total dose given. However, the tolerance of the normal tissues surrounding the tumour limits this dose. It is not known why some patients develop radiation toxicity and, currently, it is not possible to predict before treatment which patients will experience adverse effects. Thus, there i...
Vibrational spectroscopic techniques have recently gained increasing clinical importance as non-invasive, rapid and inexpensive methods to obtain information on the content of biological samples. For some time Raman spectroscopy has been involved in preclinical applications, mainly in the cancer space, with evolving applications towards new horizon...
Genetic and epigenetic profile changes associated with individual radiation sensitivity are well documented and have led to enhanced understanding of the mechanisms of the radiation-induced DNA damage response. However, the search continues to identify reliable biomarkers of individual radiation sensitivity. Herein, we report on a multi-biomarker a...
Haemolysis is a very common phenomenon and is referred as the release of intracellular components from red blood cells to the extracellular fluid. Haemolysed samples are often rejected in clinics due to the interference of haemoglobin and intracellular components in laboratory measurements. Plasma and serum based vibrational spectroscopy studies ar...
Radiation therapy (RT) is used to treat approximately 50% of all cancer patients. However, RT causes a wide range of adverse late effects that can affect a patient’s quality of life. There are currently no predictive assays in clinical use to identify patients at risk of normal tissue radiation toxicity. This study aimed to investigate the potentia...
[This corrects the article DOI: 10.1371/journal.pone.0212376.].
Breast cancer is the most common cancer among women worldwide, with an estimated 1.7 million cases and 522,000 deaths in 2012. Breast cancer is diagnosed by histopathological examination of breast biopsy material but this is subjective and relies on morphological changes in the tissue. Raman spectroscopy uses incident radiation to induce vibrations...
Objective
In 2016 there were an estimated 56,870 new cases of thyroid cancer (TC) in the United States. Fine needle aspiration cytology (FNAC) is the most safe, accurate and cost‐effective method for the initial investigation of thyroid nodules. FNAC is limited by the inability to accurately diagnose malignancy in follicular‐patterned lesions, and...
Purpose: Liquid biopsies are a potentially rich store of biochemical information that can be linked to an individual’s response to therapeutic treatments, including radiotherapy, and which may ultimately play a role in the individualization of treatment regimens. Peripheral blood mononuclear cells (PBMCs) can be used for the biochemical profiling o...
Although formalin fixed paraffin preserved (FFPP) tissues are a major resource for retrospective studies of disease progression, their use in vibrational spectroscopy studies has been undermined by issues of contributions of substrate and paraffin wax which persist in the spectra and can compromise spectral analysis. Recognising the microcrystallin...
Purpose:
RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and...
Extensive research has been undertaken on the examination of tissue biopsies using vibrational spectroscopic techniques. However, fewer studies have focused on less invasive and commonly acquired blood samples. Recent studies have shown the ability of Raman and Fourier transform infrared spectroscopy (FTIR) spectroscopy to discriminate between non-...
Cervical cancer is the fourth most common cancer affecting women worldwide but mortality can be decreased by early detection of pre-malignant lesions. The Pap smear test is the most commonly used method in cervical cancer screening programmes. Although specificity is high for this test, it is widely acknowledged that sensitivity can be poor mainly...
Modern models of radiobiological effects include mechanisms of damage initiation, sensing and repair, for those cells that directly absorb ionizing radiation as well as those that experience molecular signals from directly irradiated cells. In the former case, the effects are termed targeted effects while, in the latter, non-targeted effects. It ha...
The use of Raman spectroscopy to measure the biochemical profile of healthy and diseased cells and tissues may be a potential solution to many diagnostic problems in the clinic. Although extensively used to identify changes in the biochemical profiles of cancerous cells and tissue, Raman spectroscopy has been used less often for analyzing changes t...
Raman microspectroscopy has been investigated for some time for use in label-free cell sorting devices. These approaches require coupling of the Raman spectrometer to complex data mining algorithms for identification of cellular subtypes such as the leukocyte subpopulations of lymphocytes and monocytes. In this study, three distinct multivariate cl...
This chapter outlines some developments in the applications of vibrational spectroscopy for disease diagnostics and demonstrates how the applications of the spectroscopic techniques can be extended to the analysis and evaluation of disease aetiology and the mechanisms of interaction with and the cellular and subcellular responses to, for example, c...
Vibrational spectra of biological species suffer from the influence of many extraneous interfering factors that require removal through preprocessing before analysis. The present study was conducted to optimise the preprocessing methodology and variable subset selection during regression of and confocal Raman microspectroscopy (CRM) and Fourier Tra...
Understanding the interaction of anticancer drugs with model cell lines is important to elucidate the mode of action of these drugs as well as to develop cost effective and rapid screening methods. Raman spectroscopy has been demonstrated to be a valuable technique for high throughput, noninvasive analysis. The interaction of vincristine with a hum...
Advancement of biomedical applications of carbonaceous nanomaterials is hampered by their biopersistence and pro-inflammatory action in vivo. Here, we used myeloperoxidase knockout B6.129X1-MPO (MPO k/o) mice and showed that oxidation and clearance of single walled carbon nanotubes (SWCNT) from the lungs of these animals after pharyngeal aspiration...
Supplemental methods.
(DOC)
Characterization of SWCNT employed in the study. a. Histogram detailing the length distribution of SWCNT. The mean length was determined to be 676±329 nm employing a sample size of 100. The insert depicts a TEM micrograph (500 nm scale bar) for the SWCNT sample. b. Raman spectrum for SWCNT; the D- and G- bands are marked on the spectrum. c. The spe...
Fibrinogen assays are commonly used as part of clinical screening tests to investigate haemorrhagic states, for detection of disseminated intravascular coagulation and as a predictor of a variety of cardiovascular events. The Clauss assay, which measures thrombin clotting time, is the most commonly used method for measuring fibrinogen levels. Never...
Confocal Raman Micro-spectroscopy (CRM) is employed to examine the chemical and physiological effects of anticancer agents, using cisplatin and A549 adenocarcinoma cells as a model compound and test system respectively. Spectral responses of the membrane and cytoplasm of the cell are analysed independently and the results are compared to previously...
Due to its high lateral resolution, Raman microspectrsocopy is rapidly becoming an accepted technique for the subcellular imaging of single cells. Although the potential of the technique has frequently been demonstrated, many improvements have still to be realised to enhance the relevancy of the data collected. Although often employed, chemical fix...
Raman microspectroscopy is a powerful tool for the analysis of tissue sections, providing a molecular map of the investigated samples. Nevertheless, data pre-processing and, particularly, the removal of the broad background to the spectra remain problematic. Indeed, the physical origin of the background has not been satisfactorily determined. Using...
Cervical cancer, a potentially preventable disease, has its main aetiology in infection by high risk human papillomavirus (HR-HPV). Approaches to improving cervical cancer screening and diagnostic methodologies include molecular biological analysis, targeting of biomarker proteins, but also exploration and implementation of new techniques such as v...
The study of the interaction of anticancer drugs with mammalian cells in vitro is important to elucidate the mechanisms of action of the drug on its biological targets. In this context, Raman spectroscopy is a potential candidate for high throughput, non-invasive analysis. To explore this potential, the interaction of cis-diamminedichloroplatinum(I...
Three dimensional collagen gels have been used as matrices for the imaging of live cells by Raman spectroscopy. The study is conducted on a human lung adenocarcinoma (A549) and a spontaneously immortalized human epithelial keratinocyte (HaCaT) cell line. The lateral resolution of the system has been estimated to be <1.5 μm making it possible to acc...
The main aetiology of cervical cancer is infection with high-risk human papillomavirus (HPV). Cervical cancer is almost 100% curable if detected in the early stages. Thus, information about the presence and levels of HPV in patient samples has high clinical value. As current screening methods, such as the Pap smear test, are highly subjective and i...
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Three dimensional collagen gels are evaluated as matrices for the study of live cells by Raman spectroscopy. The study is conducted on a human lung adenocarcinoma (A549) and a spontaneously immortalized human epithelial keratinocyte (HaCaT) cell line. It is demonstrated, using the Alamar Blue assay, that both cell models exhibit enhanced viability...
Vibrational spectroscopy is an attractive modality for the analysis of biological samples, providing a complete non-invasive acquisition of the biochemical fingerprint of the sample. It has been demonstrated that this data provides the means to assay multiple functional responses of a biological system at a spatial resolution as low as a micron wit...
The in vitro study of cellular species using Raman spectroscopy has proven a powerful non-invasive modality for the analysis of cell constituents and processes. This work uses micro-Raman spectroscopy to study the chemical fixation mechanism in three human cell lines (normal skin, normal bronchial epithelium, and lung adenocarcinoma) employing fixa...
The scientific literature contains an ever-growing number of reports of applications of vibrational spectroscopy as a multivariate non-invasive tool for analysis of biological effects at the molecular level. Recently, Fourier transform infrared microspectroscopy (FTIRM) has been demonstrated to be sensitive to molecular events occurring in cells an...
Vibrational spectroscopy (Raman and FTIR microspectroscopy) is an attractive modality for the analysis of biological samples since it provides a complete non-invasive acquisition of the biochemical fingerprint of the sample. Studies in our laboratory have applied vibrational spectroscopy to the analysis of biological function in response to externa...
In this study the suitability of Raman spectroscopy for the determination of carbon nanotube mediated toxicity on human alveolar carcinoma epithelial cells (A549) is explored. The exposure of this cell line represents the primary pathway of exposure in humans, that of inhalation. Peak ratio analysis demonstrates a dose-dependent response which corr...
Cervical cancer is the second most common cancer in women worldwide with 80% of cases arising in the developing world. The mortality associated with cervical cancer can be reduced if this disease is detected at the early stages of development or at the pre-malignant state (cervical intraepithelial neoplasia, CIN). The aim of this study was to inves...
Non-invasive measurements of cellular function in in vitro cultured cell lines using vibrational spectroscopy require the use of spectroscopic substrates such as quartz, ZnSe and MirrIR etc. These substrates are generally dissimilar to the original in vivo extracellular environment of a given cell line and are often tolerated poorly by cultured cel...
Raman spectroscopy, as an evaluation of the products of ionising radiation exposure in biological systems, has been utilised mainly in the evaluation of the impact of exposure in tissue, cellular constituents and live animals. It has also been recently demonstrated that Raman spectroscopy can demonstrate key spectroscopic changes in the live cell a...
There are numerous methods for assessing image quality in diagnostic X ray. In our study we assessed how imaging quality assurance
methods perform in practice. Physics assessments were based on IPEM protocols using Leeds test objects. Clinical assessment
was based on a questionnaire. A total of 15 systems in three European locations were assessed,...