Thesis (Ed. D.)--University of Toronto, 2005.

The most common type of thyroid cancer, differentiated thyroid cancer (DTC), is diagnosed by radioactive iodine whole body scanning (WBS) and treated with radiotherapy using iodine-131 (131I). The success of this diagnosis/treatment approach relies on the relatively selective localisation of the sodium/iodide symporter (NIS) in cells of the thyroid gland. However, in some de-differentiated thyroid cancers, NIS expression is lost. This results in the inability of WBS to stage the disease and it also decreases the effectiveness of treatment with 131I. A number of reports have shown that de-differentiated thyroid carcinomas, however, continue to express thyroid stimulating hormone receptor (TSHR). TSHR is, therefore, a potential target for the diagnosis and treatment of radioiodine resistant de-differentiated thyroid carcinoma. In this study an anti-TSHR monoclonal antibody (mAb9) and human recombinant TSH (rhTSH) were radiolabelled and evaluated for their potential use in the diagnosis and treatment of radioiodine resistant thyroid cancer. A number of radiolabelling methods and quality control experiments were initially carried out to ensure high purity radiolabelled mAb9 and rhTSH were produced. In vitro studies were conducted to assess the binding affinity of 125I-mAb9, 111In-mAb9 and 125I-rhTSH to the TSHR in thyroid cancer cell lines, TPC-1, FTC-133, and FRTL5, and in a TSHR transfected cell line, GPI. SPECT/CT animal studies were performed in mice to investigate whether 125I-mAb9, 111In-mAb9 and 125I-rhTSH bound to TSHR in the thyroid of mice in vivo. 125I-mAb9, 111In-mAb9 and 125I-rhTSH bound to GPI cells but did not bind specifically to the TSHR in FTC-133, TPC-1 and FRTL5 cells as well as to the thyroid of normal mice in vivo. Radiolabelled mAb9 and radiolabelled rhTSH are therefore unlikely to be of use in the diagnosis and treatment of radioiodine resistant de-differentiated thyroid cancer.

Thesis (M.D.)--University of New South Wales, 2001. / Also available online.

The main subject of my thesis is the investigation of mechanisms of glioma tumorigenesis associated with the recently identified mutations in isocitrate dehydrogenase. Gliomas account for 80% of primary brain cancers. They represent a diverse group of tumours, and are graded from I-IV based on histopathological features. Whilst grade I tumours may be curable with surgery alone, grade II and III gliomas inevitably progress to glioblastoma multiforme (GBM), which is highly resistant to current therapies and carries a very poor prognosis. Despite an improved understanding of the pathways and mechanisms involved in the development of glioma and its progression to grade IV disease, current and novel treatments have so far failed to significantly improve outcome. Isocitrate dehydrogenase (IDH) enzymes catalyse the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). Somatic mutations in genes encoding IDH1 and IDH2 were first identified in glioma and subsequently in acute myeloid leukemia and other solid tumours. These heterozygous point mutations occur at the arginine residue of the enzymes active site and cause both loss of normal enzyme function and gain-of-function, causing the reduction of α-KG to D-2-hydroxyglutarate (D-2HG), which accumulates. D-2HG may act as an oncometabolite through the inhibition of various α-KG dependent enzymes, stimulating angiogenesis, histone modifications and aberrant DNA methylation. Possibly, IDH1/2 mutations may also cause oncogenic effects through dysregulation of the tricarboxylic acid (TCA) cycle, or by increasing susceptibility to oxidative stress. The exact role of mutant IDH1/2 in tumorigenesis however remains unclear. In the work outlined in this thesis, I have demonstrated that the expression of mutant IDH1/2 in glioma cell lines leads to 2-HG accumultation and a reduction in α-KG production and results in HIF1α accumulation and a reduction in 5hmC production. Furthermore, the brain-specific expression of mutant Idh1 in mice also results in 2-HG accumulation and reduced α-KG production, whilst a reduction in 5hmC levels are also seen. This data appears to support the theory that IDH1/2 mutant activity results in the inhibition of α-KG dependent enzymes, either through the accumulation of 2-HG or due to a reduction in α-KG levels. The brain-specific expression of mutant Idh1 in mice also results in increased cellular proliferation and an increase in the expression of the neural stem cell marker, nestin. However gliomas do not develop, perhaps suggesting that additional mutations are required in conjunction with those occuring in IDH1/2 in order to initiate tumourigenesis. Clinically, IDH1/2 mutations may represent a novel therapeutic target in glioma and may also serve as useful diagnostic, prognostic and predictive biomarkers. However, a better understanding of the pathogenesis of mutant IDH is required, to enable effective IDH1/2 directed therapies to be developed in the future.

Thesis (M.Sc. (Hons.))-University of Western Sydney, 2007. / A thesis submitted to the University of Western Sydney, College of Arts, School of Education, in fulfilment of the requirements for the degree of Master of Science (Honours). Includes bibliographical references.

Thesis (M.S.)--State University of New York at Binghamton, Department of Physics, Applied Physics and Astronomy, 2009. / Includes bibliographical references.

Background: Despite advances in cancer prognosis and increased survival rates for childhood cancer, having a child diagnosed with cancer can be considered one of the most stressful life events in a parent’s life. The adverse psychological impact of childhood cancer on parents has been found to be higher than in any other childhood chronic illness. Parents can find it difficult to adjust and use effective coping strategies to deal with the illness-related demands. Dispositional optimism (i.e. positive outcome expectancies for the future) has become a key theoretical component in positive and health psychological research, aiming to explain adjustment and coping in distressing life situations. However, optimism in the context of caregiving for a child with chronic illness and especially cancer has received little research attention, but may be important as optimistic people tend to show greater psychological adjustment and effective coping. Aims: To identify the characteristics of optimistic parents of children with cancer. To examine the relationship between optimism, anxiety, depression, life satisfaction, coping and subjective health perception in parents of children with cancer and parents of healthy children. Also, to provide a more in-depth understanding of the needs and experiences of parents in relation to their level of optimism/pessimism. Methods: A mixed methodological approach (quantitative and qualitative methods) was adopted to study optimism as well as the impact and the experiences of parents caring for their child with cancer. The mixed method design comprised two phases of data collection and analysis. In Phase I, quantitative methods were used. 100 parents of children with cancer were recruited during attendance at Oncology Out-patients Clinics at a UK regional Cancer Centre. A comparison group of 117 parents of healthy children were also recruited. All parents completed a questionnaire, providing demographic and medical information relating to their child, dispositional optimism, psychological distress, life satisfaction, coping and subjective health perception. Descriptive statistics, unrelated t-tests and x2 tests were used where appropriate to examine differences on optimism, psychological distress, life satisfaction and coping variables between the SG and CG. Bivariate Pearson correlations were used to identify any possible differences between the two groups. In Phase II, qualitative data were collected and analysed using Interpretative Phenomenological Analysis (IPA). 10 semi-structured interviews were conducted with 5 high optimistic and 5 high pessimistic parents of children with cancer given their optimism score in the quantitative study. Results: In the Phase I of the study, findings showed that the parents of children with cancer had higher levels of anxiety, depression, lower levels of optimism, satisfaction with life and subjective health perception than the comparison group. Optimism was significantly correlated with satisfaction with life, subjective health perception, anxiety and depression in both groups. The interviews in Phase II of the study explained better the role of optimism and pessimism in parental experience of adjusting to and coping with childhood cancer. Interviewees described the way that their child’s diagnosis of cancer had affected their lives and their journey from shock to acceptance and adjustment for the optimistic parents or despair and feelings of helplessness and inability to cope for the pessimistic parents. Regardless of level optimism/pessimism, interviews underlined the importance and parents’ need for social support, ongoing communication with health professionals and contact with other parents of children with cancer. Conclusion: The findings highlight the importance of optimism and pessimism in relationship to psychological distress in parents of children with cancer. Interventions targeting parents’ optimism are recommended as a potential source of coping with adversity within this population.

This study examined the association between neuropathy limitations and depression in chemotherapy patients currently on treatment with a taxane-based, platinum-based or plant alkaloid chemotherapy drug. The Overall Neuropathy Limitations Scale (ONLS) and the Beck Depression Inventory-Short Form (BDI-SF) were used to assess neuropathy limitations and depression in 24 chemotherapy patients with reported symptoms of peripheral neuropathy. Average age of patients was 65 years, 66.6% were female, and average number of chemotherapy cycles completed was 5.6. Of the 24 patients, 37.5% of patients were on a single agent taxane-based drug, 37.5% of patients were on a taxane-based drug with a platinum based drug, 16.6% of patients were on a plant alkaloid, and 8.3% were on a combination of a taxane-based and another non-neurotoxic chemotherapy drug. The scores on both the BDI-SF and ONLS were very low. The mean score on the BDI-SF was 4.1 with a standard deviation of 2.7. The mean score on the ONLS was 2.2 with a standard deviation of 1.5. The study showed a non-significant relationship between neuropathy limitations and depression in chemotherapy patients. These findings show no association between neuropathy limitations and depression. Although all of these patients had symptoms of peripheral neuropathy, they were not severe enough to interfere with daily activities. The lack of relationship was not unexpected given the low scores on both the BDI-SF and ONLS. Future research should re-evaluate this relationship with a larger, more diverse sample.

HNC incidence and mortality is greater in men and is associated with high risk behaviours and social deprivation. HNC is frequently diagnosed at advanced stages requiring multi-modality treatment which can have a significant impact on appearance and function. Gender can influence health behaviours yet research into male experiences of cancer has primarily focussed on prostate cancer and HNC is an area which is under investigated. The aim of this study was to explore how men with HNC experience appearance and functional change in the first 12 months following diagnosis. Grounded theory methodology (GT) was chosen as the overall purpose of GT is the generation of theory from the data which has explanatory power and advances the understanding of social and psychological phenomena. Retrospective semi-structured interviews were performed with 12 men who were 12 to 24 months post-diagnosis. Key components of GT practice used were simultaneous data collection and analysis, constructing analytic categories from the data, constant comparison, memo-writing and theoretical sampling. Three categories emerged from the data which were inter-related: normalising change; “under siege”: getting through treatment; and reclaiming self. The core category was reconciling change; a new normal which reflects the social and psychological processes involved in accommodating and assimilating change in appearance and function for men with HNC. The substantive theory provides insight into how men with HNC prioritise function and actively distance themselves from concerns regarding appearance. Furthermore, it identifies men who are at risk of social anxiety and isolation due to multiple changes or body incompetence. This study builds on theories of masculinity, body image and disfigurement. The substantive theory developed provides health and social care professionals with new knowledge to support clinical practice and improve care provision.