Research Profile - College of Medicine and Health Science - United ...

Department of Physiology
The cancer laboratory
The overall thrust of the pancreatic cancer
program is elucidating the molecular
mechanisms underlying its rapid growth and
invasion and in developing novel strategies to
treat it. Prof. Adrian investigates various aspects
of this pancreatic cancer, including growth and
differentiation signaling pathways, the role of
the lipoxygenase pathways in tumor growth
and escape from apoptosis, the interactions
between pancreatic cancer cells and the
pancreatic endocrine islet tissue, as well as the
reasons for the severe metabolic disturbance
and cachexia that accompany this devastating
disease. With his collaborators, he has developed
some novel therapeutic agents, one of which
recently entered clinical trials. New anti-cancer
compounds have been isolated from marine
organisms, including the sea cucumber. The
mechanisms by which these agents cause cell
cycle arrest and induce apoptosis in cancer cells
are currently under investigation. Recently, he
has used oligonucleotide microarrays to identify
novel growth-related genes from their expressed
sequence tags and this has led to the discovery
of a new tumor suppressor gene in the
endoplasmic reticulum.
Recently we have shown that the gene for the
BLT2 leukotriene receptor is switched on in all
pancreatic intraepithelial neoplasias (PanIN
lesions), which are the precursor lesions for
pancreatic cancer. The BLT2 receptor is also
upregulated in pancreatic cancer tissues.
Overexpression of these BLT2 receptors provides
a growth advantage compared with the wild
type cells, while knockdown of overexpression
using siRNA causes growth inhibition. These
findings suggest that the BLT2 receptor would
be valuable target for chemoprevention or
therapy of pancreatic cancer.
In other studies we have shown that the sea
cucumber-derived triterpene glycoside,
frondoside A causes marked growth inhibition
of human pancreatic cancer cells, both in vitro
Immunohistochemical localization of BLT2 in human pancreatic tissues stained by the AP-Red system. Pictures include an
unstained duct in normal pancreas; a PanIN-3 lesion with intense cytoplasmic staining; infiltrating tumor cells in a
pancreatic cancer with marked positive staining in the cytoplasm; positive stained tumor cells in a lymph node metastasis
(all x400);
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