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Cubis, Lee M. "Staying Connected after Brain Tumour: Changes in Social Networks and Relationship to Wellbeing after Brain Tumour." Thesis, Griffith University, 2020. http://hdl.handle.net/10072/395565.
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People with primary brain tumour typically experience high levels of functional impairment with an uncertain and often poor prognosis. Outcome studies highlight that up to 48% of people with brain tumour experience clinical levels of psychological distress that can persist throughout the course of living with the illness. Strong social ties can protect against the adverse effects of chronic illness on psychological wellbeing; however, the functional impairments associated with brain tumour can affect relationships and reduce social participation. There is currently poor understanding of the impact of primary brain tumour on social participation, and how social networks influence wellbeing for this population.
Comprising four studies, the broad objective of this thesis was to advance understanding of the impact of brain tumour on social groups and the implications for psychological wellbeing.
Study 1 employed a cross-sectional design to investigate how social group memberships influence the relationship between subjective functional impairment and psychological wellbeing. Seventy adults (60% female; aged 22-75 years) with primary brain tumour (46% benign; 18% low-grade; 36% high-grade) undertook a telephone-based assessment including self-report measures of cognitive and physical impairment, social group memberships, confidence in support, and psychological wellbeing. Higher functional impairment was associated with a loss of pre-existing social groups which, in turn, was associated with greater depression and anxiety symptoms. Further, confidence in social groups moderated the relationship between functional impairment and psychological wellbeing. Specifically, those perceiving high levels of functional impairment who had high confidence in their social groups reported lower depression and anxiety than those who had low confidence in their social groups.
Study 2 involved a meta-synthesis that aimed to identify, appraise and integrate the findings of qualitative studies that reveal the impact of brain tumour on social networks. The findings of 21 eligible studies were synthesised to reveal three core themes depicting the social trajectory of living with brain tumour: 1) Life disrupted; 2) Navigating the new reality of life; and 3) Social survivorship versus separation. The findings of the meta-synthesis highlighted that changes to social participation commonly occurred throughout the illness including a loss of pre-existing social networks and the emergence of new ones. This review identified a need for further qualitative research to understand how brain tumour affects peoples’ ability to maintain and/or rebuild social networks, and how social networks influence psychological wellbeing.
Studies 3 and 4 employed a phenomenological qualitative methodology to explore the lived experience of the social and psychological impacts of brain tumour. Twenty participants (65% female; aged 22-69 years) were purposively selected from the Study 1 sample (N = 70) according to the following characteristics: type and grade of brain tumour (i.e., benign, low grade glioma, malignant/high grade glioma); sex; age (<40, 40-55, >55 years) and time since diagnosis (≤ 24 months or >24 months). Two interviews, three months apart, comprised a Social Identity Mapping exercise (Cruwys et al., 2016) and semi-structured interview exploring changes in social groups and the impact of social groups on psychological wellbeing.
Study 3 aimed to understand how brain tumour influences peoples’ ability to manage, maintain, and rebuild their social networks. The main research questions were: 1) how does brain tumour affect people’s ability to stay connected to their social groups? and 2) how do they manage to stay connected or build new connections despite their functional impairments? Two overarching and interrelated themes emerged: engaging and connecting and then versus now. Many individuals experienced significant barriers to social participation including functional impairments, fear of negative evaluation and attributions about the discomfort of others. The ability to harness facilitators and/or develop strategies to overcome these barriers influenced whether individuals experienced stability, maintenance and expansion, loss and rebuilding, or loss and shrinkage of their social networks over time. Study 4 aimed to explore the meaning and functions of social groups, and how these influence wellbeing after brain tumour. The main research questions were: 1) what are the meaning and functions of social groups after brain tumour? and 2) how do individuals perceive that social groups influence their wellbeing? Two major themes emerged relating to the ways in which social groups contribute to and/or detract from wellbeing. The first theme, feeling understood and fulfilled by social groups, depicted perceptions of social groups as positively contributing to wellbeing and sense of identity. The second theme, feeling disappointed in, devalued or drained by social groups, highlighted ways in which social groups detract from wellbeing.
Overall, this thesis advances understanding of how primary brain tumour affects people’s ability to stay connected to their social networks and how social groups influence wellbeing. Specifically, Study 1 highlighted both mediating and moderating pathways through which social groups can influence the relationship between functional impairments and psychological wellbeing. Study 2 yielded a novel framework depicting the changes in social roles and relationships across the trajectory of living with brain tumour. Study 3 highlighted that an interplay of barriers, facilitators and strategies influence people’s ability to manage, maintain and/or rebuild social networks after brain tumour. Study 4 revealed that social networks can both contribute to and detract from psychological wellbeing after brain tumour. Collectively, these findings highlight the need for supportive care interventions to focus on enhancing social participation as an avenue for improving psychological wellbeing after brain tumour.Thesis (Professional Doctorate)
Doctor of Philosophy in Clinical Psychology (PhD ClinPsych)
School of Applied Psychology
Griffith Health
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Zumel, Marne María Ángela 1984. "Environmental factors and brain tumour risk in young people." Doctoral thesis, Universitat Pompeu Fabra, 2019. http://hdl.handle.net/10803/668182.
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Risk factors and diagnosis in young people have been little explored, despite brain tumours (BT) is one of the most frequent tumour type in children and adolescents. The purpose of this doctoral thesis is to study 1) the clinical characteristics and symptoms of BTs in young people, based on the international MOBI-Kids case-control study; 2) a systematic review (SR) of the literature on risk of BTs in young people in relation to environmental factors; 3) the BT risk in relation to chemicals present in drinking water and to heavy metals.
The analyses of clinical characteristics revealed that the vast majority of tumours were neuroepithelial (mostly gliomas), followed by embryonal tumours and meningiomas. Overall, the most frequent symptoms were headache, followed by focal neurological signs and symptoms, nausea/ vomiting and visual signs and symptoms, being a 4% of the cases asymptomatic. The average time of diagnosis tended to be short (median 1.42 months), though this varied according to tumour type, age and type of symptom.
I found many studies that showed an association between environmental factors (including tobacco smoke, pesticides and diet, among other exposures) and BT risk in the SR. Because of methodological limitations however, the evidence about the role of these factors in the aetiology of this disease is still uncertain.
Our analyses in relation to water chemicals showed ORs below 1 for exposures to THMs, and ORs above 1 for nitrate exposure, for both pre- and postnatal exposure periods, some statistically significant so. Our analyses of heavy metals showed ORs below 1for exposures to chromium. However, literature is scarce about this association.
Overall, this thesis served to fill a gap in knowledge concerning 1) the clinical characteristics of BT in young people, useful to both clinical practice and aetiological research; 2) causes of this disease; 3) the role of heavy metals and ubiquitous chemicals in water. Further research needs on the aetiology and prevention of BTs in young people are provided.Los factores de riesgo y el diagnóstico en los jóvenes han sido poco explorados, a pesar de que los tumores cerebrales (TC) son uno de los tipos de tumores más frecuentes en los niños y jóvenes. El propósito de esta tesis doctoral es el estudio de 1) de las características clínicas y los síntomas de los TC en los jóvenes, basados en el estudio internacional de casos y controles MOBI-Kids; 2) una revisión sistemática de la literatura sobre el riesgo de TC en jóvenes en relación con factores ambientales; 3) el riesgo de TC en relación con los productos químicos presentes en el agua potable y con los metales pesados. Los análisis de las características clínicas revelaron que la gran mayoría de los tumores eran neuroepiteliales (principalmente gliomas), seguidos de tumores embrionarios y meningiomas. En general, los síntomas más frecuentes fueron dolor de cabeza, seguido de signos y síntomas neurológicos focales, náuseas/ vómitos y problemas en la visión, siendo un 4% de los casos asintomáticos. El tiempo promedio de diagnóstico tendió a ser corto (mediana 1,42 meses), aunque esto varió según el tipo de tumor, la edad y el tipo de síntoma. Encontré muchos estudios que encontraron asociación entre los factores ambientales (incluido el humo del tabaco, los pesticidas y la dieta, entre otras exposiciones) y el riesgo de TC en la revisión sistemática. Sin embargo, debido a limitaciones metodológicas, la evidencia sobre el papel de estos factores en la etiología de esta enfermedad aún es incierta. Nuestros análisis en relación con los productos químicos del agua mostraron unos OR por debajo de 1 para exposiciones a THMs, y OR por encima de 1 para exposición a nitrato, tanto en períodos de exposición prenatales como postnatales, algunos estadísticamente significativos. Nuestros análisis de metales pesados mostraron ORs por debajo de 1 para la exposición al cromo. Sin embargo, la literatura es escasa sobre esta asociación. En general, esta tesis sirvió para llenar un vacío en el conocimiento sobre 1) las características clínicas de la TC en los jóvenes, útiles tanto para la práctica clínica como para la investigación etiológica; 2) causas de esta enfermedad; 3) el papel de los metales pesados y los químicos ubicuos en el agua. Se ha identificado la necesidad de realizar más investigaciones sobre la etiología y la prevención de las TC en los jóvenes.
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Richards, R. "Understanding the role of the solid tumour microenvironment in brain tumour progression." Thesis, University of Liverpool, 2017. http://livrepository.liverpool.ac.uk/3005579/.
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Glioblastoma (GBM) is the most common malignant brain tumour and has an extremely poor prognosis. The invasion of tumour cells into normal brain tissue makes complete surgical removal impossible; GBM is also resistant to treatment with chemotherapy and radiotherapy. Our aim was to investigate how GBM cell proliferation, survival and invasion is affected by the solid tumour microenvironment. Although GBM is highly vascularised, the abnormal structure and function of tumour blood vessels results in an inadequate supply of oxygen (hypoxia). Hypoxia is known to promote tumour progression; however, the effect of hypoxia on cell proliferation has not been well characterised. We performed a systematic investigation into the effects of different oxygen levels on the cell cycle. In contrast to the prevailing hypothesis, we found that long-term exposure to pathophysiological levels of hypoxia (1–8% O2) does not affect cell proliferation and viability and that even severe hypoxia (0.1% O2) has only minimal effects. We next sought to characterise the effect of hypoxia in multicellular tumour spheroids: 3D cell clusters that replicate important aspects of the tumour microenvironment. We characterised spheroids in terms of proliferation, survival and oxygenation and found that, in this more complex model, hypoxia was associated with reduced proliferation. We then used spheroids to develop a novel method for imaging cellular migration and invasion in 3D using lightsheet fluorescence microscopy (LSFM). We imaged spheroids over 24 h and then quantified the movements of up to 1200 cells per spheroid in terms of speed and straightness of movement. We were able to compare the movement of cells in different regions of spheroids, gaining insight into the behaviour of quiescent cells in the core of large (~500 μm), heterogeneous spheroids that had been exposed to hypoxia. This technique can be used to investigate the effect of the tumour microenvironment on cell motility and to gain insight into the mechanism of drugs that hinder the process of invasion.
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Pedapati, Praveena, and Rama Vaishnavi Tannedi. "BRAIN TUMOUR DETECTION USING HOG BY SVM." Thesis, Blekinge Tekniska Högskola, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-15905.
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Detection of a brain tumour in medical images is always a challenging task. Factors like size, shape, and position of tumour vary from different patient’s brain. So, it's important to know the exact shape, size and position of a tumour in the brain making it a challenging task for detection. Some patients exhibit high glioma (HG) type tumor while others show low glioma (LG) type. So, knowing the detailed properties of a tumour to detect them in medical images is mandatory. So far many algorithms have been implemented on how to detect and extract the tumours in medical images, they used techniques such as hybrid approach with support vector machine (SVM), back propagation and dice coefficient. Among these algorithm which used back propagation as base classifier had a highest accuracy of 90%. In this work feature extraction of the medical images of patients’ tumors in database is extracted using Histogram of Oriented Gradient, later these images are classified into tumor and non tumor images using SVM. The detection of brain tumours in patient’s image is achieved by testing the performance of SVM based on Receiver Operating Characteristics (ROC). ROC include true positive rate, true negative rate, false positive rate and false negative rate. Using ROC we calculated accuracy, sensitivity and specificity values for all the medical images of the database. For image data folder of HG in vector form, SVM gave an accuracy of 97% for 95th slice of T1 modality with high true positive rate of 0.97 remaining highest among other modalities. Whereas SVM gave an accuracy of 87% for 135th slice of T1 modality with high true positive rate of 0.8 and low false positive rate of 0.06 among other image data folder of HG. For image data folder of LG, SVM gave an accuracy of 62% for the 90th slice of FLAIR modality with the high true positive rate of 0.5 and low false positive rate of 0.25 among all others. For synthetic data folder of HG, SVM gave an accuracy of 62% for a 100th slice of FLAIR modality with the high true positive rate of 0.5 and low false positive rate of 0.06 among all others. For synthetic data folder of LG, SVM gave an accuracy of 62% for a 100th slice of FLAIR modality with the high true positive rate of 0.5 and low false positive rate of 0.06 among all others.
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Jaroudi, Rym. "Inverse Mathematical Models for Brain Tumour Growth." Licentiate thesis, Linköpings universitet, Tekniska fakulteten, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-141982.
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We study the following well-established model of reaction-diffusion type for brain tumour growth:
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Jordaan, Carike. "The relationship between tumour characteristics, depressive symptoms, and neuropsychological profiles in brain tumour patients." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/96700.
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Thesis (MA)--Stellenbosch University, 2015ENGLISH ABSTRACT : Worldwide there are various reports on the prevalence of depression in patients diagnosed with brain tumours. In South Africa, psychological research in relation to psychiatric symptoms among patients with brain tumours is lacking. The aims of this study were to determine the incidence of depression in patients diagnosed with brain tumours and to clarify our understanding of the relationship between depression and tumour localisation, histopathological type of tumour, and participant characteristics. The study sample consisted of 35 patients (11 males and 24 females) aged between 21 and 64 years with a solitary primary brain tumour. The patients were treated at the neurosurgery clinics located at Tygerberg Hospital in the Western Cape and Universitas Hospital in the Free State between mid-2010 and 2013. The major histological subgroup consisted of meningiomas (47%), glioblastomas (22%), astrocytomas (19%), gliomas (9%) and epidiomas (3%). The tumour distribution was as follows: 52% in the left hemisphere, 37% in the right hemisphere, and 11 % in the midline. The psychiatric symptoms of the patients were assessed before treatment by the Beck Depression Inventory and Mini International Neuropsychiatric Interview. In addition, the patients’ neuropsychological functions were evaluated by a short neuropsychological test battery (Mini Mental State Examination, Trail Making Test (Part A), Letter Number Sequencing subtest, Hopkins Verbal Learning Test – Revised, and Brief Visuospatial Memory Test – Revised). Results from the quantitative data, showed the prevalence of mild depression was 26% for men and 43% for women. Overall 37% of the total sample had depressive symptoms. No significant relationship was found between depression and tumour location or between the various neuropsychological characteristics and neurological symptoms and tumour location. The study showed that depression is a common symptom in patients diagnosed with brain tumours and therefore depression symptoms have to be recognised and treated by psycho-educating the patients and their families, pharmacotherapy, or psychotherapy as soon as possible. However, due to the relatively small sample size, the results are of limited generalisability.
AFRIKAANSE OPSOMMING : Wêreldwyd is daar verskeie verslae oor die voorkoms van depressie in pasiënte gediagnoseer met breingewasse. In Suid-Afrika is daar ’n tekort aan sielkundige navorsing met betrekking tot psigiatriese simptome by pasiënte. Die doel van hierdie studie was om die voorkoms van depressie te bepaal in pasiënte gediagnoseer met breingewasse en om duidelikheid te kry oor die verband tussen depressie en die ligging van breingewasse, histopatologiese tipe gewas en karakter eienskappe van die deelnemers. Die steekproef van die studie het bestaan uit 35 pasiënte (11 mans en 24 vroue) tussen die ouderdomme 21 en 64 jaar met ‘n soliede breingewas. Die pasiënte is behandel by die neurochirurgiese klinieke by Tygerberg Hospitaal in die Wes-Kaap en by Universitas Hospitaal in die Vrystaat vanaf middel 2010 tot 2013. Die mees algemene histologiese subgroep het bestaan uit meningiome (47%), glioblastomas (22%), astrocytomas (19%), gliomas (9%) en epidiomas (3%). Die verspreiding van die gewasse was soos volg: 52% in die linkerhemisfeer, 37% in die regterhemisfeer en 11% in die middel. Die psigiatriese simptome van die pasiënte is voor behandeling geëvalueer met behulp van die Beck Depression Inventory en die Mini International Neuropsychiatric Interview. Bykomend is die pasiënte se neurosielkundige funksies geëvalueer met behulp van ‘n neurosielkundige toetsbattery (Mini Mental State Examination, Trail Making Test (Part A), Letter Number Sequencing subtest, Hopkins Verbal Learning Test – Revised en Brief Visuospatial Memory Test – Revised). Die resultate van die kwantitatiewe data het getoon die voorkoms van matige depressie was 26% vir mans en 43% vir vroue. In geheel het 37% van die totale steekproef depressiewe simptome getoon. Daar was geen beduidende verhouding tussen depressie en die ligging van die gewas of tussen die verskeie neurosielkundige eienskappe en die ligging van die gewas nie. Die studie het getoon dat depressie ’n algemene simptoom is in pasiënte gediagnoseer met breingewasse en daarom moet depressiewe simptome herken en so gou as moontlik behandel word deur psigo-opvoeding van die pasiënte en hul familie, farmakoterapie of psigoterapie. As gevolg van die relatiewe klein steekproef grootte het die resultate ’n beperkte veralgemeenbaarheid.
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Christidou, Maria. "The role of flavonoids on brain tumour invasion." Thesis, King's College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414780.
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Li, Xiaofei. "The IL-33/ST2 pathway in CNS : Traumatic brain injury and brain tumour." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-183937.
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Interleukin 33 (IL-33) is a dual function cytokine. It is a member of the IL-1 family and it acts as a pro-inflammatory factor (18 kilo Dalton, 18 kD) like other cytokines in IL-1 family. IL-33 is also a transcription factor (32 kD - form) which can suppress or activate gene transcription in diverse cases. A variety of cell types and tissues in the central nervous system (CNS) can release IL-33 after injury. The 18 kD IL-33 binds to the membrane receptor protein ST2 ligand, then regulates downstream gene expression, triggers cytokine synthesis, and modulates the immune system response. After traumatic brain injury (TBI) in the CNS, glial cells become key players in the nervous tissue response. Astrocytes undergo activation, proliferation, release pro-inflammatory factors and, as a consequence, a glial scar barrier around the injury is formed. Simultaneously, resting microglia are activated and able to remove debris. Lastly, oligodendrocytes together with microglia and astrocytes are activated and communicate with the immune system. In addition, as a severe kind of injury to the CNS, brain tumours share some similar characteristics of brain injury, such as hypoxia and inflammation. Therefore, IL-33 may play a role in neuroinflammation and also in brain tumours. In this project, our aim was to investigate the role of IL-33 and the IL-33/ST2 pathway in traumatic brain injury and brain tumours (e.g glioma). We found that IL-33 can influence the CNS immune resonse, and may be important in CNS pathology.
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Shen, Shan. "MRI brain tumour classification using image processing and data mining." Thesis, University of Strathclyde, 2004. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=21543.
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Detecting and diagnosing brain tumour types quickly and accurately is essential to any effective treatment. The general brain tumour diagnosis procedure, biopsy, not only causes a great deal of pain to the patient but also raises operational difficulty to the clinician. In this thesis, a non-invasive brain tumour diagnosis system based on MR images is proposed. The first part is image preprocessing applied to original MR images from the hospital. Non-uniformed intensity scales of MR images are standardized relying on their statistic characteristics without requiring prior or post templates. It is followed by a non-brain region removal process using morphologic operations and a contrast enhancement between white matter and grey matter by means of histogram equalization. The second part is image segmentation applied to preprocessed MR images. A new image segmentation algorithm named IFCM is developed based on the traditional FCM algorithm. Neighbourhood attractions considered in IFCM enable this new algorithm insensitive to noise, while a neural network model is designed to determine optimized degrees of attractions. This extension can also estimate inhomogenities. Brain tissue intensities are acquired from segmentation. The final part of the system is brain tumour classification. It extracts hidden diagnosis information from brain tissue intensities using a fuzzy logic based GP algorithm. This novel method imports a fuzzy membership to implement a multi-class classification directly without converting it into several binary classification problems as with most other methods. Two fitness functions are defined to describe the features of medical data precisely. The superiority of image analysis methods in each part was demonstrated on synthetic images and real MR images. Classification rules of three types and two grades of brain tumours were discovered. The final diagnosis accuracy was very promising. The feasibility and capability of the non-invasive diagnosis system were testified comprehensively.
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Mcgahan, Jennifer Anne. "Exploring memory and memory rehabilitation in paediatric brain tumour survivors." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/exploring-memory-and-memory-rehabilitation-in-paediatric-brain-tumour-survivors(194abbcb-6a1a-47aa-bbe7-8cca023f659f).html.
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This collection of studies begins by exploring the development of recognition memory in a group of healthy children and adolescents using experimental memory tests developed as part of this thesis. Various versions of these recognition memory tests were trialled in order to establish age appropriate tests for children aged 6-14 years. In keeping with previous literature in this area, these tests showed relatively stable familiarity memory throughout childhood compared to a steep developmental course for recollection memory. Paediatric brain tumour survivors are known to suffer from significant memory deficits following treatment. However, a clear description of this clinical group’s deficits, in terms of recognition and recall (and therefore also familiarity and recollection), has not previously been established. Using standard clinical memory assessments, the current body of work contributes to this area by characterising this population’s memory deficits as primarily recall-based, particularly when recalling information presented as prose. A sex difference is also noted; with female brain tumour survivors being significantly more impaired than their age-matched male counterparts. This finding is discussed with respect to the differing neural development of males and females. The experimental memory tests developed with normal children were also administered to a group of paediatric brain tumour patients. They were found to have a varied pattern of performance, including auditory recognition impairments but intact visual recognition, even when the test format incorporated similar foils. Associative memory tests revealed impairments in recollection-based recognition; this effect was dependant on the type of information being associated and the length of the encoding-test delay. A learning intervention was developed (and trialled with healthy children), using a method known as the ‘testing effect’, in an attempt to enhance recall of prose at long delays in a group of paediatric brain tumour survivors. Structured repeated retrieval was compared to repeated study for prose passages. This was found, with some patients, to be a successful method of improving recall after a delay of one week. Taken together, the work described in this thesis provides further understanding of recognition memory development in healthy children, novel insights into the residual memory function of paediatric brain tumour survivors and an exciting foundation on which to build a rehabilitation programme for this vulnerable group.
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Pigot, T. J. D. "Clinical and cellular prognostic variables in glioblastoma multiforme." Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.277401.
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Grant, John William. "Immunohistochemistry in the diagnosis and characterisation of neoplasms affecting the central nervous system." Thesis, University of Aberdeen, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278778.
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This work describes 5 groups of tumours seen in routine neuropathological practice in Southampton between 1980 and 1986. The clinical and light microscopic findings in a total of 44 tumours are described. A panel of monoclonal and polyclonal antibodies was used in immunohistochemical studies on each group, and this made important contributions to the diagnosis and characterisation of these tumours. Six primary central nervous system lymphomas were shown to be 5 follicle centre cell lymphomas (Kiel-classification) and 1 T-cell lymphoma. 15 lymphomas causing spinal cord compression were typed as 11 follicle centre cell lymphomas, 3 T-cell lymphomas and 1 lymphoblastic lymphoma. T-cell lymphomas appear to be more likely to be localised in the spine and to have a better prognosis. In all these tumours admixed reactive cell populations were also identified immunohistochemically. Ten primitive neuroectodermal tumours of the cerebrum were examined and immunohistochemistry assisted in their distinction from lymphoma and metastatic carcinoma. It also showed evidence of differentiation in apparently poorly differentiated parts of the tumours. Immunohistochemical studies facilitated the distinction of pleomorphic xanthoastrocytoma from a monstrocellular astrocytoma and a meningeal malignant fibrous histiocytoma. The recognition of this first entity has important prognostic implications. In 10 cerebellar haemangioblastomas a panel of antibodies was used to investigate the histogenesis of the stromal cell component of these tumours. Endothelial and stromal cells were found to be antigenically distinct and neurone specific enolase activity was found in the latter. The implications of this finding are discussed. The studies confirm the important and increasing role played by immunohistochemistry in our understanding of central nervous system neoplasia.
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Thwaites, Charlene Louise. "Neural correlates of verbal fluency and associations with demographic, mood, cognitive and tumour factors in brain tumour patients." Thesis, University of Leeds, 2018. http://etheses.whiterose.ac.uk/22711/.
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Verbal fluency tests are one of the most commonly used measures of executive functioning in neuropsychological testing and play an important role in the assessment, diagnosis and care planning of patients with a variety of conditions, including brain tumour. There is little conclusive evidence about which factors may influence verbal fluency outcomes. No studies to date have investigated the interactions between a comprehensive range of demographic variables, mood scores, tumour factors and key cognitive skills with the focus of verbal fluency outcomes in brain tumour patients. Similarly, clarification is required across studies assessing the localisation effects of verbal fluency skills. To address these gaps in the evidence base this study used a retrospective cohort design of cross-sectional data from patients with brain tumours, to investigate their performance of both phonemic and semantic verbal fluency. More specifically this study used simple linear and multiple regression calculations to analyse the interactions between these variables and other potentially important factors such as localisation, depression and anxiety (using the HADS), age, gender, education, premorbid functioning (using the TOPF), semantic memory (using the GNT), and tumour type. The results showed that an increase in phonemic fluency performance was significantly correlated with being educated, an increase in semantic memory, and an increase in premorbid functioning. Phonemic fluency was also significantly correlated with localisation. In general, a decrease in phonemic fluency was significantly associated with tumours in the left frontal lobe. An increase in semantic fluency was correlated with an increase in semantic memory. No other factors showed significant associations with phonemic or semantic fluency. The outcomes from the hierarchical multiple regressions indicated that localisation, gender, education, tumour type, depression, semantic memory, and premorbid functioning when combined can predict phonemic fluency variance. Combining localisation effects, semantic memory, depression and education together do not result in a model that predicts semantic fluency, as within this model the only significant relationship was between semantic memory and semantic fluency. These findings show that, for brain tumour patients, it is important to take into consideration tumour localisation, education, semantic memory, and premorbid functioning when assessing and care planning for deteriorations in phonemic fluency. Similar patients with deteriorations in semantic fluency need to have their results considered in light of performance in semantic memory tests.
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Bennett, Emily. "Predicting parenting stress in caregivers of children treated for brain tumour." Thesis, University of Nottingham, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.537800.
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Pauly-Takacs, Katalin. "Learning and episodic memory following childhood brain tumour : a case study." Thesis, University of Leeds, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.590298.
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This thesis presented the case of an adolescent boy, CJ (age at diagnosis: 11: 1 0 years, age range at time of assessment: 13:07 - 16:08), who became amnesic as a consequence of a metastatic central nervous system malignancy and subsequent treatment. Survivors of childhood brain tumours often acquire complex cognitive difficulties, however, extreme memory disorders consistent with an amnesic condition are rarely reported in this clinical population. Neuropsychological assessment of CJ indicated a profound and global memory impairment in the context of well preserved premorbid semantic knowledge and verbal skills (Chapter 2). Thus, CJs neuropsychological profile afforded questions relevant to the fractionation of human memory from a functional perspective. A central question of the research presented here was whether CJs amnesia could be described in classic dichotomies of long-term memory. The experiments presented in this thesis adopted a classical neuropsychology framework to examine episodic and semantic memory with particular attention to relative preservation of function. Throughout this thesis CJ's performance was compared to a carefully selected group of control participants. Results showed that CJ was capable of demonstrating novel semantic learning in the absence of a functional episodic memory system (Chapter 2). Related to this, the focus of Chapter 3 was to ascertain Cl's deficit in contextual memory relative to item memory. Consistent with the adult amnesia literature, CJ was generally able to report whether or not an item was presented, however, he permanently failed at accurately reporting the source characteristics of the learning episode. A number of experiments demonstrated that CJ was unable to benefit from encoding conditions that facilitate elaborative processing, including self-generation (Chapter 4) and deeper semantic processing (Chapter 5; Chapter 6). He did however learn semantically related materials more effectively, and was also able to build up a strong gist representation based on pre-existing semantic relationships (Chapter 5). An emergent finding of this thesis is that CJ's memory largely relies on automatic processes in the complete absence of recollection (Chapter 6). Consistent with this, his memory was best under conditions where gains in performance could be achieved through fluent processing (Chapter 6) and implicit memory (Chapter 7). Results are discussed in terms of contemporary dichotomies of long-term memory and clinical relevance. Finally, future directions for research in the growing field of neuropsycho-oncology are outlined.
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Choy, Catherine Theresa. "Kallmann syndrome-associated protein anosmin-1 contributes to brain tumour malignancy." Thesis, St George's, University of London, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.656859.
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Anosmin-l, encoded by KALl gene, is an extracellular matrix (ECM)-associated protein, which plays essential roles in the migration of olfactory and gonadotropinreleasing hormone (GnRH) neurons during early brain development. Loss-of-function mutations in KALl result in Kallmann syndrome, a developmental genetic disorder with delayed puberty and anosmia. However, there is little comprehension of its role in the developed brain. Since reactivation of developmental signal pathways often contributes to tumourigenesis, I investigate if anosmin-l-mediated cellular mechanisms are involved in brain tumours. Meta-analysis of public microarray data sets and expression profile analysis of patient biopsy samples revealed that KALl mRNA was significantly upregulated in increasing grades of primary brain tumours compared to normal brain and metastasised tumours. Anosmin-l enhanced motility and proliferation of glioblastoma (GBM) cells via fibroblast growth factor receptor 1 (FGFR 1) and urokinase plasminogen activator (uPA) pathways in vitro. Anosmin-l formed a complex with ~l integrin and co-localised with active ~ 1 at the leading edge of GBM cells, inducing downstream signalling pathways including focal adhesion kinase (F AK), protein kinase B (PKBI AKT) and extracellular signal regulated kinase (ERK). Knockdown of anosmin-l attenuated cellular motility and growth but induced apoptosis. Anosmin-l also modulated fibronectin-mediated cell adhesion and activated extracellular proteinases uPA and matrix metalloproteinases (MMP)-2/9. Anosmin-l showed pro-angiogenic effects in endothelial cell culture. Combined, anosmin-l may promote GBM cell proliferation, migration, invasion, adhesion and survival. In a mouse xenograft model, anosmin-l-expressing tumours grew faster and showed increased vasculature and infiltrations. To predict the localisation of anosmin-l and its interact ants within the tumour architecture, the xenograft tissues were analysed by immunohistological methods. These studies provided novel insights for the function of anosmin-l within the tumour microenvironment, contributing to the neoplastic progression. Therefore, anosmin-l is required for normal GnRH neuronal migration, but inappropriate expression in adult brain may be a potential mechanism of malignant brain tumours.
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Bruce, M. "Posttraumatic stress symptoms in childhood brain tumour survivors and their parents." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445380/.
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Recent years have witnessed a rapid acceleration in the recognition and documentation of Posttraumatic Stress Disorder (PTSD) and posttraumatic stress symptomatology (PTSS) in childhood cancer survivors and their parents. However, the applicability of PTSD both diagnostically and conceptually to cancer-related traumatic responses remains poorly articulated within the current literature. Following an outline of childhood cancer and PTSD, this paper critically examines the applicability of such a diagnosis to this clinical population. It then systematically reviews the current evidence base (24 studies) on PTSD and PTSS in childhood cancer survivors and their parents. Prevalence of PTSD and PTSS, as well as number of correlates, varies widely in this clinical population. Findings are considered in the light of a number of contemporary theories of PTSD. Limitations within current conceptualisations of PTSD are highlighted with respect to the nature of cancer as a traumatic event and the specific features of traumatic stress manifestations in childhood cancer survivors and their parents. Finally, a number of pertinent research areas are elucidated which are argued to warrant further investigation.
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Jaworek, Karolina. "Screening for novel brain tumour initiation mechanisms at single cell resolution." Thesis, Bangor University, 2016. https://research.bangor.ac.uk/portal/en/theses/screening-for-novel-brain-tumour-initiation-mechanisms-at-single-cell-resolution(3bb44859-bc78-4fce-a7df-0f47d2dd6b4e).html.
Full textAbstract:
Despite progress in our understanding of origin and development of brain tumours, more efficient therapeutic approaches addressing the high recurrence rate and poor prognosis of brain tumours remain urgently needed, in particular for the most aggressive glioblastomas (GBMs). In this work, I used the Drosophila brain tumour (brat) mutant as an in vivo model to identify potential mechanisms of brain tumour initiation. The human brat orthologue, Trim3, has a conserved tumour suppressor function in GBMs. I applied a single cell transcriptome microarray technique to compare intermediate neural progenitor cells harvested from live brat versus control larval brains, at a developmental stage when the first signs of molecular transformation into tumour initiation cells are observed in the mutants but no over-proliferation can yet be detected. I identified 1132 transcripts differentially expressed (threshold: -0.5Log2FC0.5). My gene ontology-based analysis revealed that metabolic pathways, RNA processing and protein synthesis are among the most represented functional categories. I validated the screen data via qPCRs, and translated gene expression findings into human GBM tissues and cell lines. I found 21 out of 24 human orthologue transcripts tested to be also differentially expressed in GBMs compared to control human brain tissues, suggesting the possibility of conserved roles. Finally, I examined in more detail selected individual transcripts. Of note, I showed that loss of two candidates found upregulated in brain tumour initiation cells and in GBMs, mob3 and l(2)k09022, causes severe impairment of normal postembryonic neural stem cell proliferation. I also demonstrated that another candidate, YME1L1, which contributes to mitochondrial proteostasis and respiration, is up regulated in tumour initiation cells and in GBMs at both mRNA and protein levels, suggesting it may promote tumour initiation by altering mitochondria function. In summary, the work I developed lays an original foundation for future studies of brain tumour initiation mechanisms.
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De, Mattos Arruda Leticia. "Genomic characterisation of brain malignancies through liquid biopsies: The cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/394019.
Full textAbstract:
Los recientes avances en la secuenciación masiva en paralelo y en las técnicas genómicas digitales apoyan la validez clínica del ADN libre tumoral circulante (ctDNA) como una "biopsia líquida” en el cáncer humano. La presencia de ctDNA en el plasma puede ser útil para identificar alteraciones genómicas, monitorizar la respuesta al tratamiento, identificar la resistencia terapéutica, y potencialmente caracterizar la heterogeneidad del tumor.
El estudio de prueba de concepto en el campo de las biopsias líquidas titulado “Capturing intra-tumor genetic heterogeneity by de novo mutation profiling of circulating cell-free tumor DNA: a proof-of-principle” publicado en la revista Annals of Oncology en julio de 2014, es el artículo complementario analizado en esta tesis. Este artículo es uno de los primeros en demostrar que la secuenciación masiva en paralelo del ctDNA derivado del plasma constituye una herramienta potencial para la identificación y el seguimiento de las alteraciones genómicas somáticas durante el curso de la terapia dirigida, y que esta herramienta no invasiva se puede emplear para superar los retos planteados por la heterogeneidad del tumor.
El ctDNA derivado del plasma ha demostrado ser capaz de identificar las alteraciones genómicas de los pacientes con cáncer. Sin embargo, los pacientes con tumores cerebrales tienen cantidades bajas o indetectables de ctDNA en el plasma lo que excluye la caracterización genómica del cáncer de cerebro a través del ctDNA en el plasma. La prueba de concepto en el campo de las biopsias líquidas del sistema nervioso central, que es el artículo fundamental analizado en este tesis: “Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma”, fue publicado en Nature Communications en noviembre de 2015. El ctDNA derivado de tumores malignos del sistema nervioso central primario y secundario esta enriquecido en el líquido cefalorraquídeo (LCR) y retrata las alteraciones genómicas de las enfermedades del sistema nervioso central mejor que el plasma. Los niveles de CSF ctDNA fluctúan longitudinalmente en el tiempo y siguen los cambios en la carga tumoral cerebral, proporcionando biomarcadores para monitorizar los canceres cerebrales. Además, el LCR ctDNA ha demostrado facilitar y complementar el diagnóstico del carcinomatosis leptomeníngea.
El ctDNA presente en el LCR de neoplasias cerebrales y el ctDNA presente en el plasma de los cánceres de mama con metástasis sistémicas extra-craneales podría ser utilizado para caracterizar las alteraciones genómicas de las metastasis de estos cánceres. El uso de los CSF ctDNA representa una herramienta mínimamente invasiva que puede cambiar el paradigma para el manejo clínico de los pacientes con tumores malignos en el sistema nervioso central. Las biopsias líquidas tienen el potencial de proporcionar la información genómica completa del tumor, secuencial y en tiempo real y que permitirá mejorar el manejo terapéutico de los pacientes con cáncer.Recent developments in massively parallel sequencing and digital genomic techniques support the clinical validity of cell-free circulating tumour DNA (ctDNA) as a ‘liquid biopsy’ in human cancer. ctDNA in plasma may be useful to identify actionable genomic alterations, monitor treatment responses, unravel therapeutic resistance, and potentially to characterise tumour heterogeneity. The proof-of-principle study in the field of liquid biopsies, which is the ancillary article analysed in this thesis entitled: “Capturing intra-tumor genetic heterogeneity by de novo mutation profiling of circulating cell-free tumor DNA: a proof-of-principle” was published in Annals of Oncology in July 2014. This article is one of the first to demonstrate that high-depth targeted massively parallel sequencing of plasma-derived ctDNA constitutes a potential tool for de novo mutation identification and monitoring of somatic genomic alterations during the course of targeted therapy. This article demonstrated that plasma ctDNA may be employed to overcome the challenges posed by tumour heterogeneity. Plasma-derived ctDNA has been shown to be informative of the genomic alterations of patients with cancers. Nevertheless, patients with brain tumours have low or undetectable amounts of ctDNA in plasma precluding the genomic characterisation of brain cancer through plasma ctDNA. The proof-of-principle in the field of central nervous system liquid biopsies, which the fundamental article analysed in this thesis entitled: “Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma” was published in Nature Communications in November 2015. ctDNA derived from primary and secondary central nervous system malignancies was shown to be more abundantly present in the cerebrospinal fluid (CSF) than in plasma and it portrayed the genomic alterations of central nervous system disease better than plasma. CSF ctDNA levels longitudinally fluctuated in time and followed the changes in brain tumour burden providing biomarkers to monitor brain malignancies. Additionally, CSF ctDNA was shown to facilitate and complement the diagnosis of leptomeningeal carcinomatosis. Taken together, ctDNA present in the CSF of brain malignancies and ctDNA present in the plasma of breast cancers with extra-cranial systemic metastases may be used to characterise metastasis-specific genomic alterations. CSF ctDNA represents a minimally invasive tool that may change the paradigm for the clinical management of cancer patients with central nervous system malignancies. Liquid biopsies have the potential to provide comprehensive, sequential and real-time tumour-derived genomic information that will improve the therapeutic management of cancer patients.
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LeCouteur, Richard Andrew. "Novel approaches to the diagnosis and treatment of brain tumours, and other investigations in clinical neurology." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/25082.
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The primary goal of this thesis is to report results of a veterinary clinician-scientist’s career in the field of brain tumor research. The overarching goal of the research was to establish spontaneous canine gliomas as a model for brain tumor research in humans, and to reduce the translational gap between pre-clinical studies in mice, and human clinical trials. An ideal pre-clinical model for human brain tumour research would be a tumour that: (1) arises spontaneously; (2) grows intra-parenchymally; (3) is uniformly and rapidly fatal; (4) is capable of growing in vitro; (5) is transplantable both intracranially and subcutaneously in syngeneic animals; (6) correlates with the therapeutic sensitivities of its human counterparts; (7) occurs in a species that is genetically out-bred; and (8) occurs in a large animal with immune system intact. Dogs with a naturally-occurring brain tumour offer an opportunity to apply a “comparative” perspective, with translational applications, for new diagnostic, drug and other therapeutic trials. Results of research presented in this thesis support the premise that dogs with a spontaneous glioma represent a formidable large animal pre-clinical model for human brain tumour investigations. In translational medicine, clinician-scientists are the essential conduit between laboratory and clinic. The secondary goal of this thesis is to present research advances in the areas of neuromuscular disorders, equine electroencephalography, equine anaesthesia, and experimental intraoperative radiation therapy, with a view to emphasizing the role of the veterinary clinician-scientist in the advancement of these emerging areas.
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Le, Couteur Richard Andrew. "Novel approaches to the diagnosis and treatment of brain tumours, and other investigations in clinical neurology." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/27406.
Full textAbstract:
The primary goal of this thesis is to report results of a veterinary clinician-scientist’s career in the field of brain tumor research. The overarching goal of the research was to establish spontaneous canine gliomas as a model for brain tumor research in humans, and to reduce the translational gap between pre-clinical studies in mice, and human clinical trials. An ideal pre-clinical model for human brain tumour research would be a tumour that: (1) arises spontaneously; (2) grows intra-parenchymally; (3) is uniformly and rapidly fatal; (4) is capable of growing in vitro; (5) is transplantable both intracranially and subcutaneously in syngeneic animals; (6) correlates with the therapeutic sensitivities of its human counterparts; (7) occurs in a species that is genetically out-bred; and (8) occurs in a large animal with immune system intact. Dogs with a naturally-occurring brain tumour offer an opportunity to apply a “comparative” perspective, with translational applications, for new diagnostic, drug and other therapeutic trials. Results of research presented in this thesis support the premise that dogs with a spontaneous glioma represent a formidable large animal pre-clinical model for human brain tumour investigations. In translational medicine, clinician-scientists are the essential conduit between laboratory and clinic. The secondary goal of this thesis is to present research advances in the areas of neuromuscular disorders, equine electroencephalography, equine anaesthesia, and experimental intraoperative radiation therapy, with a view to emphasizing the role of the veterinary clinician-scientist in the advancement of these emerging areas.
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Vouri, Mikaella. "The role of TAM receptors in brain tumour cell signalling and behaviour." Thesis, University of Portsmouth, 2016. https://researchportal.port.ac.uk/portal/en/theses/the-role-of-tam-receptors-in-brain-tumour-cell-signalling-and-behaviour(df1c22b0-d917-4960-a96d-49ed30a3e91d).html.
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Tumour invasion is the key element in the high rate of mortality and morbidity in glioma patients. Increased expression, in neoplastic cells, of receptor tyrosine kinases (RTKs) of the TAM family (comprising Tyro3, Axl and MerTK), has been reported in several cancers including gliomas, in which they play a key role in tumour invasion. Axl RTK, with molecular weight of 120-140 kDa, mediates glioma cell adhesion and invasion through a variety of ways. Within the scope of this thesis, Western blotting, quantitative polymerase chain reaction (qRT-PCR) and glioblastoma multiforme (GBM) tissue microarray revealed an upregulation of Axl and Tyro3 in brain tumours and two adult GBM cell lines, SNB-19 and UP007. Both cell lines were treated with the TAM ligand Gas6 and/or the specific Axl small molecule inhibitor BGB324, and analysed in assays for survival, 3D colony growth, motility, migration and invasion. Western blotting was used to detect protein expression and signal protein phosphorylation. In both cell lines, BGB324 inhibited specifically phosphorylation of Axl as well as Akt kinase further downstream. BGB324 also inhibited survival and proliferation of both cell lines in a concentration-dependent manner, as well as completely suppressing migration and invasion. Axl inhibition by BGB324 also sensitised GBM cells to golden standard chemotherapeutic agent temozolomide. Furthermore, novel, unconventional activation mechanisms for the TAMs in human GBM cells were investigated. With the use of Western blotting, co-immunoprecipitation and in vitro kinase assays, Axl was shown to both interact with and be activated by the RTK EGFR. With the aid of qRT-PCR screens, EGFR was shown to promote GBM cell invasion through the Axl/TIMP1/MMP9 signalling axis. Additionally heterodimerisation of Axl with its sister RTK, Tyro3, in GBM cells was confirmed using co-immunoprecipitation assays; the functional significance of this complex was determined to be promotion of GBM cell survival. In conclusion, this thesis demonstrates the importance of TAM signalling in GBM, identifies novel molecular pathways employed by GBM cells for their survival, growth and spread, and thereby further strengthens the case for targeting TAM receptors as a novel therapeutic approach to combat both primary tumours as well as secondary tumours arising from drug resistance.
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Vicente, Robledo Javier. "Clinical Decision Support Systems for Brain Tumour Diagnosis: Classification and Evaluation Approaches." Doctoral thesis, Editorial Universitat Politècnica de València, 2012. http://hdl.handle.net/10251/17468.
Full textAbstract:
A lo largo de las últimas décadas, la disponibilidad cada vez mayor de grandes cantidades de información biomédica ha potenciado el desarrollo de herramientas que permiten extraer e inferir conocimiento. El aumento de tecnologías biomédicas que asisten a los expertos médicos en sus decisiones ha contribuido a la incorporación de un paradigma de medicina basada en la evidencia centrada en el paciente.
Las contribuciones de esta Tesis se centran en el desarrollo de herramientas que asisten al médico en su proceso de toma de decisiones en el diagnóstico de tumores cerebrales (TC) mediante Espectros de Resonancia Magnética (ERM).
En esta Tesis se contribuye con el desarrollo de clasificadores basados en Reconocimiento de Patrones (RP) entrenados con ERM de pacientes pediátricos y adultos para establecer el tipo y grado del tumor. Estos clasificadores especializados son capaces de aprovechar las diferencias bioquímicas existentes entre los TC infantiles y de adultos.
Una de las principales contribuciones de esta Tesis consiste en el desarrollo de modelos de clasificación enfocados a discriminar los tres tipos de tumores cerebrales pediátricos más prevalentes. El cerebelo suele ser una localización habitual de estos tumores, resultando muy difícil distinguir el tipo mediante el uso de Imagen de Resonancia Magnética. Por lo tanto, obtener un alto acierto en la discriminación de astrocitomas pilocíticos, ependimomas y meduloblastomas mediante ERM resulta crucial para establecer una estrategia de cirugía, ya que cada tipo de tumor requiere de unas acciones diferentes si se quiere obtener un buen pronóstico del paciente.
Asimismo, esta Tesis contribuye en la extracción de características para ERM mediante el estudio de la combinación de señales de ERM adquiridas en dos tiempos de eco: tiempo de eco corto y tiempo de eco largo; concluyendo que dicha combinación mejora la clasificación de tumores cerebrales pediátricos frente al hecho de usar únicamente los ERM de unVicente Robledo, J. (2012). Clinical Decision Support Systems for Brain Tumour Diagnosis: Classification and Evaluation Approaches [Tesis doctoral]. Editorial Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/17468
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Petch, Amelia K. "DNA chip designed antisense oligodeoxynucleotides targeting EGFR MRNA for brain tumour therapy." Thesis, Aston University, 2002. http://publications.aston.ac.uk/10998/.
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Glioblastoma multiforme (GBM) is a malignant brain tumour for which there is currently no effective treatment regime. It is thought to develop due to the overexpression of a number of genes, including the epidermal growth factor receptor (EGFR), which is found in over 40% of GBM. Novel forms of treatment such as antisense therapy may allow for the specific inhibition of aberrant genes and thus they are optimistic therapies for future treatment of GBM. Oligodeoxynucleotides (ODNs) are small pieces of DNA that are often modified to increase their stability to nucleases and can be targeted to the aberrant gene in order to inhibit it and thus prevent its transcription into protein. By specifically binding to mRNA in an antisense manner, they can bring about its degradation by a variety of mechanisms including the activation of RNase H and thus have great potential as therapeutic agents. One of the main drawbacks to the utilisation of this therapy so far is the lack of techniques that can successfully predict accessible regions on the target mRNA that the ODNs can bind to. DNA chip technology has been utilised here to predict target sequences on the EGFR mRNA and these ODNs (AS 1 and AS2) have been tested in vitro for their stability, uptake into cells and their efficacy on cellular growth, EGFR protein and mRNA. Studies showed that phosphorothioate and 2'O-methyl ODNs were significantly more stable than phosphodiester ODNs both in serum and serum-free conditions and that the mechanism of uptake into A431 cells was temperature dependent and more efficient with the use of optimised lipofectin. Efficacy results show that AS 1 and AS2 phosphorothioate antisense ODNs were capable of inhibiting cell proliferation by 69% ±4% and 65% ±4.5% respectively at 500nM in conjunction with a non-toxic dose of lipofectinTM used to enhance cellular delivery. Furthermore, control ODN sequences, 2' O-methyl derivatives and a third ODN sequence, that was found not to be capable of binding efficiently to the EGFR mRNA by DNA chip technology, showed no significant effect on cell proliferation. AS 1 almost completely inhibited EGFR protein levels within 48 hours with two doses of 500nM AS 1 with no effect on other EGFR family member proteins or by control sequences. RNA analysis showed a decrease in mRNA levels of 32.4% ±0.8% but techniques require further optimisation to confirm this. As there are variations found between human glioblastoma in situ and those developed as xenografts, analysis of effect of AS 1 and AS2 was performed on primary tumour cell lines derived from glioma patients. ODN treatment showed a specific knockdown of cell growth compared to any of the controls used. Furthermore, combination therapies were tested on A431 cell growth to determine the advantage of combining different antisense approaches and that of conventional drugs. Results varied between the combination treatments but indicated that with optimisation of treatment regimes and delivery techniques that combination therapies utilising antisense therapies would be plausible.
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Lurie, P. "Coping with a childhood brain tumour : a qualitative analysis of parents' experiences." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1448225/.
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Pre-existing research on the stress reactions of caregivers of children with brain tumours was reviewed. Four overarching stress reactions were notably present for parents: burden from adjusting to changes in routine, burnout from fatigue and emotional exhaustion, residual stress from diagnosis and treatment, and future-oriented uncertainty. There is evidence to suggest that psychosocial implications for parents are a concern and that they require support from professionals long into the survival period. As part of the empirical research, ten parents of paediatric brain tumour survivors were retrospectively interviewed about their experiences of coping from diagnosis through to the survival period. Interviews were transcribed and four domains were devised from a thematic analysis: Focusing on the here-and-now in which parents concerned themselves with taking one day at a time rather than thinking about what may arise later; Overcoming helplessness reflected the desire to provide care-giving duties; Different needs met across the system included emotional bonding with other parents on the ward, whilst wanting family to offer respite; Finding a new normal featured in the survival period when parents reflected on new values for the family. Coping mechanisms were seen as a process, changing dependant on the time period. The literature review and empirical study are rounded off by a critical appraisal of the research process, which focuses on the clinical utility of working qualitatively with a paediatric brain tumour population, a discussion of homogeneity versus heterogeneity when sampling, and an appraisal of thematic analysis.
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Balathasan, Lukxmi. "Characterising the role of circulating immune cells in brain metastasis." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:e7620d30-7e4a-468b-b819-db4cf27eaef6.
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Brain metastasis is a frequent occurrence in cancer patients and carries a high mortality rate. The incidence of brain metastasis is on the rise, highlighting the need for improved therapeutic intervention. Immune cells have been shown to promote disseminated tumour cells to colonise the lung and liver. Therefore, we aim to determine whether immune cells also facilitate brain metastasis by describing the host immune response to tumour cells attached to the brain vasculature. We developed a model of brain metastasis by using ultrasound guidance to perform intracardiac injection of tumour cells. Using this method, we identified highly and weakly brain metastatic cell lines. To understand how cancer cells develop into brain metastases, we analysed brains harvested 4 h- 14 d after tumour injections. At 4 h after intracardiac injection, only cell lines that developed into brain metastases were found adhered to the brain vasculature in high numbers. A small number of arrested tumour cells clustered with CD45⁺ immune cells. These tumour-CD45 clusters persisted over time whilst the frequency of solitary tumour cells declined. Tumour-associated CD45⁺ immune cells were identified to be Ly6G⁺Gr-1⁺CD11c⁻ myeloid cells. Considerably more tumour-CD45⁺ immune cell clusters were found within the brain vasculature when tumour cells were injected into mice bearing a primary tumour. Increased tumour-CD45⁺ immune cells clusters correlated with an increased number of brain metastases in the same group of mice. We also found a positive association between increased tumour-immune clusters and levels of tumour and host derived G-CSF. To establish a causal relationship between tumour cell-CD45 clusters and metastases, we developed an experimental setup for transcranial imaging. Our results suggest that tumour recruited immune cells may promote tumour cell colonisation of the brain and provides a framework for further investigation.
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Ivanov, Delyan Pavlov. "Assessment of drug-loaded nanoparticles in a 3D in vitro brain tumour model." Thesis, University of Nottingham, 2015. http://eprints.nottingham.ac.uk/43559/.
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This work describes the creation of a three-dimensional model of the children’s brain tumour medulloblastoma using primarily human cells. This in vitro cell culture model was created as a platform for testing novel drug delivery systems for local delivery in the brain. The aim of the local delivery strategy was to reduce radiotherapy through the use of nanoparticle-based chemotherapy. The nanoparticles would be delivered after surgery in the cavity left by the excised tumour tissue. The model was intended to evaluate the selective cytotoxicity of advanced drug delivery systems towards tumour tissue and the benefit of nanoparticle therapy compared to free drug. Normal tissue was modelled using human foetal brain tissue and tumour tissue was represented by a variety of medulloblastoma cell lines. Both were cultured as three-dimensional spheroids free of artificial matrix in ultra-low attachment plates. The tumour and normal cells could be cultured either separately or together and the viability for each cell population determined using a battery of methods. Co-cultures of both cell types had the additional benefit of mimicking the interaction between normal and tumour tissue. The use of physiologically relevant single and co-culture in vitro models could provide information on the relative safety and efficacy of novel brain tumour treatments. The high-throughput platforms used, the algorithms and the validation of a battery of tests in 3D may be extrapolated to other cancer models as well. Moreover the universal marking procedure employed can be employed to label, culture and analyse any two cell types, while preserving tissue heterogeneity and viability. The key benefit from this thesis is the framework for designing in vitro models of tumours that include normal tissue as an internal control. This is an important contribution that can substantiate IC50 values by putting them in the context of drug safety and efficacy. It also highlights the minimum checks and feasibility experiments that need to be done before an in vitro assay is accepted for 3D spheroids.
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Brown, Frances Kessler. "Memory After Tumours of the CNS in Childhood (MATCCh) study : long-term memory and forgetting in paediatric brain tumour survivors." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/6719/.
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Background The literature suggests that working and long-term memory are impaired in paediatric brain tumour survivors (Robinson Fraley, Pearson, Kuttesch & Compas, 2013; Robinson et al., 2014). Survivors report difficulties remembering information they learned days before, including for school exams. Sleep and psychological problems can affect memory performance and may exacerbate memory difficulties in this population. Aims Assess learning and long-term memory in paediatric brain tumour survivors relative to healthy controls, and explore associations between memory, sleep and mood. Method A learning paradigm was used to teach verbal and visual material to an 80 percent criterion in ten young brain tumour survivors and ten matched healthy controls (sibling, cousin or best friend) aged between 11 and 24. A between-subjects design compared recall between groups at delays of 30 minutes and one week. Sleep quality (measured by Actigraphy), anxiety and depression were also assessed. Results Verbal learning was significantly impaired in brain tumour survivors relative to controls. There was very tentative evidence of increased visual forgetting in the tumour group, however definitive conclusions could not be drawn from results due to the study lacking power. Some participants had significant impairments in verbal learning or verbal and visual long-term memory, and others did not. Memory was not associated with sleep or psychological variables in the tumour group, although this may be due to the study lacking power. Discussion The variability in memory within the tumour sample emphasises the heterogeneity in the brain tumour population and the need for memory to be monitored in individuals. Education and occupational settings could offer further support to those that require it. Future research should assess memory after delays longer than 30 minutes and further explore how tumour, treatment, sleep and mood variables affect memory.
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Cavers, Debbie Grant. "Understanding the supportive care needs of glioma patients and their relatives : a qualitative longitudinal study." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/10630.
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Background: Malignant cerebral glioma is a rare cancer but has a devastating impact on patients and their families. In Scotland each year, around 450 people are diagnosed with glioma. Prognosis is generally poor and treatment is essentially palliative. There is a growing recognition that non-clinical aspects of care for both patients and their families need to be acknowledged and integrated into health care provision in line with a patient-focused ethos of care. Currently, there is relatively little research exploring the psychosocial issues and needs of this patient group. Aims: To give patients being investigated for malignant cerebral glioma and their families the opportunity to describe their shared experiences of their illness journey and voice their concerns and unmet needs. To examine how these experiences and needs change over time as the patient progresses through the illness journey. To ascertain the extent to which these needs are recognised and supported, taking into accounts professionals’ views and making suggestions for steps forward in improving patients’ psychosocial care. Methods: A total of 80 qualitative prospective longitudinal interviews (30 paired and 50 separate) were conducted with 26 people with a suspected or confirmed diagnosis of malignant cerebral glioma being treated at a regional hospital and 24 primary relative/informal carers. Patients and carers were interviewed at the following five times: leading up to diagnosis; following a formal diagnosis; around the end of initial treatment (radiotherapy); at a designated six-month follow-up stage; and bereavement interviews with carers. One-off interviews were carried out with 66 health professionals (19 case-linked GPs and 47 other health, health-related and social care professionals involved in patients' care). Interviews were recorded and transcribed verbatim and analysed using the constant comparative method from a grounded theory approach assisted by QSR NVivo Version 7. Findings: Distress, anxiety and shock were overwhelming reactions in the period leading up to a diagnosis of glioma, making it difficult for participants to make sense of their experience. Over time, participants employed a range of strategies in order to cope with their diagnosis. Social and emotional support from professionals and friends, family and other patients were vital in many cases but support often felt inadequate. The role of information and the manner in which it was communicated was closely linked to participants’ ability to cope. Information needs were variable but on the whole patients and carers did not feel well informed. Dealing with cognitive and physical symptoms of their illness and side effects of treatment inhibited patients’ ability to resume their everyday activities. The lives of relatives were also affected as they struggled to care for their loved ones. People with a diagnosis of glioma were faced with the possibility of death from an early point in their illness trajectory and awareness of this, coupled with ability to make sense of existential issues, varied across participants. Issues around support, communication, information and palliative care were considered to be important among health professionals involved in the care of people with a diagnosis of glioma but provision fell short. Conclusions: Concerns regarding information, communication and support reported elsewhere in the literature are enduring in glioma patients and their relatives. Reporting of unmet psychosocial and supportive care issues by patients and recognition by professionals of the need to improve these dimensions of care for people affected by glioma emphasises previous recommendations yet to be fully implemented into patient care.
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Vilamala, Muñoz Albert. "Multivariate methods for interpretable analysis of magnetic resonance spectroscopy data in brain tumour diagnosis." Doctoral thesis, Universitat Politècnica de Catalunya, 2015. http://hdl.handle.net/10803/336683.
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Malignant tumours of the brain represent one of the most difficult to treat types of cancer due to the sensitive organ they affect. Clinical management of the pathology becomes even more intricate as the tumour mass increases due to proliferation, suggesting that an early and accurate diagnosis is vital for preventing it from its normal course of development. The standard clinical practise for diagnosis includes invasive techniques that might be harmful for the patient, a fact that has fostered intensive research towards the discovery of alternative non-invasive brain tissue measurement methods, such as nuclear magnetic resonance. One of its variants, magnetic resonance imaging, is already used in a regular basis to locate and bound the brain tumour; but a complementary variant, magnetic resonance spectroscopy, despite its higher spatial resolution and its capability to identify biochemical metabolites that might become biomarkers of tumour within a delimited area, lags behind in terms of clinical use, mainly due to its difficult interpretability. The interpretation of magnetic resonance spectra corresponding to brain tissue thus becomes an interesting field of research for automated methods of knowledge extraction such as machine learning, always understanding its secondary role behind human expert medical decision making. The current thesis aims at contributing to the state of the art in this domain by providing novel techniques for assistance of radiology experts, focusing on complex problems and delivering interpretable solutions. In this respect, an ensemble learning technique to accurately discriminate amongst the most aggressive brain tumours, namely glioblastomas and metastases, has been designed; moreover, a strategy to increase the stability of biomarker identification in the spectra by means of instance weighting is provided. From a different analytical perspective, a tool based on signal source separation, guided by tumour type-specific information has been developed to assess the existence of different tissues in the tumoural mass, quantifying their influence in the vicinity of tumoural areas. This development has led to the derivation of a probabilistic interpretation of some source separation techniques, which provide support for uncertainty handling and strategies for the estimation of the most accurate number of differentiated tissues within the analysed tumour volumes. The provided strategies should assist human experts through the use of automated decision support tools and by tackling interpretability and accuracy from different anglesEls tumors cerebrals malignes representen un dels tipus de càncer més difícils de tractar degut a la sensibilitat de l’òrgan que afecten. La gestió clínica de la patologia esdevé encara més complexa quan la massa tumoral s'incrementa degut a la proliferació incontrolada de cèl·lules; suggerint que una diagnosis precoç i acurada és vital per prevenir el curs natural de desenvolupament. La pràctica clínica estàndard per a la diagnosis inclou la utilització de tècniques invasives que poden arribar a ser molt perjudicials per al pacient, factor que ha fomentat la recerca intensiva cap al descobriment de mètodes alternatius de mesurament dels teixits del cervell, tals com la ressonància magnètica nuclear. Una de les seves variants, la imatge de ressonància magnètica, ja s'està actualment utilitzant de forma regular per localitzar i delimitar el tumor. Així mateix, una variant complementària, la espectroscòpia de ressonància magnètica, malgrat la seva alta resolució espacial i la seva capacitat d'identificar metabòlits bioquímics que poden esdevenir biomarcadors de tumor en una àrea delimitada, està molt per darrera en termes d'ús clínic, principalment per la seva difícil interpretació. Per aquest motiu, la interpretació dels espectres de ressonància magnètica corresponents a teixits del cervell esdevé un interessant camp de recerca en mètodes automàtics d'extracció de coneixement tals com l'aprenentatge automàtic, sempre entesos com a una eina d'ajuda per a la presa de decisions per part d'un metge expert humà. La tesis actual té com a propòsit la contribució a l'estat de l'art en aquest camp mitjançant l'aportació de noves tècniques per a l'assistència d'experts radiòlegs, centrades en problemes complexes i proporcionant solucions interpretables. En aquest sentit, s'ha dissenyat una tècnica basada en comitè d'experts per a una discriminació acurada dels diferents tipus de tumors cerebrals agressius, anomenats glioblastomes i metàstasis; a més, es proporciona una estratègia per a incrementar l'estabilitat en la identificació de biomarcadors presents en un espectre mitjançant una ponderació d'instàncies. Des d'una perspectiva analítica diferent, s'ha desenvolupat una eina basada en la separació de fonts, guiada per informació específica de tipus de tumor per a avaluar l'existència de diferents tipus de teixits existents en una massa tumoral, quantificant-ne la seva influència a les regions tumorals veïnes. Aquest desenvolupament ha portat cap a la derivació d'una interpretació probabilística d'algunes d'aquestes tècniques de separació de fonts, proporcionant suport per a la gestió de la incertesa i estratègies d'estimació del nombre més acurat de teixits diferenciats en cada un dels volums tumorals analitzats. Les estratègies proporcionades haurien d'assistir els experts humans en l'ús d'eines automatitzades de suport a la decisió, donada la interpretabilitat i precisió que presenten des de diferents angles.
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Seyed, Sadr Mohamad. "SLIT proteins inhibit malignant brain tumour cell invasion via downregulation of pro-invasive genes." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110340.
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Most cancer deaths result from the progression of the tumour pathology whereby a localised mass evolves into an invasive and metastatic disease, spreading away from the main tumour mass. Malignant brain tumours such as glioblastoma and medulloblastoma are among the most invasive human cancers. The Slit-Robo pathway is extensively characterised as a repellent of axons and neural cells. Therefore we hypothesised that Slit proteins would repel invasive brain tumour cells. The first chapter of this thesis provides a thorough introduction of the oncology field as it pertains to malignant brain tumour biology and to the field of Slit-Robo family of proteins. The second chapter provides evidence for Slit proteins and their inhibitory effect on malignant brain tumour cell invasion. We further characterise the signaling pathway employed by Slit proteins to impart an inhibitory effect on tumour cell invasion. We present data suggesting that Slit proteins decrease the transcriptional expression of numerous pro-invasive and pro-angiogenic genes in malignant brain tumour cells. We characterise the product of one of these genes, MMP14, as a protease of Robo proteins. A model is proposed that explains the observation that decreasing the expression of MMP14 leads to a decrease in brain tumour cell invasion. These results suggest that malignant brain tumour cells respond to Slit by modulating a series of transcripts critical for cell invasion. Therefore, targeting malignant brain tumour cells with Slit proteins or chemical analogues that mimic Slit's effects may provide a potentially novel anti-invasive therapy.La transformation d'une tumeur primaire en tumeur maligne et métastatique, s'éloignant du point d'origine, est souvent la principale cause de décès chez le patient. Les tumeurs cérébrales malignes tel les glioblastomes et les médulloblastomes sont parmi les plus invasives cancers humains. La voie de signalisation de Slit-Robo a été largement caractérisée et montre l'implication de Slit-Robo dans la répulsion des axones et cellules neuronales. Dans cette étude, nous avons étudié la possibilité que Slit-Robo pourraient repousser les cellules cancéreuses invasives cérébrales. Le premier chapitre de cette thèse présente une introduction approfondie du rôle de la famille des protéines Slit-Robo dans le contexte du cancer et de la biologie des tumeurs cérébrales. Le deuxième chapitre présente des preuves de l'implication des protéines Slit et leur rôle dans l'inhibition de l'invasion des cellules de tumeurs cérébrales. Aussi, la caractérisation de la voie de signalisation employée par les protéines Slit dans l'inhibitionde l'invasion des cellules cancéreuses a été montrée. De plus, cette étude présente des résultats qui suggèrent que les protéines Slit diminuent l'expression de la transcription degènes pro-angiogénique et pro-invasif des cellules tumorales. Nous avons aussi identifié MMP14 comme une protéase des protéines Robo et dont l'expression est influencée par les protéines Slit. Finalement, nous proposons un modèle démontrant qu'une diminution de l'expression de MMP14 induit une réduction de l'invasion des cellules tumorales du cerveau.
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Cowman, S. J. "Elucidation of the effects of hypoxia on DNA repair machinery in brain tumour cells." Thesis, University of Liverpool, 2018. http://livrepository.liverpool.ac.uk/3028185/.
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Glioblastoma (GBM) and Medulloblastoma (MB) are the most common brain tumours of adults and children respectively. These tumours are hypoxic as their oxygen levels are lower than the physiological 5-8% O2 found in the brain. Tumour hypoxia can promote tumour cell invasion, increase metastatic potential and leads to resistance to conventional cancer therapies. Chemotherapeutic agents and irradiation induce excessive DNA damage in order to overwhelm the DNA repair pathways and initiate apoptosis. This thesis aimed to examine the impact of hypoxia on DNA repair mechanisms in GBM and MB, which has not yet been reported. Hypoxic tumours are associated with poor patient outcome, in part due hypoxia-induced resistance to treatment. Work in this thesis showed that, in MB and GBM cells, chronic hypoxia was necessary to induced a resistance phenotype. Downregulation of critical components of the double strand break repair pathway was found to be responsible for treatment resistance in some, but not all hypoxic MB cells. Since hypoxia can directly influence transcription of DNA repair proteins, a NanoString assay was used to obtain a comprehensive assessment of DNA repair gene expression in multiple MB and GBM cell lines exposed to hypoxia. Moderate and severe hypoxic exposure had a variable impact on gene expression, with no clear-cut impact of different oxygen tensions. The level of transcripts of several DNA repair genes were downregulated across multiple GBM cell lines, especially LIGIV, which encodes DNA Ligase IV responsible for joining double strand breaks during DNA repair. A multiphoton laser microirradiation protocol was used to assess, in living cells, the functional impact of LIGIV downregulation. Reduced double strand break repair efficiency in hypoxia was observed, which may lead to genomic instability that drives tumour progression. Investigations into GBM and MB tumour cell biology, such as that described in this thesis, will aid in the development of new treatment methods, which are desperately needed.
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Kinyany-Schlachter, Susan. "Woman as healer : a dialogical narrative analysis of online brain tumour (GBM) caregiving stories." Thesis, City, University of London, 2017. http://openaccess.city.ac.uk/19801/.
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A diagnosis of glioblastoma multiforme (GBM), a World Health Organisation (WHO) grade IV brain tumour, is devastating for patients and their families who bear the impetus of caregiving. GBM caregivers act as de facto health professionals when their loved ones are discharged prematurely from hospitals. Faced with complex healthcare needs, GBM caregivers report the highest psychological burden, and highest unmet needs of all cancer caregivers. Despite this, they rarely accessed rehabilitation services. Researchers hardly engaged with their stories. The current research on GBM caregiving is predominantly from a biomedical perspective, not only offering limited understandings of psychosocial experiences, but also, evidencing the need for caregiver stories in caregiving research. The researcher recruited 7 bereaved caregivers, who had previously narrated stories online about caring for their loved ones diagnosed with GBM and; consented to the use of their stories as research data. These stories covered a period of between 1-3+ years, throughout the illness trajectory and post-bereavement. The researcher further conducted email interviews focussed on the retrospective perspectives of sharing stories online. Participants provided feedback on the preliminary findings of the DNA. The findings consisted of multiple layers of interpretations drawn from social constructionism, narrative and feminist relational theories, beginning with subjective stories, collective story typologies and core narratives, thereby illuminating the relationships between GBM caregivers, the stories they narrated and the event of narrating stories online. An additional layer of interpretation served to shed light on the relational, dialogical, performative and hindsight perspectives of storytelling and the storytelling landscape. This research decentres the dominance of biomedicine in caregiving research to present a perspective from GBM caregivers using their own stories, in their own voices, so as to inform counselling psychology research and practice.
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Cea, Leire. "Psychosocial adjustment of children who have ended brain tumour treatment: child and parent reports." Thesis, Högskolan för lärande och kommunikation, Jönköping University, HLK, CHILD, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-50860.
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Scotland, Jennifer L. "Inspection time in patients with intracranial tumours before and after neurosurgery." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4425.
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Introduction: Many patients with brain tumours experience dysfunction in several cognitive domains. Given the limited survival times of the majority of patients with brain tumours, maintenance or improvement of quality of life is as important as increasing survival time. Impaired cognition has a negative impact on quality of life and as such, cognitive function is becoming an increasingly important endpoint in clinical trials in neuro-oncology. However, measuring cognition in patients with brain tumours is problematic for a number of reasons. Most intracranial tumours are initially treated with surgery and studies of neurosurgical morbidity often evaluate physical as opposed to cognitive domains, yet the latter can have a greater negative impact on the patient’s quality of life. This thesis therefore details cognition in brain tumour patients at the time of presentation (pre-operatively) and examines the effects of surgical intervention on cognitive function. Of particular interest is the potential utility of inspection time, a computer-based measure of the brain’s information processing efficiency, as a measure of brain slowing as a result of the tumour and as an indicator of response to surgical intervention. Methods: The study is based on a cohort of 118 newly-presenting patients with a supratentorial brain tumour who were to have surgery (biopsy or resection). Each patient was administered a comprehensive battery of cognitive tests prior to surgery (baseline). The battery comprised inspection time testing, other standardised cognitive measures and assessment of mood, quality of life and functional status. Post-operatively, each patient repeated the inspection time test in addition to a selected number of the other tests administered at baseline. For comparison, a group of patients admitted for elective spinal surgery (n = 85) were also tested pre- and post-operatively. A group of healthy volunteers provided a second control group by being tested twice (n = 80). Results: The brain tumour cohort were significantly impaired by comparison with both control groups at baseline (pre-operatively) on the majority of the cognitive measures, including inspection time. Baseline inspection time scores were significantly related to some scores on the EORTC Quality of Life Questionnaire in the brain tumour group, but not in the spinal surgery group. There was no significant difference between the brain tumour and spinal surgery groups in term of the levels of pre-operative anxiety and depression. The brain tumour cohort showed significantly greater relative deterioration on inspection time following surgery by comparison with both control groups. The brain tumour cohort also deteriorated significantly on several other measures postoperatively by comparison with the healthy control group. Detailed analyses were carried out to determine the differential effects of tumour type, location, and type of surgery (biopsy or resection) on inspection time and other functions in the brain tumour group. Conclusions: Tumour-related cognitive impairment appears to be common in a heterogeneous group of brain tumour patients with a variety of different tumours located throughout the brain. Surgical intervention has a negative impact on function in brain tumour patients, although this deterioration may be transient. General slowing of visual information processing appears to be common to brain tumour patients and the inspection time task provides a feasible and useful method of assessment in brain tumour patients. The task is sensitive to tumour-related brain slowing and can provide a reliable assessment of response to surgery. Given the task’s advantages over more commonly-used cognitive measures, it could be usefully incorporated into cognitive tests batteries in neuro-oncology.
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Brem, Franziska Katharina. "Magnetic characterisation of iron phases in human brain tissue: Applications to epileptic and tumour tissue /." Zürich : ETH, 2006. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=16739.
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Najim, Nigar. "A study of the cytotoxic effects of methionine depletion in human brain tumour cell lines." Thesis, University of Salford, 2007. http://usir.salford.ac.uk/26832/.
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The aim of this project was to investigate the importance of methionine depletion as a cause of cytotoxicity for paediatric CNS tumour cell lines, and also to investigate the in vitro cellular biochemical responses, as measured by changes in cellular levels of L-methionine, glutathione and O6 - alkylguanine DNA - alkyltransferase (MGMT) activity in glioma (D54) and medulloblastoma (Daoy) cell lines. A characteristic feature of many solid tumours is their requirement for both endogenous and exogenous L-methionine in order to support cellular proliferation. Normal cells are generally methionine-independent and utilise L-homocysteine to produce sufficient levels of L-methionine for cellular proliferation. The work presented in this thesis shows that Daoy and D54 cells are methionine-dependent cell lines in that they stop proliferating in methionine-depleted media supplemented with L-homocysteine. Whereas D54 cells do not exhibit detectable MGMT activity, methionine depletion markedly down-regulates the activity of this DNA repair enzyme in Daoy cells. Methionine depletion gives rise to a demonstrable decrease in methionine levels and an increase in glutathione levels for both tumour cell lines. Moreover, Daoy and D54 cells are found to be significantly more resistant to methotrexate (MTX), temozolomide (TMZ), and cisplatin (CDDP) under conditions of methionine depletion, compared to controls under normal cell culture conditions, a finding that may, at least in part, be related to the increased glutathione levels found. Further studies are required to determine the relative contribution of glutathione levels and modulation of apoptosis to explain the reasons for the reduced chemosensitivity to MTX, CDDP and TMZ for both Daoy and D54 cells. Evidence suggests that TMZ, CDDP and MTX may modulate cellular determinants of chemosensitivity through effects on methionine metabolism and MGMT levels. Therefore, the potential synergies of TMZ, CDDP and/or MTX for Daoy and D54 cells were investigated in methionine-replete conditions, and the combination of MTX and TMZ in particular was found to demonstrate synergistic effects. Further studies are needed to determine the reasons for this effect, and these may give insights into the further clinical development of these drugs in the setting of childhood CNS tumour therapy.
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Dungey, Fiona A. "Targeting replication-specific DNA repair pathways to enhance the therapeutic ratio of brain tumour radiotherapy." Thesis, University of Sussex, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506947.
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Glioblastoma multiforme is associated with poor prognosis and resistance to standard therapy. However the non-dividing nature of normal brain provides an opportunity for enhancing the therapeutic ratio by combining radiation with inhibitors of replication-specific DNA repair pathways. KU-0059436, an inhibitor of the base excision repair (BER) protein poly(ADP-ribose) polymerase (PARP), was demonstrated to specifically radiosensitise glioma cells during S-phase and to increase lonising radiation (IR)-induced γH2AX and Rad51 foci. This radiosensitisation was enhanced using fractionated radiation, possibly because more cells were exposed to IR whilst in S-phase. A model is proposed whereby PARP inhibition decreases repair of radiation-induced single strand breaks (SSB) which are converted at collapsed replication forks to double strand breaks (DSB) requiring homologous recombination (HR) for repair. To investigate whether inhibition of downstream HR repair potentiates the radiosensitising effect of KU-0059436, and in the absence of specific HR inhibitors, the heat shock protein 90 (HSP90) inhibitor 17-AAG was used. This compound exhibits tumour-specific cytotoxic and radiosensitising properties and downregulates the HR proteins BRCA2 and Rad5l. Work in this thesis confirmed that 17-AAG inhibits HRR and radiosensitises glioma cells. Radiosensitisation was replication-dependent and was increased in the presence of KU-0059436. The combined effect was at least partially replication-dependent, was associated with increased γH2AX foci in G2 cells, and was absent in non-malignant CHO cells. Since Rad5l-depleted cells were also radiosensitised by 17-AAG, this effect could not be attributed entirely to HRR inhibition. 17-AAG inhibits multiple tumour survival and DNA repair pathways that may contribute to its enhancement of the replication-dependent effects of KU-0059436. These multiple mechanisms may be difficult to elucidate but are likely to be therapeutically beneficial. In summary, the combination of HSP90 and PARP inhibitors may potentially improve brain tumour radiotherapy by mechanisms that include but are not restricted to inhibition of the BER and HRR DNA repair pathways.
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Opstad, Kirstie Suzanne. "Quantification and pattern recognition of ¹H magnetic resonance brain tumour spectra for automated classification." Thesis, St George's, University of London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413702.
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Chakraborty, Aabir. "The development of intra-operative ultrasound elasticity imaging techniques to assist during brain tumour resection." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1446165/.
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Brain tumour resection requires the surgeon to evaluate mechanical properties such as tumour stiffness and adherence of tumour to the surrounding normal brain. This is a subjective assessment. Ultrasound elasticity imaging techniques allow more objective measurement and imaging of mechanical properties such as strain, which is related to stiffness, in the case of ultrasound elastography. This thesis describes the implementation of ultrasound elastography intra- operatively during brain tumour surgery using both an off-line processed and real-time ultrasound elastography system in 24 patients. Elastogram results on stiffness were compared to surgical findings. Adherence of two surfaces in contact is related to slip which is a type of shear. It occurs when the frictional force binding the two surfaces is overcome. A new imaging technique called slip elastography that images the anatomical location of a slip boundary and measures the externally applied force at which slip is first detected was developed. The technique provides a measure of the frictional force binding the two surfaces together. The theoretical basis, system development, in vitro testing using gelatine phantoms and the implementation of slip elastography in 22 patients intra- operatively during brain tumour resection is described. The results indicated that ultrasound elastography is able to distinguish stiffer areas from softer areas intra-operatively during brain tumour resection. It also demonstrated the heterogeneity of brain tumour stiffness. Slip elastography was able to identify the anatomical location of the brain tumour interface and provide a measure of adherence at the interface.
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Ballantyne, Eric Sinclair. "The expression and prognostic role of proto-oncogenes and tumour suppressor genes in medulloblastoma and embryonic brain." Thesis, University of Liverpool, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366487.
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Gaskill, Alexandra Mary Angela. "Adolescent girls' experiences of school following treatment for a brain tumour : an interpretative phenomenological analysis approach." Thesis, University of Leicester, 2014. http://hdl.handle.net/2381/29154.
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Literature Review : Contemporary qualitative evidence exploring the adjustment experiences of young people treated for a brain tumour was synthesised. A systematic search of the literature was undertaken and eight papers met the criteria for inclusion in the review. A thematic synthesis of the findings revealed two superordinate themes: (a) no longer playing well; and (b) mastering the game of life. The findings from the review demonstrated the range and extent of difficulties experienced by survivors. However, the survivors showed resilience in adapting to the effects of their illness and developed a number of effective coping strategies. The findings also suggested that some survivors may experience post-traumatic growth. The review highlighted the need for multidisciplinary support and liaison between healthcare services and schools. Further implications for clinical practice and directions for future research are considered. Research Report : Young people’s experiences of reintegrating into school following treatment for a brain tumour were explored using an Interpretative Phenomenological Analysis (IPA) approach. Four girls (ages 14 to 16) were interviewed and the transcripts were analysed. Three superordinate themes emerged across the cases, relating to experiences of identity, relationships and reengaging with schoolwork. The subthemes retained the complexity of how these overarching themes were experienced differently for the individuals. The present study provided insight into the lived experiences of these young people as they returned to school following treatment for a brain tumour. The study highlighted the challenging nature of this experience, and implications for future research and clinical practice are discussed. Critical Appraisal : The processes involved in conducting a research project are discussed reflectively in the critical appraisal section. This includes personal reflections, a critique of the research, and a consideration of future research opportunities.
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Fletcher, Kimberley J. "An interpretative phenomenological analysis of the patient experience of awake craniotomy : brain tumour diagnosis to discharge." Thesis, University of Nottingham, 2011. http://eprints.nottingham.ac.uk/12124/.
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Introduction. This thesis explored patient experiences of awake craniotomy. Existing literature is scarce and dominated by quantitative methodologies. More recently two qualitative studies have provided a rich, but contrasting, understanding of the patients‟ experience of awake craniotomy. The methodological weaknesses of the existing literature are addressed, and the rationale for the study justified. Objectives. The aim of the study was to explore seven participants‟ experiences of awake craniotomy using interpretative phenomenological analysis. Methods. Single-site ethical approval was gained to conduct the study in one NHS Trust. All potential participants were approached who had undergone the awake craniotomy procedure at the NHS Trust. Semi-structured interviews were conducted with participants. Interviews were transcribed verbatim and analysed using an interpretative phenomenological analysis framework. Results. Analysis of transcripts yielded three superordinate themes: self-preservation, operation environment and information. The superordinate themes were interpreted as interconnected with each other, as well as embedded in a core theme: relationship with the neurosurgeon. The three superordinate themes are presented and discussed within the journal article. The extended paper elaborates on two of these superordinate themes. Discussion. The relationship with the neurosurgeon appears crucial to the patients‟ experience of awake craniotomy. The relationship could impact on the participants‟ decision to have the awake craniotomy, their experience of the awake operation and their acceptance of the information given. The results are discussed with reference to previous literature. The implications and recommendations for further research are outlined.
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Alderson, William. "Automatic brain tumour detection and segmentation using tissue substructure features derived from MRI diffusion tensor imaging." Thesis, University of Bristol, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.688350.
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The incidence of brain cancer has increased with the increase in average life span. To help combat this rise new diagnostic aids, such as Magnetic Resonance Imaging (MRI) and Computed tomography (CT) scans, have enabled clinicians to undertake non-invasive evaluation of biological tissue and to present this information in detailed 2D images and 3D volumes. Unfortunately the growing demand for clinical services is imposing great cost on health services and is highlighting the need for more highly skilled clinicians. The introduction of a novel automated computer-based brain tumour detection and segmentation process offers the potential to reduce cost, shorten waiting times and to provide tools to reduce the workload of clinicians. Magnetic Resonance Imaging (MRI) three dimensional diffusion data can be post-processed, in real time, to improve brain tumour detection and visualisation. In this thesis we present novel sub-structure features derived from MRI diffusion tensor imaging scans that go beyond conventional tractography, and show how automatic algorithms lead to tumour localisation and boundary identification. The effectiveness of this method is shown through the automatic localisation and candidate tumour boundary detection for five patients. Preliminary results from this computer based process show good correlation with the traditional visual inspection of images method by clinical experts. Further analysis of the tissue diffusion sub-structure features is expected to lead to improved non-invasive structural identification around the tumour. We compare tumours boundaries detected by our process with traditional image scans and discuss how this detection method of tumours may provide useful additional information above that which can be elicited by visual inspection of the scans.
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Taggart, David John. "Cross-talk between the primary tumour and brain metastases enhances the efficacy of immune checkpoint inhibition." Thesis, University of Leeds, 2016. http://etheses.whiterose.ac.uk/16116/.
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Melanoma brain metastases (MBrM) are devastating, occurring in up to 60% of melanoma patients and are increasing in incidence as systemic treatments improve. MBrM are notoriously difficult to treat and patients suffer from extremely poor survival rates, resulting in these patients being excluded from clinical trials testing new treatments, thus highlighting a need for research in this field. We developed a pre-clinical model where mice have simultaneous intracranial and extracranial B16 melanoma tumours to mimic the clinical setting. Notably, intracranial tumour growth was the survival-limiting factor, allowing the study of therapeutic effects specifically in the brain. Various combinations of anti-PD-1, anti-CTLA-4 and GM-CSF were investigated as potential therapies for MBrM. We found that the combination of anti-PD-1 and anti-CTLA-4 could prolong the survival of these mice; however, this was dependent on the presence of an extracranial tumour. Functional studies revealed that natural killer cells and cytotoxic T-cells were essential mediators of this therapy. Moreover, examination of the infiltrating immune cell populations demonstrated an increase in CD45+ immune cells in the intracranial tumours of mice also bearing a flank tumour and receiving the anti-PD-1 and anti-CTLA-4 therapy. This increase was found to be a result of the increase in infiltrating T-cells and macrophages/microglia and was reliant on the presence of an extracranial tumour. Analysis of cytotoxic T-cells revealed an increase in tumour antigen-specific cells in mice with an intracranial and extracranial tumour receiving treatment. Tumour antigen-specific T-cells within the blood showed an increased expression of homing receptors, which have been previously linked to an increase in T-cell infiltration into the brain. In conclusion, we have demonstrated that the combination of anti-PD-1 and anti-CTLA-4 can be an effective therapy for the treatment MBrM, while also identifying the main immune cell populations involved and a potential mechanism behind the therapeutic efficacy.
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Westermark, Hanna. "Deep Learning with Importance Sampling for Brain Tumor MR Segmentation." Thesis, KTH, Optimeringslära och systemteori, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-289574.
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Segmentation of magnetic resonance images is an important part of planning radiotherapy treat-ments for patients with brain tumours but due to the number of images contained within a scan and the level of detail required, manual segmentation is a time consuming task. Convolutional neural networks have been proposed as tools for automated segmentation and shown promising results. However, the data sets used for training these deep learning models are often imbalanced and contain data that does not contribute to the performance of the model. By carefully selecting which data to train on, there is potential to both speed up the training and increase the network’s ability to detect tumours. This thesis implements the method of importance sampling for training a convolutional neural network for patch-based segmentation of three dimensional multimodal magnetic resonance images of the brain and compares it with the standard way of sampling in terms of network performance and training time. Training is done for two different patch sizes. Features of the most frequently sampled volumes are also analysed. Importance sampling is found to speed up training in terms of number of epochs and also yield models with improved performance. Analysis of the sampling trends indicate that when patches are large, small tumours are somewhat frequently trained on, however more investigation is needed to confirm what features may influence the sampling frequency of a patch.Segmentering av magnetröntgenbilder är en viktig del i planeringen av strålbehandling av patienter med hjärntumörer. Det höga antalet bilder och den nödvändiga precisionsnivån gör dock manuellsegmentering till en tidskrävande uppgift. Faltningsnätverk har därför föreslagits som ett verktyg förautomatiserad segmentering och visat lovande resultat. Datamängderna som används för att träna dessa djupinlärningsmodeller är ofta obalanserade och innehåller data som inte bidrar till modellensprestanda. Det finns därför potential att både skynda på träningen och förbättra nätverkets förmåga att segmentera tumörer genom att noggrant välja vilken data som används för träning. Denna uppsats implementerar importance sampling för att träna ett faltningsnätverk för patch-baserad segmentering av tredimensionella multimodala magnetröntgenbilder av hjärnan. Modellensträningstid och prestanda jämförs mot ett nätverk tränat med standardmetoden. Detta görs förtvå olika storlekar på patches. Egenskaperna hos de mest valda volymerna analyseras också. Importance sampling uppvisar en snabbare träningsprocess med avseende på antal epoker och resulterar också i modeller med högre prestanda. Analys av de oftast valda volymerna indikerar att under träning med stora patches förekommer små tumörer i en något högre utsträckning. Vidareundersökningar är dock nödvändiga för att bekräfta vilka aspekter som påverkar hur ofta en volym används.
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Stevens, Laura Louise. "An in vivo study of angiogenesis in a brain tumour model by dynamic contrast-enhanced CT scanning." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ32513.pdf.
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Jones, Timothy L. "A novel magnetic resonance diffusion tensor imaging segmentation and visualisation technique for brain tumour diagnosis and surveillance." Thesis, University of London, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.589799.
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BACKGROUND Over 120 brain tumour subtypes have been identified, varying in presentation, treatment and life expectancy. Imaging has a role in diagnosis, treatment planning and evaluating therapeutic response. Advanced techniques e.g. diffusion tensor imaging (OTI) have been used to quantify voxel magnitudes of isotropic (P) and anisotropic (q) diffusion. It has been proposed these reflect tissue structure and may characterise tumour type as well as delineate margins. METHODS Using two 1.5T MRI scanners, OTI scans were acquired from 94 patients prior to surgery and histological diagnosis (38 glioblastoma, 19 low-grade glioma (LGG), 26 metastasis and 11 meningioma). Furthermore, OTI scans were acquired from 6 LGG patients at 3 time points. Manual tumour and oedema regions of interest (MROI) were drawn on coregistered enhanced Tj-weiqhted and FLAIR MRI. Values of p and q within MROI were entered into a discriminant analysis. A novel k-means segmentation (k=16) of p:q space was performed simultaneously across all data sets and resultant clusters labelled according to constituent p, q and T 2-weighted characteristics, generating colour-diffusion-maps. Using a flood-filling technique, segmented ROls (SROI) were determined. Constituent segment profiles (spectra) were evaluated using the same discriminant analysis. SROI were created from longitudinal LGG scans and spectral changes evaluated over time. RESULTS Despite marked differences in p and q between MROls, the discriminant model revealed poor diagnostic accuracy. The segmentation is computationally efficient, stable and presents potential tumour-specific patterns with a delineated' boundary between tumour and brain. The SROI analysis provided an overall diagnostic sensitivity of 86%. LGG spectra identified early features of malignant transformation not evident on conventional MRI. CONCLUSIONS We present a novel visualisation of tumours from OTI and a diagnostic tool with good diagnostic accuracy and ability to identify changes in LGG. It delineates a margin which may represent a clinically relevant boundary for treatment planning and volumetric analysis.
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Torrealdea, F. "Investigation of brain tumour metabolism using naturally occurring chemical exchange saturation transfer agents with magnetic resonance imaging." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1490928/.
Full textAbstract:
This thesis presents a thorough study on the newly developed glucoCEST magnetic resonance imaging (MRI) technique and its application for the assessment of malignant brain tumours. The key asset of glucoCEST is that it allows the detection of small concentration of glucose with standard MRI scanners and has the potential to provide a novel imaging tool to investigate diseases in which glucose metabolism is affected, in particular cancer. The physical principles and the rationale behind the glucoCEST technique are described in detail and factors influencing the measurements (both physiological and hardware related) are analysed using computer simulations and evaluated with in vitro experiments. Special attention is given to the analysis of the first four sugars along the glycolytic pathway i.e. glucose, glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-biphosphate as contributors to the overall observed signal. The results of this analysis give grounds for the argument of the intracellular origin of the glucoCEST signal, which opens the possibility of characterising tumours based on their metabolism with MRI. A preclinical glucoCEST study on mice bearing human xenograft glioblastoma is also presented in which cancers with diverse phenotype are scanned longitudinally throughout the different stages of tumour development. While not conclusive, the results suggest that the glucoCEST technique is able to identify the presence of cancer at an earlier stage than standard MRI methods.
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Hart, Michael Gavin. "Network approaches to understanding the functional effects of focal brain lesions." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/274018.
Full textAbstract:
Complex network models of functional connectivity have emerged as a paradigm shift in brain mapping over the past decade. Despite significant attention within the neuroimaging and cognitive neuroscience communities, these approaches have hitherto not been extensively explored in neurosurgery. The aim of this thesis is to investigate how the field of connectomics can contribute to understanding the effects of focal brain lesions and to functional brain mapping in neurosurgery. This datasets for this thesis include a clinical population with focal brain tumours and a cohort focused on healthy adolescent brain development. Multiple network analyses of increasing complexity are performed based upon resting state functional MRI. In patients with focal brain tumours, the full complement of resting state networks were apparent, while also suggesting putative patterns of network plasticity. Connectome analysis was able to identify potential signatures of node robustness and connections at risk that could be used to individually plan surgery. Focal lesions induced the formation of new hubs while down regulating previously established hubs. Overall these data are consistent with a dynamic rather than a static response to the presence of focal lesions. Adolescent brain development demonstrated discrete dynamics with distinct gender specific and age-gender interactions. Network architecture also became more robust, particularly to random removal of nodes and edges. Overall these data provide evidence for the early vulnerability rather than enhanced plasticity of brain networks. In summary, this thesis presents a combined analysis of pathological and healthy development datasets focused on understanding the functional effects of focal brain lesions at a network level. The coda serves as an introduction to a forthcoming study, known as Connectomics and Electrical Stimulation for Augmenting Resection (CAESAR), which is an evolution of the results and methods herein.