Dissertations / Theses on the topic 'Primary brain tumor'

A brain tumor diagnosis is traumatic and has a devastating impact upon the caregiver and the family unit. The effects of the tumor growth and treatment often cause significant neurologic injury and dramatically affect the quality of life (QOL) for the patient and their entire family unit. Caregivers are constantly challenged to provide care, yet they feel untrained and underprepared as they struggle to adjust to new roles and responsibilities. The purpose of this study is to gain an understanding of the lived experiences of caregivers of individuals with primary benign brain tumor (PBBT). An interpretive phenomenological analysis approach was used to explore the experiences of 10 caregivers. Bowen's family systems theory provided an understanding of how families respond to changes in their family system resulting from a member of the family having a PBBT. A nonprobability sampling technique was used to recruit participants from 2 virtual support groups. Data were collected through semistructured interviews guided by an interview template. Interviews were transcribed and analyzed following the Smith tradition of inquiry until data saturation was reached. Three major themes emerged from the data: experiencing new challenges, responding to initial diagnosis, and facing challenges with family and friends. Caregivers experience a wide variety of responsibilities that are physically and psychologically challenging, which can negatively affect the QOL for the caregiver and the patient. These findings can be used by healthcare providers to identify resources to alleviate the unanticipated demands caregivers experience. Future studies are needed to explore how best to decrease challenges experienced by caregivers of individuals with PBBT.

Thesis advisor: Ellen Mahoney
The diagnosis of a primary malignant brain tumor (PMBT) can be devastating for individuals and their families due to the limited treatment options and poor prognosis. Patients often rely on family members to manage their care; however, many caregivers feel under-prepared and overwhelmed by the experience. Though caring for a person with a PMBT is challenging and complex, little research has addressed the family caregiver's performance. The purpose of this study was to identify the extent to which preparedness and caregiver role strain explained the family caregiver’s performance in symptom management. An adapted theoretical framework, The Theory of Unpleasant Symptoms for Family Caregivers, guided this study. The study employed a descriptive, correlational research design in which the researcher obtained cross-sectional data during one collection period. The participants were adults who identified themselves as family caregivers of persons with a PMBT. Forty caregivers were enrolled in the study at the Brain Tumor Center at Beth Israel Deaconess Medical Center. Results from the regression analyses indicated that caregiver role strain and preparedness explained 31% of the variance (adjusted R2) in perceived psychological symptom distress and 29% (adjusted R2) of the variance in perceived physical symptom distress. Caregiver role strain was the major contributor to psychological (B=.68, p=.000) and physical symptoms (B=.48, p=0.001), indicating that higher levels of caregiver role strain were predictive of higher levels of perceived symptom distress and this relationship was strong. Preparedness contributed less to the explained variance in psychological (B=-.24, p=.20) and physical symptoms (B=-.21, p=.14). The negative beta indicates that higher preparedness was related to lower perceived symptom distress, but this relationship was small when compared with role strain. This study informs clinicians in neuro-oncology that care giver role strain is often high in family caregivers of patients with a PMBT and can have a negative impact on caregiver performance. These findings also support the need for more tailored nursing interventions to assist caregivers with ways to decrease caregiver role strain and improve caregiver preparedness
Thesis (PhD) — Boston College, 2008
Submitted to: Boston College. Connell School of Nursing
Discipline: Nursing

The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on September 25, 2009). Thesis advisors: Dr. N. Scott Litofsky & Dr. Anand Chandrasekhar. Includes bibliographical references.

Brain tumors are abnormal tissue masses found, either malignant or benign in nature. Medulloblastoma is a brain tumor subtype found to arise in the hind region of the brain, which is highly malignant and has poor long term prospects in general. On the basis of the driving force behind the tumor, medulloblastoma is further subgrouped into 4 categories: WNT; SHH; Group 3 and Group 4 tumors. Group 3 tumors show a high expression of N-Myc protein which is seen in certain types of cancerous cells. The cell cycle is regulated at several checkpoints by cyclin/cdk inhibitors. The primary cilium is an organelle found on the cellular surface, which has functions in cell growth, differentiation and neurogenesis. Aurora kinase is a protein kinase involved in the regulation and maintainence of the cilium. Often the cilium gets deleted from the cellular surface in tumors coupled with an increase in the kinase level inside the cells. Hence aurora kinase is found to be a viable target for therapy. Aurora kinase is also involved in stabilizing the MYCN gene by protecting it from degradation. In this project, the primary cilum was studied in neural stem cells and followed by study of its presence on tumor cells in culture. The gene involved in cilium development i.e. Kif3a was mutated and its aggressive nature was compared with that of the tumor cells. Aurora kinase was commonly found to be over-expressed in both the tumors and the mutants whereas N-Myc over-expression was seen only in tumors. Experiments suggest that cilia repression in Kif3a mutants takes place via an aurora kinase dependent pathway.

Sleep impairments for caregivers are multifactorial. Assumptions are that caregivers of those with primary malignant brain tumors (PMBT) are similar to caregivers of persons with dementia as cognitive impairments are present at diagnosis. The shorter trajectory of PMBTs and rapid deterioration of recipients’ health may influence sleep in caregivers of persons with a PMBT. The purposes of this study were to use a sleep impairment model to characterize caregiver sleep using objective and subjective measures, and to examine sleep loss effects on psychosocial and physiologic health outcomes. A secondary data analysis using baseline data from a larger study of mind-body interactions in caregivers of family members with PMBTs was used. Caregiver data included standardized questionnaires, serum blood draw, and three-day sleep-wake activity data from an accelerometer. Analyses included descriptive statistics, correlations, t-tests, and hierarchical regression models. Caregivers (N = 133) were White (94%), female (69.2%) spouses (75.2) and on average 52 years old (SD = 11.8). Care recipients were mainly White males of similar age with a highly malignant glioma (57.4%). Sleep latency was longer (35 min, SD = 34.5), with shorter total sleep time (TST) (357 min, SD = 84.6) and more frequent wake after sleep onset (WASO; 15.1%, SD = 9.2) than in the general population. Caregivers reported high anxiety (59.4%). Caregiver comorbidities and care recipient functioning explained higher perceptions of health (R2 = 26, F(2, 84) = 14.94, p < .001). Whereas, longer TST, more WASO and poorer sleep quality explained poorer quality of life (R2 = .27, F(4, 66) = 6.19, p < .001). Sleep loss variables explained little variance in physical health status, interleukin-1ra and interleukin-6 levels, fatigue, depressive symptoms, spiritual health, social support, and work limitations. Nurses need to assist caregivers with anxiety management and ways to improve sleep at time of PMBT diagnosis. Sleep impairments place these caregivers at risk for physical and mental health problems, and compromise their ability to continue in the role.

Abstract The findings on depression and anxiety among brain tumor patients have so far been based on case series and case samples. In Finland, psychiatric research in relation to psychiatric symptoms among patients with different types of brain tumors is lacking. The study population of this thesis consisted of 101 patients (39 males and 62 females) aged between 20 and 82 years with a solitary primary brain tumor treated surgically at the Oulu Clinic for Neurosurgery, Oulu University Hospital between February 1990 and March 1992. The major histological subgroup consisted of gliomas (40%), and the rest were meningiomas (33%), acoustic neurinomas (13%), pituitary adenomas (8%) and other types (6%). The psychiatric symptoms of the patients were assessed at three time points, namely before tumor operation as well as at three months and at one year after operation by two valid measurement instruments, the Beck Depression Inventory and the Crown Crisp Experiential Index. In addition, the patients' functional state was evaluated by the Karnofsky Performance Scale and their quality of life according to Sintonen 15 D. Prevalence of at least mild depression before tumor operation was 30% for males and 38% for females. The mean depressive scores decreased significantly for up to one-year during follow-up for both males and females, but they remained notably high in all patients. Decreased functional status (KPS under 70) in the patients was significantly associated with high depressive scores at all measurement points. The decrease in the mean depressive scores was significant among patients with an anterior tumor and those with a pituitary adenoma. Five-year survival of the brain tumor patients was found to be mainly associated with the histology of the tumor. Survival time in months (SD) of the patients with high-grade (III–IV) gliomas was shown to be 22.5 (21.4), while it was 50.2 (19.9) for the patients with low-grade (I–II) gliomas, and 58.2 (9.4) for the rest of the patients. Depression among low-grade glioma patients was significantly associated with worse survival at five years follow-up. The level of anxiety was shown to be significantly higher among patients with a primary brain tumor in the right hemisphere compared to the anxiety scores among patients with left hemispheric tumors. A significant increase was found in the level of obsessionality over time in the female patients with a brain tumor in the left anterior location of the brain at three months after operation. The level of quality of life (QOL) was significantly worse among female brain tumor patients compared to males. Depressive females had significantly lower quality of life compared to that of non-depressive females up to one-year follow-up after surgical operation of the tumor. Depression, anxiety and obsessive-compulsive symptoms have to be recognized and be treated by psychotherapy and pharmacotherapy as soon as possible at every unit where brain tumor patients are followed and encountered.

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’adolescent
High-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

Melanoma brain metastases (MBrM) are devastating, occurring in up to 60% of melanoma patients and are increasing in incidence as systemic treatments improve. MBrM are notoriously difficult to treat and patients suffer from extremely poor survival rates, resulting in these patients being excluded from clinical trials testing new treatments, thus highlighting a need for research in this field. We developed a pre-clinical model where mice have simultaneous intracranial and extracranial B16 melanoma tumours to mimic the clinical setting. Notably, intracranial tumour growth was the survival-limiting factor, allowing the study of therapeutic effects specifically in the brain. Various combinations of anti-PD-1, anti-CTLA-4 and GM-CSF were investigated as potential therapies for MBrM. We found that the combination of anti-PD-1 and anti-CTLA-4 could prolong the survival of these mice; however, this was dependent on the presence of an extracranial tumour. Functional studies revealed that natural killer cells and cytotoxic T-cells were essential mediators of this therapy. Moreover, examination of the infiltrating immune cell populations demonstrated an increase in CD45+ immune cells in the intracranial tumours of mice also bearing a flank tumour and receiving the anti-PD-1 and anti-CTLA-4 therapy. This increase was found to be a result of the increase in infiltrating T-cells and macrophages/microglia and was reliant on the presence of an extracranial tumour. Analysis of cytotoxic T-cells revealed an increase in tumour antigen-specific cells in mice with an intracranial and extracranial tumour receiving treatment. Tumour antigen-specific T-cells within the blood showed an increased expression of homing receptors, which have been previously linked to an increase in T-cell infiltration into the brain. In conclusion, we have demonstrated that the combination of anti-PD-1 and anti-CTLA-4 can be an effective therapy for the treatment MBrM, while also identifying the main immune cell populations involved and a potential mechanism behind the therapeutic efficacy.

Deficits in social interaction, communication and repetitive patterns of behaviour are common characteristics of autistic spectrum disorders (Autism). Visuo-motor neurons (known as mirror neurons), that fire both when observing or executing goal directed actions, have been shown by research to play a role in motor action and intention understanding. This has led to a link suggesting that a dysfunction of mirror neurons may be involved in some aspects of Autism difficulties. Frequent research updates are providing a greater understanding and clarification for the important specification of this hypothesis. This leads the way to suggesting the possibility of the further development and support for novel interventions such as neurofeedback for this condition. This review represents a selective overview of core documents on the topic area. Declaration of Position My interest in the potential link between Autism and a dysfunctional mirror nemon system (MNS) was inspired by reading literature on the topic 'while I was completing a Masters in Neuropsychology. What became clear to me, both from the literature and from my limited clinical exposure, is the considerable heterogeneity of Autism. Furthermore, in the absence of distinct and consistent, nemo or physiological markers, accurate identification and diagnosis of autistic spectrum disorders can be problematic and consequently the ability of clinicians and researchers to detect this condition early in development is often restricted.

碩士
高雄醫學大學
公共衛生學研究所
88
The study used the hospitalization records from the Kaoping Division of the Bureau of National Health Insurance to discover incidences of primary brain tumors among populations 30 years of age and under living in the 26 townships and municipal areas in Kaohsiung for the 1996-1999 period. The study's aim was to explore the relationship between primary brain tumors in young people and their distance of residence from pollution from the petrochemical industrial complexes (PICs). We examined cases of primary brain tumor in young people living less than 1 km, from 1-2 kms, from 2-3kms and more than 3 kms distant from one of the four PICs in the study area. The distance more than 3kms from one of the four PICs was defined as the reference area. Results indicated that the cumulative incidence rate of primary brain tumors among young people living within 1 kilometer from the PICs was 1.28 times greater than the incidence rate for the reference area (95% CI=0.77-2.12); for those living from 1 to 2 kilometers from the PICs, the cumulative incidence rate was 1.13 times greater than that of the reference area(95% CI=0.50-2.57); for young people within 2-3 kiliometers from the PICs, the cumulative incidence rate was 061 times than that of the reference area (95% CI=0.23-1.65). However, malignant tumors, particularly gliomas, showed a higher incidence rate in residents living from 1-2 kilometers of the PICs than for those living more than 2 kilometers from the PICs (RR=1.91,95%CI=0.69-5.31), particular in females (RR=3.23, 95%CI=0.97-10.80). Benign brain tumer in males showed a higher incidence for residents living within 1-2 kilometers from the PICs as opposed to those living at a distance of more than 2 kilometers (RR=5.16,95%CI=1.11-23.88). Due to limitation in sample size, the present study cannot draw a conclusion about the relationship between incidence of brain tumors in young people and the distance at which they live from the PICs. However, this study does mark the first effort to a convenient and easy to use system to collect data from the Bureau of National Health Insurance to examine cases of primary brain tumors. Results of this study indicate that the incidence of gliomas in both sexes and of benign brain tumers in males may be related to residential distance from the petrochemical plants; particularly in gliomas. It is well worth further investigation.

碩士
臺北巿立體育學院
身心障礙者轉銜及休閒教育研究所
96
This purpose of the study is to explore benefits of participating interactive leisure activities on hospitalized children with brain tumor and primary caregivers. Three children aged 2-7 who received radiation therapy and their primary caregivers were provided 4- week interactive leisure activities. In-depth interview was utilized to collect qualitative information. The finding identified that primary caregivers went through the psychological course of strong denial, seeking physician’s aid, cooperating to medical management, and finally calming down. The major stress of primary caregivers came from environment and the patients’ responses under medical procedures. After experienced the leisure activities for 4 weeks, the primary caregivers felt that leisure activities could release their stress and empowered them to face their routine daily life enthusiastically. Primary caregivers identified that leisure activities are crucial but ignored under over-devoting to taking care of their children. The finding also found that nurses’ attitude and leisure services affected their quality of life during hospitalization. The study suggest that providing leisure education and temporarily child care services to primary caregivers would be able to enhance the quality of life for children with brain tumor and their caregivers. In addition, making the best use of existing resources (e.g. playroom operation) to create a friendly environment is highly recommended.

碩士
高雄醫學大學
護理學研究所
102
The purpose of this study was to explore the care needs and its related factors of the primary caregivers for patients undergoing brain tumor surgery. The study used a prospective and descriptive research design, which incorporated structured questionnaires to collect data from 80 pairs of patients and primary caregivers, before the brain tumor operation and 4 weeks after the discharge from a hospital at Southern Taiwan. Data analysis methods included descriptive statistics, inferential statistics consisting of t-tests, one-way ANOVA, Pearson Product-Moment Correlation, and multiple regression analysis. The data collection duration was from 1st March 2004 to 31st March 2004. The results show that the pre-operative score for care needs was 51.03 (SD=16.96), and the post-operative score was 42.73 (SD=15.13). Among the 4 aspects of care needs, information needs (pre-operative score 63.80, post-operative score 51.46) and health care service needs (pre-operative score 56.44, post-operative score 45.72) received the highest score both before and after the operation. Besides, the results also showed that the lesser the care needs met before the operation, the more the anxiety and depression experienced, and more post-operative care needs needed as well. The diagnosis of malignant tumor, poor post-operative performance status, experiencing of post-operative anxiety and depression would lead to higher level of healthcare needs. When pre-operative healthcare needs are not met, higher level of post-operative care needs would also be required. The only important predictor variable of pre-operative care needs was pre-operative anxiety, accounting for 12.8% of the variance. The only significant predictor variable of post-operative care needs is post-operative anxiety, explaining 11.3% of the variance. When entering the pre-operative care needs into the regression model, pre-operative healthcare needs and post-operative depression were selected as significant predictors of post-operative care needs. Together they accounted for 19.5% of the variance in post-operative care needs. This study supports that the primary caregivers had higher level of pre-operative care needs, and such level of care needs improved after the operation. Besides, prominent anxiety and depression will yield higher level of care needs. Therefore, healthcare providers should always evaluate the care needs and emotional states of primary caregivers, so that appropriate and adequate medical information and services could be provided on time, and in turn avoid any events that will cause or exacerbate the anxiety and depression state.

Brain tumors are the second leading cause of cancer deaths in young adults ages 20- 39. (Armstrong et al., 2004) According to the South African Medical Research Council, there was an estimate 801 deaths because of brain cancer in South Africa in 2000. If these statistics are compared to other types of cancers like breast-, lung- and prostate cancers, is the prevalence of the diagnoses of brain tumors, a very small percentage. According to the Mayo clinic in South Africa, the estimate number of brain tumor incidences was 3% in 2007. Despite of these statistics with regards Brain tumors, one in six South African men and one in seven South African women will be diagnosed with cancer during their life times. Despite this small percentage, the diagnoses of brain tumors have escalated the last few years. The reason for these new statistics is still unknown. With exercise that is becoming one of the most important adjuvant therapies for most diseases or illnesses, we may sustain this idea of using exercise intervention as an adjuvant therapy for brain tumor cancers we can prove this through many researches that has been done in the last few years. (Schwartz, 2003) Studies done by different researchers they found that exercise intervention is becoming increasingly recognized as a safe, feasible and beneficial supportive therapy for cancer patients both during and after the cessation of adjuvant therapy. (Jones et al., 2006) Exercise influences a lot of different systems in the body, to the advantage of the cancer patient (Schwartz, 2003) and emerging new research shows that physical exercise may boost brain function, which include improve mood. (Kong, 1999) Exercise, according to Cotman and Berchtold (2002) is commonly believed to be a behavioral strategy to relieve stress, and reduce depression and anxiety in humans. Exercise intervention further influence following aspects of the human body, namely brain deprived neurotrophic factor (BDNF) and 5-HT (Serotonin). Improvement of these could, in fact, lead to a better quality of life (QoL) of a brain tumor patient (Cotman&Berchtold, 2002). Fatigue that sets in, due to the different cancer therapies, is also a factor that has an affect on depression and anxiety of the patient. Keeping still and rest to prevent fatigue were followed in previous regiment when working with cancer patients was followed. This approach, in fact, has a very negative effect on the patient. Being diagnosed with a brain tumor the patient will never be emotionally prepared for this type of information and it usually shatters their sense of well being and their personal security. All of these factors, especially depression, affect the patient’s QoL. (Vaynman et al., 2004) An exercise regiment for brain tumor patients has not yet been developed properly, because exercise intervention for familiar cancers could be problematic and not suitable for brain tumor patients. (Schwartz, 2003) Therefore, the purpose of this study is to further the knowledge and the field of expertise of exercise as an adjuvant therapy in brain tumor patients to better QoL over a larger period of time. AFRIKAANS : Die tweede grootste leier in siektes tussen die ouderdomme van 20-39 jaar wat lewens eis is Brein gewasse (brein kanker). (Armstrong et al., 2004) Volgens die Suid- Afrikaanse Mediese Navorsingraad, is daar tot 801 gevalle van breingewas sterftes in die jaar 2000 aangemeld. As hierdie statistieke vergelyk word met statistieke van kanker wat meer prominent voorkom soos byvoorbeeld bors-, long-, en protaatkanker, lyk die voorkoms van breinkanker diagnosis maar na ‘n baie klein persentasie. Die Mayo Kliniek in Suid-Afrika het in 2007 bevind dat die voorkoms van breinkanker in Suid-Afrika ‘n persentasie van 3% uitgemaak het. Ten spyte van hierdie statistieke betreffende breingewasse, sal een uit elke ses mans en een uit elke sewe vroue, gediagnoseer word met een of ander kanker gedurende hulle leeftyd. Alhoewel die persentasie wat reeds genoem is maar na ‘n klein hoeveelheid lyk, het die voorkoms van breingewasse baie toegeneem in die laaste paar jaar en selfs maande. Die rede vir hierdie aansienlike toename is steeds onbekend. Oefening word al hoe belangriker en word al hoe meer deur verskeie dokters voorgeskryf om te dien as ‘n bykomende behandeling vir verskeie siekte toestande. Dit word veral ook vir kanker pasiënte voorgeskryf. Oefen intervensie kan dus gebruik word vir breinkanker pasiënte, hierdie stelling gestaaf kan word, aangesien daar verskeie navorsings reeds bewys het dat oefening as bykomende terapie gebruik is vir kanker pasiënte. (Schwartz, 2003) Hierdie studies het bevind dat oefening as ‘n veilige, uitvoerbare en voordelige bykomende intervensie vir kanker pasiënte erken word. Hierdie intervensie kan tydens en na hoof kanker behandeling gebruik word (Jones et al., 2006). Oefening beinvloed verskeie sisteme in die liggaam, tot voordeel van die kanker pasiënt. (Schwartz, 2003) Nuwe navorsing het ook aan die lig laat kom dat fisieke aktiwiteit ‘n persoon se breinfunksie bevorder, wat onder andere ‘n baie groot invloed het om die pasiënt se gemoedstoestand. (Kong, 1999) Volgens, Cotman and Berchtold (2002), is daarvolgens studies bewys dat oefenterapie ‘n manier is om stres te verlig, sowel as depressie en angstigheid in meeste mense. Oefenterapie beinvloed ook die volgende aspekte positief in die menslike liggaam naamlik, Brein ontnemende neurtrofiese-faktor (BDNF) en 5-HT (Serotonien). Verbetering van hierdie faktore, kan ly tot ‘n beter kwaliteit van lewe van ‘n pasiënt wat met ‘n breingewas gediagnoseer is (Cotman&Berchtold, 2002). Uitputting (moegheid) wat gewoonlik intree as gevolg van kanker terapie, is ook ‘n faktor wat ‘n effek het op die depressie- en angsvlakke van ‘n pasiënt. In vroeë behandelingsprotokol van kankerpasiënte, moes die pasiënt so stil as moontlik verkeer om sodoende uitputting of moegheid te voorkom. Hierdie benadering het in die uiteinde ‘n baie negatiewe effek op die pasiënte tot gevolg gehad. ‘n Persoon wat met ‘n breingewas gediagnoseer word sal nooit emosioneel voorbereid wees op hierdie diagnose nie en sodoende kan dit lei tot ‘n ineenstorting van die persoon se geestestoestand en persoonlike sekuriteit. Hierdie “ineenstorting” kan ‘n groot invloed hê op die kwaliteit van lewe van hierdie pasiënt (Vaynman et al., 2004). ‘n Oefenintervensie protokol vir breinkanker pasiënte is nog nie voldoende vasgestel nie, aangesien oefenterapie intervensies wat vir bekende kankers problematies en selfs gevaarlik kan wees vir breingewas pasiënte nie. (Schwartz, 2003) Daarom is die doel van die studie, om inligting te verkry en kennis in te samel om die veld van deskundiges uit te brei om sodoende ‘n oefenterapie protokol neer te lê vir breinkanker pasiënte. Hierdie protokol sal dus dien as ‘n bevordering van kwaliteit van lewe van hierdie pasiente deur middel van oefen intervensie as bykomende behandeling. Copyright
Dissertation (MA)--University of Pretoria, 2012.
Biokinetics, Sport and Leisure Sciences
unrestricted

Wong Chun Lung.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2005.
Includes bibliographical references (leaves 202-225).
Abstracts in English and Chinese.
Thesis Committee --- p.ii
Abstract --- p.iii
摘要 --- p.vi
Acknowledgements --- p.ix
Table of Contents --- p.x
List of Abbreviations --- p.xv
List of Figures --- p.xix
List of Tables --- p.xx iii
Chapter Chapter 1 --- Introduction
Chapter 1.1 --- "Neurodegeneration, Inflammation and Gliosis" --- p.1
Chapter 1.2 --- Anatomy of the CNS --- p.5
Chapter 1.3 --- Astrocytes --- p.6
Chapter 1.3.1 --- Morphology and Identification of Astrocytes --- p.6
Chapter 1.3.2 --- Physiological Functions of Astrocytes in the CNS --- p.7
Chapter 1.3.2.1 --- Induction of Blood-brain Barrier (BBB) --- p.7
Chapter 1.3.2.2 --- Metabolism of Neurotransmitters --- p.9
Chapter 1.3.2.3 --- Nursing Role of Astrocytes --- p.9
Chapter 1.3.2.4 --- Immunological Functions of Astrocytes --- p.10
Chapter 1.3.3 --- Neonatal Rat Cortical Astrocytes as In Vitro Model --- p.12
Chapter 1.4 --- Cytokines in Brain Damage --- p.14
Chapter 1.4.1 --- Lipopolysaccharides (LPS) --- p.16
Chapter 1.4.2 --- Tumor Necrosis Factor-α (TNF-α) --- p.17
Chapter 1.4.3 --- Interleukin-1 (IL-1) --- p.19
Chapter 1.4.4 --- Interleukin-6 (IL-6) --- p.20
Chapter 1.4.5 --- Interferon-γ (IFN-γ) --- p.21
Chapter 1.5 --- Cytokines-induced Signaling Cascade --- p.22
Chapter 1.5.1 --- TNF Receptors --- p.23
Chapter 1.5.2 --- Ca2+ --- p.25
Chapter 1.5.3 --- MAPK --- p.26
Chapter 1.5.4 --- PICA --- p.27
Chapter 1.5.5 --- NFkB --- p.29
Chapter 1.6 --- Glucose Metabolism in the Brain and Glucose Transporters --- p.31
Chapter 1.6.1 --- Glucose Transporters in the Brain --- p.32
Chapter 1.6.2 --- Glucose Transporters in Brain Damage --- p.34
Chapter 1.7 --- Ascorbic Acid Metabolism in the Brain --- p.36
Chapter 1.8 --- Aim and Scope of this Project --- p.39
Chapter Chapter 2 --- Materials and Methods
Chapter 2.1 --- Materials
Chapter 2.1.1 --- Neonatal Sprawley 一Dawley Rats --- p.43
Chapter 2.1.2 --- Plain Dulbecco Modified Eagle Medium ´ؤ Formula 12 (pDF12) --- p.43
Chapter 2.1.3 --- Complete DF-12(cDF12) --- p.43
Chapter 2.1.4 --- Phosphate Buffered Saline (PBS) --- p.44
Chapter 2.1.5 --- Hank's Buffer (HSB) --- p.44
Chapter 2.1.6 --- D/L-Homocysteine Buffer --- p.44
Chapter 2.1.7 --- "LPS, Cytokines and Pentoxifylline" --- p.45
Chapter 2.1.8 --- Specific TNF Receptor Agonist: TNF antibodies --- p.45
Chapter 2.1.9 --- Calcium Modulators --- p.45
Chapter 2.1.10 --- PKA Modulators --- p.46
Chapter 2.1.11 --- NFkB Inhibitors --- p.47
Chapter 2.1.12 --- MAPK Inhibitors --- p.47
Chapter 2.1.13 --- β-Adrenergic Receptor Modulators --- p.47
Chapter 2.1.14 --- Reagents for RNA and Protein Isolation --- p.48
Chapter 2.1.15 --- Reagents for Reverse Transcription-Polymerase Chain Reaction (RT-PCR) --- p.48
Chapter 2.1.16 --- Reagents for DNA Electrophoresis --- p.49
Chapter 2.1.17 --- Reagents for Real-time PCR --- p.51
Chapter 2.1.18 --- Reagents for Western Blotting --- p.51
Chapter 2.1.19 --- Reagents for MTT Assay --- p.51
Chapter 2.1.20 --- Reagents for 3H-Thymidine Incorporation Assay --- p.52
Chapter 2.1.21 --- Reagents for Glucose Uptake Assay --- p.52
Chapter 2.1.22 --- Reagents for Ascorbic Acid Accumulation Assay --- p.53
Chapter 2.1.23 --- Reagents for Immunostammg --- p.53
Chapter 2.1.24 --- Other Chemicals and Reagents --- p.53
Chapter 2.2 --- Methods
Chapter 2.2.1 --- Preparation of Primary Cultured Rat Astrocytes --- p.55
Chapter 2.2.2 --- Measuring Cell Viability: MTT Assay --- p.56
Chapter 2.2.3 --- Measuring Cell Proliferation: 3H Thymidine Incorporation Assay --- p.57
Chapter 2.2.4 --- Measuring Glucose Uptake: Zero-trans Glucose Uptake Assay --- p.58
Chapter 2.2.5 --- Measuring Ascorbic Acid Accumulation --- p.60
Chapter 2.2.6 --- Total Protein Extraction --- p.61
Chapter 2.2.7 --- Western Blotting --- p.62
Chapter 2.2.8 --- Immunostaining --- p.64
Chapter 2.2.9 --- Isolation of RNA --- p.64
Chapter 2.2.10 --- Measurement of RNA Yield --- p.65
Chapter 2.2.11 --- RNA Gel Electrophoresis --- p.66
Chapter 2.2.12 --- Reverse Transcription (RT) --- p.66
Chapter 2.2.13 --- Polymerase Chain Reaction (PCR) --- p.67
Chapter 2.2.14 --- Separation of PCR Products by Agarose Gel Electrophoresis --- p.67
Chapter 2.2.15 --- Quantization of PCR Products and Western Blotting --- p.68
Chapter 2.2.16 --- Real-time PCR --- p.68
Chapter Chapter 3 --- Results
Chapter 3.1 --- Role of Calcium Ions (Ca2+) in TNF-α-induced Astrocyte Proliferation --- p.70
Chapter 3.1.1 --- Effects of Changes of Extracellular Ca2+ on Astrocyte Viability --- p.72
Chapter 3.1.2 --- Effects of Other Divalent Ions on Astrocyte Viability --- p.74
Chapter 3.1.3 --- Effects of Changes of Intracellular Ca2+ on Astrocyte Viability --- p.78
Chapter 3.1.4 --- Role of Ca2+ on TNF-α-mduced Proliferation in Astrocytes --- p.85
Chapter 3.1.5 --- Role of Other Divalent Ions on tnf-α-mduced Proliferation in Astrocytes --- p.90
Chapter 3.2 --- Effect of Cytokines on Glucose Uptake in Rat Astrocytes --- p.95
Chapter 3.2.1 --- Basal level of Glucose Uptake in Astrocytes and Effects of Cytokines on Glucose Uptake in Astrocytes --- p.95
Chapter 3.2.2 --- Signaling Cascade of LPS- and TNF-α-induced Glucose Uptake in Astrocytes --- p.120
Chapter (A) --- TNFR Subtypes Mediating TNF-a-induced Glucose Uptake --- p.121
Chapter (B) --- MAPK --- p.125
Chapter (C) --- PKA --- p.133
Chapter (D) --- NFkB --- p.139
Chapter (E) --- Other Mechanisms / Signalling molecules --- p.150
Chapter (1) --- Interaction with β-Adrenegic Mechanism
Chapter (2) --- Role of cGMP --- p.154
Chapter (3) --- Effect of Mg2+ on LPS- / TNF-α- induced Glucose Uptake in Astrocytes --- p.156
Chapter (4) --- Possible Involvement of IGF-1 System --- p.160
Chapter 3.2.3 --- Summary --- p.163
Chapter 3.3 --- Effects of LPS and Cytokines on AA Accumulation in Astrocytes --- p.164
Chapter Chapter 4 --- Discussion
Chapter 4.1 --- Role of Calcium ions (Ca2+) in TNF-α-induced Astrocyte Proliferation --- p.177
Chapter 4.1.1 --- Drastic Changes in Extracellular Ca2+ Caused Astrocyte Death --- p.178
Chapter 4.1.2 --- Extraordinary Role of Ca2+ in Astrocytes Survival --- p.178
Chapter 4.1.3 --- Elevation of [Ca2+]i Reduced Astrocyte Viability --- p.180
Chapter 4.1.4 --- Failure of Verapamil to Block TNF-α-induced Astrocyte Proliferation --- p.182
Chapter 4.2 --- Hypothesis for the Relationship between Cytokines and Energy Metabolism --- p.185
Chapter 4.2.1 --- Mechanism and Signaling Cascade of the Elevated Glucose Uptake --- p.186
Chapter 4.2.2 --- Increased Glucose Uptake by Cytokines: Friend or Foe? --- p.191
Chapter 4.2.3 --- Depletion of AA Pool by LPS --- p.194
Chapter 4.2.4 --- Possible Bedside Application of the Findings --- p.195
Chapter 4.3 --- Prospects of This Study and Concluding Remarks --- p.197
Appendix --- p.201
References --- p.202

碩士
長庚大學
護理學系
100
A pre-post test design was selected to identify the changes and associated factors of quality of life in major family caregivers during the admission and discharge of patients undergoing brain tumor operations. A total of 162 major caregivers of patients undergoing brain tumor operations were recruited by purposive sampling. Data was collected by structured questionnaires such as: perception of stress for major caregivers, caregiving burden, caregiver’s social support, personnel information of both the patient and caregivers. The characteristics of brain tumor patients were: mean age 52.68 y/o, female, onset at 50.99 y/0, mean length of stay 20.99 days, and ADL mean score 62.84. The characteristics of caregivers were: mean age 45.7 y/o, female, high school educated, married, spouses of patients, and having families participating into patient care. These data are analyzed by descriptive and analytic statistics. The results were: 1.Moderate quality of life was reported during study periods, however, levels at admission were significantly higher than the levels at discharge. The ranking of each subscale were similar at admission and at discharge. The sequence was: social relationship, environment, psychological health and physical health. 2.The associated factors of changes of quality of life for caregivers included: relationship with the patient, marriage; caregiving types, weekly resting hours and length of stay. Spouse caregivers reported greater change of quality of life than the children caregivers. Those who had other’s assistance in caregiving and had weekly resting hours reported better quality of life. 3. A moderate level of caregiving burden was reported by the major caregivers. The levels of burden at discharge was significantly lower than the levels at admission. The rankings each subscale was different between the admission and discharge. The highest subscale was self-esteem and followed by the economic burden at admission. Whereas the highest subscale was economic burden and followed by the health burden at discharge. 4.The significant predictor of changes of quality of life for caregivers during hospitalization was the changes of social support. It indicated that the caregivers with greater changes of social support reported greater changes of quality of life. 5.A moderate overall perception of stress during hospitalization was reported by the major caregivers. The level of stress was lower at discharge than the levels of admission. However, the ranking of each assessment was similar at admission and discharge. It was: symptom; recognition of illness; and psychological burden of caregivers. 6.Length of stay, relationship with the patients, and changes of social support were predictors of the changes of quality of life for caregivers during hospitalization.

碩士
國立清華大學
生醫工程與環境科學系
104
Malignant glioma is one of the toughest tumors to be treated at present due to the complexity of the tumor microenvironment and the intrinsic resistant to therapy. Previous studies have shown that CD11b+ myeloid cells play essential role in recurrent prostate and brain tumors following radiation therapy. In this study, the CD11b-diphtheria toxin receptor (CD11b-DTR) transgenic mouse model was used to evaluate the role of CD11b+ myeloid cells in TK/GCV suicide gene therapy for brain tumor using a murine astrocytomal tumor model, ALTS1C1-TK. The results show that the depletion of peritoneal macrophages (CD11b+F4/80+) and blood monocyte (CD11b+Ly6G-Ly6C-) could be achieved after two injections of DT, but the neutrophil (CD11b+Gr-1+) were increased transiently. Results also found that the depletion of CD11b+ myeloid cells enhanced the efficacy of TK/GCV therapy as shown by the increase of median surviving time of GCV-treated ALTS1C1-TK tumor-bearing mice from 30.6 days to 37.6 days with significant tumor growth reduction. Interestingly, the depletion of CD11b+ myeloid cells did not benefit the surviving time of tumor-bearing mice after receiving two doses of DT injections compared to the control PBS group (22.4 days vs 25.0 days, respectively). The immunohistological analysis of the tumor tissues revealed that F4/80+ macrophages were significantly increased after GCV administration associated with increasing micro-vascular density (MVD) of the tumor. Selective depletion of these macrophages resulted in reduced MVD and increasing iNOS+ macrophages and myeloid cells. On the other hand, selective depletion of the macrophages without GCV treatment resulted in the increase of the ARG-1+ myeloid cells in the tumor. These results indicate that macrophages could change their roles from the anti-tumor activity in the primary tumor to the pro-tumor function in the therapy-induced recurrent tumors. This study also found the best time for macrophages/monocytes depletion was performed during the administration of GCV, but not before or after GCV treatment. In summary, this study demonstrates that macrophages play different roles in the primary and the recurrent tumors. This study also provides a feasible strategy for combining conventional therapies with macrophage targeting for brain tumor therapy.

碩士
國立陽明大學
臨床醫學研究所
98
Objectives: Atypical teratoid/rhabdoid tumors (AT/RTs) of central nervous system (CNS) are rare, highly malignant CNS embryonal tumors primarily affecting infant and young children. Because the clinical presentation and radiographic features of AT/RTs is indistinguishable from that of medulloblastomas (MBs), AT/RTs were misclassified as MBs in the past. Although lack of INI1 protein in the majority of AT/RTs while retained INI1 expression in all MBs was agreed, we found INI1 mutation is rarely occurred in Taiwanese AT/RTs. INI1 protein is expressed in 55.6% of examined cases, suggesting INI1 is not a good marker for the diagnosis of Taiwanese AT/RTs. Besides, the clinical outcomes of AT/RT and MB are extremely different. Despite intensive multimodality treatment, the overall survival for patients with AT/RTs (2-year survival is around 15%) is still worse than standard-risk MBs (5-year survival is around 85%). Compare to MB, AT/RT is more chemo- and radio-resistant. Nowadays, there is growing evidence that miRNAs play substantial roles in the pathogenesis and prognosis of human malignancies. We assume that different mRNA/miRNA expression patterns in AT/RT and MB influence treatment response and prognosis. In this study, we used microarray as a platform to distinguish AT/RTs and MBs with the profile of transcriptome and miRNoms. Materials and Methods: In order to clarify the pathogenesis and find the better IHC markers for AT/RTs in Taiwanese, the differential mRNA profiles of 5 AT/RTs and 14 MBs fresh frozen samples from Taipei Veterans General Hospital using AffymetrixTM HG-U133 plus 2.0 whole genome array were analyzed. To find the possible novel therapeutic targets, distinct miRNA signatures in AT/RTs and MBs were obtained by analyzing the profiles of 5 AT/RTs and 11 MBs fresh frozen samples using Agilent Human miRNA Microarray Kit V2. Results: AT/RT and MB can be separated into two distinct groups according to different expression profiles. 312 probe sets were abundantly over-expressed in AT/RT specimens, while 238 probe sets were abundantly over-expressed in MB specimens (q&lt;0.005). Among the top 45 strongly expressed genes in AT/RT, we validated cyclin D1 (CCND1) and dual specificity phosphatase 6 (DUSP6) were over-expressed in AT/RTs samples by qPCR. According to the gene ontology categories of biological processes, genes associated with cell proliferation, cell development and apoptosis, are significantly activated in AT/RT group. In contrast with genes in AT/RT, the principal functions of up-regulated genes in the MB group include those related to cell differentiation and nerve system development. We also identified over-expression of miRNA 34a, 34a*, 221 and 222 in AT/RT samples. We validated the higher level of miR221, 222 in AT/RTs by qPCR. Using integration of microRNA and genes with microRNA gene-target prediction algorithms, down-regulation of MEX3A, RNF165, SOX11, AP3B2, PCGF3, SBK1, UNC84B as a consequence of over-expression of miR221/222, indicate potential pathogenesis and therapeutic targets of AT/RTs. Conclusions: Our study demonstrated the differential transcriptomes and miRNA signatures between AT/RTs and MBs. Based on the microarray finding, we provide better IHC markers and potential therapeutic targets of AT/RTs in Taiwanese.

This qualitative multi case research asks how the needs of caregivers of primary malignant brain tumour (PMBT) patients are met through structured neuro-oncology programs in Canadian centres. Utilizing telephone interviews with eleven social workers and one psychologist the study analyses their perspectives on the scope and nature of services to brain tumour patients and their caregivers. PMBT is a rare and palliative disease often with neurocognitive and neurobehavioral effects posing special challenges for caregivers. Health care system reliance on family caregivers has resulted in significant implications for their emotional and physical risk. Findings show exclusive patient focused health care in ambulatory programs with fragmented care resulting in marginalization and invisibility of caregivers. This approach is inconsistent with current literature promoting collaborative family centered care, recommended for continuity of care throughout the illness trajectory. Recommendations focus on systemic caregiver service improvements.