To see the other types of publications on this topic, follow the link: Cancer; Brain tumours.
Dissertations / Theses on the topic 'Cancer; Brain tumours'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Cancer; Brain tumours.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Maxwell, Marius. "Expression of proto-oncogenes and growth factors in glioblastoma multiforme." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259967.
Full text
2
Florian, Catarina Ligia. "Proton nuclear magnetic resonance studies of human glioma cell lines." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309218.
Full text
3
Gill, Simrandip Kaur. "Single voxel proton magnetic resonance spectroscopy of childhood brain tumours." Thesis, University of Birmingham, 2014. http://etheses.bham.ac.uk//id/eprint/4899/.
Full textAbstract:
Conventional magnetic resonance imaging (MRI) is essential for the management of childhood brain tumours. However, it is increasingly being supplemented with functional techniques such as magnetic resonance spectroscopy (MRS). This thesis investigates how pre-treatment single voxel MRS can aid in diagnosis and surveillance of paediatric brain tumours and identify prognostic biomarkers. Data from multiple centres, scanners from three leading manufacturers and field strengths of 1.5 T and 3 T are incorporated. MRS was analysed using TARQUIN software with metabolite peaks fitted using a simulated basis set to provide metabolite concentrations. Univariate and multivariate statistical tests were used to compare variables. Multi-scanner spectroscopy detected significant differences in common and rare paediatric brain tumours. Diagnostic metabolite profiles were able to confirm tumour on follow-up imaging. Elevated creatine and total choline determined good prognosis in medulloblastoma. Myo-inositol and citrate aided in the characterisation of diffuse pontine gliomas (DIPG). While conventional MRI was unable to identify prognostic markers for DIPG, elevated taurine was found to be significantly associated with a better prognosis. The results encourage the use of MRS as an adjunct to conventional MRI in routine clinical practice. For future studies, accurate assignment of biomarkers will be determined in tumour tissue using in vitro high-resolution spectroscopy methods.
4
Schmiegelow, Marianne. "Endocrinological late effects following radiotherapy and chemotherapy of childhood brain tumours. /." København : Lægeforeningens Forlag, 2005. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=014566238&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
Full text
5
Punjaruk, Wiyada. "The contribution of drug resistant cancer stem cells to paediatric brain tumours." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/13403/.
Full textAbstract:
Introduction: Recent studies have revealed that cancer stem cells (CSCs) exist in malignant disease. Additionally, it is proposed that these cells may survive following chemotherapy, and hence contribute to tumour relapse. A significant mechanism of drug resistance in CSCs is believed to be the expression of ATP-binding cassette (ABC) transporters that efflux cytotoxic agents out of cells. The objective of this study was to study the existence of CSCs in a panel of primary paediatric brain tumours (PBTs) and to determine if these were drug resistant via functional ABC transporters. Materials and Methods: The main cell lines characterised were: EPN-2 (primary ependymoma); MED-2 (recurrent medulloblastoma); SPNET-1 [primary CNS primitive neuroectodermal tumour (CNS PNET)]; and a commercial CNS PNET (PFSK-1). Basic characterisation of our cell lines were assessed by Telomeric Repeat Amplification Protocol (TRAP) assay, Terminal Restriction Fragments (TRF) assay, metaphase spread analysis and doubling time. To determine the proportion of cancer stem-like cells in the parental cell lines, CD133 and SOX2 co-staining immunofluorescence was performed and validated by Western blotting analysis. The expression of ABC transporters (ABCB1, ABCC1 and ABCG2) was also investigated by co-staining for CD133 and ABC transporters using immunofluorescence and Western blotting analysis. Flow cytometry was performed to examine ABCB1 function. Four clinically relevant drugs (etoposide, cisplatin, irinotecan and methotrexate) were used to assess the degree of drug resistance of these lines. Clonnogenic assay and neurosphere formation assay were then performed to investigate colony survival and the ability of cells to form neurospheres, respectively, after drug treatment. Finally, the potential to increase chemosensitivity by drug treatment in the presence of the ABCB1 inhibitor, Verapamil, was assessed. Results: Basic characterisation results demonstrated that a high level of telomerase activity and maintenance of telomere length was found in all cell lines (grown both as monolayers and neurospheres). Metaphase spread analysis showed a wide range of aberrant chromosome numbers in PFSK-1 cells whereas our cell lines demonstrated a more stable chromosome number. Neurospheres grew slower than monolayers and monolayers had constant growth rate with increasing passage number. It was found that for each cell line, a small subpopulation (8-12%) of cultured monolayer cells are positive for both CD133 and SOX-2 immunofluorescent staining whilst cultured neurospheres contained 35-45% of co-stained cells. No co-stained cells were identified in the commercial PFSK-1 line and these findings were consistent with the results from Western blotting analysis. Approximately 10% of the parental cell lines comprised cells co-expressing CD133 and ABCB1 or ABCC1 at a low level whilst none of our cell lines were positive for ABCG2. Additionally, the parental cell lines contained a small proportion of cells expressing functional endogenous ABCB1 (34±5.2% in EPN-2, 26.5±3.9% in MED-2 and 13.9±3.2% in SPNET-1). During multiple rounds of drug treatment, ABCB1 was consistently expressed at a high level throughout and the proportion of functional ABCB1 expressing cells increased in all cell lines almost 2 fold compared to the parental cell lines and the selected control sublines. Whilst ABCC1 expression was gradually upregulated after multiple rounds of treatment but ABCG2 expression remained negative. Drug combined with Verapamil treatment significantly decrease survival rate approximately 5 fold compared to drug treatment alone although the majority of surviving cells were still CD133 and ABCB1 positive. Conclusion: Newly established paediatric cell lines (EPN-2, MED-2 and SPNET-1) represented significant histological and biological features of the original tumours from which they were derived and were stable in standard culture condition for a prolonged period of time. The parental cell lines contained a small proportion of cells expressing endogenous functional ABCB1 at a low level indicating intrinsic drug resistance. After multiple rounds of drug treatment, ABCB1 was the major mechanism of drug resistance in our cell lines. ABCC1 were upregulated later in our cell lines after multiple rounds of drug treatment whereas none of our cell lines expressed ABCG2 during drug treatment.
6
Neal, Anthony James. "Optimisation of radiotherapy treatment planning for tumours of the breast, prostate and brain." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306922.
Full text
7
Gorgolewski, Krzysztof Jacek. "Using functional magnetic resonance imaging to plan surgical resections of brain tumours." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/7861.
Full textAbstract:
Brain tumours, even though rare, are one of the deadliest types of cancer. The five year survival rate for the most malignant type of brain tumours is below 5%. Modern medicine provides many options for treating brain cancer such as radiotherapy and chemotherapy. However, one of the most effective ways of fighting the disease is surgical resection. During such a procedure the tumour is partially or completely removed. Unfortunately, even after a complete resection some tumourous tissue is left behind and can grow back or metastasise to a different location in the brain. It has been shown, however, that more aggressive resections lead to longer life expectancy. This does not come without risks. Depending on tumour location, extensive resections can lead to transient or permanent post-operative neurological deficits. Therefore, when planning a procedure, the neurosurgeon needs to find balance between extending patients life and maintaining its quality. Recent developments in Magnetic Resonance Imaging (MRI) fueled by the field of human cognitive neuroscience have led to improved methods of non-invasive imaging of the brain function. Such methods allow the creation of functional brain maps of populations or individual subjects. Adapting this technique to the clinical environment enables the assessment of the risks and to plan surgical procedures. The following work aims at improving the use of functional MRI with a specific clinical goal in mind. The thesis begins with description of etiology, epidemiology and treatment options for brain tumours. This is followed by a description of MRI and related data processing methods, which leads to introduction of a new technique for thresholding statistical maps which improves upon existing solutions by adapting to the nature of the problem at hand. In contrast to methods used in cognitive neuroscience our approach is optimized to work on single subjects and maintain a balance between false positive and false negative errors. This balance is crucial for accurate assessment of the risk of a surgical procedure. Using this method a test-retest reliability study was performed to assess five different behavioural paradigms and scanning parameters. This experiment was performed on healthy controls and was aimed at selecting which paradigms produce reliable results and therefore can be used for presurgical planning. This allowed the creation of a battery of task that was applied to glioma patients. Functional maps created before the surgeries were compared with electrocortical stimulation performed during the surgeries. The final contribution of this work focuses on technical aspects of performing neuroimaging data analysis. A novel data processing framework which provides means for rapid prototyping and easy translation and adaptation of already existing methods taken from cognitive neuroscience field is introduced. The framework enables fully automatic processing of patient data and therefore greatly reduced costs while maintaining quality control. A discussion of future directions and challenges in using functional MRI for presurgical planning concludes the thesis.
8
Tomson, Derek. "Evaluating the association between adult primary brain tumours and a family history of cancer." Thesis, University of Ottawa (Canada), 2006. http://hdl.handle.net/10393/27301.
Full textAbstract:
There are very few established causes of primary brain tumours in adults. Associated with short survival times, increasing effort is being put forth in an attempt to better understand the risk factors of these neoplasms, including investigating the possible relationship with a family history of cancer and germline genetic polymorphisms. This thesis was conducted to evaluate both of these potential associations.
Using an international population-based case-control study, the self-reported family histories of cancer were compared between 1089 glioma cases and 1922 matched controls and between 307 meningioma cases and 1095 controls. Significantly lowered odds of glioma were associated with the reporting of any type of cancer in a first degree relative (OR = 0.8, 95% CI = 0.7-0.99) and with any type of cancer excluding brain tumours (OR = 0.8, 95% CI = 0.7-0.9). No significant associations were found amongst the meningioma cases and controls, though elevated point estimates were found for those reporting parental lung and genitourinary cancers, while the presence of breast, lip, oral, pharyngeal and unspecified cancers all produced great reductions in meningioma odds, suggesting that further study is required.
In order to evaluate the association between adult brain tumours and genetic polymorphisms, a systematic review of the literature was completed. A total of 41 case-control studies were included, covering 46 separate genes and more than 100 different single nucleotide polymorphisms. When possible, quantitative data synthesis was performed to establish a more refined point estimate and confidence intervals. Heterogeneity across the studies and variability in the subject matter often prevented any possible data synthesis so establishing associations that were statistically significant was difficult. All told, there were 41 significant associations found amongst the included studies and each varied by the particular polymorphism or histology studied. None of the estimates produced in the quantitative data syntheses suggested a statistically significant association.
The results of this thesis suggest that a family history of cancer is not a risk factor for primary brain tumours in adults and that further work is necessary to better establish the possible association between various genetic polymorphisms and adult brain tumours.
9
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.
Full textAbstract:
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.
10
Ferguson, Anthea Elizabeth Women's & Children's Health Faculty of Medicine UNSW. "Gene polymorphisms influencing the cause and disease outcome of childhood central nervous system tumours." Awarded By:University of New South Wales. Women's & Children's Health, 2009. http://handle.unsw.edu.au/1959.4/44816.
Full textAbstract:
Tumours of the central nervous system (CNS) are the second most common cancers diagnosed in children, yet the cause of this disease remains largely unknown. This thesis examines whether polymorphisms in folate-metabolising and glutathione S transferase (GST) genes influence the risk and disease outcome of childhood CNS tumours. 204 children aged ≤18 years diagnosed with a CNS tumour at the Sydney Children??s Hospital between 1989 and 2004 were included in the study. DNA samples were isolated from archival frozen and formalin-fixed paraffin-embedded tumour tissue. Polymorphisms in GST and folate pathway genes were examined using real-time PCR. Genotype distributions in children with CNS tumours were compared to those observed in a control panel of cord blood samples from 363 healthy newborns. Children carrying at least one variant allele for each of MTHFR 677 C>T, MTHFR 1298 A>C, MTR 2756 A>G, MTRR 66 A>G, and RFC 80 G>A were found to have a 2.8-fold greater risk of developing a CNS tumour than non-carriers (OR=2.80; 95%CI: 1.08-7.56, P=0.022), an association which was even more apparent in those children with an embryonal tumour (OR=4.54; 95%CI: 1.13-15.85, P=0.016). Results also showed that children with the GSTP1 105 Val/Val genotype were three times more likely to develop a CNS tumour of embryonal cell origin than children with the GSTP1 105 Ile/Ile or Ile/Val genotypes (OR=3.02; 95%CI: 1.34-6.46, P=0.005). No such association was observed for CNS tumours of glial cell origin. The GSTM1, GSTT1, and GSTP1 Ala114Val polymorphisms did not appear to be associated with the development of a childhood CNS tumour. In addition, children with the MTHFR 677 TT or RFC 80 AA genotypes were found to have a higher risk of death within 5 years of diagnosis compared to children with one or more MTHFR 677 C or RFC 80 G alleles, respectively (HR=5.52, 95%CI: 1.00-30.37, P=0.049 and HR=5.69, 95%CI: 1.38-23.51, P=0.016, respectively), after adjusting for other prognostic factors such as sex, age at diagnosis, period of diagnosis, and tumour grade. Conversely, children with the MTR 2756 AG or GG genotypes, or MTRR 66 AG or GG genotypes, were more likely to survive compared to those with the MTR 2756 AA or MTRR 66 AA genotypes, respectively (HR=0.21, 95%CI: 0.05-0.93, P=0.040 and HR=0.11, 95%CI: 0.02-0.53, P=0.006). Results presented in this thesis indicate that polymorphisms in folate-metabolising and GST genes may play a role in the aetiology and survival of childhood CNS tumours, and that this may vary depending on the histological sub-type of tumour.
11
Mylonas, Nicos. "Development of positioning devices for MRI-guided high intensity focused ultrasound (HIFU) for abdominal, thyroid and brain, tumours." Thesis, City University London, 2012. http://openaccess.city.ac.uk/2417/.
Full textAbstract:
High intensity focused ultrasound (HIFU) is a promising technology for a variety of therapeutic applications. This concept initiated in 1942 by Lynn Zwemer [1]. HIFU has long been known as a minimal invasive or non-invasive procedure that destroys tissue through ablation. However, it is only in recent years that clinical applications are becoming feasible, with the development of high power ultrasound transducers compatible with the MRI scanner which is used to monitor these non-invasive HIFU applications. New technologies, combined with more sophisticated treatment methods and monitoring methods allow non-invasive procedures in many areas such as the brain, eye, breast, kidney, liver, pancreas, thyroid, uterine fibroids and pancreas. Meanwhile, new investigations are underway for treading cardiac arithmia, strokes, palliative pain treatment of bone metastases and brain disorders such as Parkinson’s disease, essential tremor, and neuropathic pain. These optimistic investigations have encouraged physicians and provided them new valuable tools for medical research.
12
Omoruyi, Sylvester Ifeanyi. "Investigating the anti-cancer activity of novel phenothiazines in glioblastoma." University of the Western Cape, 2018. http://hdl.handle.net/11394/6329.
Full textAbstract:
Philosophiae Doctor - PhDGlioblastoma multiforme (GBM) remains the most malignant of all primary adult brain tumours. It is a highly invasive and vascularized neoplasm with limited treatment options and very low survival rate. GBM tumours are heterogeneous in nature with cellular hierarchy and at the apex of this hierarchy are the glioblastoma stem cells, known to promote tumourigenesis and resistance to chemotherapeutic agents and tumour recurrence. Currently, the standard care for GBM involves surgical resection, radiation, and chemotherapy treatment with temozolomide. Unfortunately, median survival after treatment is still daunting and tumour relapse is very frequent. Indeed, patients with recurrent glioblastoma have less than a year survival. To address this, novel therapies need to be developed with the early introduction of promising agents into clinical trials and subsequent approval for use. Importantly, for these novel therapies to be approved for GBM, they need to be safe, effective as well as being able to penetrate the blood-brain barrier (BBB). Due to the high cost and process time for the development of new drugs, existing approved drugs are currently being repurposed for new indications and this is gaining significance in clinical pharmacology as it allows rapid delivery of useful drugs from bench to bedside. Drugs of the antipsychotic class are well known to cross the BBB due to their neuroleptic action. To this end, the aim of this study was to identify and characterize the anti-cancer activities of novel phenothiazine-derivatives belonging to the antipsychotic class of drugs in glioblastoma. To achieve this, several novel phenothiazine-derivatives were initially screened for possible anti-cancer activity in the U87 and U251 malignant GBM cells. Two lead compounds, DS00326 and DS00329, were identified and their anti-cancer activities were determined in U87 and U251 cells as well as in primary patient-derived xenograft (PDX) glioblastoma cultures. DS00326 and DS00329 significantly inhibited glioblastoma cell viability, with minimal effects observed in the non-cancerous FG0 fibroblasts. The IC50 values of DS00326 and DS00329 for U251, U87 and PDX cells ranged from 1.61 to 12.53μM. Flow cytometry analyses showed that DS00326 and DS00329 treatment led to an increase in the G1 population of cells. Additionally, DS00326 and DS00329 induced double-strand DNA breaks, which lead to activation of the canonical DNA damage response pathway. Furthermore, DS00326 and DS00329 induced apoptosis as shown by morphological markers, flow cytometry with annexin V-FITC/propidium iodide staining, as well as western blotting with an antibody to detect levels of cleaved PARP. Interestingly, treatment with DS00326 and DS00329 also induced autophagy as evident by the increase of acidic vesicular organelles in cells following staining with acridine orange as well as an increase in levels of the autophagy marker LC3-II. Autophagy was seen as a pro-death pathway in the U87 and U251 cells as inhibition of autophagy led to a reversal of cytotoxicity and consequently increased cell survival. Moreover, it was demonstrated that DS00326 and DS00329 inhibited the PI3/Akt pathway while modulating the mitogen-activated protein kinases p38, ERK1/2 and JNK signalling pathways. Importantly DS00326 and DS00329 displayed anti-cancer stem cell activities by the inhibition of neurosphere formation and regulation of stem cell markers SOX2 and GFAP in PDX cells. Together, the findings from this study suggest that DS00326 and DS00329 may be effective in the treatment of glioblastoma and provide a strong rationale for further clinical studies exploiting phenothiazines and their derivatives as treatments for glioblastoma.
2021-09-01
13
Wams, Emma J. "Neurodegeneration and brain cancer : a longitudinal field study of rest-activity and sleep." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:23d242cd-45c7-4dca-a3c5-b1e83747af13.
Full textAbstract:
This thesis investigates rest-activity and sleep profiles in neurodegeneration and brain cancer. Study 1 comprised longitudinal field assessments of rest-activity, sleep and memory in controls and memory-impairment individuals with: subjective memory complaint (SMC), amnestic mild cognitive impairment (aMCI), mild and moderate Alzheimer’s disease (AD). Four questions were addressed: (1) is SMC a prodromal stage of AD? (2) do characteristics of SMC predict future decline? (3) does cholinergic medication (ChEI) impact rest-activity and sleep of moderate AD patients? and (4) are there factors predicting response to ChEI? Study 2 assessed rest-activity and melatonin rhythms in a brain cancer patient (JJB), and post-mortem analysis of brain tissue assessed infiltration of cancer cells on the circadian clock (SCN). Both studies used questionnaires, cognitive tests, electroencephalography and actigraphy simultaneously at patients’ homes. In Study 1, the SMC group showed a reduced activity amplitude to be correlated with increasing memory impairment severity, lower sleep quality and efficiency. Increased sleep fragmentation was observed in all memory-impaired groups, although not correlated to impairment severity. Increased fragmentation of rest-activity rhythm correlated with increasing memory impairment severity in all groups except SMC. Following ChEI medication with donepezil, moderate AD patients showed increased sleep fragmentation, probably due to potentiation of available acetylcholine known to maintain arousal. Higher daytime-activity and lower activity in the rest-phase, when drug-naïve, predicted improved cognition following ChEIs. In Study 2, cancer cell infiltration of the patient’s SCN was confirmed. However, a robust circadian rest-activity period with a misaligned melatonin phase, was recorded, indicating that the effects of partial SCN lesions in humans are complex and this result was possibly in part are due to the masking effect of social behaviour.
14
Edvardsson, Tanja. "Consequences of brain tumours from the perspective of the patients and of their next of kin." Doctoral thesis, Örebro universitet, Hälsoakademin, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-1742.
Full textAbstract:
A disease has consequences not only for the afflicted person but also for those who interact with him or her. A low-grade glioma is a brain tumour whose regarding its psychosocial implications for adult patients and their next of kin has received little attention in the literature. In the light of this the overall aim of the present thesis was to provide increased knowledge about how patients with low-grade glioma and their next of kin experience and deal with everyday life. The methods of the studies were mainly qualitative. Thirty-nine patients and 28 next of kin were interviewed and all except one next of kin completed a quality of life questionnaire. The onset of low-grade glioma was described from the patients’ perspective as a process, either rapid (up to a few months) or prolonged over several years. This phase of low-grade glioma encompassed repeated visits to physicians and care institutions. The onset of low-grade glioma was accompanied by stress, anxiety and uncertainty in the case of both the patients and those nearest. The symptoms and problems the patients experienced covered a broad range of consequences, physical, psychological and social. The patients presented a wide range of ways to cope with illness-related problems. The next of kin were often deeply involved in the patients’ situation and many of them experienced extremely stressful emotions mainly in the early period of the illness. They had experience of positive encounters in health care but more often they had had a sense both of powerlessness and of being invisible and neglected. Relations and roles changed in ways that mostly were experienced as negative. Enabling strength in everyday life had to do with alleviation of strain and having a positive outlook upon life. By means of the questionnaire Subjective estimation of Quality of Life (SQoL) the patients and those nearest estimated their quality of life as being comparatively high. Only one variable, among the patients the absence of work/meaningful occupation and among the next of kin the absence of own children, being estimated at below 60% of the maximum score.
15
Connell, John J. "Selective permeabilisation of the blood-brain barrier at sites of metastasis." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:8c027208-8ea6-4de4-be78-ccead5121509.
Full textAbstract:
Over one in five cancer patients will develop brain metastases and prognosis remains poor. Effective chemotherapeutics for primary systemic tumours have limited access to brain metastases owing to the blood-brain barrier (BBB). The aim of this study was to develop a strategy for specifically permeabilising the BBB at sites of cerebral metastases. Tumour necrosis factor was injected intravenously into mouse models of haematogenously induced brain metastasis. BBB permeability was assessed through histology and in vivo MRI and SPECT. Tumour burden and neuroinflammation were assessed after injection of TNF with Caelyx or a novel therapeutic. Mechanism of permeabilisation was investigated through histology and receptor-specific agonist antibodies. Administration of TNF dose-dependently permeabilised the BBB to exogenous tracers selectively at sites of brain metastasis, with peak effect after six hours. Metastasis-specific uptake of radiolabelled trastuzumab was also demonstrated following systemic cytokine administration. Administration of liposomal doxorubicin formulations in conjunction with TNF reduced tumour burden and mean metastasis size. Localised expression of TNFR1 was evident on the vascular endothelium associated with brain metastases. Human brain metastases displayed a similar TNF receptor profile compared to the mouse model. These findings describe a new approach to selectively permeabilise the BBB at sites of brain metastases, thereby enabling detection of currently invisible micrometastases and facilitating tumour-specific access of chemotherapeutic agents. We hypothesize that this permeabilisation works primarily though TNFR1 activation and, owing to the similar TNFR1 expression profiles in mouse models and human condition, the strategy has the potential for clinical translation.
16
Siesjö, Peter. "Immunotherapy of rat brain tumors with mutagen induced, cross-reactive tumor cell variants." Lund : Section of Tumor Immunology, Dept. of Cell and Molecular Biology, University of Lund, 1997. http://books.google.com/books?id=TXZrAAAAMAAJ.
Full text
17
Soldatelli, Jéssica Silveira. "Efeitos da combinação de temozolomida e ditelureto de difenila em linhagens celulares de glioblastoma." reponame:Repositório Institucional da UCS, 2018. https://repositorio.ucs.br/11338/4064.
Full textAbstract:
Os gliomas representam mais de 70% dos tumores cerebrais primários. Os glioblastomas multiformes são gliomas malignos caracterizados por baixa incidência, mas altas taxas de mortalidade. Apesar da responsividade inicial ao tratamento padrão realizado com o quimioterápico alquilante temozolomida (TMZ), poucos foram os avanços para o prognóstico dos pacientes nos últimos 10 anos. Isso deve-se ao fato desses tumores serem raramente passíveis de ressecção cirúrgica e apresentarem alta taxa de recorrência. Além disso, a eficácia de seu tratamento encontra barreiras como efeitos colaterais indesejáveis e resistência quimioterápica. Nesse cenário, a descoberta de novas substâncias que possam atuar com efeito aditivo ou sinérgico e aumentem a sensibilização de células tumorais ao tratamento, torna-se uma estratégia terapêutica no campo da oncologia. O ditelureto de difenila (DTDF) é um composto orgânico contendo telúrio que apresenta interessantes efeitos biológicos in vitro, como antioxidante, quimioprotetivo, citotóxico e antitumoral. Sendo assim, o objetivo deste estudo foi avaliar os efeitos do DTDF e do quimioterápico TMZ, em regimes isolados e em associação. Para tal foram investigados seus efeitos citotóxicos, após exposição aguda e crônica, em culturas celulares de glioma não-resistente (M059J) e resistente à TMZ (GBM). No ensaio de viabilidade celular a TMZ apresentou citotoxicidade para as linhagens celulares testadas, com valor de IC50 maior na linhagem resistente do que quando comparado à linhagem não-resistente. Este dado foi confirmado pelo teste de duplicação cumulativa de população e, também, pela coloração com laranja de acridina, após o tratamento de 120 h, por observar-se um aumento na frequência de células positivas para a formação de organelas vesiculares ácidas em ambas as linhagens, sendo predominantemente em células GBM. Além disso, foi observado que o tratamento associando DTDF e a TMZ apresentou uma maior citotoxicidade quando comparado aos tratamentos isolados, após 120 h de tratamento. Portanto, o DTDF sensibilizou as células ao tratamento com TMZ. Essa sensibilização ocorreu em níveis aproximados para ambas as linhagens, sendo os efeitos do DTDF independentes do perfil de resistência à TMZ. Em conjunto, os dados desse trabalho sugerem o uso do DTDF em associação à TMZ como uma estratégia para reduzir as doses de TMZ empregadas na clínica e diminuir efeitos colaterais aos pacientes em tratamento de gliomaGliomas represent more than 70% of primary brain tumors. Malignant gliomas are characterized by low incidence, but high mortality rates. Despite the initial responsiveness to the standard treatment with the chemotherapeutic alkylating temozolomide (TMZ), few advances have been made in the prognosis of patients in the last 10 years. This is due to the fact that these tumors are rarely amenable to surgical resection and have a high rate of recurrence. Moreover, the effectiveness of this treatment encounters barriers such as undesirable side effects and chemotherapeutic resistance. In this scenario, the discovery of new substances that may act with additive or synergistic effect and increase the sensitization of tumor cells to the treatment becomes a therapeutic strategy in the field of oncology. Diphenyl ditelluride (DPDT) is a derivative of tellurium used in various reactions of organic synthesis and has interesting in vitro biological effects, as antioxidant, chemoprotective, cytotoxic and antitumor agent. Therefore this work aimed to evaluate the cytotoxic effects of this organotellurium compound and the chemotherapeutic, TMZ, in isolated and in association regimens, after acute and chronic exposure, of non-resistant (M059J) and TMZ- resistant (GBM) glioma cells. Through the cell viability assay, it was shown that TMZ is cytotoxic for both cell lines tested, showing a higher IC50 value in the resistant line when compared to the other line. This data was confirmed by the cumulative population doubling test. In addition, by the acridine orange staining, it was verified that autophagy might favor the chemoresistance, although not being the main resistance mechanism in the lines tested. It was observed that DPDT clearly has a dose-dependent cytotoxic effect on the M059J and GBM cell lines, in a lower concentration range than that used with TMZ. DPDT sensitized the cells to TMZ treatment as evidenced by the decline in cell viability. It is important to point out that this sensitization occurred in low and approximate IC50 values after both 24 h and 120 h of treatment, being the effects of the DPDT independent of the resistance profile to TMZ. Taken together, data from this work suggest the use of DPDT in association with TMZ as an interesting strategy to reduce the doses of TMZ used in the clinic and to reduce side effects to patients under treatment of glioma.
18
Kiebish, Michael Andrew. "Mitochondrial lipidome and genome alterations in mouse brain and experimental brain tumors." Thesis, Boston College, 2008. http://hdl.handle.net/2345/27.
Full textAbstract:
Thesis advisor: Thomas N. SeyfriedMitochondria are the key regulators of the bioenergetic state of the cell. Damage to mitochondrial protein, DNA, or membrane lipids can result as the cause or affect of disease pathology. Regardless, this damage can impair mitochondrial function resulting in a decreased ability to produce ATP to support cellular viability. This thesis research examined the mitochondrial lipidome by shotgun lipidomics in different populations of C57BL/6J (B6) brain mitochondria (non-synaptic and synaptic) and correlated lipid changes to differences in electron transport chain (ETC) activities. Furthermore, a comparison was made for non-synaptic mitochondria between the B6 and the VM mouse strain. The VM strain has a 1.5% incidence of spontaneous brain tumors, which is 210 fold greater than the B6 strain. I determined that differences in the brain mitochondrial lipidome existed in the VM strain compared to the B6 strain, likely corresponding to an increased rate of spontaneous brain tumor formation. Analysis of the mitochondrial genome in the CT-2A, EPEN, VM-NM1, and VM-M3 brain tumors compared to their syngeneic controls mouse strains, C57BL/6J (B6) and VM mice, was examined to determine if mutations existed in experimental brain cancer models. No pathogenic mtDNA mutations were discovered that would likely cause a decrease in the mitochondrial functionality. A novel hypothesis was devised to examine the tumor mitochondrial lipidome to determine if quantitative or molecular species differences existed that could potentially alter the functionality of the ETC. Brain tumor mitochondria were examined from tumors grown in vivo as well as in vitro. Numerous lipid differences were found in the mitochondria of brain tumors, of which the most interesting involved the unique molecular speciation of cardiolipin. ETC activities were significantly decreased in the primary ETC complexes which contribute protons to the gradient as well as the linked complexes of brain tumor mitochondria compared to controls. Taken together, it is likely that differences in the mitochondrial lipidome of brain tumors results in severe impairment of the mitochondria’s ability to produce ATP through the ETC. This research has provided a new understanding of the role of mitochondrial lipids in brain as well as brain cancer and offers an alternative explanation for metabolic dysfunction in cancer
Thesis (PhD) — Boston College, 2008
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Biology
19
Fortin, Ensign Shannon Patricia. "THE TWEAK-FN14 LIGAND RECEPTOR AXIS PROMOTES GLIOBLASTOMA CELL INVASION AND SURVIVAL VIA ACTIVATION OF MULTIPLE GEF-RHO GTPASE SIGNALING SYSTEMS." Thesis, The University of Arizona, 2015. http://hdl.handle.net/10150/528171.
Full textAbstract:
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.Glioblastoma (GB) is the highest grade and most common form of primary adult brain tumors, characterized by a highly invasive cell population. GB tumors develop treatment resistance and ultimately recur; the median survival is nearly fifteen months and importantly, the invading cell population is attributed with having a decreased sensitivity to therapeutics. Thus, there remains a necessity to identify the genetic and signaling mechanisms that promote tumor spread and therapeutic resistance in order to develop new targeted treatment strategies to combat this rapidly progressive disease. TWEAK-Fn14 ligand-receptor signaling is one mechanism in GB that promotes cell invasiveness and survival, and is dependent upon the activity of multiple Rho GTPases including Rac1. Here, we show that Cdc42 is essential in Fn14-mediated Rac1 activation. We identified two guanine nucleotide exchange factors (GEFs), Ect2 and Trio, involved in the TWEAK-induced activation of Cdc42 and Rac1, respectively, as well as in the subsequent TWEAK-Fn14 directed glioma cell migration and invasion. In addition, we characterized the role of SGEF in promoting Fn14-induced Rac1 activation. SGEF, a RhoG-specific GEF, is overexpressed in GB tumors and promotes TWEAK- Fn14-mediated glioma invasion. Moreover, we characterized the correlation between SGEF expression and TMZ resistance, and defined a role for SGEF in promoting the survival of glioma cells. SGEF mRNA and protein expression are regulated by the TWEAK-Fn14 signaling axis in an NF-B dependent manner and inhibition of SGEF expression sensitizes glioma cells to TMZ treatment. Lastly, gene expression analysis of SGEF depleted GB cells revealed altered expression of a network of DNA repair and survival genes. Thus TWEAK-Fn14 signaling through the GEF-Rho GTPase systems which include the Ect2, Trio, and SGEF activation of Cdc42 and/or Rac1 presents a pathway of attractive drug targets in glioma therapy, and SGEF signaling represents a novel target in the setting of TMZ refractory, invasive GB cells.
20
Perry, James David. "Chemo and Radioresistance in Brain-Related Tumors." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1397567849.
Full text
21
Aljohani, Hashim M. "Targeting Tyrosine Kinase Drug Resistance Mechanisms and Metastatic Pathways in Brain Tumors." University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595846160285645.
Full text
22
Prasanna, Prateek. "NOVEL RADIOMICS FOR SPATIALLY INTERROGATING TUMOR HABITAT: APPLICATIONS IN PREDICTING TREATMENT RESPONSE AND SURVIVAL IN BRAIN TUMORS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case149624929700524.
Full text
23
Ailion, Alyssa S. "Longitudinal Analysis of Risk Factors Affecting Reading Trajectories in Children Diagnosed with Pediatric Brain Tumors." Digital Archive @ GSU, 2012. http://digitalarchive.gsu.edu/honors_theses/7.
Full textAbstract:
Prior research suggests aggressive cancer treatments contribute to cognitive impairments in children diagnosed with pediatric brain tumors. The literature also suggests that younger age at diagnosis (AAD) and treatment may result in disrupted cognitive trajectories due to limited brain plasticity. In line with this research, we hypothesized an interaction between radiation therapy (RT) and young AAD of brain tumors, where young AAD and RT results in lower standard scores on the WRAT-R Reading Comprehension Subtest. Analyses included archival data; the sample consists of 134 children diagnosed with pediatric brain tumors with multiple assessments resulting in 487 cases for analysis. Participants were diagnosed with mixed tumor types and locations. A two level multilevel model was used to analyze reading trajectories while taking into account AAD, time since diagnosis, socioeconomic status (SES), and RT. Results detected a positive interaction between AAD and RT (γ =2.08, p=.02). For participants with RT, younger AAD was associated with lower reading scores, whereas AAD had no effect for participants without RT. Results also detected a negative interaction between radiation and time (γ =-2.29, p=.00) indicating that children treated with RT have reading scores that decrease over time. These data suggested that children diagnosed with pediatric brain tumors treated with RT are at higher risk of reading impairment as reflected in their reading scores.
24
Falla, Karen M. "The Relationship between Executive and Psychosocial Functioning in Children Treated for a Brain Tumor." Thesis, University of North Texas, 2001. https://digital.library.unt.edu/ark:/67531/metadc2848/.
Full textAbstract:
This study examined the relationship between executive and psychosocial functioning in 45 children and adolescents age 6 to 17 years who had been treated for a brain tumor. Executive functioning deficits can profoundly impact an adult's ability to function successfully in life. The purpose of the study was to evaluate the potential impact of executive functioning deficits on the day-to-day functioning in a pediatric population. The domains of executive functioning assessed included cognitive flexibility, conceptual thinking, sustained attention, and response inhibition. Psychosocial functioning was assessed using both parent and child report. Several significant relationships were found for adolescents ages 15 and older, with effect sizes ranging from medium to large. In particular, cognitive flexibility and conceptual thinking were significantly related to parent report of depression and adaptive functioning. Fewer significant relationships with smaller effect sizes were found for younger children. The results may reflect the developmental emergence of executive functioning abilities and late effects of executive functioning deficits upon psychosocial functioning. The correlational design of this study precludes definitive statements regarding the temporal nature of the relationship. Additional research, including longitudinal research and replicatory studies, will be needed to further investigate the developmental consequences of executive functioning impairment.
25
Meisen, Walter Hans. "Improving Oncolytic Viral Therapy for Primary and Metastatic Tumors in the Brain." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429187113.
Full text
26
Vagena, Eirini. "Your brain on fat : the role of diet in depression like behaviours." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5800/.
Full textAbstract:
Epidemiological and clinical studies indicate that overweight and obesity are associated with increased risk for depression, but the mechanisms linking dietary components with the development of depression phenotype are poorly understood. To investigate this relationship, we utilized lipidomic and transcriptomic methods to evaluate the effects of diet on the brain.
27
Itoh, Yoshiyuki, Nobukazu Fuwa, and Kozo Morita. "Radiation therapy for metastatic brain tumors from lung cancer : a review to devise individualized treatment plans." Nagoya University School of Medicine, 2003. http://hdl.handle.net/2237/5396.
Full text
28
Davis, Jonathan. "Cancer risk in children of agricultural health study participants." Diss., University of Iowa, 2017. https://ir.uiowa.edu/etd/5926.
Full textAbstract:
This study examines the risk of cancer in children of pesticide applicators from the Agricultural Health Study. The study includes 36,537 children of Iowa participants who were evaluated for cancer incidence during 1975 through 2013 from birth through the age of seventeen. Standard incidence rates for any cancer and specific groups of cancers classified using the International Classification of Childhood Cancer was calculated using rates from the general population of Iowa controlling for year of follow, age, sex, and race. Hazard ratios for Group I-III cancers and paternal exposure to specific pesticides were calculated using exposure information collected on 50 pesticides during phase 1 and 2 of the Agricultural Health Study. The exposure information allowed for calculation of intensity-weighted days of exposure to pesticides using the Agricultural Health Study exposure algorithm. Additionally, maternal ever exposure to specific pesticides was used to evaluate risk of childhood cancer.
There were 118 cancers identified in children of Agricultural Health Study participants. The all-cancer standardized incidence ratio was significantly elevated (SIR = 1.27 95% CI: 1.04-1.50). The most common groups of cancers were Group I leukemia, myeloproliferative disease, and myelodysplastic disease (n=34) followed by Group III central nervous system (CNS) and miscellaneous intracranial and intraspinal neoplasms (n=25).
For paternal intensity-weighted days of exposure, there were 31 of 50 specific pesticides that had sufficient cases of cancer to investigate using Cox proportional hazard models. The herbicide trifluralin significantly increased the risk for Group I childhood cancers for any parental pesticide exposure 2 years before birth through birth when compared to children with no paternal exposure (HR = 2.72 95% CI: 1.15, 6.44). This was consistent with results found from analyzing exposure split into two quantiles based on median exposure of exposed children with a Group I cancer. Parental use of the herbicide S-Ethyl-dipropylthiocarbamate (EPTC) did not result in a sufficient number of Group III cancer cases to look at levels of exposure to EPTC, but ever exposure showed an increased hazard ratio when compared to children with unexposed fathers (HR = 2.56 95% CI: 1.06, 6.20). Other pesticides (dicamba, cyanazine, and terbufos) showed mixed evidence of an association with specific childhood cancers, but were either under powered to evaluate with sensitivity analysis or showed inconsistent risk across exposure levels. Less extensive exposure information was available for mothers of children of the Agricultural Health Study, so analysis was restricted to ever or never exposure to pesticides during a mother’s lifetime. Additionally, there were a limited number of cases of cancer for which maternal exposure to specific pesticides was reported resulting in only 4 pesticides being evaluated for childhood cancer risk (glyphosate, 2,4-dichlorophenoxyacetic acid (2,4-D), carbaryl, and malathion). For these four pesticides, this study did not detect any increased risk of childhood cancer from maternal exposure.
In summary, this study provides the first epidemiological evidence of an increased risk of childhood cancer for trifluralin and EPTC. Since this study provides the first evidence of this increased risk, additional analysis is needed to validate the results. This study demonstrates how pesticide exposure information from participants of the AHS can be used in the evaluation of their children’s cancer risk. Additional follow-up and analysis of this cohort beyond the age of 17 would provide further insight into cancer risk during early adulthood from early life pesticide exposure.
29
Munson, Jennifer Megan. "Novel nanocarriers for invasive glioma." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/41226.
Full textAbstract:
The invasive nature of glioblastoma (GBM) represents a significant challenge to the standard of care and contributes to poor clinical outcomes. Invasion of tumors into healthy brain restricts chemotherapeutic access and complicates surgical resection. The central hypothesis of the thesis is that an effective anti-invasive agent can enhance the standard chemotherapeutic response in invasive brain tumors. Through a screen of novel compounds, a new anti-invasive small molecule, Imipramine Blue (IB), was identified. This triphenylmethane compound inhibits invasion of highly invasive glioma in vitro and in vivo. To elicit a response in vivo, Imipramine Blue was liposomally encapsulated to yield better delivery to tumor. Using this formulation, it is shown that IB attenuates invasion of glioma in vivo leading to a more compact tumor in an aggressively invasive rodent glioma model. Further, it is shown that this novel compound binds NADPH oxidases and alters expression of actin regulatory elements to elicit this anti-invasive activity. To test our hypothesis that anti-invasive therapy coupled with chemotherapy will enhance efficacy, nano-IB therapy was followed by liposomally encapsulated doxorubicin (DXR) chemotherapy. Additionally, a co-encapsulated formulation of IB and DXR was developed and tested in vivo. This combination therapy significantly enhanced survival compared to IB or DXR alone, resulting in long-term survival in the syngeneic invasive rat astrocytoma model RT2. It was seen that sequential treatment was more effective than the co-encapsulated treatment indicating a benefit of pre-treating the tumor with the anti-invasive. This thesis demonstrates that novel anti-invasive IB mediated 'containment' of diffuse glioma significantly enhances the efficacy of DXR chemotherapy compared to chemotherapy or anti-invasive therapy alone.
30
Lakkadwala, Sushant. "Dual Functionalized Liposomes for Co-delivery of Anti-cancer Chemotherapeutics for Treatment of Brain Tumor." Diss., North Dakota State University, 2019. https://hdl.handle.net/10365/29394.
Full textAbstract:
Glioblastoma is a hostile brain tumor associated with high infiltration leading to poor prognosis. Currently available treatment options are insufficient to increase median survival time. The combination therapy has emerged as an efficient way to deliver chemotherapeutics for treatment of glioblastoma. It provides collaborative approach of targeting cancer cells by acting via multiple mechanisms, thereby reducing drug resistance. However, the presence of selective and impermeable blood brain barrier (BBB) restricts the delivery of chemotherapeutic drugs into the brain. To overcome this limitation, we designed a dual functionalized liposomes by modifying their surface with transferrin (Tf) and a cell penetrating peptide (CPP) for receptor and adsorptive mediated transcytosis, respectively. In this study, we used various CPPs based on their physicochemical properties (TAT, penetratin, QLPVM and PFVYLI) and investigated the influence of insertion of CPP to Tf-liposomes on cytotoxic potential, cellular uptake, hemocompatibility and transport across the BBB both in vitro and in vivo. In addition, anti-tumor efficacy of dual functionalized liposomes was evaluated in vitro as well as in vivo. The liposomes were encapsulated with chemotherapeutics agents, doxorubicin and erlotinib for delivery to brain. Co-delivery of doxorubicin and erlotinib loaded Tf-CPP liposomes revealed significantly (p < 0.05) higher translocation more than 12 % across the co-culture endothelial barrier resulting in regression of tumor in the in vitro brain tumor model. The biodistribution of Tf-CPP liposomes demonstrated more than 10 and 2.7 fold increase in doxorubicin and erlotinib accumulation in mice brain, respectively compared to free drugs. Histological evaluation of tissue sections showed no signs of toxicity. In addition, Tf-Pen liposomes showed excellent antitumor efficacy by regressing ~90% of tumor in mice brain with significant increase in the median survival time (36 days). In conclusion, we have developed a high efficiency liposomal drug delivery carrier that can cross the BBB and co-deliver doxorubicin and erlotinib to desired target tumor site in vivo in mice, thereby 1) increased concentration of chemotherapeutics in brain, 2) regression in glioblastoma tumor size, 3) reducing the possibility of drug resistance in cancer cells, without eliciting undesired toxicity.National Institutes of Health (NIH Grant RO1 AG051574)
ND EPSCoR
31
Koglin, Ryan W. "Efficient Image Processing Techniques for Enhanced Visualization of Brain Tumor Margins." University of Akron / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=akron1415835138.
Full text
32
Cousino, Melissa K. "Childhood cancer and brain tumor late effects: The impact on families and associated survivor psychological outcomes." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1406733750.
Full text
33
Lal, Priya Kumari. "Maternal prenatal consumption of bioflavonoids and phenolic acids and risk of childhood brain cancer." Columbus, Ohio : Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1080569687.
Full textAbstract:
Thesis (Ph. D.)--Ohio State University, 2004.Title from first page of PDF file. Document formatted into pages; contains xvii, 274 p.; also includes graphics (some col.). Includes abstract and vita. Advisor: J. Schwartzbaum, School of Public Health. Includes bibliographical references (p. 171-203).
34
Kanli, Georgia. "Method for the classification of brain cancer treatment's responsiveness via physical parameters of DCE-MRI data." Thesis, Stockholms universitet, Fysikum, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-116822.
Full textAbstract:
Tumors have several important hallmarks; anomalous and heterogeneous behaviors of their vascular structures, and high angiogenesis and neovascularization. Tumor tissue presents high blood flow (F) and extraction ratio (E) of contrast molecules. Consequently there is growing interest in non invasive methods for characterizing changes in tumor vasculature. Toft's model has been extensively used in the past in order to calculate Ktrans maps which take into consideration both F and E. However, in this thesis we argue that for accurate tumor characterization we need a model able to compute both F and E in tissue plasma. This project has been developed as part of a larger project, working toward building a Clinical Decision Support System (CDSS): an interactive expert computer software, that helps doctors and other health professionals make decisions regarding patient treatment progress. Using the Gamma Capillary Transit Time (GCTT) pharmacokinetic model we calculate F and E separately in a more realistic framework; unlike other models it takes into account the heterogeneity of the tumor, which depends on parameter a-1. a-1 is the width of the distribution of the capillary transit times within a tissue voxel. In more detail, a-1 expresses the heterogeneity of tissue microcirculation and microvasculature. We studied 9 patients pathologically diagnosed with glioblastoma multiforme (GBM), a common malignant type of brain tumor. Several physiological parameters including the blood flow and extraction ratio distributions were calculated for each patient. Then we investigated if these parameters can characterize early the patients' responsiveness to current treatment; we assessed the classification potential based on the actual therapy outcome. To this end, we present a novel analysis framework which exploits the new parameter a-1 and organizes each voxel into four sub-region. Our results indicate that early characterization of response based on GCCT can be significantly improved by focusing on tumor voxels from a specific sub-region.
35
Sinks, Thomas H. "N-nitroso compounds, pesticides, and parental exposures in the workplace as risk factors for childhood brain cancer : a case-control study /." The Ohio State University, 1985. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487260859497125.
Full text
36
Ach, Emily Lauren. "An Analysis of a Model of Risk and Resilience Among Parents of Pediatric Brain Tumor Survivors." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1366284661.
Full text
37
Norris, Gregory. "Targeting the Hippo Signaling Pathway in Atypical Teratoid Rhabdoid Tumor." Thesis, The University of Arizona, 2017. http://hdl.handle.net/10150/623631.
Full textAbstract:
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.Atypical teratoid rhabdoid tumor (ATRT) is a highly malignant pediatric central nervous system tumor. The prognosis is often poor, with a 2‐year survival rate estimated at 15%. This dismal prognosis highlights the need to develop new treatment modalities for this devastating pediatric tumor. Recently, a tumor suppressing signaling pathway known as Hippo has emerged as a possible cancer treatment target. The Hippo signaling pathway is involved in organ growth and maintenance, and is dysregulated in many diverse cancers. We used quantitative real‐time PCR to evaluate the mRNA expression profile of Hippo pathway genes. We then used determined the protein expression of various Hippo components using Western blots. The results of this study suggest that Hippo plays a definite role in atypical teratoid rhabdoid tumor.
38
Li, Xiaobing. "Automatic image segmentation based on level set approach: application to brain tumor segmentation in MR images." Reims, 2009. http://theses.univ-reims.fr/exl-doc/GED00001120.pdf.
Full textAbstract:
L'objectif de la thèse est de développer une segmentation automatique des tumeurs cérébrales à partir de volumes IRM basée sur la technique des « level sets ». Le fonctionnement «automatique» de ce système utilise le fait que le cerveau normal est symétrique et donc la localisation des régions dissymétriques permet d'estimer le contour initial de la tumeur. La première étape concerne le prétraitement qui consiste à corriger l'inhomogénéité de l'intensité du volume IRM et à recaler spatialement les volumes d'IRM d'un même patient à différents instants. Le plan hémisphérique du cerveau est recherché en maximisant le degré de similarité entre la moitié du volume et de sa réflexion. Le contour initial de la tumeur est ainsi extrait à partir de la dissymétrie entre les deux hémisphères. Ce contour initial est évolué et affiné par une technique de « level set » afin de trouver le contour réel de la tumeur. Les critères d'arrêt de l'évolution ont été proposés en fonction des propriétés de la tumeur. Finalement, le contour de la tumeur est projetée sur les images adjacentes pour former les nouveaux contours initiaux. Ce traitement est itéré sur toutes les coupes pour obtenir la segmentation de la tumeur en 3D. Le système ainsi réalisé est utilisé pour suivre un patient pendant toute la période thérapeutique, avec des examens tous les quatre mois, ce qui permet au médecin de contrôler l'état de développement de la tumeur et ainsi d'évaluer l'efficacité du traitement thérapeutique. La méthode a été évaluée quantitativement par la comparaison avec des tracés manuels des experts. De bons résultats sont obtenus sur des images réelles IRMThe aim of this dissertation is to develop an automatic segmentation of brain tumors from MRI volume based on the technique of "level sets". The term "automatic" uses the fact that the normal brain is symmetrical and the localization of asymmetrical regions permits to estimate the initial contour of the tumor. The first step is preprocessing, which is to correct the intensity inhomogeneity of volume MRI and spatially realign the MRI volumes of the same patient at different moments. The plan hemispherical brain is then calculated by maximizing the degree of similarity between the half of the volume and his reflexion. The initial contour of the tumor can be extracted from the asymmetry between the two hemispheres. This initial contour is evolved and refined by the technique "level set" in order to find the real contour of the tumor. The criteria for stopping the evolution have been proposed and based on the properties of the tumor. Finally, the contour of the tumor is projected onto the adjacent images to form the new initial contours. This process is iterated on all slices to obtain the segmentation of the tumor in 3D. The proposed system is used to follow up patients throughout the medical treatment period, with examinations every four months, allowing the physician to monitor the state of development of the tumor and evaluate the effectiveness of the therapy. The method was quantitatively evaluated by comparison with manual tracings experts. Good results are obtained on real MRI images
39
Smithson, Evans Francesca. "Professionals' diagnostic and prognostic communication practices in cancer, and the mediating effect of illness perceptions on quality of life in brain tumour patients." Thesis, University of Hull, 2016. http://hydra.hull.ac.uk/resources/hull:14523.
Full textAbstract:
The portfolio has three parts. Part one is a systematic literature review, in which the empirical literature relating to general disclosure practices of clinicians regarding the diagnosis and prognosis of cancer is reviewed. Part two is an empirical paper, which explores the potential mediating effect of illness perceptions on the relationship between diagnosis communication and quality-of-life in people with a brain tumour. Part three comprises the appendices. Background: Oncology patients have expressed the wish to be informed of diagnostic and prognostic information in an open and timely manner. The positive outcomes of having these discussions has been researched, both in relation to patients and their caregivers. Investigations of clinicians’ personal opinions about disclosure have revealed the majority believe patients should be told their diagnosis. However, historically it has not always been the case that clinicians disclose this information in practice. Procedure: A systematic literature search was conducted, and the relevant data was extracted and presented using a narrative synthesis approach. Participants: 3479 qualified clinicians with a range of specialities working with oncology patients were included in this review. Findings: This review suggests clinicians do not consistently disclose diagnosis and prognosis to cancer patients, which stands in conflict with patient preferences and service guidelines. There is an apparent difference between clinicians’ opinion and their clinical practice, with more clinicians believing the diagnosis and prognosis should be disclosed in comparison to their reported practice. A vast array of factors contributed to clinicians’ disclosure practices, but due to a high level of inconsistency, general disclosure practices cannot be attributed to any consistent clinician, personal, or patient factors alone. Conclusions: Not all clinicians report they routinely disclose diagnostic and prognostic information to patients, and there are a number of factors they consider when making this decision. More should be done within services to increase disclosure rates to bring this in line with patient preferences and current guidelines.
40
Beccaria, Kévin. "Evaluation de la diffusion intracérébrale des drogues antinéoplasiques après ouverture de la barrière hémato-encéphalique induite par ultrasons : Application aux gliomes malins de l’enfant Brainstem Blood-Brain Barrier Disruption and Enhanced Drug Delivery with an Unfocused Ultrasound Device – A Preclinical Study in Healthy and Tumor-Bearing Mice Ultrasound-Induced Blood-Brain Barrier Disruption for the Treatment of Gliomas and other Primary CNS Tumors Blood-Brain Barrier Disruption with Low-Intensity Pulsed Ultrasound for the Treatment of Pediatric Brain Tumors: A Review and Perspectives." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASS044.
Full textAbstract:
Les gliomes de haut grade représentent près de 15% de l’ensemble des tumeurs cérébrales de l’enfant. Aucun progrès thérapeutique n’a été fait depuis 30 ans et leur pronostic reste effroyable. La barrière hémato-encéphalique (BHE) est l’une des causes de l’échec des traitements médicaux car elle limite le passage de la majorité des molécules vers le cerveau, empêchant la plupart des drogues antinéoplasiques d’atteindre le tissu tumoral. L’ouverture de la BHE par les ultrasons pulsés de faible intensité en association avec des microbulles injectées par voie intraveineuse est une technique qui permet d’ouvrir transitoirement la BHE de manière localisée et sécurisée. Dans cette étude, nous avons confirmé la capacité d’un nouvel agent de contraste (microbulles) à ouvrir la BHE avec des ultrasons. Nous avons par ailleurs montré qu’il était possible d’ouvrir la BHE dans le tronc cérébral avec un dispositif ultrasonore non focalisé (SonoCloud®), à la fois sur des souris saines et des modèles murins de DIPG. Nous avons pu augmenter la distribution de l’irinotécan et du panobinostat dans le tronc cérébral de souris saines et de modèles de DIPG après ouverture de la BHE, sans cependant améliorer la survie de notre modèle de DIPG. Des études préliminaires ont été réalisées avec des inhibiteurs de chekpoints et des cellules natural killer, qui n’ont pas permis d’améliorer la survie d’un modèle murin de gliome malin sus-tentoriel. Enfin, nous avons mis au point le premier essai clinique pédiatrique qui visera, dès le premier semestre 2020, à évaluer la faisabilité et la tolérance de l’ouverture de la BHE avec le dispositif SonoCloud® chez l’enfant et l’adolescentHigh-grade gliomas represent about 15% of pediatric brain tumors. No progress has been made in the treatment of these tumors during the last decades, and their prognosis remains dismal. The blood-brain barrier (BBB) plays a major role in the failure of medical treatments since it prevents most molecules to reach the brain, thus limiting the delivery of antineoplastic drugs to brain tumors. Disruption of the BBB (BBBD) with low intensity pulsed ultrasound in association with intravenous microbubbles is a technique that allows for safe, transient, and localized opening of the BBB. In this thesis, we confirmed the capacity of a new microbubble contrast agent to induce BBBD with ultrasound. We showed that opening of the BBB in the brainstem is possible with a nonfocused ultrasound device (SonoCloud®), in both healthy mice and a murine model of DIPG. We were able to increase irinotecan and panobinostat delivery in the brainstem of both healthy and tumor-bearing mice after BBBD, but we did not observe increased in overall survival. Preliminary studies have also been performed with checkpoints inhibitors and natural killer cells in a murine model of supra-tentorial high-grade glioma, but we were not able to increase survival in these models anymore. Finally, we prepared the first clinical trial that will evaluate the feasibility and tolerance of ultrasound-induced BBBD with the SonoCloud® device in the pediatric population. This trial will begin during the first semester of 2020
41
S, Roos Weronica, and Camilla Hjälmeskog. "Livskvalitet och upplevelse av att leva med hjärntumör." Thesis, University of Gävle, Department of Caring Sciences and Sociology, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-263.
Full textAbstract:
Brain tumour can be a chronic disease that affects individuals in many aspects. The course of events in the disease, the treatment and prognosis has an effect on the physical, as well as mental and social health and therefore influences individuals’ quality of life and wellbeing. The aim of this study was to describe the experience of quality of life and living with a brain tumour as an adult. A descriptive systematic literature study was used to analyze eleven scientific articles. The analysis resulted in four categories, physical changes involves difficulties in the daily life, emotional distress involves suffering, to feel anxiety at the thought of death and feel the need of social support. The result showed that people that lived with a brain tumour were submitted to changes that had a negative effect on their daily life. They experienced an emotional distress and suffering that further added in a negative way on their daily life. The constant threat of death leads to a feeling of death anxiety. To be able to cope with their everyday life and manage the process that the disease brought it was important to have social support and understanding from their next of kin and surroundings. The knowledge about this disease and the consequences it has for the single individual contributes to a greater understanding for the person that is affected. Further research about experiences amongst people that lives with serious diseases is necessary so that they get treated adequately and get help and understanding within the care system. This literature study shows that people who lived with brain tumor experienced sadness and depression that made its mark on daily life. Together with constant worries and the mental fatigue brought these problems to each individual.
Hjärntumör kan vara en kronisk sjukdom som påverkar människan på många olika sätt. Sjukdomens förlopp, behandling och prognos inverkar på den fysiska psykiska och sociala hälsan och därmed påverkar människors livskvalitet och välbefinnande. Syftet med denna litteraturstudie var att beskriva upplevelse av livskvalitet och att leva med hjärntumör hos vuxna människor. En beskrivande systematisk litteraturstudie användes för att analysera de elva vetenskapliga artiklarna. Analysen resulterade i fyra kategorier: fysiska förändringar medför svårigheter i det dagliga arbetet, känslomässig påfrestning innebär lidande, att känna dödsångest och att känna behov av socialt stöd. Resultatet visade att människorna som levde med hjärntumör var utsatta för förändringar som hade inverkan på det dagliga livet. De upplevde en känslomässig påfrestning och lidande som ytterliggare negativt påverkade livskvalitet. Det ständiga hotet om döden skapade känsla av dödsångest. För att kunna klara av vardagen och gå igenom den processen som sjukdomen förde med sig var det viktigt att känna socialt stöd och förståelse från närstående och omgivningen. Kunskapen om denna sjukdom och vilka konsekvenser den har för den enskilde individen bidrar till ökad förståelse för den drabbades livssituation. Vidare forskning om upplevelser hos människor som lever med svåra sjukdomstillstånd är nödvändig för att de människorna ska få adekvat bemötande, hjälp och förståelse i vården. Denna litteraturstudie visar att människor som levde med hjärntumör upplevde nedstämdhet och depression som präglade det dagliga livet. I kombination med ständig oro och den mentala tröttheten medförde det problem för den enskilda människan.
42
Garcia, Paulo A. "Irreversible Electroporation for the Treatment of Aggressive High-Grade Glioma." Diss., Virginia Tech, 2010. http://hdl.handle.net/10919/77269.
Full textAbstract:
Malignant gliomas (MG), most notably glioblastoma multiforme (GBM), are among the most aggressive of all malignancies. High-grade variants of this type of brain cancer are generally considered incurable with singular or multimodal therapies. Many patients with GBM die within one year of diagnosis, and the 5-year survival rate in people is approximately 10%. Despite extensive research in diagnostic and therapeutic technologies, very few developments have emerged that significantly improve survival over the last seven decades.
Irreversible electroporation (IRE) is a new non-thermal focal tissue ablation technique that uses low-energy electric pulses to destabilize cell membranes, thus achieving tissue death. The procedure is minimally invasive and is performed through small electrodes inserted into the tissue with treatment duration of about one minute. The pulses create an electric field that induces an increase in the resting transmembrane potential (TMP) of the cells in the tissue. The induced increase in the TMP is dependent on the electric pulse parameters. Depending on the magnitude of the induced TMP the electric pulses can have no effect, transiently increase membrane permeability or cause spontaneous death.
In this dissertation we hypothesize that irreversible electroporation is capable of ablating normal (gray and white matter) and pathological (MG and/or GBM) brain tissue in a highly focused non-thermal manner that is modulated through pulse parameters and electrode configuration. Through a comprehensive experimental and numerical investigation, we tested and attained results strongly supporting our hypothesis. Specifically, we developed numerical models that were capable of simulating an entire IRE treatment protocol and would take into account pulse parameters (e.g. duration, frequency, repetition rate and strength) in addition to the dynamic changes in tissue electrical conductivity due to electroporation and joule heating, as well as biologically relevant processes such as blood perfusion and metabolic heat. We also provided a method to isolate the IRE effects from undesired thermal damage in models that were validated with real-time temperature measurements during the delivery of the pulses. Finally we outlined a procedure to use 3D volumetric reconstructions of IRE lesions using patient specific MRI scans in conjunction with the models described for establishing field thresholds or performing treatment planning prior to the surgical procedure; thus supplying the readers with the tools and understanding necessary to design appropriate treatment protocols for their specific application.
Experimentally we presented the first systematic in vivo study of IRE in normal canine brain and the multimodal treatment of a canine MG patient. We confirmed that the procedure can be applied safely in the brain and was well tolerated clinically. The lesions created with IRE were sub-millimeter in resolution and we achieved 75% tumor volume reduction within 3 days post-IRE in the patient. In addition to the sharp delineation between necrotic and normal brain, the treatments spared the major blood vessels, making it appropriate for treatment of tumors adjacent to, or enveloping critical vascular structures. We believe that irreversible electroporation will play a key role in the treatment of intracranial disorders including malignant brain cancer in which the intent is to focally kill undesired tissue while minimizing damage to surrounding healthy tissue.Ph. D.
43
Lanser, Brittany. "Characterization of checkpoint adaptation in human fibroblastic glioma cells and an analysis of protein phosphatase inhibitors." Thesis, Lethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences, c2012, 2012. http://hdl.handle.net/10133/3390.
Full textAbstract:
This thesis reports that checkpoint adaptation occurs in human brain cancer cells. M059K cells, after treatment with camptothecin (CPT), recruited γ-histone H2AX, phosphorylated Chk1 and arrested in the G2 phase. Strikingly, cells escaped the checkpoint, became rounded and entered mitosis as measured by phospho-histone H3 signals. Lamin A/C immunofluorescence microscopy revealed that 48% of the cells that survived checkpoint adaptation contained micronuclei. These data suggest that brain cancer cells undergo checkpoint adaptation and may have an altered genome. This thesis also explored if phosphatases participate in checkpoint adaptation. Human colon cancer cells were treated with CPT and the PP2A inhibitor cantharidin. Following treatment the cells became rounded and 65% were positive for phospho-histone H3 signals indicating that cantharidin caused cells to be in mitosis following CPT treatment. These data suggest that PP2A might have a role in checkpoint adaptation, or participate in a pathway that bypasses checkpoint adaptation.xi, 114 leaves : ill. (some col.) ; 29 cm
44
Shen, Daniel Hueng-Yuan. "Sodium iodide symporter based strategy for treatment of thyroid and non-thyroid malignancy." Connect to this title online, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1047493162.
Full textAbstract:
Thesis (Ph. D.)--Ohio State University, 2003.Title from first page of PDF file. Document formatted into pages; contains xiv, 133 p.; also includes graphics Includes bibliographical references (p. 116-133). Available online via OhioLINK's ETD Center
45
Begyn, Elizabeth. "The psychosocial functioning in pediatric cancer survivors: The role of neurocognitive abilities." Thesis, University of North Texas, 2007. https://digital.library.unt.edu/ark:/67531/metadc4003/.
Full textAbstract:
With the increase in survival for children with cancer, part of the focus of current research is aimed towards evaluating how these children are adapting psychosocially. Neurocognitive deficits have been well established. However, there are multiple facets encompassing quality of life, including general mental health, lifestyles and health behaviors, and academic and cognitive functioning. The relationship between neurocognitive and psychosocial functioning has yet to be thoroughly evaluated. The purpose of this study was to investigate the relationship between neurocognitive and psychosocial functioning in survivors of brain tumors and acute lymphoblastic leukemia. Data was collected from existing archival database comprised of patients of the at Cook Children's Medical Center in Texas. The sample consisted of 177 patients between the ages of 3 and 12 who were at least two years post-diagnosis. Measures used included the NEPSY and the Behavioral Assessment for Children. Statistical analyses included a several one-way analysis of variances, an independent samples t-test, a univariate analysis of variance, a hierarchical multiple regression, and odds ratio analyses. Results indicated survivors treated with neurosurgery alone appear to be less at risk for developing behavior problems than other treatment modalities. Also, brain tumor survivors demonstrate more problematic behaviors than survivors of acute lymphoblastic leukemia. Visuospatial functioning, diagnosis, and type of treatment were found to be predictive variables of behavior problems. Attention, and perhaps language, deficits may predispose children to more problems in their behavior. It is concluded that there are other factors affecting behavior in this population that were not accounted for in this analysis. It is recommended for future studies to research the individual clinical scales of the Behavior Assessment System for Children, obtain information from multiple informants, study this relationship longitudinally, and research additional factors that may be influencing the relationship between neurocognitive and psychosocial functioning. This provides evidence of risk factors that should be monitored as the child returns home and to school.
46
Sistigu, Antonella. "Inflammatory and immune reactions in response to chemotherapy-induced cell death. Viral mimicry chemotherapy : ds RNA sensors and IFNAR signalling indispensable for immunogenic tumor cell death." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T052.
Full textAbstract:
Certains motifs moléculaires associés à la mort cellulaire semblent identifier les cancers prompts à répondre à une thérapie cytotoxique. Ceci en élaborant une réponse anti-tumorale basées sur une réponse T protectrice. Mon travail de thèse montre que le traitement par chimiothérapie immunogène active des voies moléculaires mimant une infection virale. Ceci conduit au niveau des cellules tumorales à une signalisation autocrine via l’IFNαβ / IFNAR1/2, initiée par la reconnaissance d’ARN double brin (dsRNA) endogène par les Récepteurs endosomaux de Reconnaissance des Motifs (PRRs). De façon plus détaillée, nous montrons que les axes TLR3/TRIF (senseurs endosomaux de dsRNA) et IFNAR1/2 (Récepteurs de l’IFN de Type I) doivent signaliser au niveau de la cellule tumorale pour que la chimiothérapie puisse aboutir à l’induction de l’axe CXCL10/CXCR3 et éliciter une réponse efficace in vivo. L’analyse du profil ARN de cellules tumorales Tlr3+/+ (mais pas Tlr3-/-) exposées aux anthracyclines a révélé une forte empreinte virale/IFN, indispensable à l’efficacité/activité anti-tumorale. Le fait d’affecter les axes TLR3 ou IFNAR1/2 au niveau tumorale soit à l’aide d’anticorps neutralisants, soit à l’aide de modèles KO abroge le relarguage de CXCL10 induit par la chimiothérapie, et ainsi la capacité à contrôler la pousse tumorale à moins que de l’IFNαβ ou du CXCL10 exogène soit co-administré aux anthracyclines. De plus la chimiorésistance des tumeurs traitées par des molécules n’induisant pas de signature virale peux être réversée par de l’IFN de Type I exogène. Enfin, la détection d’une signature IFN au niveau de biospies de cancers du sein humains permet de prédire la bonne réponse au traitement adjuvant par anthracyclines. D’un point de vue de l’évolution, alors que les tumeurs (comme les virus) ont élaboré des mécanismes pour échapper aux réponses IFN, la signature virale induite par la chimiothérapie devrait contribuer à contrecarrer cette immunoéditionDistinct cell death-associated molecular patterns might define cancers proned to respond to a cytotoxic therapy by mounting a protective T cell-based anticancer immunity. My PhD Thesis work shows that immunogenic chemotherapy phenocopies viral infection leading to autocrine IFNαβ/IFNAR1/2 signalling in tumor cells initiated by recognition of self dsRNA by endosomal pattern recognition receptors (PRRs). In detail, TLR3/TRIF (endosomal dsRNA sensors) and IFNAR1/2 (Type I IFN receptors) must signal within the tumor cells so that chemotherapy can induce downstream CXCL10/CXCR3 axis and elicit therapeutic responsiveness in vivo. RNA profiling of Tlr3+/+ (but not Tlr3-/-) tumor cells exposed to anthracyclines revealed a strong IFN/viral fingerprint, indispensable for the tumoricidal activity. Neutralization by antibodies or genetic defects affecting tumor –associated TLR3 or IFNAR1/2 compromised chemotherapy-induced CXCL10 release and tumor control unless exogenous IFNαβ or CXCL10 are concomitantly supplied to anthracyclines. Moreover, chemoresistance of tumors treated by drugs failing to induce a viral signature can be reversed by exogenous Type I IFN. Finally, the IFN fingerprint of human breast cancers allowed to predict tumors proned to benefit from adjuvant anthracyclines. From an evolutionary viewpoint, while tumors (like viruses) have evolved mechanisms to evade an IFN response, chemotherapy-induced viral mimicry might contribute to bypass such as immunoediting
47
Johansson, Fredrik. "Screening for Candidate Brain Tumor Genes : Identifying Genes that Cooperate with Platelet-Derived Growth Factor in Glioma Development and Progression." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis Univ.-bibl. [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7185.
Full text
48
Thomaz, Amanda Cristina Godot. "Avaliação do papel da sinalização por BDNF/TRKB na viabilidade e sobrevivência de células de meduloblastoma humano." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/131184.
Full textAbstract:
Meduloblastoma é o tumor maligno intracranial mais comum em crianças. A desregulação da sinalização BDNF/TrkB tem sido associada a aumento da proliferação, invasão e resistência a quimioterapia, em diversos tipos de câncer, incluindo tumores de sistema nervoso. No entanto, seus efeitos biológicos e relevância clínica em meduloblastoma não estão compreendidos. Neste estudo foram analisados os efeitos do inibidor seletivo de TrkB, ANA-12, na viabilidade, sobrevivência e ciclo celular de linhagens de meduloblastoma humano. Este estudo demonstrou que o bloqueio seletivo de TrkB reduziu significativamente a viabilidade e sobrevivência de linhagens celulares representativas de diferentes subgrupos moleculares de meduloblastoma. Estes resultados fornecem uma base racional para investigar a inibição de TrkB como uma nova e potencial estratégia para o tratamento de meduloblastoma.Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Deregulation of BDNF/TrkB signaling has been associated with increased proliferative capabilities, invasiveness and chemo-resistance in several types of cancer. However, the relevance of this pathway in MB remains unknown. Here, we show that the selective TrkB inhibitor ANA-12 markedly reduced the viability and survival of human cell lines representative of different MB molecular subgroups. These findings provide a rationale to further investigate TrkB inhibition as a potential novel strategy for MB treatment.
49
Braun, Martin [Verfasser], and Sven [Akademischer Betreuer] Perner. "ERG rearrangement is specific to prostate cancer and does not occur in any other common tumor / Martin Braun ; Betreuer: Sven Perner." Tübingen : Universitätsbibliothek Tübingen, 2012. http://d-nb.info/116051819X/34.
Full text
50
Delgado, Irene. "Neurocognitive Sequelae of Pediatric Cancers: A Prospective Study of Late Effects." Scholarly Repository, 2009. http://scholarlyrepository.miami.edu/oa_dissertations/280.
Full textAbstract:
Nearly 80% of children treated for cancer are expected to survive, but not without cost. Survivors face unprecedented challenges associated with long-term consequences of treatment, also called late effects. Approximately half of children treated for cancer are at risk for experiencing cognitive late effects, which typically emerge several years post diagnosis. The nature and extent of cognitive late effects appear to be developmental and related to patient, disease, and treatment variables. However, the relationships between these variables is not well understood because there have been few prospective and longitudinal studies that report on the contributions of these variables over time. This dissertation examined the effects of patient, disease, and treatment variables, as well as their interactions over time on neurocognitive functioning in childhood cancer survivors. It comprises part of a large prospective, randomized clinical trial designed to examine changes in cognitive function over three years as a function of different levels of monitoring of school-based intervention based on individual educational plans (IEPs). This dissertation uniquely contributed a new measure (the Treatment Intensity Rating Scale) that was used to systematically classify treatment severity across different types of cancer and cancer treatments. Participants included 61 children ages 7 to 12 years at enrollment who were two to five years from completion of treatment for a brain tumor, leukemia, or lymphoma. Participants received yearly neuropsychological evaluations for a follow-up period of 3 years. Results of these evaluations were used to develop IEPs. Participants were randomized to have their IEPs monitored on a quarterly or annual basis for the duration of the study. Contrary to the progressive decline in neurocognitive functioning that is typically anticipated in pediatric cancer survivors, analyses revealed relative stability of performance on neurocognitive measures over time. Higher neurocognitive performance was noted in children whose IEPs were monitored more frequently versus less frequently. Results also supported gender-specific risk for late effects, with lower performance on select neurocognitive measures in females compared to males. Results of this study provide encouraging evidence of the positive effects of school-based interventions and their close monitoring. This has important implications for quality of life as these children survive well beyond childhood into adulthood.