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Biomedical subjects

Grace Ng

Publications and source records attributed to Grace Ng.

4 recordsLinked to original sources

Lytic rib lesion in a 1-year-old child: group A beta streptococcal osteomyelitis mimicking tumor.

Pediatric osteomyelitis commonly occurs in the long bones and has rarely been reported in small bones such as the vertebrae and ribs. Rib osteomyelitis occurs in approximately 1% or less of all cases of hematogenous osteomyelitis, and is usually caused by Staphylococcus aureus. We present a case of acute osteomyelitis in the rib of an otherwise healthy and afebrile 1-year-old infant that appeared as a lytic bone lesion on imaging studies and was mistaken for a tumor. Biopsy was needed to rule out malignancy and establish the diagnosis of osteomyelitis caused by group A Streptococcus. This is one of the few reported cases of pediatric rib osteomyelitis caused by this organism.

Anti-Bacterial Agents↗

Defining ploidy-specific thresholds in array comparative genomic hybridization to improve the sensitivity of detection of single copy alterations in cell lines.

Array comparative genomic hybridization (CGH) is being widely used to screen for recurrent genomic copy number alterations in neoplasms, with imbalances typically detected through the application of gain and loss thresholds. Review of array CGH publications for the year 2005 showed that a wide range of thresholds are used. However, the effect of sample ploidy on the sensitivity of these thresholds for single copy alterations (SCAs) has not been evaluated. Here, we describe a method to evaluate the detection accuracy of thresholds for detecting SCAs in cell line array CGH data. By applying a hidden Markov model-based method, we segmented array CGH data from well-karyotyped cell lines and generated ploidy-specific sensitivity-specificity plots, from which we identified optimum thresholds relevant to sample ploidy. We demonstrate that commonly used nonploidy-specific thresholds are suboptimal in their ability to call SCAs, particularly when applied to hypertriploid or tetraploid cell lines. We conclude that the use of ploidy-specific thresholds improves the sensitivity of thres-hold-based array CGH for detecting SCAs in cell lines. Because polyploidy is a common feature of cancer cells, the application of ploidy-specific thresholds to cell lines (and potentially to clinical samples) may improve the detection sensitivity of SCAs of biological significance.

Carcinoma, Squamous Cell↗

The significance of autophagy in cancer.

Autophagy, a vacuolar process of cytoplasmic degradation, is implicated in a form of programmed cell death distinct from apoptosis. The regulation of autophagy is complex and signalling pathways such as the target of rapamycin (Tor) kinase pathway, play important roles in tumourigenesis. Beclin 1, an autophagic protein, has been found to be a tumour suppressor. Conversely, cancer cells may exploit autophagy as a means to adapt to hypoxic and nutrient-limiting environments. The relative importance of autophagic cell death and apoptosis in carcinogenesis remains to be established, and the Bcl-2 family of proteins may be instrumental in coordinating the two pathways of programmed cell death.

Animals↗

Evaluation of 3 methods of whole-genome amplification for subsequent metaphase comparative genomic hybridization.

A common aim in cancer research is to investigate mechanisms of malignant progression by genetic analysis of key stages, including pre-malignancy, microinvasion, and micrometastases. As such lesions are small and require microdissection from clinical samples, the amount of DNA that can be recovered is limited and frequently inadequate for commonly used techniques of genomic analysis, such as comparative genomic hybridization (CGH). There is a critical requirement for techniques of whole-genome amplification that minimize representation bias in the amplified sample. Several techniques have been described, although their relative suitability for CGH has not been examined adequately. Here we compare the abilities of degenerate oligonucleotide-primed PCR (DOP-PCR), multiple-strand displacement amplification (MDA), and balanced PCR accurately to amplify limited amounts of template DNA for use in CGH. Amplification by DOP-PCR and MDA, but not balanced PCR faithfully preserved the original genomic content following amplification, as evidenced by generally concordant CGH copy number karyograms. Whereas the amplification products of DOP-PCR were immediately available for labeling and hybridization, the products of MDA required a further digestion step to produce optimal-sized probes for CGH. Moreover, MDA was less reliable overall than DOP-PCR at the lowest starting amount of 10 pg of template DNA. We conclude that DOP-PCR is the method of choice for whole-genome amplification of minute quantities of DNA to enable global genomic analysis to be performed on limited clinical samples.

Metaphase↗