Paediatrics (RCH) - Research Publications
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ItemNo Preview AvailableGenomic imprinting and environmental disease susceptibility.(Environmental Health Perspectives, 2000-03)Genomic imprinting is one of the most intriguing subtleties of modern genetics. The term "imprinting" refers to parent-of-origin-dependent gene expression. The presence of imprinted genes can cause cells with a full parental complement of functional autosomal genes to specifically express one allele but not the other, resulting in monoallelic expression of the imprinted loci. Genomic imprinting plays a critical role in fetal growth and behavioral development, and it is regulated by DNA methylation and chromatin structure. This paper summarizes the Genomic Imprinting and Environmental Disease Susceptibility Conference held 8-10 October 1998 at Duke University, Durham, North Carolina. The conference focused on the importance of genomic imprinting in determining susceptibility to environmentally induced diseases. Conference topics included rationales for imprinting: parental antagonism and speciation; methods for imprinted gene identification: allelic message display and monochromosomal mouse/human hybrids; properties of the imprinted gene cluster human 11p15.5 and mouse distal 7; the epigenetics of X-chromosome inactivation; variability in imprinting: imprint erasure, non-Mendelian inheritance ratios, and polymorphic imprinting; imprinting and behavior: genetics of bipolar disorder, imprinting in Turner syndrome, and imprinting in brain development and social behavior; and aberrant methylation: methylation and chromatin structure, methylation and estrogen exposure, methylation of tumor-suppressor genes, and cancer susceptibility. Environmental factors are capable of causing epigenetic changes in DNA that can potentially alter imprint gene expression and that can result in genetic diseases including cancer and behavioral disorders. Understanding the contribution of imprinting to the regulation of gene expression will be an important step in evaluating environmental influences on human health and disease.
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ItemMast cells dysregulate apoptotic and cell cycle genes in mucosal squamous cell carcinoma(BMC, 2006)BACKGROUND: Mucosal squamous cell carcinoma of the head and neck is a disease of high mortality and morbidity. Interactions between the squamous cell carcinoma and the host's local immunity, and how the latter contributes to the biological behavior of the tumor are unclear. In vivo studies have demonstrated sequential mast cell infiltration and degranulation during squamous cell carcinogenesis. The degree of mast cell activation correlates closely with distinct phases of hyperkeratosis, dysplasia, carcinoma in-situ and invasive carcinoma. However, the role of mast cells in carcinogenesis is unclear. AIM: This study explores the effects of mast cells on the proliferation and gene expression profile of mucosal squamous cell carcinoma using human mast cell line (HMC-1) and human glossal squamous cell carcinoma cell line (SCC25). METHODS: HMC-1 and SCC25 were co-cultured in a two-compartment chamber, separated by a polycarbonate membrane. HMC-1 was stimulated to degranulate with calcium ionophore A23187. The experiments were done in quadruplicate. Negative controls were established where SCC25 were cultured alone without HMC-1. At 12, 24, 48 and 72 hours, proliferation and viability of SCC25 were assessed with MTT colorimetric assay. cDNA microarray was employed to study differential gene expression between co-cultured and control SCC25. RESULTS: HMC-1/SCC25 co-culture resulted in suppression of growth rate for SCC-25 (34% compared with 110% for the control by 72 hours, p < 0.001), and dysregulation of genes TRAIL, BIRC4, CDK6, Cyclin G2 and CDC6 in SCC25. CONCLUSION: We show that mast cells have a direct inhibitory effect on the proliferation of mucosal squamous cell carcinoma in vitro by dysregulating key genes in apoptosis and cell cycle control.
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ItemClinical presentation and endoscopic features of primary gastric Burkitt lymphoma in childhood, presenting as a protein-losing enteropathy: a case report.(Springer Science and Business Media LLC, 2009-06-09)INTRODUCTION: Burkitt lymphoma and B cell lymphomas in childhood may arise in many atypical locations, which on rare occasions can include gastric mucosa. A case of primary gastric Burkitt lymphoma is described in a child presenting as a protein-losing enteropathy, including the direct monitoring of the disease response by sequential endoscopic biopsy and molecular analysis. CASE PRESENTATION: We report a 9-year-old boy who presented with gross oedema, ascites and respiratory distress caused by a protein-losing enteropathy. Initial imaging investigations were non-diagnostic but gastroduodenal endoscopy revealed massive involvement of the gastric mucosa with a primary Burkitt lymphoma. His subsequent clinical progress and disease response were monitored directly by endoscopy and he remains in clinical remission 4 years after initial diagnosis. CONCLUSIONS: This is the first case report of primary Burkitt lymphoma presenting as a protein-losing enteropathy. The clinical course and progress of the patient were monitored by sequential endoscopic biopsy, histology and molecular analysis by fluorescence in situ hybridisation.