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No description available.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the interaction between CD46 and Helicobacter pylori (a bacterium that colonizes the human gastric mucosa and causes gastritis), peptic ulcers, and cancer. METHODS: Using gastric epithelial cells, we analyzed a set of H pylori strains and mutants for their ability to interact with CD46 and/or influence CD46 expression. Bacterial interaction with full-length CD46 and small CD46 peptides was evaluated by flow cytometry, fluorescence microscopy, enzyme-linked immunosorbent assay, and bacterial survival analyses. RESULTS: H pylori infection caused shedding of CD46 into the extracellular environment. A soluble form of CD46 bound to H pylori and inhibited growth, in a dose- and time-dependent manner, by interacting with urease and alkyl hydroperoxide reductase, which are essential bacterial pathogenicity-associated factors. Binding of CD46 or CD46-derived synthetic peptides blocked the urease activity and ability of bacteria to survive in acidic environments. Oral administration of one CD46 peptide eradicated H pylori from infected mice. CONCLUSIONS: CD46 is an antimicrobial agent that can eradicate H pylori. CD46 peptides might be developed to treat H pylori infection.

Gastric cancer is one of the worldwide leading cancers which is highly prevalent in Eastern Asia. In Hong Kong, there were 1101 new cases and 687 cancer death in year 2011. So far gastric cancer is known to have poor prognosis and high relapse rate, for which a more effective therapy is sorely needed. With increasing knowledge in the role of HER2 in gastric cancer, a novel targeting agent, Trastuzumab, in combination with chemotherapy has become a promising personalized therapy for advanced gastric cancer and gastro-oesophageal junction cancer patients, particularly effective in HER2 positive patient subgroup. The clinical efficacy and safety of Trastuzumab therapy were ascertained by a recent worldwide phrase III randomized controlled trial called ToGA study in 2010. The assessment of the HER2 status has become crucial in selecting the right patient that will benefit most for the trastuzumab therapy. The aim of our study is to evaluate the local HER2 amplification rate in a group of gastric cancer patients and the associated tumour characteristics as well as sharing our technical experience in optimizing/standardizing the Silver ISH protocol including problem shooting in some difficult cases. From Oct 2012 to Apr 2014, we have accessed 68 requests of gastric cancer for HER2 status determination using Ventana Silver ISH assay, 61 were from stomach or gastro-oesophageal junction, 40 of them were endoscopic biopsy and 21 were resection specimens. Among them the majority were poorly differentiated (65.8%) and of intestinal sub-type (59.1%) according to Lauren classification. Thirteen out of 61 (21.3%) samples were found to be HER2 amplified. Majority of the HER2 positive cases were found in intestinal type and moderately differentiated adenocarcinoma. Eighty percent of the IHC 3+ cases and 29.6% of the IHC 2+ equivocal cases that required reflex tested with SISH were found to be HER2 amplified. There exists a great variation in the reported HER2 amplification rates in previous studies, which are apparently due to the difference in methodology and scoring algorithm apart from the different population groups. Recently, the introduction of the Hofmann’s modification on the scoring algorithm of HER2 assay dedicated for gastric cancer, and the increasing popularity in using DISH/SISH as a reliable alternative to FISH in detecting the HER2 status, have standardized the test and hence narrowed the variation. In order to achieve a more reliable staining result and accurate interpretation, optimization/ standardization of the analytical procedures, as well as the pre-analytical procedures become necessary. The standardization of the formalin fixation time seems to be a crucial factor in this regard. Therefore, the establishment of gastric cancer specimen handling guideline hospital-wide, and specific guideline recommendations for gastric cancer from ASCO/CAP are warranted. / published_or_final_version / Pathology / Master / Master of Medical Sciences

Thesis (Ph.D.)--University of California, San Francisco, 2004. / Bibliography: leaves 138-166. Also available online.

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

The Best PhD Thesis in the Faculties of Dentistry, Engineering, Medicine and Science (University of Hong Kong), Li Ka Shing Prize,2001-2003 / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

No description available.