Biomedical subjects

I M Siu

Publications and source records attributed to I M Siu.

5 recordsLinked to original sources

PubMed2001

A database for regional gene expression in the human brain.

Alterations in gene expression levels have been widely studied for various neurological diseases, but few studies have sought to characterize genome-wide gene expression patterns from various regions of the normal brain. A sensitive method for quantifying transcript levels, Serial Analysis of Gene Expression (SAGE), was used to assay expression levels in white matter, thalamus, and cerebellum from the same normal brain, obtained by rapid autopsy. The complete dataset for these SAGE libraries are posted on the Cancer Genome Anatomy Project sponsored SAGEmap website where library comparisons can be made, or the data downloaded for local analysis. The expression of several region-specific genes--neurogenic differentiation 1 (cerebellum), cocaine- and amphetamine-regulated transcript (thalamus), and neurogranin (white matter)--was confirmed using quantitative fluorescent real-time RT-PCR. Further informatics analysis of the data yielded a list of brain-specific genes. The database formed by this analysis provides a means to investigate the expression status of genes involved in the region specific functions of the normal brain. These normal brain gene expression levels also are useful for comparison to pathological expression levels and a sensitive means to determine gene expression in a normal adult brain prior to formulating therapeutic strategies.

Journal Article↗

PubMed2000

Identifying potential tumor markers and antigens by database mining and rapid expression screening.

Genes expressed specifically in malignant tissue may have potential as therapeutic targets but have been difficult to locate for most cancers. The information hidden within certain public databases can reveal RNA transcripts specifically expressed in transformed tissue. To be useful, database information must be verified and a more complete pattern of tissue expression must be demonstrated. We tested database mining plus rapid screening by fluorescent-PCR expression comparison (F-PEC) as an approach to locate candidate brain tumor antigens. Cancer Genome Anatomy Project (CGAP) data was mined for genes highly expressed in glioblastoma multiforme. From 13 mined genes, seven showed potential as possible tumor markers or antigens as determined by further expression profiling. Now that large-scale expression information is readily available for many of the commonly occurring cancers, other candidate tumor markers or antigens could be located and evaluated with this approach.

Algorithms↗

PubMed1999

The identification of monoclonality in human aberrant crypt foci.

Malignant neoplasms, including colon cancers, are thought to arise from a single initiated progenitor cell. Aberrant crypt foci (ACF) are putative precursors of at least some colon cancers. The pattern of X chromosomal inactivation, which is identified by the differential methylation of a site near a polymorphic CAG repeat in the androgen receptor gene, was used to determine the clonality status of 11 ACF from eight female patients. Ten of 11 ACF were found to be monoclonal aberrations. The eleventh ACF appeared monoclonal, but nonrandom inactivation of the X chromosome was also seen in normal crypts from this patient. These results clearly demonstrate that: (a) a high percentage of ACF lesions are neoplastic rather than hyperplastic; and (b) ACF are the earliest identified neoplastic lesions in the colon.

Chromosome Aberrations↗

PubMed1997

Identification of dysplasia in human colonic aberrant crypt foci.

Aberrant crypt foci (ACF) are grossly invisible putative premalignant lesions in the colon. As dysplasia is considered an important precursor of colon carcinoma, we wanted to determine the presence and severity of dysplasia in human ACF. Fifty ACF from 28 patients were embedded in paraffin, cut serially, and stained with hematoxylin and eosin. Multiple slides from each ACF were evaluated for dysplasia according to a defined set of criteria. Of 50 ACF, 3 (6%) contained focal areas with severe dysplasia, ie, carcinoma in situ, 4 (8%) contained focal areas with moderate dysplasia, and 20 (40%) contained focal areas with mild dysplasia. Twenty-three ACF (46%) contained no detectable dysplasia. In 15 of 27 ACF with dysplasia, less than 50% (eg, 4 of 28, 10 of 54, and 10 of 30 sections) of the sections cut and evaluated from each ACF demonstrated dysplasia. The presence of dysplasia in a large proportion of ACF supports the hypothesis that they may be precarcinomatous.

Adult↗

PubMed1996

Human aberrant crypt foci with carcinoma in situ from a patient with sporadic colon cancer.

Aberrant crypt foci are putative preneoplastic lesions found in the colons of carcinogen-treated rodents and at an increased frequency in humans at increased risk for colon cancer. There is a strong association between aberrant crypt foci and colon cancer, including many shared phenotypic and genetic alterations. The aim of this study is to present further evidence of a relationship between aberrant crypt foci and colon cancer in humans. Multiple aberrant crypt foci from a single patient were identified in unembedded colonic mucosa. Histological sections of the aberrant crypt foci and adjacent mucosa were evaluated for dysplasia, proliferative activity, and pigment-laden macrophages that were characterized with histochemical techniques. The first patient with sporadic colon cancer identified with aberrant crypt foci with carcinoma in situ is described. It is interesting that this 99-year-old patient had multiple carcinomas in situ, pseudomelanosis coli, and two metachronous colon cancers. These data lend support to the hypothesis that aberrant crypt foci are precursors of some colon cancers.

Aged↗