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The development of pulsed dendritic cell therapeutic vaccine strategies for the treatment of paediatric leukaemias and solid tumorsNabarro, Stephen Ralph January 2004 (has links)
No description available.
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Follow-up for survivors of childhood cancerAbsolom, Kate L. January 2005 (has links)
No description available.
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Identification of point mutations and fusion genes in paediatric cancers using transcriptome sequencingAl-Balool, Haya Homoud Yacoub January 2013 (has links)
Acute Lymphoblastic Leukaemia (ALL) is the most common leukaemia in childhood (Hemminki and Jiang 2002), and Neuroblastoma (NB) is the most common extracranial solid tumour (Eng 2008). Here, transcriptome sequencing has been used to screen for novel point mutations and fusion genes in four paediatric ALLs, three primary neuroblastomas, and 1 cell line (IMR32). A total of 9,648 Mb of sequence was generated using both lIIumina and FLX platforms. In ALL, a (G-7A) substitution in exon 14 of the mitochondrial membrane protein SAMM50 gene was identified, however sequencing of the SAMM50 coding region in a further 47 ALLs did not uncover additional mutations. In one neuroblastoma sample a fusion transcript between GATC and COX6A1 was recovered and shown to be due to an ~18.9Kb germline microduplication spanning two genes including the p53 interacting inhibitor of apoptosis, TRIAP1 (Park and Nakamura 2005). This gene maps to 12q24.31, a prognostically important region of common gain in NB (Mosse et al 2007, Wolf et al 2010) and TRIAP1 expression was found to be high in stage 4 neuroblastoma and associated with poor prognosis in multiple datasets, highlighting its potential relevance to 12q24.31 gain. Finally, across all samples a total of 205 transcripts with rearranged exon order relative to genomic structure were identified (referred to here as posttranscriptional exon shuffling events or PTES). Although these were subsequently found to be abundantly expressed in a wide variety of normal tissues, PTES transcripts from MAN1A2, TLE4 and CDK13 were found to be both highly expressed relative to other isoforms, and conserved in mice. This is the first genome wide experimental analysis of such transcripts, and suggests that some could be of functional importance.
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Pre-clinical metabolism studies with Fenretinide in paediatric cancerIllingworth, Nicola Ann January 2011 (has links)
Fenretinide (4-HPR) is a retinoic acid analogue used in clinical trials for the treatment of neuroblastoma and Ewing’s sarcoma. The work described involves investigations into factors that may impact on 4-HPR drug disposition. Metabolism of 4-HPR is of particular interest due to production of the active metabolite 4’-oxo 4-HPR and the clinical challenge of obtaining consistent 4-HPR plasma concentrations. The enzymes involved in 4-HPR metabolism were characterised and the impact of metabolism on efficacy in neuroblastoma and Ewing’s sarcoma cell lines assessed. In addition, the potential for 4-HPR to act as a substrate for common drug transporters was explored. 4-HPR was metabolised to 4’-oxo 4-HPR and 4’-OH 4-HPR primarily by CYPs 3A4, 3A5 and 2C8. Genetic variance in CYP2C8 affected oxidative metabolism, with much lower affinity for 2C8*4 (km of 59.8μM compared to 19.3μM for wild-type), and may be of clinical relevance. Both 4-HPR and 4’-oxo 4-HPR were glucuronidated. 4-HPR was glucuronidated by UGTs 1A1, 1A3 and 1A6, whilst 4’-oxo 4-HPR was glucuronidated by UGTs 1A1, 1A3, 1A8 and 1A9. However, very high Km values were observed (ranging from 389μM to 716μM for 4-HPR). Methylation of 4-HPR to the major metabolite 4-methoxyphenyl retinamide (4-MPR) was determined to be carried out by amine N-methyltransferases. Neuroblastoma and Ewing’s sarcoma cell lines metabolised 4-HPR to 4’-oxo 4-HPR, 4’-OH 4-HPR and 4-MPR. Although upregulation of CYP26A1 expression increased metabolism, inhibition of CYP26A1 had no effect on cell sensitivity. It is therefore unlikely that CYP26A1 expression will have a significant impact on 4-HPR efficacy. 4-HPR appears to be a substrate for the drug transporters MDR1, MRP2 and BCRP. However evidence for the role of these transporters is weak with no difference in 4-HPR sensitivity observed in cell lines over-expressing individual transporters in the presence or absence of specific transporter inhibitors. The major metabolites and metabolising enzymes of 4-HPR have been identified and characterised. This provides the potential to increase plasma concentrations of 4-HPR, and therefore optimise drug efficacy, through modulation of drug metabolism.
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Applications of non-mixture cure models in childhood cancer studiesWeston, Claire Louise January 2008 (has links)
The United Kingdom Children's Cancer Study Group (UKCCSG) was formed in 1977 with the aims of improving the management and advancing knowledge and Ludy of childhood cancers. UKCCSG studies are usually analysed using Cox models to assess whether certain prognostic factors may have an influence on survival. Cox models assume that proportional hazards exist and that all individuals will eventually experience the event of interest resulting in a long-term survival of zero. In childhood cancer, this may not be the case, as survival rates in excess of 70% are often observed. Parametric cure models have been proposed as an alternative method for analysing long term outcome aata m cases such as these.
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Pain in Lebanese children with cancerMadi, Dina January 2013 (has links)
Pain is a significant health issue in the paediatric oncology population. No study to date exists documenting the experience and characteristics of pain in Lebanese children with cancer. The primary aim of this research study is to identify the characteristics of the painful experience of paediatric cancer pain in Lebanese children and how pain is managed from the child’s own perspectives. A secondary aim is to assess the cross-cultural context of the Adolescent Paediatric Pain Tool (APPT) and the Functional Disability Inventory (FDI). The specific objectives that will be addressed are:1. To describe the demographic and clinical characteristics of Lebanese children experiencing cancer pain at the CCCL including: type of cancer, time since diagnosis, metastasis, and current treatment in outpatients and inpatients.2. To describe the characteristics of pain including: intensity, frequency, duration, location, and quality in Lebanese children with cancer at the CCCL. 3. To identify the major sources of pain (cancer-related, treatment-related, or procedure-related) in Lebanese children with cancer at the CCCL.4. To examine the impact of pain on activities of daily living in Lebanese children with cancer at the CCCL. 5. To determine the factors associated with the intensity of pain in Lebanese children with cancer at the CCCL. 6. To determine how pain is managed in Lebanese children with cancer at the CCCL from their own perspective. To meet the above aims and objectives a cross-sectional correlational design was used. A consecutive sample (n=62) was recruited from the Children Cancer Centre of Lebanon at the American University of Beirut Medical Centre (CCCL-AUBMC). Data was collected through face-to-face interviews using a structured questionnaire. The mean age of participants was 12.3 (SD 2.9). The mother was the primary caregiver in the majority of cases (69.4%). The overall mean intensity rating was 5.06 (SD 1.87) on a 10 cm Word Graphic Rating Scale. The majority (57.4%) of children reported a frequency of “sometimes”. The median duration of pain was two hours per pain episode. The most frequent locations were: the forehead, the abdomen, and lower back. Sensory words were most often used to qualify pain. The functional disability levels were moderate as measured by the FDI. Factors associated with overall pain intensity were: frequency, duration, location, affective words, and treatment-related pain. Time since diagnosis, treatment, surgery in the past, radiotherapy, pain duration and frequency of pain predicted pain intensity in the sample. Children reported receiving pharmacological help from nurses, and non-pharmacological measures from their mothers. The main self-initiated coping strategies used by children were behavioural avoidance and behavioural distraction. The most suggested coping strategy was stressor modification. The majority (56/62) did not expect to experience that much pain from cancer and treatment modalities.Pain assessment and management in Lebanese children with cancer are of concern. Health care professionals, policy makers, and institution stakeholders are urged to take action.
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