Dissertations / Theses on the topic 'Tumors in children'
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1
Britt, Deanna C. "Thoughts, feelings, and actions : a restrospective study of the coping efforts of pediatric cancer patients in the context of the home, institution, and community /." This resource online, 1992. http://scholar.lib.vt.edu/theses/available/etd-07282008-134837/.
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Cornman, Barbara Jane. "Impact of childhood cancer on the family /." Thesis, Connect to this title online; UW restricted, 1988. http://hdl.handle.net/1773/7827.
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Castro, Cynthia M. "Relationships between nonprocedural pain and psychological distress in children and adolescents with cancer /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 1997. http://wwwlib.umi.com/cr/ucsd/fullcit?p9726021.
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McCormack, Sarah (Sarah Smith). "Memory Functions among Children Irradiated for Brain Tumor." Thesis, University of North Texas, 1995. https://digital.library.unt.edu/ark:/67531/metadc278041/.
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Children who have received radiation therapy for the treatment of brain tumors have been shown to experience neurocognitive deficits which appear to increase over time. The purpose of this study was to examine the memory functioning of 22 children irradiated for brain tumor and 22 healthy children of the same age who had not received irradiation. Subjects were administered a brief form of the WISC-III, to obtain an IQ, and the Wide Range Assessment of Memory and Learning (WRAML), to evaluate visual and verbal memory. Results indicated that, although there were no significant differences between the IQ scores of healthy children and children who had been irradiated, children who have received radiation therapy for brain tumor evidence memory deficits which effect visual and verbal memory abilities. Among the children who had been irradiated, as time since treatment increased, visual memory and overall memory functioning appeared to decline. Findings also suggested that children who received total tumor resection may evidence greater memory deficits than those who received only a partial resection. Visual memory was more closely related to IQ in the children irradiated for brain tumor than in the healthy children. The overall importance of research with this population lies in refining the understanding of memory deficits and strengths in order to formulate more effective remediation compensation, strategies.
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Niesen-Vertommen, Sherri. "The recovery patterns and effects of exercise rehabilitation on the physiological and psychological health of children who have survived treatment for a malignancy." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0008/NQ34599.pdf.
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Britt, Deanna C. "Thoughts, feelings, and actions: a retrospective study of the coping efforts of pediatric cancer patients in the context of the home, institution, and community." Diss., Virginia Tech, 1992. http://hdl.handle.net/10919/38914.
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This study was a retrospective examination of the experiences of pediatric cancer patients and their families from a contextual perspective. The home, institution, and community contexts were investigated to reveal their influences on the coping efforts of the study participants. Ten families of children with cancer were interviewed, and data were analyzed qualitatively. Walker's (1985) family stress model and Lazarus' (1984) coping paradigm guided the study.
The findings indicated that children were ambivalent in their attitudes toward the disease process. While they did not enjoy painful procedures, sickness, frequent hospitalizations, and baldness, they did welcome the special attention brought about by these stressors. Many of the children in the study understood the impact of their illness on the family. They felt guilty about family financial pressures, parental marital problems, and sibling conflicts that resulted from their cancer. Most feared relapse and death but hid their feelings to protect their parents.
Mothers handled the stress of their child's illness by learning all they could about the disease, focusing completely on the sick child, and protecting the child from further harm. Fathers tended to take on the role of "strong one" while worrying about finances and attempting to keep the families together. Differing ways of coping between mothers and fathers often caused feelings of resentment and marital difficulties. Parental attitudes toward the staff at the medical center varied from trust, to wariness, to dependency. Parents enjoyed the support of family, friends, and community during the diagnosis phase, but felt bitter about the lack of support they received during the treatment and completion stages. Some parents believed that their exposure to the
stressors of the illness process led to personal growth that they would not have experienced otherwise. Many parents emerged from the cancer ordeal with a desire to help others who were battling childhood cancer. They became involved in a variety of community agencies that served the families of children with cancer.Ph. D.
7
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/.
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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.
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Monterrubio, Martínez Carles. "Delivery of SN-38 in pediatric solid tumors." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/399596.
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A new combined microdialysis – tumor homogenate method for the determination of compartmental (vascular, extra- and intracellular) SN-38 distribution in patient-derived xenografts (PDX) generated from pediatric solid tumors from fresh tumor samples from patients of Sant Joan de Deu Barcelona Hospital was developed. SN-38 in late-stage (chemoresistant) tumors presented limited distribution into the intracellular compartment while drug distribution into this compartment was significantly higher in early-stage (sensitive) models when SN-38 was administered as its prodrug irinotecan. Furthermore, two polymeric drug delivery systems were developed for the local and systemic administration of SN-38. Poly(lactic) acid electrospun nanofiber matrices with microcrystals of SN-38 were developed for the local administration of SN-38. Matrices showed maintained release of SN-38 over 48 h with local distribution and efficacy delaying tumor growth over PDX models. Dialysates showed limited SN-38 diffusion from the matrices through the tumor tissue, suggesting this therapy could only be useful for the local tumor control after successful surgery of the tumor or where only microscopic tumor seeds are left. Systemic administration of SN-38 was possible by encapsulating the drug into poly(lactic-co-glycolic) acid with polyethylene glycol nanoparticles, which were decorated with 3F8 monoclonal antibody, an anti-GD2 antibody that recognizes the ganglioside GD2 overexpressed on the surface of neuroblastoma cells surface for active targeting. Nanoparticles released SN-38 over 2 days and tumor exposition to SN-38 was increased when compared with the administration of an equimolar dose of irinotecan, and that was correlated with improved efficacy over the conventional irinotecan where 10 administrations of the drug had reduced efficacy compared to the direct administration of SN-38 in the targeted nanoparticles. Both nanofiber matrices and nanoparticles showed to be good platforms for SN-38 administration reducing systemic exposition by localizing SN-38 at the tumor microenvironment and significantly delaying tumor growth as shown in the efficacy studies. Thus, polymeric local drug delivery systems strategy should be of high interest for the potential future treatment of chemoresistant tumors.
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Chan, David Wai 1968. "The role of EWS/FLI-1 fusion gene in Ewing's sarcoma." Monash University, Institute of Reproduction and Development, 2001. http://arrow.monash.edu.au/hdl/1959.1/8307.
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Robbins, Kathryn H. "Parent-child communication about the cancer experience in families of pediatric cancer patients /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/9109.
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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.
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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.
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Huber, James Richard. "Mothers' adaptation to childhood cancer: an analysis of family process stressors, family system resources, parental coping patterns, and parental adaptation among mothers of children with cancer." Diss., Virginia Polytechnic Institute and State University, 1989. http://hdl.handle.net/10919/53842.
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Family process stressors, family system resources, parental coping patterns, and parental adaptation were assessed for 58 mothers who had a child with cancer who was being seen at selected pediatric hematology-oncology centers in two Southeastern states. The respondents completed a self-report questionnaire containing the Coping and Health Inventory for Parents, five subscales from the Family Environment Scale, and items asking demographic questions. The dependent measure was the Parental Adaptation Assessment, a modified version of the Spinetta Family Adjustment Scale, developed for this study to measure parents’ perception of their adaptation to the experience of caring for a child with cancer. The criteria for subject inclusion in the study were: (a) two parents living in the home; and, (b) the child’s cancer diagnosis was to have occurred not less than 3 months and not more than 4 years prior to data collection. The Double ABCX Model of Family Adaptation was used as the basis for variable selection.
Frequency distributions, correlations between the 11 independent variables and mother’s adaptation, and a stepwise regression analysis were used to analyze the data. Two family process stressors (conflict and control) and two family system resources (cohesion and expressiveness) were significantly (p < .05) correlated with mother’s adaptation. The regression analyses showed that two variables (cohesion and mother’s age) explained 34% of the variance in mother’s adaptation.
Results show family cohesion and mother’s age to be the only significant predictors of her perceived adaptation. Family process stressors and parental coping patterns failed to account for any significant variance in mother’s adaptation. Implications for family stress theory, psychosocial oncology research, and family therapy practice are discussed. Recommendations for further research are suggested.Ph. D.
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Lam, Ching-yee. "The impacts of childhood cancer on siblings among Hong Kong Chinese : from parents' perspectives /." View the Table of Contents & Abstract, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36396801.
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Jayasooriya, Shamanth. "Immune control of Epstein-Barr virus infection in African children." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/4173/.
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Epstein-Barr virus (EBV) establishes a chronic infection, usually effectively controlled by the cellular immune response. However, EBV has the potential to escape immune control, such as during malaria exposure, or modulate the immune response. In this study, immune control of EBV was examined in Gambian children in two situations: during malaria exposure and early after EBV infection. Additionally, EBV infection may also inhibit vaccine induced antibody responses, hence its impact on a childhood pentavalent vaccine was studied, but infection had no effect. In contrast to historical studies, acute malaria infection was not associated with impaired immunity to EBV, a finding potentially explained by the declining malaria exposure in The Gambia. Children recently infected with EBV had evidence of activated EBV-specific T-cell responses, with latent and lytic epitope-specific responses of equal magnitude. Several donors identified as undergoing primary asymptomatic EBV infection had virus genome loads equivalent to those of acute infectious mononucleosis (AIM) patients. In contrast to AIM patients they did not show a peripheral lymphocytosis but did have significant expansions of activated EBV-specific CD8+ T-cells, which were lower or perhaps more focused than in AIM patients, suggesting that the highly expanded T-cell populations and not virus load drives AIM pathogenesis.
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Adzo, Fugar Enyonam. "Exploring nurses’ role in the management of children diagnosed with cancer in Ghana." Thesis, Cape Peninsula University of Technology, 2015. http://hdl.handle.net/20.500.11838/1544.
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Submitted in fulfilment of the requirement for the degree
Masters of Nursing
in the Faculty of Health and Wellness Sciences
2015Background: Oncology nursing continues to evolve in response to advances in cancer treatment. The role of the oncology nurse in the management of cancer in children is very significant as these children go through a lot of emotional trauma due to the disease. Aim and objectives: The aim of the study is to explore and examine the quality of nursing care given to children diagnosed with cancer in Ghana. Some of the objectives are to examine strategies nurses use in planning care; and to determine processes nurses use to evaluate care given. Methodology: A mixed-methods qualitative cross-sectional descriptive design was used. Population and samples: Komfo Anokye Teaching Hospital in Ghana is selected as the research site. The population consists of all nurses working in the hospital and parents/carers looking after children diagnosed with cancer. The samples was nurses working on paediatric wards/clinics, parents/carers, and key informants. Selection of sample groups was opportunistic. Methods of data collection: three sources were used to collect data, i.e. questionnaires for nursing working on paediatric wards/clinics, interviews with nurses and carers, and key informant interviews. Analysis: descriptive statistical analysis of data was undertaken and the three data sources were triangulated to determine similarities and differences of responses. Benefits of the study: The results of the study will be submitted to the hospital management and articles will be submitted to peer-reviewed nursing journals. Key words: paediatric oncology, nurses, oncology nurses, Kumasi, Ghana, Komfo Anokye teaching hospital.
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Shen, Ying. "Individual Growth Models of Change in Peabody Picture Vocabulary Scores of Children Treated for Brain Tumors." Digital Archive @ GSU, 2007. http://digitalarchive.gsu.edu/math_theses/41.
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The individual growth model is a relatively new statistical technique. It is now widely used to examine the trajectories of individuals and groups in repeated measures data. This study examines the association of the receptive vocabulary over time and characteristics of children who were treated for brain tumors. The children undertook different types of treatment from one to any combinations of surgery, radiation and chemotherapy. The individual growth model is used to analyze the longitudinal data and to address the issues behind the data. Results of this study present several factors' influences to the rate of change of PPVT scores. The conclusions of this thesis indicate that the decline in the PPVT scores is associated with gender, age at diagnosis, socioeconomic status, type of treatment and Neurological Predictor Scale.
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Papazoglou, Aimilia. "Cognitive Predictors of Adaptive Functioning in Children with Tumors of the Cerebellar and Third Ventricle Regions." Digital Archive @ GSU, 2007. http://digitalarchive.gsu.edu/psych_theses/33.
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As pediatric brain tumor survival rates increase, research has begun to further explore the influence of brain tumors and their treatment on functioning. The current study explored the ability of attention, learning, and memory abilities as measured by the Rey Auditory Verbal Learning Test and receptive language abilities as measured by the Peabody Picture Vocabulary Test to predict adaptive functioning on the Vineland Adaptive Behavior Scales. Children with tumors of the cerebellar region were hypothesized to display relative impairments in attention, whereas children with tumors of the third ventricle region were hypothesized to display relative impairments in learning and memory. The cognitive measures also were hypothesized to be differentially predictive of adaptive functioning performance. No significant differences were found between the groups on cognitive performance, but attention was the best predictor of adaptive functioning in the cerebellar group, whereas receptive verbal knowledge was the best predictor for the third ventricle group.
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Micklewright, Jackie L. "Verbal Learning and Memory Abilities in Children with Brain Tumors: The Role of the Third Ventricle Region." Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/psych_theses/11.
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The third ventricle region houses several neuroanatomical structures that are primary components of the human memory system, and provides pathways through which these brain regions communicate with critical regions of the frontal and medial temporal lobes. Archival data was obtained for 42 children with cerebellar or third ventricle tumors, and was examined for tumor and treatment related confounds. Children with third ventricle tumors were hypothesized to exhibit; 1) better performance on a measure of auditory attention, 2) greater impairment in learning across trials, 3) greater memory loss over a 20-minute delay, and 4) greater impairment across delayed memory tests than the cerebellar group. Children with third ventricle tumors demonstrated significantly better auditory attention, but greater impairments in verbal learning, and greater verbal memory loss following a 20-minute delay. In contrast, children with third ventricle tumors did not demonstrate significantly greater memory impairments across long delay memory tests.
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Adams, Madeleine Ruth. "Studies of angiogenesis in osteocytes : implications for pathogenic mechanisms of osteonecrosis in children with acute lymphoblastic leukaemia." Thesis, Cardiff University, 2015. http://orca.cf.ac.uk/76508/.
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The work presented in this thesis is the result of 2 years of investigation into pathogenic mechanisms resulting in the development of osteonecrosis in children and young people treated for acute lymphoblastic leukaemia (ALL). This was a study using in vitro methods to investigate the effects of corticosteroids (namely dexamethasone which is used in the treatment of ALL) on osteocyte angiogenesis with particular focus on vascular endothelial growth factor (VEGF) and markers of bone remodelling. Interactions between dexamethasone and vitamin D were investigated in order to identify potential preventative or therapeutic strategies for osteonecrosis that could be studied in vivo. The actions of sex steroids on osteocyte biology and their interactions with dexamethasone were also studied in order to begin to explain the increased susceptibility to osteonecrosis that is exists in both adolescent and female patients. Results demonstrate a number of novel findings including; i) significant interactions between dexamethasone and vitamin D on osteocyte VEGF gene expression and protein secretion as well as the RANKL: OPG ratio which is crucial to bone remodelling, ii) dexamethasone treatment leading to significant alterations in expression levels of an array of genes expressed by osteocytes that are involved in angiogenesis pathways and iii) significant effects of sex steroids on osteocyte VEGF production and modulation of the effects of dexamethasone by oestradiol. Osteonecrosis is an extremely disabling side effect of the treatment for ALL which in the vast majority of cases is now a curable disease. The results of this thesis contribute to the current understanding of the pathogenesis and have identified a number of potential therapeutic pathways to target.
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Micklewright, Jackie L. "Verbal learning and memory abilities in children with brain tumors the role of the third ventricle region /." unrestricted, 2005. http://etd.gsu.edu/theses/available/etd-11172005-133342/.
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Thesis (M.A.)--Georgia State University, 2005.Title from title screen. Tricia Z. King, committee chair; Robin Morris, Mary Morris, committee members. Electronic text (102 p. : col. ill.) : digital, PDF file. Description based on contents viewed July 17, 2007. Includes bibliographical references (p. 91-102).
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Ferguson, Smith Ayanay Camille. "The Predictive Contributions of Spatial Planning to Adaptive and Cognitive Functioning in Children Diagnosed with Brain Tumors." Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/psych_diss/17.
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To date, the effect of planning ability on adaptive functioning has not been extensively examined in children treated for brain tumors. Findings indicate that individuals with brain tumors are more likely to experience poor planning ability (Boyd & Sautter, 1993) and that children with even mild neurological complications demonstrate impairments in adaptive functioning (Fletcher et al., 1990). The purpose of this study is to assess spatial planning and to examine its utility in predicting adaptive and cognitive functional impairment in children diagnosed and treated for brain tumors. Forty children diagnosed with a brain tumor (mean age at diagnosis 8.6 years) were administered the Rey-Osterrieth Complex Figure (ROCF) task, the Vineland Adaptive Behavior Scale (VABS), and the Stanford-Binet Intelligence Scale: Fourth Edition (SB:IV) at an average of one year post diagnosis (post acute) and again at two years post diagnosis (long term). The results of this investigation did not support the use of spatial planning skills as a predictor of adaptive functioning at one year or two years post diagnosis. However, spatial planning skill was an important predictor of cognitive functioning, accounting for a significant amount of variance at both one year and two years post diagnosis. These results were not expected and therefore further analyses were performed in order to better understand the data and results. Additional analyses suggest that it is spatial skill and not spatial planning that predicts adaptive functioning. Further research should continue to ask questions that will impact how we understand executive, adaptive, and cognitive functioning outcomes in children diagnosed with brain tumors.
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Gómez, González Soledad. "Tumores del Desarrollo, Epigenética y miRNAs." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/457765.
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Evidencias recientes han mostrado que los tumores sólidos pediátricos, incluidos el neuroblastoma y el meduloblastoma, albergan una baja cantidad de mutaciones genéticas recurrentes, pero presentan una proporción significativa de alteraciones recurrentes en los mecanismos epigenéticos. Además, la epigenética es un mecanismo regulatorio fundamental durante el desarrollo en mamíferos.
En este proyecto hemos estudiado los cambios epigenéticos que afectan a dos tumores neuronales pediátricos prototípicos, el neuroblastoma y meduloblastoma. Mediante el estudio de los cambios de metilación del ADN, los miRNA y la expresión génica, hemos identificado modificaciones genéticas y epigenéticas que subyacen a la base molecular de la patogénesis y tienen implicación clínica en la evolución de estos tumores neurales. El objetivo principal de nuestro proyecto era identificar marcadores moleculares y posibles dianas de interés para el desarrollo de nuevas estrategias terapéuticas.
Este proyecto fue el primer estudio completo de metilación del ADN en neuroblastoma empleando microarrays de alta densidad. Detectamos por primera vez en neuroblastoma la presencia de metilación del ADN en citosinas no-CpG, asociada a tumores de bajo riesgo clínico. El estado de metilación detectado en el contexto no-CpG indica un papel potencial de esta metilación en la diferenciación y regulación transcripcional de genes clave el en desarrollo, como por ejemplo ALK. Observamos que la metilación del ADN en el neuroblastoma afecta no sólo a los promotores, sino también a las regiones intragénicas e intergénicas tanto en sitios CpG como no-CpG en dominios funcionales de la cromatina de genes implicados en desarrollo y cáncer.
Los cambios de metilación del ADN en sitos CpG y no-CpG tanto dentro como fuera de islas CpG (CGI) y localizados en el cuerpo del gen podian estar asociados con el comportamiento clínico del neuroblastoma. Detectamos cambios en contexto no-CpG que sugieren que el neuroblastoma puede ser epigenéticamente diferente a lo largo de la terapia. Además, analizando citosinas fuera de las regiones promotoras, en el cuerpo del gen y de las regiones intergénicas, en sitios CpG asociados a CGI y en sitios no-CpG dentro y fuera de CGIs observamos una asociación de la metilación con el comportamiento clínico en neuroblastoma.
La segunda parte del proyecto se centró en tratar de dar respuesta a la creciente necesidad de aplicar en la práctica clínica el sistema de clasificación del meduloblastoma en los subgrupos moleculares WNT, SHH, Grupo 3 y Grupo 4, recientemente identificados y propuestos mediante análisis (epi)genómicos. El reconocimiento de los subgrupos consenso ha cambiado la forma en que se estudia el meduloblastoma en el contexto de la investigación y cómo se diagnostica y trata en el contexto clínico. Estos subgrupos moleculares se definen actualmente mediante robustos sistemas de clasificación basados técnicas difícilmente incorporables a la rutina clínica de la mayoría de hospitales que tratan tumores cerebrales infantiles.
Hemos desarrollado una metodología clínicamente aplicable, robusta, rápida y reproducible para la predicción exacta de subgrupos de meduloblastoma de muestras individuales en base a dos paneles compuestos por conjuntos reducidos de biomarcadores epigenéticos, y por tanto, potencialmente incorporables en la rutina de diagnóstico. Los biomarcadores epigenéticos identificados podían aplicarse a muestras individuales de ADN de meduloblastoma obtenidas a partir de tejido congelado o FFPE. El patrón bimodal de los paneles permitía el análisis mediante diversas técnicas moleculares, tanto cuantitativas como cualitativas. Nuestro enfoque era técnicamente más simple, rápido y coste efectivo en comparación con las actuales técnicas estándar de clasificación de subgrupos de meduloblastoma.Recent evidence has shown that pediatric solid tumors harbor a paucity of recurrent genetic mutations as compared to other tumors from adults, suggesting that additional mechanisms such as epigenetic alterations may play an important role in the molecular pathogenesis of developmental tumors. So far the great majority of studies that have investigated DNA methylation in developmental tumors were biased towards CpG sites and promoter regions. Recent genome- wide studies are starting to reveal a role for DNA methylation outside such genomic contexts. Furthermore, it has recently been described that cytosine methylation also occurs in sites other than CpG dinucleotides (mCHG and mCHH) in embryonic stem cells and during brain development. However, DNA methylation at non-CpG contexts has rarely been described in cancer. We have analyzed the DNA methylome of two prototypical developmental neural tumors, neuroblastoma and medulloblastoma, using high-density microarrays with the aim of detecting epigenetic modifications at a genome-wide level that may have clinical relevance in the pathogenesis of these pediatric tumors, to identify molecular markers and potential targets of interest for the development of new therapeutic strategies. Our DNA methylation studies in neuroblastoma using high-density microarrays have defined the epigenetic landscape of this pediatric tumor and its potential clinicopathological impact. Our results reveal that: - DNA methylation changes in neuroblastoma affect not only promoters but also intragenic and intergenic regions at CpG sites and, for the first time in neuroblastoma, at non-CpG sites. - These epigenetic changes show a non-random distribution relative to functional chromatin states, and frequently target development and cancer-related genes relevant for neuroblastoma, such as CCND1 and ALK. - DNA methylation patterns in non-CpG sites provide new insights into the differentiation stage of high and low-risk neuroblastomas. - DNA methylation changes at CpG and non-CpG sites are strongly associated with clinicopathological features of neuroblastoma and with patient outcome. Furthermore, we have developed a simplified and reproducible approach to classify medulloblastoma tumors into clinically relevant subgroups applying epigenetic markers. Using this strategy, MB patients can be accurately classified into the three consensus subgroups WNT, SHH and non-WNT/non-SHH. In addition, we propose a similar approach for the specific classification of Group 3 and Group 4 medulloblastoma tumors. The proposed strategies allows for classification of single DNA samples from biopsies both frozen as well as FFPE of primary, metastasis or relapse compartments, using diverse molecular approaches. Our results show that the proposed strategy is robust, accurate, and cost-effective, making it adequate for molecular subgrouping of medulloblastoma in daily diagnostic practice of most centers treating children with brain tumors.
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Akhavanfard, Sara. "NEXT-GENERATION SEQUENCING APPROACHES TO CHARACTERIZE GENOMIC PREDISPOSITION OF SOLID TUMORS IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS (C-AYA)." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1575571085728229.
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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.
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Fanlo, Escudero Lucía. "Neuroblastoma cancer stem cells: The role of NXPH1 and its receptor α-NRXN1." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/668504.
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Neuroblastoma (NB) is a devastating paediatric cancer that originates in the developing sympathetic nervous system. These tumours account for 40% of the cases of cancer diagnosed during the first year of life and 8% of the cases detected overall during childhood. They show a striking clinical diversity, ranging from spontaneous remission to fatal metastatic dissemination. To optimize therapeutic approaches, NB patients have been stratified into risk groups. For the high risk (HR} patients, the 5 years overall survival probability remains below 30-40%. The failure to successfully treat these HR patients mainly results from the therapy-resistance and metastatic potential harboured by these tumours. The large intra-tumour heterogeneity of the HR tumours seems to be a key factor contributing to tumour progression. Thereby, there is an urgent need to understand the biological diversity of the HR-NBs in order to develop efficient therapies for these patients. lnterestingly, NBs show a marked scarcity of recurrent genetic changes even during relapse, pointing towards a relevant role of non-genetic sources of tumour heterogeneity. Compelling evidences suggest the existence of cells possessing a tumour-propagating capacity, called cancer stem cells or tumour-propagating cells (eses/TPes}, in these HR-NB tumours. Defining the heterogeneity of NBs and their CSCs: their self-renewal ability.
The general aim of this doctoral thesis was to identify a genetic signature for neuroblastoma cancer stem cells (NBcsc), with the ultimate goal of providing new specific molecular markers of these NBcsc and candidate genes that might be useful for the development of future therapeutic strategies targeting the NBcsc in HR-NBs. lt is assumed that NBcsc share many similarities with their normal stem cells counterparts, the neural crest cells (NCCs), which represents transient embryonic population of pluripotent stem cells that give rise to the peripheral nervous system. Therefore, we compared the transcriptomic signature of NCCs with the transcriptomic profiles established for clinically relevant groups of NB patients. Among the candidates identified by our double screening, we retrieved Neurexophilin 1 (NXPHl }: an extracellular glycoprotein known to bind to the transmembrane receptors of the alpha-Neurexin (a-NRXN) family. To determine whether NXPHl/a-NRXNs activity is effectively related to NBcsc, we analysed their expression in a panel of human NB cell lines in conditions of stem cell enrichment. The marked induction of a-NRXNl/2 mRNA levels in the stem cell-enriched fraction suggested that they might be NBcsc markers. We identified the existence of a low subpopulation of a-NRXNl+ cells in samples from human NB cell lines and patient-derived xenografts. We further established that these a-NRXNl+ cells represents functionally discrete subpopulation of NB cells characterized by: 1} an active cycling behaviour, 2} an increased self-renewal capacity, and 3) a higher probability to survive upon chemotherapeutic insult. Our data suggest that these a-NRXNl+ NB cells are endowed with a tumour-propagating capacity and that they are required to sustain tumour growth in vivo. In parallel, we investigated whether NXPH1 is implicated in NB malignancy.
Our data revealed that NXPH1 promotes NB growth, possibly by stimulating the proliferation of actively dividing NB cells and by increasing the proportion of NB cells expressing the NCC stem cell marker p75NTR. Finally, we showed that inhibiting NXPH1 or a-NRXN1 activity abrogates NB tumour growth in xenograft models.
Our work provides the first experimental evidence that NXPH1, probably acting through its receptor a-NRXN1, exerts a functional role in NB progression. We suggest that NXPH1, present in the tumour microenvironment, controls the tumour-propagating capacity of NBcsc and that its reduced activity might facilitate the malignant progression of these tumours by enabling NBcsc to acquire a metastatic capacityEl neuroblastoma (NB) es un tumor pediátrico del sistema nervioso simpático en desarrollo. La probabilidad de supervivencia de los pacientes de alto riesgo no supera el 30-40%. El estudio de la heterogeneidad celular del NB revela la probable existencia de células con capacidad de propagación tumoral (en inglés cancer stem cells, CSCs). Su identificación y caracterización es fundamental en la búsqueda de nuevos fármacos para dichos pacientes. El objeto de esta tesis doctoral ha sido la identificación de la huella genética de las CSCs en el NB con la finalidad de identificar marcadores moleculares específicos y nuevas dianas terapéuticas. Para ello, partimos de la premisa de que las CSCs de los NBs deben de compartir ciertas características con sus equivalentes en el tejido sano, las células de la cresta neural (en inglés neural crest cells, NCCs), una población embrionaria de células madre que origina el sistema nervioso periférico. Al comparar el transcriptoma de las NCCs con el extraído de una comparación entre grupos de pacientes con relevancia clínica, seleccionamos la Neurexofilina 1 (NXPHl), un ligando extracelular de las Neurexinas alfa (a-NRXN). Para determinar si ambos están relacionados con el fenotipo de eses, analizamos su expresión en una colección de líneas celulares en condiciones de enriquecimiento para dicho fenotipo. El marcado aumento en los niveles de RNA mensajero de a-NRXNl/2 sugirió que podrían fun cionar como marcadores de las CSCs . Hemos confirmado la existencia de una población a-NRXNl+ caracterizada por una mayor capacidad de proliferación, de replicación y de pervivencia a quimioterapia. Las células a-NRXNl+ presentan características de eses y son requeridas para el crecimiento tumoral. En paralelo vemos que NXPHl promueve el crecimiento tumoral estimulando la proliferación y la presencia de células p75NTR+, marcador asociado a las NCCs . Además, la inhibición de NXPHl o a-NRXNl impide el crecimiento tumoral en modelos experimentale . Este trabajo constituye la primera evidencia funcional del papel de NXPHl en la progresión del NB. Sugerimos que NXPHl , probablemente a través de a-NRXNl, participa en la regulación de la capacidad de propagación tumoral y que su pérdida favorece la adquisición de rasgos asociados a pacientes de alto riesgo.
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Viana, Lêda Guimarães. "Mães-acompanhantes de filhos no tratamento do câncer:um estudo compreensivo." Universidade Católica de Pernambuco, 2004. http://www.unicap.br/tede//tde_busca/arquivo.php?codArquivo=77.
Full textAbstract:
A realidade de ter um filho com câncer e hospitalizado, é uma situação penosa para toda família. Na maioria dos casos, é a mãe que acompanha o internamento, sendo sua participação reconhecida como fundamental no tratamento e recuperação do filho. Para tanto, é necessário uma compreensão de suas reais necessidades frente ao universo do câncer infantil. Este estudo vem focalizar, portanto, o sentido das vivências de mães-acompanhantes de filhos no tratamento do câncer. Trata-se de uma pesquisa qualitativa de base fenomenológica, na qual buscamos trabalhar com observações livres e narrativas de mães que estão vivenciando o acompanhamento ao tratamento de filhos com câncer. Dentre as singularidades dessas vivências, destacamos algumas expressões que são compartilhadas e narradas pelas mães: diante do diagnóstico de câncer, expressam sentimentos de incredulidade, revolta, desespero; na hospitalização, relatam sentir temor, desamparo; buscam incessantemente uma causa para o adoecimento dos filhos; explicitam gratidão pelo hospital; demonstram necessidade de obter informações sobre o câncer. Entendemos que as mães- acompanhantes, durante a internação, necessitam, sobretudo, de suporte emocional, atenção efetiva e sistêmica, para que, assim, possam contribuir ativamente no tratamento e restabelecimento dos filhosTo have a child with cancer and hospitalized is a painful situation to all family. In most cases, is the mother who stays whit the child in the hospital, being her involvement recognized as fundamental for medical treatment and his recovery. Thats why, its necessary an understanding about her real necessities faced with universe of infant cancer. Therefore this study focus on sense of the livings of mothers-being close of children in cancer treatment. This research is quality, with phenomenologic grounding, in which, we used like devices the free observations and mothers-being close talks. In among specialties about the livings of mothers-being close, we highlight some expressions that are shared and told by her: faced with diagnosis cancer, they express feelings of unbelievable, despair and disgust; during the going with her child, the mothers tell to feel fear, helpless; they seek desperately a cause for the sickness of their children; they express grateful to the hospital; they show necessity for obtain information about cancer. We understand the mothers-being close, during the going into the hospital, need, especially, emotion support, effective and systemic careful, so that, can contribute effectively in the treatment and recovery of their children
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Almacellas, Rabaiget Olga. "Caracterització funcional de LOXL2 en el rabdomiosarcoma alveolar." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/664080.
Full textAbstract:
El rabdomiosarcoma (RMS) és el sarcoma de parts toves més comú en nens i adolescents que representa un 3-4 % dels càncers infantils. En canvi, és molt menys freqüent en adults. Principalment consisteix en dues variants histològiques: l’embrionari (ERMS) i l’alveolar (ARMS), tot i que hi ha altres variants minoritàries. Molts dels tumors classificats com ARMS (un 80 %) contenen la translocació cromosòmica t(1;13) o t(2;13), on el domini d’unió a l’ADN de PAX3 o PAX7 s’uneix al domini de transactivació de FOXO1, formant les proteïnes de fusió PAX3-FOXO1 i PAX7-FOXO1, respectivament. La metàstasi és el principal factor que limita el pronòstic: en pacients amb metàstasi la supervivència lliure de malaltia als 5 anys cau dràsticament d’un 70 % a un 20-29 %. A més, els pacients amb presència de metàstasi que expressen PAX3-FOXO1 són els que presenten un pitjor pronòstic, on la supervivència als 4 anys és d’un 8 %.
LOXL2 (lysyl oxidase-like 2) ha sorgit com un important regulador de la progressió tumoral i el procés metastàtic, esdevenint un fort candidat per tal de desenvolupar inhibidors i teràpies dirigides en diferents càncers. Degut a que LOXL2 s’ha descrit com un factor clau en la progressió tumoral vam decidir caracteritzar la seva expressió i funció en el RMS. LOXL2 es troba àmpliament expressada en línies de RMS i, a més, els pacients amb RMS que expressen LOXL2 presenten una menor supervivència. LOXL2 localitza intracel·lularment i es troba N-glicosilada, modificació essencial per a la seva secreció al medi extracel·lular, on es processada proteolíticament.
El conjunt de resultats d’aquest treball evidencien per primer cop que LOXL2 és important en la progressió tumoral i metastàtica del RMS. Aquest fet és de gran rellevància en els pacients amb aquesta malaltia, on la metàstasi limita el seu pronòstic. Els resultats posen de manifest que LOXL2 promou el fenotip neoplàstic en el RMS independentment de la seva activitat catalítica, incrementant la capacitat clonogènica, proliferativa, migratòria, invasiva i metastàtica de les cèl·lules. La caracterització de LOXL2 intra- i extracel·lular és un altre tema de gran importància. En aquesta tesi s’ha confirmat que la N-glicosilació de LOXL2 no solament és essencial per a la seva secreció sinó també per duu a terme algunes de les seves funcions. Concretament, LOXL2 intracel·lular no glicosilat és capaç d’incrementar la capacitat migratòria i invasiva de les cèl·lules, descartant un paper de LOXL2 extracel·lular en aquestes funcions. D’altra banda, aquest mutant no glicosilat i no secretat no és capaç de promoure la capacitat clonogènica i proliferativa de les cèl·lules, ni tampoc amb el tractament amb LOXL2 recombinant humà extracel·lular, suggerint que les N-glicosilacions de LOXL2 afecten aquestes dues funcions.
La identificació de nous partners de LOXL2 és de gran rellevància per tal d’incrementar el coneixement de la funció de LOXL2. Per primer cop s’ha descrit la interacció de LOXL2 amb vimentina, proteïna important durant la migració i invasió en el RMS. A més, LOXL2 regula aquesta proteïna del citoesquelet incrementant la seva proteòlisi parcialment deguda a calpaïna-2, proteasa que també interacciona amb LOXL2. Aquests resultats suggereixen que LOXL2 té un paper important en la regulació del citoesquelet en les cèl·lules de RMS promovent la migració, invasió i metàstasi. No obstant, el mecanisme pel qual la interacció LOXL2-vimentina-calpaïna-2 és important s’ha d’examinar amb més detall en el futur. Conjuntament, la inhibició de LOXL2 podria aportar benefici terapèutic en un futur pels pacients de RMS on el tractament convencional, sobretot en pacients amb metàstasi, no resulta efectiu.Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in childhood and adolescence. Lysyl oxidase-like 2 (LOXL2) is an amine oxidase that catalyzes the covalent crosslinking of collagen and elastin in the extracellular matrix. Apart from its traditional role, novel functions have been attributed to both intra- and extracellular LOXL2 related to tumor progression. In this thesis we reported that LOXL2 is overexpressed in several RMS cell lines compared to other sarcoma cells. We also functionally characterized LOXL2 in RMS cell lines. LOXL2 stable and transient silencing in RMS cell lines resulted in a decrease in the clonogenic, cell proliferative, migratory and invasive capabilities. On the other hand, the reintroduction of LOXL2 in RMS non-expressing cells (RH28) using wild type or mutated (catalytically inactive) constructs resulted in an increase in the clonogenic capacity, cell proliferation, migration and invasion, independently of its catalytic activity. Moreover, we performed an in vivo assay injecting tumor cells orthotopically at the gastrocnemius muscle of mice and observed that LOXL2-expressing cells had an increased frequency and number of lung metastasis. At the same time, the metastatic capacity was increased independently of LOXL2 catalytic activity. In addition, in order to explore LOXL2 role according its subcellular localization we developed a non-secretable LOXL2 mutant (N-glycosylated sites were mutated) and confirmed that LOXL2 pro-migratory and pro-invasive effects depend on intracellular LOXL2. In contrast, non-glycosylated and non-secretable mutant was not able to increase the clonogenic and proliferative capacities of the cells. Furthermore, in order to decipher the molecular mechanisms associated to LOXL2 oncogenic activity in RMS a pull-down assay on RH28 transfected cells was performed and analyzed using mass spectrometry. Among the results, we confirmed the intermediated filament protein vimentin as a LOXL2-interactor, as well as the relevance of this protein in RMS cell migration and invasion. More interestingly, LOXL2 regulated cytoskeleton dynamics of RMS cells as the reintroduction of LOXL2 in RH28 cells increased the proteolysis of vimentin, process partially dependent on the protease calpain-2, another novel LOXL2-interactor. Finally, more research would be crucial to evaluate the role of LOXL2-vimentin-calpain-2 interaction in tumor progression. Altogether, blocking LOXL2 function may be promising for the treatment of RMS.
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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.
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Nguyen, Tue Gia Women's & Children's Health Faculty of Medicine UNSW. "Combined transcription modulating agents to overcome MycN-mediated retinoid reistance in hish risk neuroblastoma." Publisher:University of New South Wales. Women's & Children's Health, 2007. http://handle.unsw.edu.au/1959.4/44285.
Full textAbstract:
Neuroblastoma (NB) is the most common solid tumor of early infancy. Despite a significant improvement in the general survival rate for children with cancer, the prognosis of high-risk NB remains low, at about 30%, despite the use of intensive chemo-radiotherapy followed by differentiation therapy with retinoic acid (RA). Relapses in this category of NB are often due to the emergence of multi-drug and RA-resistant minimal residual cancer cells. The use of natural 13-cis RA, as a single chemo-preventive agent, has improved the survival rate to 50% for high-risk NB patients. However, the prevalence of RA-resistance is high in high-risk NB, and in solid cancers, in general. RA-resistance in cancer cells is mediated by a number of factors. Loss of RA-induced expression of the putative tumor suppressor gene, retinoic acid receptor-beta (RARβ), is one of the most common factors that have been reported in RAresistant phenotypes of a wide range of cancer cells. The transcriptional regulation of RAR(β) gene and other retinoid responsive-genes is believed to be regulated by the ligand-dependent transactivation of the homo- or heterodimer complexes of the retinoic acid receptor (RAR) and retinoid X receptor (RXR) subtypes, namely alpha (α), beta (β) and gamma (γ). It is believed that the anti-cancer activities of natural all-trans RA and 13-cis RA are mediated through activation of RAR-complexes. The loss of RA-induced RAR β expression can be caused by aberrant recruitment of chromatin structure modifying enzymes, histone deacetylases (HDACs), which have major roles in the global regulation of gene transcription. However, the mechanism of RA-resistance in NB cells is unclear. This thesis set out to identify the molecular mechanism of RA-resistance and to develop a new therapeutic approach to overcome RA-resistance in NB cells. The data in this thesis demonstrated that deregulation or over-expression of proto-oncogene MYCN caused a total RA-resistance in NB cells in vitro and in vivo, despite the strong induction of RARI3 expression. The data also indicated that the activation of RAR-dependent pathways by aRA or 13RA alone is not sufficient to overcome MYCN-mediated RA-resistance in NB cells. In the light of this observation, this thesis went on to examine whether combined targeting activation of RAR and RXR subtypes with receptor specific ligands could enhance the therapeutic efficacy of the retinoid signaling pathway. NB cells were treated with a panel of receptor-specific retinoids, namely aRA, l3RA, 9RA (RAR-specific), CD 417, CD 2314 (RARβ-specific), CD 666 (RARγ-specific), CD 336 (RARα-specific), CD 3640, CD 2872 (RXR-specific), as a single agent or in combination at a low concentration of 0.1 ??M. The results showed that combined targeting activation of RARα and RXR was not only the most effective combination, but also overcame MYCN-mediated RA-resistance in NB cells in vitro.Collectively, these data demonstrated the combined targeting activation of RAR and RXRs as a new approach to enhance the efficacy of retinoid therapy and overcome RA-resistance in the treatment of high-risk NB, and other cancers. The emerging therapeutic potential of HDAC inhibitors (HDACi) as front line anti-cancer agents, or adjuvants to other agents such as RA, has suggested a new approach in the treatment of cancer. However, the molecular mechanism of the remarkably specific anticancer actions of HDACi is still largely speculation. The data presented in this study was the first to demonstrate a novel sequential order and the dosage-dependent roles of basal p21Wafl expression and G2/M arrest as protective mechanisms against HDACi-induced apoptosis. In addition, this thesis also examined and compared the therapeutic efficacy of HDACi as a single agent and in combination with other anti-cancer agents such as RA, IFNα and chemotherapeutic agents. Evaluation of the therapeutic effects of combinations of aRA, IFN and HDACi showed that combination of HDACi and IFNα exhibited the strongest synergy against NB cells in vitro. Treatment of MYCN transgenic mice, which consistently develop abdominal NB tumors that closely mirror the human disease in both physiological and biological aspects, with hydroxamic acid-based HDACi, trichostatin A (TSA), alone reduced tumor growth by nearly 50%, compared to the solvent control and IFNα alone, which had no effect on NB tumor growth. The most exciting finding was that the combination of HDACi and IFNα synergistically reduced tumor mass and angiogenesis by over 80% without any apparent systemic side-effects. The therapeutic effect of treatment with HDACi correlated with the induction of acetylation of histone 4 protein (H4) in both tumor and organ tissues, indicating a wide therapeutic index for HDACi in vivo. Collectively, the data in this study have demonstrated basal p21 Wafl expression as a potential marker of sensitivity to HDACi-based therapy, and the therapeutic efficacy of a novel combination of HDACi with IFNα in vivo. These preclinical data have provided an evidence-based rationale for a clinical trial of the combination of HDACi and IFNα in the treatment of high risk NB.
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Torner, Rubies Ferran. "Estudio mediante elementos finitos de prótesis tumorales de rodilla en niños y adolescentes." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/397733.
Full textAbstract:
INTRODUCCIÓN:
Se considera a Ferguson (1861) el primer comunicante de una resección de rodilla, Verneuil (1863) el autor de la primera artroplastia de interposición y Gluck (1890) responsable de las primeras artroplastias protésicas.
Los sarcomas óseos primarios en niños y adolescentes se localizan habitualmente alrededor de la rodilla, existiendo diferentes modelos comercializados de megaprótesis tumorales para pacientes jóvenes o niños esqueléticamente inmaduros.
Los análisis de elementos finitos han sido progresivamente incorporados en el campo de la cirugía ortopédica y traumatología para el estudio de implantes de diversas formas y solicitaciones mecánicas.
HIPÓTESIS DE TRABAJO:
La diferente colocación del implante protésico endomedular y la posición de la rodilla, alteran la distribución de tensiones en el conjunto hueso-prótesis.
OBJETIVOS DE LA TESIS:
1.- Realizar un modelo informático de prótesis total de rodilla con vástagos endomedulares largos dotada de constricción y estudiarla mediante un análisis de elementos finitos.
2.- Localizar las zonas de la prótesis total de rodilla y del hueso receptor donde se acumulan mayores tensiones.
3.- Demostrar que el centrado del vástago protésico en el canal medular modifica la transmisión de esfuerzos en el conjunto articular.
4.- Valorar si el grado de flexión de la rodilla modifica las tensiones sobre el conjunto Hueso-prótesis total de rodilla.
5.- Realizar una valoración clínica en pacientes menores de dieciocho años del comportamiento de las prótesis totales de rodilla tumorales.
RESULTADOS:
Estudio experimental:
Los materiales más rígidos (metal) soportan una mayor tensión y los materiales más elásticos (plástico) presentan unas mayores deformaciones. El mayor nivel de tensión se produce en el extremo de la prótesis. Las magnitudes máximas de las deformidades que se producen en todas las piezas son similares, independientemente de si la prótesis está centrada, variando las tensiones en la parte metálica de la prótesis.
Estudio clínico:
Se han estudiado 14 casos de pacientes menores de 18 años portadores de artroplastia tumoral de rodilla.
Patología: Osteosarcoma 12; Sarcoma de Ewing: 2
Afectación tumoral femoral/tibial: 8/6
Se han valorado los parámetros clínicos de dolor; arco de movilidad; marcha; utilización de escaleras y grado de satisfacción.
CONCLUSIONES:
1.- Se ha obtenido un modelo informático de prótesis total de rodilla dotada de constricción, de vástagos endomedulares largos y ha sido estudiado mediante un sistema de análisis por elementos finitos.
2.- Del conjunto de materiales que componen la articulación protésica, aquellos que son más rígidos (materiales metálicos) soportan una mayor tensión, mientras que los más elásticos (materiales plásticos) presentan una mayor variación de deformaciones que alivian
los esfuerzos recibidos.
3.- La parte crítica de la estructura hueso-prótesis es la sección en la que finaliza el vástago de la prótesis, ya que en ella se produce una fuerte variación en la rigidez, lo que conlleva un mayor nivel de tensiones.
4.- Las magnitudes máximas de las deformaciones que se producen en todas las piezas, independientemente que se encuentre la prótesis centrada o no, son similares, aunque sus distribuciones varían.
5.- En los materiales plásticos y en el fémur, no se aprecia una variación importante de tensiones por la diferente posición de la prótesis. Sin embargo, en la parte metálica de la prótesis descentrada sí que existen aumentos considerables de tensión.
6.- Las tensiones en el conjunto aumentan con el grado de flexión tanto si los vástagos protésicos están centrados como si no lo están.
7.- Los parámetros clínicos de dolor, arco de movilidad de la rodilla, marcha, utilización de escaleras y grado de satisfacción han presentado unos buenos resultados en la mayoría de los casos de artroplastias tumorales de rodilla en pacientes menores de dieciocho años al año de la intervención quirúrgica.Introduction Primary bone sarcomas in children and adolescents are usually located around the knee. Different models of megaprosthesis are available for the treatment of young patients. Finite element analysis has been used to study implants in orthopedic surgery and traumatology. Hypothesis The different positioning of the intramedullary stem and the prosthetic knee position, modifies the stress distribution. Material and Methods experimental study: An finite element analysis of a knee prosthesis in different position has been made. clinical study: We have studied 14 cases of patients under 18 years of age with knee megaprosthesis after knee tumor resection.(Osteosarcoma 12 patients; Ewing Sarcoma 2 patients). Conclusions 1. A computer model of constricted total knee prosthesis with long intramedullary stems has been obtained and studied by a finite element analysis. 2. The more rigid materials (metallic materials) support greater tension, while the more elastic (plastics) have a greater variation of strain. 3. The critical part of the bone-prosthesis structure is located at the end of the prosthesis stem. 4. Tensions increase with the degree of knee flexion in all models. 5. The clinical parameters of pain, range of knee motion, walking distance, use of stairs and satisfaction have shown good results in most cases of knee replacements in patients under eighteen year of age.
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Slegtenhorst, Sonja. "Antioxidant intake in paediatric oncology patients." Thesis, Stellenbosch : Stellenbosch University, 2011. http://hdl.handle.net/10019.1/18050.
Full textAbstract:
Thesis (MNutr)--Stellenbosch University, 2011.ENGLISH ABSTRACT: Background: The role of antioxidants and adequate nutrition in the prevention and course of cancer treatment is globally recognised in nullifying the effects of free radicals and increasing the nutritional status of children during treatment. Objective: To investigate whether children with cancer meet their Dietary Reference Values and Safe Intakes for antioxidants, energy and protein. Design: Single centre prospective study. Setting: Children were recruited from the East of England Primary Treatment Centre using convenience sampling over 8 months. Forty-two children and adolescents diagnosed with a Solid tumour, Lymphoma or Leukaemia were eligible for data analysis (n=20 male; n=22 female). Method: Data was collected with an Estimated Food Record (EFR) in the 1st (EFR1) and 3rd month (EFR2) post-diagnosis. In the week following EFR completion, parents and/or children were contacted to complete four non-consecutive days of 24-hr food recalls. Data was categorised into diet alone, diet + food supplement (FS), tube feeding (tube) or diet + multi-vitamin-mineral supplementation (VMS). Malnutrition was determined by weight-for-age z-scores. Nutrient intake was compared to the Recommended Nutrient Intake (RNI), the Estimated Average Requirements (EAR) and the Lower Recommended Nutrient Intake (LRNI). Result: The sample consisted of 33% (n=14) diagnosed with Leukaemia, 24% (n=10) with Lymphoma and 43% (n=18) with Solid tumours. Sixty seven percent (n=28) underwent chemotherapy and 33% (n=14) a combination of therapies. Significant correlations were seen between the assessment tools in the diet alone category for both months for; vitamins A, C, E, selenium and protein and for EFR1 for zinc and energy. In both months greater numbers of children achieved ≥100% of requirements for diet + VMS (EFR 1; p<0.05; EFR2 p<0.05) than for other feeding modes. Vitamin C achieved the highest intakes compared to the RNI at 773% (EFR1) and 829% (EFR2). Intakes above 200% of the RNI were seen for vitamins A, C, E, selenium and zinc. No significant differences were seen between modes of feeding in either month for selenium or zinc. Vitamin A (EFR1≤ 100% diet alone p<0.05) and zinc (EFR1≤ 100% diet alone p=0.02) met the least of the LRNI in the 1st month compared to other antioxidants. No statistical significant difference was observed between the number of children attaining their EAR’s between the 3 modes of feeding in the 1st month and 3rd month. In the 1st month 27% (n=8) of participants consumed vitamin and/or mineral supplements, 18% in the 3rd month (n=4). In the 1st month 5% (n=2) of children were moderately malnourished and 10% (n=4) in 3rd month. Conversely in the 1st month 3% (n=1) were overweight and 3% (n=1) obese; the leukaemia group predominant. Conclusion: The research tools showed good correlation. Children using vitamin and/or mineral supplements mostly achieved their RNI’s compared to other feeding modes. Across feeding modes some children achieved antioxidant intakes above 200% RNI. LRNI’s on diet alone were not achieved for vitamin A and zinc. The study showed Leukaemics as having a higher prevalence of obesity. More research is required to determine the clinical implications of these findings.
AFRIKAANSE OPSOMMING: Agtergrond: Die rol van anti-oksidante en voldoende voeding in die voorkoming en verloop van kanker behandeling word wêreldwyd erken vir vernietiging van die effek van vry radikale en die verbetering van voedingstatus van kinders tydens behandeling. Doelwit: Om ondersoek in te stel of kinders met kanker hul Dieet Verwysingswaardes en Veilige Innames vir anti-oksidante, energie en proteïen bereik. Ontwerp: Enkel sentrum prospektiewe studie. Omgewing: Kinders was gewerf deur middel van gerieflikheidsteekproefneming oor 8 maande vanaf die “East of England Primary Treatment Centre”. Twee-en-veertig kinders en adolessente gediagnoseer met 'n Soliede tumor, Limfoom of Leukemie het in aanmerking gekom vir dataanalise (n=20 manlik, n=22 vroulik). Metode: Data was ingesamel met ‘n Geskatte Voedsel Rekord (GVR) in die eerste (GVR1) en derde maand (GVR2) na diagnose. In die week na voltooiing van die GVR is ouers en/of kinders gekontak om vier onopeenvolgende dae van 24-uur herroepe te voltooi. Data was verdeel in dieet alleen, dieet + voedsel supplement (VS), buisvoeding (buis) of dieet + multi-vitamien-mineraal supplementasie (VMS). Wanvoeding was bepaal deur middel van gewig-vir-ouderdom z-tellings. Nutriënt inname was vergelyk met die Aanbevole Nutriënt Inname (ANI), die Geskatte Gemiddelde Behoeftes (GGB) en die Laer Aanbevole Nutriënt Inname (LANI). Resultate: Die steekproef het bestaan uit 33% (n=14) gediagnoseer met Leukemie, 24% (n=10) Limfoom en 43% (n=18) Soliede tumore. Sewe-en-sestig persent (n=28) het chemoterapie ontvang en 33% (n=14) ‘n kombinasie van terapieë. Betekenisvolle korrelasies was waargeneem tussen die assesseringsinstrumente in die dieet alleen kategorie vir beide maande vir vitamiene A, C, E, selenium en proteïen en vir GVR1 ook vir sink en energie. In beide maande het ‘n groter aantal kinders ≥100% van hul behoeftes bereik vr dieet+VMS (GVR1; p<0.05; GVR2 p<0.05) as vir ander modi van voeding. Vitamien C het die hoogste innames bereik vergeleke met die ANI teen 773% (GVR1) en 829% (GVR2). Innames bo 200% van die ANI was waargeneem vir vitamiene A, C, E, selenium en sink. Geen betekenisvolle verskille was waargeneem tussen modi van voeding in enige maand vir selenium en sink nie. Vitamien A (GVR1≤100% dieet alleen p<0.05) en sink (GVR1≤100% dieet alleen p=0.02) het die minste van die LANI bereik in die eerste maand vergeleke met ander anti-oksidante. Geen statisties beduidende verskil was waargeneem tussen die aantal kinders wat hul GGB’s bereik het tussen die 3 voedingswyses in die eerste en derde maande nie. In die eerste maand het 27% (n=8) van deelnemers vitamien en/of mineraal supplemente ingeneem, en 18% (n=4) in die derde maand. In die eerste maand was 5% (n=2) van kinders matig wangevoed en 10% (n=4) in die derde maand. In die eerste maand was 3% (n=1) van kinders oorgewig en 3% (n=1) vetsugtig, die leukemie groep spesifiek. Gevolgtrekking: Die navorsingsinstrumente het goeie korrelasie getoon. Kinders wat vitamien en/of mineraal supplemente gebruik het het meestal hul ANI’s bereik vergeleke met ander modi van voeding. Oor voeding modi het sommige kinders anti-oksidant innames bo 200% ANI bereik. LANI’s op dieet alleen was nie bereik vir Vitamien A en sink nie. Hierdie studie het aangetoon dat dié met Leukemia ‘n hoër prevalensie van oorgewig/vetsug getoon het. Meer navorsing is nodig om die kliniese implikasies van die bevindinge te bepaal.
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Lam, Ching-yee, and 林靜宜. "The impacts of childhood cancer on siblings among Hong Kong Chinese: from parents' perspectives." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B45011837.
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Kleinhans, Alicia. "The effects of home health care on psychosocial adaptation of families to pediatric cancer." Honors in the Major Thesis, University of Central Florida, 2000. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/196.
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This item is only available in print in the UCF Libraries. If this is your Honors Thesis, you can help us make it available online for use by researchers around the world by following the instructions on the distribution consent form at http://library.ucf.edu/Systems/DigitalInitiatives/DigitalCollections/InternetDistributionConsentAgreementForm.pdf You may also contact the project coordinator, Kerri Bottorff, at kerri.bottorff@ucf.edu for more information.Bachelors
Health and Public Affairs
Nursing
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Vega, García Nerea. "Estudi del perfil d’expressió de les histones deacetilasa (HDAC) en pacients pediàtrics amb leucèmia aguda." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/666190.
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NTECEDENTS: els inhibidors d’histona deacetilasa (HDACi) han emergit els últims anys com potencials tractaments dirigits, amb la finalitat de revertir els canvis epigenètics associats a diferents tipus de càncer, incloent les neoplàsies hematològiques. La falta d’especificitat dels HDACi, però, dificulta la predicció dels seus efectes biològics i provoca una toxicitat no menyspreable, el que ha limitat el seu ús en la pràctica clínica. L’expressió de les HDACs no ha estat estudiada en les leucèmies agudes pediàtriques més que de manera parcial i en sèries amb un limitat número de pacients; per tant, són necessaris estudis que ajudin a aclarir el paper de cadascuna de les HDACs com a possibles biomarcadors i com a dianes terapèutiques, de cara a dirigir el tractament específic i personalitzat amb HDACi.
HIPÒTESI: en aquest context, l’estudi global del perfil transcripcional de les HDACs en una sèrie àmplia i representativa de pacients pediàtrics amb diferents subtipus de leucèmia aguda permetria definir millor el seu impacte pronòstic i definir el seu rol com a dianes terapèutiques, ajudant a dirigir el tractament específic amb HDACi de forma més racional i individualitzada.
OBJECTIUS: estudiar de forma global el perfil d’expressió de les HDAC1-11, SIRT1, SIRT7 i d’altres gens co-reguladors, MEF2C i MEF2D, en una sèrie de pacients pediàtrics amb leucèmia aguda diagnosticats i tractats en un sol centre.
METODOLOGIA: anàlisi de l’expressió de l’mRNA de les HDAC1-11, SIRT1, SIRT7, MEF2C i MEF2D mitjançant PCR quantitativa en 211 pacients pediàtrics (0-18 anys), diagnosticats de leucèmia de novo des de l’any 2003 al 2017 en el nostre centre. Els pacients es van tractar uniformement d’acord als protocols consecutius de la Sociedad Española de Hematología y Oncología Pediátrica (SEHOP). Es va emprar un pool de pacients no-neoplàsics com a calibrador i també es va analitzar l’expressió dels diferents gens en cèl·lules CD34+ normals de moll d’os i a cèl·lules B CD19+ madures i limfòcits T madurs de sang perifèrica.
RESULTATS: l’expressió de les HDACs va diferir en els diferents subtipus de cèl·lules hematopoètiques normals d’acord amb el grau de maduració i el llinatge. En els pacients amb leucèmia es va observar, en general, una sobreexpressió de les HDACs, amb perfils específics que correlacionaven amb característiques clíniques i biològiques i, fins i tot en algunes ocasions, amb la supervivència dels pacients. Així, alguns perfils d’expressió d’HDAC i el perfil de MEF2C semblaven reflectir, probablement, el llinatge i la maduresa dels blasts, mentre que d’altres identificaven la via oncogènica activa en les cèl·lules leucèmiques. Concretament, es va identificar un perfil d’expressió distintiu pels pacients amb reordenament del gen KMT2A (MLL), amb nivells elevats d’HDAC9 i MEF2D, independentment de l’edat, el partner del gen de fusió i el llinatge. A més, es va observar en els pacients amb LLA-B un pronòstic advers de la sobreexpressió de l’HDAC9, independentment de l’estat del gen KMT2A.
CONCLUSIONS: en aquest treball s’han observat diferents perfils d’expressió segons els diferents subtipus de leucèmia aguda pediàtrica. Concretament, s’ha identificat un perfil distintiu dels pacients amb reordenament del gen KMT2A, amb la sobreexpressió de l’ HDAC9 i MEF2D, independentment del llinatge, de l’edat i del partner del gen de fusió.
Aquests resultats aporten una imatge global de l’expressió de les HDACs en els pacients pediàtrics amb leucèmia aguda i recolzen el tractament dirigit amb HDACi més específics en seleccionats grups de pacients d’alt risc, com els pacients amb reordenament del gen KMT2A.Histone deacetylase inhibitors (HDACi) emerged as promising drugs in leukaemia, but their toxicity due to lack of specificity limited their use. Therefore, there is a need to elucidate the role of HDACs in specific settings. The study of HDAC expression in childhood leukaemia could help to choose more specific HDACi for selected candidates in a personalized approach. We analysed HDAC1-11, SIRT1, SIRT7, MEF2C and MEF2D mRNA expression in 211 paediatric patients diagnosed with acute leukaemia. We found a global overexpression of HDACs, while specific HDACs correlated with clinical and biological features, and some even predicted outcome. Thus, some HDAC and MEF2C profiles probably reflected the lineage and the maturation of the blasts and some profiles pointed out specific oncogenic pathways active in the leukaemic cells. Specifically, we identified a distinctive signature for patients with MLL rearrangement, with high HDAC9 and MEF2D expression, regardless of age, MLL-partner and lineage. Moreover, we observed an adverse prognostic value of overexpression of HDAC9, regardless of MLL rearrangement. Our results provide useful knowledge on the complex picture of HDACs expression in childhood leukaemia and support the directed use of specific HDACi to selected paediatric patients with acute leukaemia.
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Garcia, Gerique Laura. "Study of disseminated high-risk neuroblastoma in the bone marrow niche; from microenvironmental modelling to therapeutic targeting." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/672256.
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Neuroblastoma (NB) is the most common extracraneal solid tumor diagnosed in the first 5 years of childhood and accounts for approximately 15% of all pediatric cancer-related deaths. At the time of diagnosis, about half of NB patients present disseminated disease, being the bone marrow (BM) the most common site of dissemination. The persistence of infiltrated BM during treatment or relapse is predictive of patient poor outcome. The BM microenvironment has unique biologic properties that favor progression of disseminated NB tumor cells. In this environment, the receptor CXCR4 has a pivotal role for BM homeostasis and is involved in metastatic dissemination in several cancers. In NB, CXCR4 is expressed in tumor cells; however, its oncogenic role in relation with its ligand CXCL12 has shown contradictory results. Using an in vitro model that recapitulates low oxygen levels and chemokine signaling present in the BM environment, we explored whether CXCR4 together with MIF, a second ligand, is critical for NB survival and proliferation in the niche. We also evaluated MIF inhibition as a therapeutic option for NB.
To develop a BM-based in vitro model, NB cells were cultured in different conditioned media (CMs) derived from supernatants of patient-derived BM primary cells (CM-BM) and NB cell lines (CM-NB) cultured alone, or in combination (CM-BM/NB). To mimic BM oxygen levels, NB cells were cultured under hypoxia (1% O2), as compared to cell culture normoxia (21% O2). Expanded BM cultures used to generate CMs contained a heterogenic population with a predominant cellularity positive for mesenchymal stromal markers measured by flow cytometry. Cytokine arrays and ELISA assays of CMs revealed MIF as the highest NB released cytokine, whereas CXCL12 was not detected. The expression of MIF and CXCL12 signaling pathways was analyzed with different public NB databases. Among the analyzed genes, the high expression of CXCR4 and MIF was associated with patient poor outcome and high-risk disseminated staging. To further explore the role of CXCR4/MIF axis in high- risk disseminated NB, in vitro and in vivo functional studies were performed with or without the covalent MIF inhibitor 4-IPP and the CXCR4 antagonist AMD3100.
When exposed to BM-derived CMs and hypoxia, BM-derived NB cell lines showed increased surface expression of CXCR4 by flow cytometry. The same culture condition increased
phosphorylated levels of AKT/PI3K and ERK/MAPK measured by western blot. Cell viability assays showed that hypoxic conditions and BM-derived CMs enhanced NB cell proliferation at different time points. Similarly, in vivo, the co-injection of BM cells favored NB tumor progression by reducing engraftment times in contrast to NB injection alone. Using wound healing assays and Matrigel-coated Transwells, CM-BM/NB chemoattracted and enhanced migration and invasion of LAN-1 cells cultured under hypoxic conditions. These aggressive phenotypes promoted by the BM-based model were reverted by adding sub-lethal concentrations of the MIF inhibitor 4-IPP. We also explored whether MIF present in our CMs affected response to chemotherapy. After treatment with doxorubicin and etoposide at IC50 values LAN-1 cell viability increased in CM-BM/NB compared to control media. In both cases, chemo-sensitivity was restored when 4-IPP was added to CM-BM/NB. Finally, the administration of 4-IPP delayed the tumor progression and increased mice survival in a LAN- 1 subcutaneous xenograft model.
In conclusion, our findings provide new understanding of the contribution of BM microenvironment to NB progression. Based on our BM-model, the relationship between the BM microenvironment and NB cells appears mediate, in part, by the autocrine CXCR4/MIF signaling axis. Furthermore, our results suggested that MIF could represent a therapeutic target for the treatment of patients with high-risk NB.
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Kelly, Katherine Patterson Ganong Lawrence H. "Stepping up, stepping back, being pushed, and stepping away the process of making treatment decisions for children with cancer by parents who no longer live together /." Diss., Columbia, Mo. : University of Missouri-Columbia, 2008. http://hdl.handle.net/10355/6867.
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The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on April 1, 2010). Vita. Thesis advisor: Lawrence H. Ganong. "May 2008" Includes bibliographical references
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Rochelle, Gary B. "Concurrent Validity of the Wide Range Assessment of Memory and Learning and the Woodcock-Johnson Tests of Cognitive Ability-Revised with a Neurologically Compromised Pediatric Population." Thesis, University of North Texas, 2000. https://digital.library.unt.edu/ark:/67531/metadc2700/.
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The Wide Range Assessment of Memory and Learning (WRAML) is a relatively new instrument used in the assessment of memory in children. The purpose of this study was to examine the validity of the WRAML by comparing the performance of children on both the WRAML and the Woodcock-Johnson Tests of Cognitive Ability- Revised (WJTCA-R). Subjects for the study were children in treatment for a brain tumor at a regional children's medical center. Fifty children participated in the study ranging from ages 6 to 17. A multiple regression analysis was conducted to determine which of four selected clusters from the WJTCA-R would have the highest correlation with the Verbal Memory Index (VERI) from the WRAML. The Short-Term Memory (GSM) cluster had the highest correlation ( r = .82) as predicted. A Pearson's product-moment correlational analysis was conducted between the Visual Processing (GV) cluster from the WJTCA-R and the Visual Memory Index (VISI) from the WRAML. GV was found to have a high positive correlation ( r = .63) with VISI. A similar analysis was conducted between the Long-Term Retrieval (GLR) cluster from the WJTCA-R and the Learning Index (LRNI) from the WRAML. GLR was found to have a high positive correlation ( r = .81) with LRNI. Finally, a correlational analysis was conducted between the Broad Cognitive Ability (BCA) scale from the WJTCA-R and the General Memory Index (GENI) from the WRAML. A high positive correlation ( r = .87) was found between these most global measures from the two batteries. The observed correlation between BCA and GENI was much higher than anticipated. The author concluded that neurological impairment had affected subject memory and intellectual functioning in similar ways. The results do not generalize to children who have not had similar decrements in cognitive functioning. Future research should establish a baseline correlation between the two instruments with a non-impaired population.
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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.
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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
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Saz, Roy Mª Ángeles. "Impacto de la enfermedad oncológica infantil: Percepción de las familias y de las enfermeras." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/664277.
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INTRODUCCIÓN:
Vivir la experiencia de tener un hijo con cáncer es una situación que genera una crisis en la familia que afecta no sólo a nivel estructural sino también emocional. Las enfermeras son los profesionales, miembros del equipo multidisciplinar, que interrelacionan de manera específica con estas familias, por lo que es de interés saber cómo evidencian esta experiencia y su impacto en las familias. Por tal de poder mejorar la practica asistencial que debe contemplar una orientación holística dentro de los cuidados de alta complejidad que precisa un niño con enfermedad oncológica.
OBJETIVOS:
El objetivo principal fue comprender y analizar en profundidad la vivencia en el momento del diagnóstico de la enfermedad oncológica infantil en las familias y la percepción del fenómeno en las enfermeras. Los objetivos específicos consistieron en analizar el impacto en las familias del debut de enfermedad oncológica infantil, explorar la percepción de las enfermeras sobre el impacto y la vivencia de las familias en el inicio de una enfermedad oncológica infantil, y comparar la percepción que tienen las familias con la percepción de las enfermeras respecto el debut de la enfermedad oncológica infantil.
METODOLOGÍA:
Estudio cualitativo siguiendo un enfoque basado en la fenomenología hermenéutica de Heidegger cuyo ámbito de estudio fueron las unidades de Oncología y Hospital de día del Hospital Sant Joan de Déu de Barcelona. Los informantes fueron las familias de niños con cáncer y las enfermeras dedicadas a su cuidado. En la selección de dichos informantes se usó la técnica de muestreo teórico o intencionado teniendo en cuenta variables sociodemográficas que ayudaron a definir el perfil del informante en ambos grupos de estudio hasta conseguir la saturación teórica de la información. Dicha saturación se consiguió antes de acabar con el proceso de recolección de información ya que interesaba poder disponer de la visión de los diferentes perfiles de informantes de cada grupo. Para la recogida de datos se utilizó la entrevista semiestructurada siguiendo un guión de tópicos preparado previamente y el diario de campo. El tipo de análisis utilizado fue temático bajo el método de análisis del contenido, siguiendo método de análisis Guía QUAGOL (Qualitative Analysis Guide of Leuven). Se utiliza como herramienta informática el programa de Nvivo10. Al ser el análisis un proceso circular y continuo, al ir profundizando en la información recibida, se fueron cambiando o añadiendo categorías y subcategorías.
RESULTADOS:
Las entrevistas realizadas fueron 14 en el grupo 1 (familias) y 17 en el grupo 2 (enfermeras).En el grupo 1 (familias) se obtuvieron 1060 unidades de significado que se agruparon en 11 categorías y 9 subcategorias. En el grupo 2(enfermeras) se obtuvieron 822 unidades de significado que se agruparon en 12 categorías y 7 subcategorias. En el grupo 1(familias), se pudo observar que la categoría que obtuvo un mayor número de referencias en unidades de significado fue repercusión de la enfermedad en la familia (REPERENFER) (n=121) y, la que menos, fue cuidado del hijo enfermo (CUIDADOHIJO) (n=10) que se referia a quién se centraba en cuidar al niño enfermo de cáncer. En el grupo 2 (enfermeras), se pudo observar que la categoría que obtuvo un mayor número de referencias en unidades de significado fue emociones observadas (EMOENFER) (n=134) y la que menos, presencia de fatiga por compasión (FATIGAENFERMERA) (n=1). Los resultados de este estudio describen el impacto y la experiencia de las familias ante el inicio de la enfermedad oncológica de sus hijos. Muestran que es una experiencia difícil de vivir y que afecta a todos los niveles (económico, organizativo, emocional, social) alterando los procesos familiares. Asimismo, existe un impacto emocional que les imposibilita procesar la situación que viven, dado que el primer sentimiento que sienten es dolor y miedo ante la información que reciben sobre el diagnóstico de cáncer. Muchas veces las reacciones vividas son rabia, enfado, negación, bloqueo emocional, culpa, tristeza. También los resultados permitieron detectar que las enfermeras no sólo expusieron el cómo perciben el impacto del inicio de la enfermedad oncológica en las familias sino que también se pudo evidenciar cómo afecta a las enfermeras la experiencia de cuidado de estas familias y sus hijos.
CONCLUSIÓN:
La enfermedad oncológica infantil provoca una situación de impacto emocional en las familias que se experimenta en todas las esferas de la vida. Contrariamente a la presunción adoptada en la premisa de investigación, las enfermeras perciben todas las vivencias descritas por las familias sobre el impacto de la enfermedad oncología infantil. Asimismo, fruto del cuidado humanizado y la relación terapéutica, las enfermeras muestran indicios de desgaste emocional que puede dificultar el cuidado.INTRODUCTION: Living the experience of having a child with cancer is a situation that creates a family crisis that affects not only structurally but also emotional. Nurses are professionals, who together with the multidisciplinary team, interact with these families, so it is of interest to know how to show this experience and its impact on families. For this to be able to improve health care practice that should include a holistic orientation with in the highly complex care that requires a child cancer. AIMS/OBJECTIVES: The main objective was to understand and analyze in profundity the experience at the time of diagnosis of childhood oncological disease in families and the perception of the phenomenon in nurses. The specific objectives were to analyze the impact on families of the debut of childhood cancer disease, to explore the perception of nurses about the impact and the experience of families in the onset of childhood cancer, and to compare the perception that families have with the perception of nurses regarding the onset of childhood cancer. METHODOLOGY: Qualitative study following an approach based on the hermeneutical phenomenology of Heidegger whose field of study were the Oncology and Day Hospital units of the Sant Joan de Deu Hospital in Barcelona. The informants were the families of children with cancer and the nurses dedicated to their care. In the selection of these informants the theoretical or intentional sampling technique was used, taking into account sociodemographic variables that helped to define the profile of the informant in both study groups. Until getting the theoretical saturation of the information. This saturation was achieved before ending the process of gathering information as it was interesting to be able to have the vision of the different informant profiles of each group. For the data collection, the semi-structured interview was used following a previously prepared topic script and the field diary. The type of analysis used was thematic under the content analysis method, following the QUAGOL (Qualitative Analysis Guide of Leuven) analysis method. The Nvivo10 program is used as a computer tool. As the analysis was a circular and continuous process, as we went deeper into the information received, we changed or added categories and subcategories. RESULTS: The interviews carried out were 14 in group 1 (families) and 17 in group 2 (nurses). In group 1 (families) 1060 units of meaning were obtained and grouped into 11 categories and 9 subcategories. In group 2 (nurses), 822 units of meaning were obtained, grouped into 12 categories and 7 subcategories. In group 1 (families), it was observed that the category that obtained the highest number of references in units of meaning was the repercussion of the disease in the family (REPERENFER) (n = 121) and, the least, it was taken care of sick child (CUIDADOHIJO) (n = 10) that referred to who was focused on caring for the child with cancer. In group 2 (nurses), it was observed that the category that obtained the highest number of references in meaning units was observed emotions (EMOENFER) (n = 134) and the least, presence of compassion fatigue (FATIGAENFERMERA) (n = 1). The results of this study describe the impact and experience of families before the oncological onset of their children. They show that it is a difficult experience to live and that affects all levels (economic, organizational, emotional, social) altering family processes. Also, there is an emotional impact that makes it impossible to process the situation they are living, given that the first feeling They feel it is pain and fear of the information they receive about the diagnosis of cancer. Many times the reactions experienced are anger, anger, denial, emotional block, guilt, sadness. The results also allowed us to detect that the nurses not only explained how they perceive the impact of the oncological disease onset in the families, but also how the nurses experience the care of these families and their children. CONCLUSIONS: Childhood oncology sickness causes a situation of emotional impact in families that is experienced in all spheres of life. Contrary to the presumption adopted in the research premise, the nurses perceive all the experiences described by the families about the impact of the childhood oncology disease. Likewise, as a result of humanized care and the therapeutic relationship, nurses evince signs of emotional exhaustion that can make care difficult.
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Cremin, Bryan J. "Imaging of tumours of the urinary tract in children, with particular reference to Wilms' tumour." Doctoral thesis, University of Cape Town, 1986. http://hdl.handle.net/11427/27214.
Full textAbstract:
The investigation of an abdominal mass in a child is a common problem in the radiology department of the Red Cross Children's Hospital. The majority of these masses involve the urinary tract. The commonest neoplasm is a Wilms' tumour of the kidney. Against a pathological and clinical background, the investigation of Wilms' tumour by diagnostic imaging is presented. The imaging modalities currently utilised are the intravenous urogram (IVU), ultrasound (US), computed tomography (CT) and magnetic resonance (MR). Using the material available in the last decade, the principles, techniques and imaging characteristics of these modalities are investigated and compared. These results are reflected against those reported in the medical literature. This literature is not yet extensive as the current technology has only been available for the last six to seven years. The IVU has in the past been the main imaging modality and we still use it extensively. Its strengths and weaknesses are discussed. In the last five years US has taken its place as the primary method of diagnostic imaging. We have found that with our increasing experience that this is justified. The use of US and IVU in a practiced hand is a powerful diagnostic combination. CT as a primary investigation is not readily available at our institution. We have used it for comparative purposes in about 20% of our recent cases. CT has not added greatly to our initial diagnostic impression. However, it has been most useful for follow up of metastasis and for assessing the normality of the lungs before ceasing chemotherapy. Our experience with MRI is limited and confined to unusual presentations in the last year. Other modalities such as arteriography and nuclear medicine have special indications which are to be discussed. The remaining tumours of the upper urinary tracts are all rare, but are reported and the literature researched. In the lower urinary tract the main pelvic lesion is a rhabdomyosarcoma. The comparative advantages of the IVU, US, CT and MRI are also noted. In the pelvis, US has also become the primary imaging modality, and is replacing contrast medium cystography. However, examples of the latter are included as it still has a place, particularly in the less sophisticated institutes. CT and MRI, when available, have imaging advantages in the pelvis and are becoming the methods of choice for follow up. The main objective of this document has been to investigate the available imaging techniques, but, against this overall theme, the clinical care of the child is most important. With this in mind the treatment protocols that are used at our hospital are noted in the appendices to the thesis.
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MacKay, Lyndsay Jerusha, and University of Lethbridge Faculty of Health Sciences. "Exploring family-centered care among pediatric oncology nurses." Thesis, Lethbridge, Alta. : University of Lethbridge, Faculty of Health Sciences, c2009, 2009. http://hdl.handle.net/10133/2483.
Full textAbstract:
Family-centered care (FCC) is important within the practice of pediatric oncology nurses. Such nurses face challenges and barriers when attempting to provide FCC. The purpose of this study was to understand the experiences of pediatric oncology nurses in relation to FCC; identify how pediatric oncology nurses implemented FCC into their practice; identify what facilitated and enabled pediatric oncology nurses to implement FCC; and discern the barriers and challenges that were present in their setting when implementing FCC. A qualitative approach utilizing person-centered interviewing was used to collect data. Nurses (N=20) from the Alberta Children‟s Hospital were recruited through purposeful convenience sampling and were then interviewed. Five major themes were identified from the data set: ACH support f FCC, How participants defined FCC, Establishing FCC, Enhancing FCC, and Barriers and Challenges to providing FCC. Recommendations for future research and implications for practice and education are offered.xii, 191 leaves ; 29 cm
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Neto, João Evangelista Bezerra. "Análise do perfil de expressão de microRNAs em tumores adrenocorticais benignos e malignos humanos." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5166/tde-15082014-153113/.
Full textAbstract:
Introdução: Os mecanismos moleculares que levam ao desenvolvimento de tumores do córtex suprarrenal ainda são pouco compreendidos. Uma alta frequência de carcinomas adrenocorticais na infância tem sido relatada nas regiões sul e sudeste do Brasil, com a presença de uma única mutação germinativa do supressor tumoral p53 (p.R337H) sendo evidenciada em 80- 97% dos casos. Outros fatores implicados na tumorigênese adrenocortical incluem a hiperexpressão das vias IGF2 e Wnt. Os microRNAs, fragmentos de RNA que não codificam proteínas, são capazes de controlar a transcrição gênica exercendo um papel importante no crescimento e proliferação celular. O papel dos microRNA na tumorigênese adrenal ainda não está totalmente elucidado. Objetivos: Avaliar diferenças no perfil de expressão de microRNAs entre tumores benignos e malignos do córtex da suprarrenal da população adulta e pediátrica. Comparar esta expressão entre as amostras caracterizadas pela presença da mutação germinativa p.R337H do supressor tumoral p53, hiperexpressão da via Wnt e da via do IGF2. Métodos: Trinta e seis pacientes não relacionados, adultos e crianças, foram estudados. Os pacientes tiveram avaliação do perfil de produção hormonal e das vias moleculares p53, IGF2 e Wnt. O perfil de expressão de microRNAs foi determinado utilizando-se produto comercial específico TaqMan MicroRNA Human Array (AppliedBiosystems, Forster City, CA, USA). Os dados de expressão foram analisados com o programa Expression Suite (AppliedBiosystems, Forster City, CA, USA) e Realtime Statmainer (Integromics, Granada, Espanha). O estudo de alvos e das redes gênicas afetadas foram estudados com o programa Ingenuity - IPA (Ingenuity, EUA). Resultados: A comparação do perfil de expressão entre adenomas e carcinomas revelou alteração de expressão em 89 e 21 miRNAs em adultos e crianças, respectivamente. Após a correção estatística para múltiplos testes, nove miRNAs mantiveram diferenças significantes em adultos e nenhum em crianças. Dentre os microRNAs com expressão alterada em adultos estavam o miR-483-3p (p=0,011), miR-1290 (p=0,011) e miR-106b (p=0,048). Esses microRNAs foram selecionados para avaliação como biomarcadores por meio de curva ROC. O miR-1290 apresentou o melhor resultado (AUC=1,0; IC 95% 1,0; p=0,003), com valores de expressão de miR-1290 de 10,3 sendo capazes de diferenciar adenomas de carcinomas em adultos com 100% de sensibilidade e especificidade. Na população pediátrica, não foi possível diferenciar adenomas de carcinomas com o uso de microRNAs individuais. A comparação direta entre o perfil de expressão de adenomas da população adulta e pediátrica revelou 38 miRNAs com alteração de expressão. O miR-483-3p e miR-483-5p estavam dentre os mais desregulados e foram os únicos a manter diferença estatística significativa (p=0,009 para ambos), estando hiperexpressos em crianças. A comparação direta do perfil de expressão entre carcinomas da população adulta e pediátrica revelou 26 microRNAs com alteração de expressão, porém sem significância estatística após correção para múltiplos testes. A comparação entre as amostras caracterizadas pela mutação p.R337H do supressor tumoral p53 revelou 53 genes alterados. A comparação entre as amostras caracterizadas por alteração do Wnt revelou 46 genes desregulados. Entretanto, essas alterações não mantiveram significância estatística após correção estatística para múltiplos testes. A comparação entre as amostras caracterizadas por alteração do IGF2 revelou 83 genes alterados, com miR-483-3p (p < 0,001), miR-483-5p (p < 0,001), miR-296-5p (p=0,047) e miR-1290 (p=0,011) mantendo significância estatística após correção para múltiplos testes. O estudo dos potenciais alvos e das redes genicas afetadas pelos miRNAs desregulados observados nesse estudo revelou novas e promissoras vias moleculares que podem ajudar a melhor entender a tumorigenese adrenocortical. Conclusões: Diferenças no perfil de expressão de microRNAs foram observadas entre tumores benignos e malignos do córtex da suprarrenal da população adulta e pediátrica. O ganho de expressão foi o evento mais comum. Os genes miR-483-3p, miR-1290 e miR-106b foram reconhecidos em diversas comparações entre os grupos de interesse e parecem apresentar papel importante na tumorigenese adrenocortical. Além disso, o miR-1290 demonstrou atuar como biomarcador capaz de diferenciar adenomas de carcinomas na população adulta. O estudo de redes gênicas potencialmente afetadas pelos microRNAs que apresentaram alteração de expressão nesse estudo poderá ajudar no melhor entendimento da tumorigênese adrenocorticalIntroduction: The molecular mechanisms that lead to the development of tumors of the adrenal cortex are still poorly understood. A high frequency of pediatric adrenocortical carcinomas has been reported in South and Southeast of Brazil, and a single germline mutation of the tumor suppressor p53 (p.R337H) has been identified in 80-97% of cases. In addition, the overexpression of IGF2 and Wnt pathways are also involved in adrenal tumorigenesis. MicroRNAs, a class of small nonconding RNA, are able to control gene transcription regulating cellular growth and proliferation. However, the role of microRNA has not been fully elucidated in adrenal tumorigenesis. Objectives: To evaluate differences in the expression profile of microRNA between adult and pediatric adrenocortical tumors. To compare microRNA expression profile among samples with and without TP53, Wnt and IGF2 abnormalities. Methods: Thirty-six unrelated patients, adults and children, were studied. Patients had comprehensive hormonal evaluation and tumor samples were studied for TP53, Wnt and IGF2. The expression profile of microRNAs were determined using specific commercial product TaqMan MicroRNA Human Array (AppliedBiosystems, Forster City, CA, USA). The expression data were analyzed with the program Expression Suite (AppliedBiosystems, Forster City, CA, USA) and Realtime Statmainer (Integromics, Granada, Spain). The study of gene networks and affected targets genes have been studied with the Ingenuity program - IPA (Ingenuity, USA). Results: Comparing expression profile between adenomas and carcinomas revealed 89 and 21 deregulated miRNAs in adults and children, respectively. After false discovery rate correction, nine microRNA have maintained significant diferences in miRNAs between adults and none in children. Among microRNAs deregulated in adults were miR-483-3p (p = 0.011), miR-1290 (p = 0.011) and miR-106b (p = 0.048). These microRNAs were selected for evaluation as biomarkers through ROC curve. The miR- 1290 presented the best result (AUC = 1.0; IC 95% 1.0; p = 0.003), with values of expression of miR-1290 of 10.3 being able to differentiate adenomas from carcinomas with 100% sensitivity and specificity. It was not possible to differentiate adenomas from carcinomas by using microRNAs. The direct comparison between the expression profile of adult and pediatric adenomas revealed 38 degulated miRNAs. The miR-483-3p and miR-483-5p were hiperexpressed in children and were the only ones that keept a statistically significant difference (p = 0.009 for both). The direct comparison of the expression profile between adult and pediatric carcinomas revealed 26 deregulated microRNAs, but without statistical significance after correction for multiple testing. The comparison between samples characterized by the p.R337H mutation of tumor suppressor p53 revealed 53 genes deregulated. The comparison between samples characterized by alteration of Wnt reveled 46 microRNAs deregulated. However, after statistical correction for false discovery rate none of them maintained significance. The comparison between samples characterized by change in the IGF2 gene revealed 83 deregulated microRNAs, miR-483-3 p (p < 0.001), miR-483-5 p (p < 0.001), miR-296-5 p (p = 0.047) and miR-1290 (p = 0.011) maintaining statistical significance after correction for false discovery rate. The study of potential targets and molecular networks affected by the deregulatad microRNAs showed promising new molecular pathways that may help better understand the adrenocortical tumorigenese. Conclusions: There were changes in the microRNAs expression profile between malignant and benign tumors of the adrenal cortex of adult and pediatric population. Hyperexpression were the most common presentation. MiR-483-3p, miR-1290 and miR-106b were recognized in various comparisons among groups of interest and appear to have an important role in adrenocortical tumorigenese. In addition, the miR- 1290 can act as a biomarker differentiating adenomas from carcinomas in the adult population. The study of molecular networks potentially affected by the microRNAs deregulated culd contribute to better understanding of adrenocortical tumorigenesis
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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).
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Fenollosa, Artés Felip. "Contribució a l'estudi de la impressió 3D per a la fabricació de models per facilitar l'assaig d'operacions quirúrgiques de tumors." Doctoral thesis, Universitat Politècnica de Catalunya, 2019. http://hdl.handle.net/10803/667421.
Full textAbstract:
La present tesi doctoral s’ha centrat en el repte d’aconseguir, mitjançant Fabricació Additiva (FA), models per a assaig quirúrgic, sota la premissa que els equips per fer-los haurien de ser accessibles a l’àmbit hospitalari. L’objectiu és facilitar l’extensió de l’ús dels prototips com a eina de preparació d’operacions quirúrgiques, transformant la pràctica mèdica actual de la mateixa manera que en el seu moment ho van fer tecnologies com les que van facilitar l’ús de radiografies. El motiu d’utilitzar FA, en lloc de tecnologies més tradicionals, és la seva capacitat de materialitzar de forma directa les dades digitals obtingudes de l’anatomia del pacient mitjançant sistemes d’escanejat tridimensional, fent possible l’obtenció de models personalitzats. Els resultats es centren en la generació de nou coneixement sobre com aconseguir equipaments d’impressió 3D multimaterials accessibles que permetin l’obtenció de models mimètics respecte als teixits vius. Per facilitar aquesta buscada extensió de la tecnologia, s’ha focalitzat en les tecnologies de codi obert com la Fabricació per Filament Fos (FFF) i similars basades en líquids catalitzables. La recerca s’alinea dins l’activitat de desenvolupament de la FA al CIM UPC, i en aquest àmbit concret amb la col·laboració amb l’Hospital Sant Joan de Déu de Barcelona (HSJD). El primer bloc de la tesi inclou la descripció de l’estat de l’art, detallant les tecnologies existents i la seva aplicació a l’entorn mèdic. S’han establert per primer cop unes bases de caracterització dels teixits vius -sobretot tous- per donar suport a la selecció de materials que els puguin mimetitzar en un procés de FA, a efectes de millorar l’experiència d’assaig dels cirurgians. El caràcter rígid dels materials majoritàriament usats en impressió 3D els fa poc útils per simular tumors i altres referències anatòmiques. De forma successiva, es tracten paràmetres com la densitat, la viscoelasticitat, la caracterització dels materials tous a la indústria, l’estudi del mòdul elàstic de teixits tous i vasos, la duresa d’aquests, i requeriments com l’esterilització dels models. El segon bloc comença explorant la impressió 3D mitjançant FFF. Es classifiquen les variants del procés des del punt de vista de la multimaterialitat, essencial per fer models d’assaig quirúrgic, diferenciant entre solucions multibroquet i de barreja al capçal. S’ha inclòs l’estudi de materials (filaments i líquids) que serien més útils per mimetitzar teixits tous. Es constata com en els líquids, en comparació amb els filaments, la complexitat del treball en processos de FA és més elevada, i es determinen formes d’imprimir materials molt tous. Per acabar, s’exposen sis casos reals de col·laboració amb l’HJSD, una selecció d’aquells en els que el doctorand ha intervingut en els darrers anys. L’origen es troba en la dificultat de l’abordatge d’operacions de resecció de tumors infantils com el neuroblastoma, i a la iniciativa del Dr. Lucas Krauel. Finalment, el Bloc 3 té per objecte explorar nombrosos conceptes (fins a 8), activitat completada al llarg dels darrers cinc anys amb el suport dels mitjans del CIM UPC i de l’activitat associada a treballs finals d’estudis d’estudiants de la UPC, arribant-se a materialitzar equipaments experimentals per validar-los. La recerca ampla i sistemàtica al respecte fa que s’estigui més a prop de disposar d’una solució d’impressió 3D multimaterial de sobretaula. Es determina que la millor via de progrés és la de disposar d’una pluralitat de capçals independents a fi de capacitar la impressora 3D per integrar diversos conceptes estudiats, materialitzant-se una possible solució. Cloent la tesi, es planteja com seria un equipament d’impressió 3D per a models d’assaig quirúrgic, a fi de servir de base per a futurs desenvolupaments.La presente tesis doctoral se ha centrado en el reto de conseguir, mediante Fabricación Aditiva (FA), modelos para ensayo quirúrgico, bajo la premisa que los equipos para obtenerlos tendrían que ser accesibles al ámbito hospitalario. El objetivo es facilitar la extensión del uso de modelos como herramienta de preparación de operaciones quirúrgicas, transformando la práctica médica actual de la misma manera que, en su momento, lo hicieron tecnologías como las que facilitaron el uso de radiografías. El motivo de utilizar FA, en lugar de tecnologías más tradicionales, es su capacidad de materializar de forma directa los datos digitales obtenidos de la anatomía del paciente mediante sistemas de escaneado tridimensional, haciendo posible la obtención de modelos personalizados. Los resultados se centran en la generación de nuevo conocimiento para conseguir equipamientos de impresión 3D multimateriales accesibles que permitan la obtención de modelos miméticos respecto a los tejidos vivos. Para facilitar la buscada extensión de la tecnología, se ha focalizado en las tecnologías de código abierto como la Fabricación por Hilo Fundido (FFF) y similares basadas en líquidos catalizables. Esta investigación se alinea dentro de la actividad de desarrollo de la FA en el CIM UPC, y en este ámbito concreto con la colaboración con el Hospital Sant Joan de Déu de Barcelona (HSJD). El primer bloque de la tesis incluye la descripción del estado del arte, detallando las tecnologías existentes y su aplicación al entorno médico. Se han establecido por primera vez unas bases de caracterización de los tejidos vivos – principalmente blandos – para dar apoyo a la selección de materiales que los puedan mimetizar en un proceso de FA, a efectos de mejorar la experiencia de ensayo de los cirujanos. El carácter rígido de los materiales mayoritariamente usados en impresión 3D los hace poco útiles para simular tumores y otras referencias anatómicas. De forma sucesiva, se tratan parámetros como la densidad, la viscoelasticidad, la caracterización de materiales blandos en la industria, el estudio del módulo elástico de tejidos blandos y vasos, la dureza de los mismos, y requerimientos como la esterilización de los modelos. El segundo bloque empieza explorando la impresión 3D mediante FFF. Se clasifican las variantes del proceso desde el punto de vista de la multimaterialidad, esencial para hacer modelos de ensayo quirúrgico, diferenciando entre soluciones multiboquilla y de mezcla en el cabezal. Se ha incluido el estudio de materiales (filamentos y líquidos) que serían más útiles para mimetizar tejidos blandos. Se constata como en los líquidos, en comparación con los filamentos, la complejidad del trabajo en procesos de FA es más elevada, y se determinan formas de imprimir materiales muy blandos. Para acabar, se exponen seis casos reales de colaboración con el HJSD, una selección de aquellos en los que el doctorando ha intervenido en los últimos años. El origen se encuentra en la dificultad del abordaje de operaciones de resección de tumores infantiles como el neuroblastoma, y en la iniciativa del Dr. Lucas Krauel. Finalmente, el Bloque 3 desarrolla numerosos conceptos (hasta 8), actividad completada a lo largo de los últimos cinco años con el apoyo de los medios del CIM UPC y de la actividad asociada a trabajos finales de estudios de estudiantes de la UPC, llegándose a materializar equipamientos experimentales para validarlos. La investigación amplia y sistemática al respecto hace que se esté más cerca de disponer de una solución de impresión 3D multimaterial de sobremesa. Se determina que la mejor vía de progreso es la de disponer de una pluralidad de cabezales independientes, a fin de capacitar la impresora 3D para integrar diversos conceptos estudiados, materializándose una posible solución. Para cerrar la tesis, se plantea cómo sería un equipamiento de impresión 3D para modelos de ensayo quirúrgico, a fin de servir de base para futuros desarrollos.
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Bull, Kim. "A longitudinal study of health related quality of life in children treated for cerebellar tumours compared with a non-tumour group." Thesis, University of Southampton, 2012. https://eprints.soton.ac.uk/397080/.
Full textAbstract:
This thesis investigated health related quality of life (HRQoL) measured annually at three time points (T1, T2, T3) in children treated for medulloblastoma (SRM) or low grade cerebellar astrocytoma (LGCA) compared with a typically developing group of children. Four research questions were addressed. These were, first, whether HRQoL and other aspects of quality of survival differ between children treated for cerebellar tumours and a representative sample of children in the general population. Second, whether there are differences between HRQoL in children treated for SRM and LGCA. Third, whether HRQoL and the factors that impacted on it changed over time. Fourth whether there were any early modifiable predictors of subsequent HRQoL. Children treated for cerebellar tumours had a significantly poorer HRQoL and IQ than the Comparison group. In addition, those in the SRM group had significantly poorer health status, and behavioural and executive functioning, the latter by teacher-report only. Children in the SRM group had a significantly poorer HRQoL, health status (by parent-report only), and behavioural functioning (by teacher-report only) than children in the LGCA group. IQ and executive functioning were similar. Longitudinally, in the SRM group, HRQoL and health status improved but remained very poor. Behaviour and IQ did not improve, and executive functioning declined (by teacher-report only). In the LGCA group HRQoL and IQ did not improve and remained poor. Specific help at school increased in the SRM group from 40% at T1 to 57% at T3. In the LGCA group the percentages were 11 and 24 compared with a consistent 3% in the Comparison group, indicating increasing need for educational support in both tumour groups. Motor and sensory functioning, emotional functioning (except by parent-report at T3), and cognitive functioning (by child-report at T3 only) were consistent predictors of HRQoL over time. At T1, emotion and cognition (by child-and parent-report), child’s age (by child-report), and motor and sensory functioning (by parent-report) predicted subsequent HRQoL two years later. These findings show that impairment is evident early on in children treated for cerebellar tumours and persists over time. HRQoL remains poor particularly in the LGCA group where no improvement was observed. These children need to be assessed regularly and monitored as early intervention to mitigate cognitive and emotional difficulties especially in older children, may help to improve subsequent HRQoL. Future research should focus on early interventions.
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Ramis, Zaldívar Juan Enrique. "Decoding the genetic landscape of pediatric and young adult germinal center-derived B-cell non-Hodgkin lymphoma." Doctoral thesis, Universitat de Barcelona, 2021. http://hdl.handle.net/10803/672372.
Full textAbstract:
B-cell non-Hodgkin lymphoma (B-NHL) of pediatric and young adult population is a diverse group of neoplasms predominantly composed of aggressive B-cell lymphomas from the germinal center (GC). Molecular characterization of pediatric series has allowed the identification of several subtypes that predominantly occur in this subgroup of age. Despite of that, genomic features of these pediatric entities and their relationship to other B-NHL in this group of patients have not been extensively investigated. This thesis has aimed to address this gap of knowledge by performing a genetic and molecular characterization of large series of pediatric and young adult variants of GC-derived B-NHL including the Burkitt- like lymphoma with 11q aberration (BLL-11q) , pediatric type follicular lymphoma (PTFL) and large B-cell lymphomas (LBCL) such as diffuse large B-cell lymphomas (DLBCL) , high grade B- cell lymphomas, not otherwise specified (HGBCL, NOS) and large B-cell lymphoma with IRF4 rearrangement (LBCL-IRF4) entities.
In the Study 1 we have molecularly characterized a series of 11 BLL-11q observing that BLL- 11q differed clinically, morphologically and immunophenotypically from conventional BL and instead showed features more consistent with HGBCL or DLBCL. Genomic profile was also different from that of BL and DLBCL with a mutational landscape characterized by the lack of typical BL mutations in ID3, TCF3, or CCND3 genes and recurrent specific BTG2 and ETS1 mutations, not present in BL but in germinal center B-cell (GCB) DLBCL subtype. All these observations suggest that BLL-11q is a neoplasm closer to other GC-derived lymphomas rather than BL. In Study 2, we expanded our knowledge on the genetic alterations associated to PTFL by verifying the presence of MAP2K1 and IRF8 mutations in a previously well characterized series of 43 PTFL. We demonstrate the activating effect of MAP2K1 mutations by immunohistochemical analysis observing phosphorylation of the MAP2K1 downstream target extracellular signal-regulated kinase in those mutated cases. Besides, we demonstrate the specificity of MAP2K1 and IRF8-K66R mutations since they are absent in conventional FL or in t(14;18)-negative FL. Finally, in the Study 3 we characterized a large series of LBCL including DLBCL, HGBCL, NOS and LBCL-IRF4 through an integrative analysis including targeted next generation sequencing, copy number, and transcriptome data. Results showed that each subgroup displayed different molecular profiles. LBCL-IRF4 had frequent mutations in IRF4 and NF-κB pathway genes (CARD11, CD79B) whereas DLBCL, NOS was predominantly of GCB-DLBCL subtype and carried gene mutations similar to the adult counterpart (e.g., SOCS1 and KMT2D). A subset of HGBCL, NOS displayed recurrent alterations of BL-related genes such as MYC, ID3, CCND3 and SMARCA4, whereas other cases were genetically closer to GCB-DLBCL. Interestingly, we could identify age-related differences in pediatric DLBCL since pediatric and young adult cases were mainly of GCB subtype, displayed low genetic complexity and virtually lacked primary aberrations (BCL2, MYC and BCL6 rearrangements). Finally, we identify clinical and molecular features related to unfavorable outcome such as age >18 years, high LDH levels, activated B-cell (ABC) DLBCL profile, high genetic complexity, homozygous deletions of 19p13.3/TNFSF7/TNFSF9, gains of 1q21-q44/MDM4/MCL1 and TP53 mutations.
Altogether, we conclude that GC-derived B-NHL of pediatric and young adult population is a heterogeneous group of tumors including different entities with specific molecular profiles and clinical behavior. This thesis has contributed to increase the knowledge of these lymphoma entities identifying biomarkers that might be helpful to improve their diagnosis and to design management strategies more adapted to their particular biological behavior.
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Ward, C. "Behavioural and psychological outcomes in children treated for brain tumours." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1445980/.
Full textAbstract:
There is a sparcity of literature examining the outcomes of those treated for childhood brain tumours using surgery-only. Although several areas of significant long-term problems have been identified, such as deficits in executive functions and raised levels of behavioural and psychological problems, research so far has failed to consistently identify factors that predict outcomes. This makes it very difficult to make recommendations about how to lessen the impact of these cognitive, behavioural and emotional difficulties for this group of children. Nineteen studies that examine cognitive, behavioural and psychological functioning in this population were identified and are reviewed here.
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Longaud-Valès, Audrey. "Fonctions exécutives et cognition sociale chez des patients traités dans l’enfance pour une tumeur frontale bénigne ou maligne." Thesis, Paris 5, 2013. http://www.theses.fr/2013PA05H133.
Full textAbstract:
En neuro-oncologie pédiatrique, les études neurocognitives et neuropsychologiques sur les tumeurs hémisphériques (sus-tentorielles) sont plus rares que celles sur les tumeurs de la fosse postérieure (sous-tentorielles), bénignes (notamment l’astrocytome pilocytique du cervelet) ou malignes (en particulier, le médulloblastome qui est la tumeur maligne la plus fréquente chez l’enfant). A l’heure actuelle il n’existe pas, à notre connaissance, de séries publiées de cas d’enfants traités pour tumeur frontale, bénigne ou maligne et même les descriptions isolées d’un seul cas restent rares (Daigneault, S & al, 1997 ; Anderson, S.W, 2000). Il existe des séries de cas de tumeur frontale chez l’adulte (Roca & al, 2010 ; Yong-Gao & al, 2012). Il existe par contre une littérature importante porte sur le devenir et les séquelles des enfants traités pour une tumeur de la fosse postérieure. En effet, les progrès thérapeutiques ont amélioré les taux de survie, et plusieurs équipes ont examinés l’impact de différents facteurs (essentiellement mais pas exclusivement médicaux : topographie lésionnelle, âge d’apparition de la tumeur, nature des traitements et complications, etc., mais aussi niveau d’éducation des parents, etc.) sur les séquelles motrices et cognitives, le devenir et la qualité de vie de ces enfants et adolescents. Entre septembre 2010 et septembre 2011, 21 patients âgés entre 8 ans 3 mois et 27 ans 10 mois au moment de l’évaluation neuropsychologique ont été inclus dans cette étude. L’évaluation neuropsychologique, réalisée en deux temps, incluait des tests (tests papier-crayon et épreuves écologiques) évaluant l’efficience intellectuelle, des fonctions exécutives, d’attention, et de théorie de l’esprit. 44 patients contrôles ont été appariés en âge, sexe et NSC (niveau socio-économique) au groupe de patients. Au niveau statistique d’importantes différences sont relevées, notamment, dans les épreuves de reconnaissance d’expressions faciales émotionnelles. Il s’agit de la 1ère étude qui évalue les fonctions cognitives et affectives dans un groupe de patients ayant été traités dans l’enfance pour une tumeur frontale bénigne ou maligneFrontal lesions in children and adolescents have been mainly explored in traumatic brain injury (TBI). Other frontal lobe pathologies such as frontal lobe epilepsy (FLE), frontal focal lobe lesion, such as brain tumours or frontal focal lobe pathologies, can explain sequelae after frontal lobe pathologies. In the literature only two cases studies exist on benign frontal lobe tumour in children. To our knowledge there is no study group of frontal lobe tumours in children. Between September 2010 and September 2011, we observed 21 patients treated for benign/malign tumours. We examined 22 young patients aged between 8.3 years and 27.10 years old, all treated for benign or malign frontal tumour in Gustave Roussy’s Institute (in case of malign tumour) or Necker Enfants-Malades (in case of malign tumour). Treatment of this patients depended on benign or malign tumour. A total of 44 controls subjects were enrolled in study. All children and adolescents had neuropsychological tests, such as executive function tests (planning, mental flexibility, attention, working memory tasks) and measure or theory of mind tests such as face recognition test (TOM). All children were seen twice. Main differences are observed in facial recognition test between patients with malign and benign tumours and control subjects. IQ in not affected when tumours are benign, and most children obtain normal performances in executive tests. This is a first study with comprehensive neuropsychological assessment of children and adolescents with frontal lobe tumours. Findings have to be compared with classical studies of frontal lobe lesions in adults. Results suggest that many children treated for frontal lobe tumours do not present the classical dysexecutive syndrome and major behavioural changes as described in adults. However most of them present deficits in facial recognition of emotions and gesture imitations deficits
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Chai, Huayan. "Longitudinal Curves for Behaviors of Children Diagnosed with A Brain Tumor." Digital Archive @ GSU, 2007. http://digitalarchive.gsu.edu/math_theses/22.
Full textAbstract:
Change in adaptive outcomes of children who are treated for brain tumors is examined using longitudinal data. The children received different types of treatment from none to any combinations of three treatments, which are surgery, radiation and chemotherapy. In this thesis, we use mixed model to find the significant variables that predict change in outcomes of communication skill, daily living skills and socialization skill. Fractional polynomial transformation method and Gompertz method are applied to build non-linear longitudinal curves. We use PRESS as the criterion to compare these two methods. Comparison analysis shows the effect of each significant variable on adaptive behaviors over time. In most cases, model with Gompertz method is better than that with Transformation method. Significant predictors of change in adaptive outcomes include Time, Gender, Surgery, SES classes, interaction between Time and Radiation, interaction between Time and Gender, interaction between Age and Gender.
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Haslop, Maisy. "Processing speed, social functioning and resilience in children treated for brain tumours." Thesis, University of London, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.583268.
Full textAbstract:
Objectives: To investigate cognitive and motor functioning in children treated for brain tumours. To also assess processing speed as a possible mediator in the outcomes of children treated for medulloblastoma in the posterior fossa. Design: A cross-sectional design was used. There were two groups. Children treated for medulloblastomas, and an age and gender matched non-CNS control group of children treated for Wilm's tumours. There were 14 participants in each group. Participants were aged between nine and 16 years old. Methods: Participants were assessed using measures for processing speed, attention, fine motor and visual motor co-ordination. Long-term outcomes were assessed using measures of intelligence (IQ), academic achievement, adaptive functioning, social functioning, and resilience. Results: There were significant differences between the two groups. Participants treated for medulloblastoma were significantly impaired on measures of processing speed, attention, fine motor and visual motor co-ordination. The medulloblastoma group performance was also significantly worse on measures of IQ, academic, adaptive, and social functioning. Interestingly, processing speed was found to be a significant mediator in the outcomes measured. When processing speed was co- varied, the group differences were no longer significant. Conclusion: The results of this study offer information on the impact of medulloblastoma on cognitive and motor abilities. It also offers novel information concerning the processing speed as a possible mediator in long-term outcomes of 3 children treated for medulloblastoma. This information will help with the design of interventions to target specific deficits. This will also provide additional information on the links between processing speed and outcomes. 4