Mohammed I Khan
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Transcript of Mohammed I Khan
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Article presentation
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Introduction:
• Gallblader carcinoma (GBC) is the second most common malignancy of
the hepatobiliary system, 5 year survival is < 15%.
• Worldwide incidence of GBC are growing, mojority of case were observed
in Sauth America, Far Eastern and Southeast Asia and Eastern Europe.
• GBC incidence were highly correspond with ethnical background and
gender basis.
• Highest cases have been observed in female from Native American Indian
background (‘‘Mapuche Indian’’). However most cases of GBC are
diagnosed at advance level.
• Understanding molcular pathogenesis using SAGE technology enable to
identify molecular target for early detection of GBC.
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Underline principals in the sage methodology:
• Serial analysis of gene expression (SAGE) is a powerful tool that allowsdigital analysis of overall gene expression patterns.
• A short sequence tag (10-14bp) contains sufficient information touniquely identify a transcript provided that the tag is obtained from aunique position within each transcript
• Sequence tags can be linked together to from long serial molecules thatcan be cloned and sequenced
• Quantitation of the number of times a particular tag is observed providesthe expression level of the corresponding transcript.
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SAGE flowchart
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SAGE ≠MICROARRAY• SAGE – An open system which detects both known and unknown
transcripts and genes.
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SAGE library
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Materials and methods:• Three GBC samples were obtained from Hispani/Latino (‘‘H’’), Mapuche
Indian (‘‘M’’) and Caucasian (‘‘C’’).
• One gallbladder was obtained from Hispani/Latino women (“N”)
undergoing gastrectomy for gastric cancer.
• Total RNA were obtained from all four sample.
• L-SAGE libraries were constructed with NlaIII as a anchoring enzyme and
MmeI as tagging enzyme.
• The cancer Genome Anatomy Project “SAGE Tag Extraction Tool” was
used to extract SAGE tags.
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Results:
1. Identification of differentially expressed SAGE tags in GBC.
NOT COMPLETE
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2. CTGF is overexpressed in microdissected primary GBC but
not in metastatic tissues.
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3. CTGF protein is overexpressed in GBC and correlates with
improved survival.
Fig. 3. Immunohistochemistryfor CTGF protein expression in GBC and nonneoplasticgallbladder mucosa. A, absent/low CTGF expression in normal gallbladder epithelium. B, absence of negative labeling in pyloric metaplasia (PM), with CTGF expression in associated gallbladder dysplasia (DY). C and D,representativeexamples of GBC with high CTGF expression.
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