Tom: Thank you. — Steve Coles
At 04:52 PM 7/19/2014, you wrote:
Here it is…
Hard copy: PNAS Seung-gu Kang, (2012): 109(38),
Pancreatic adenocarcinoma is the most lethal of the
solid tumors and the fourth-leading cause of cancer-related death in
North America. Matrix MatalloPoteinases (MMP’s) have long been targeted
as a potential anticancer therapy because of their seminal role in
angiogenesis and ExtraCellular Matrix (ECM) degradation of tumor survival
and invasion. However, the inhibition specificity to MMP’s and the
molecular-level understanding of the inhibition mechanism remain largely
unresolved. Here, we found that endohedral metallofullerenol
Gd@C82(OH)22 can successfully inhibit the
neoplastic activity with experiments at animal, tissue, and cellular
levels. Gd@C82(OH)22 effectively blocks tumor
growth in human pancreatic cancer xenografts in a nude mouse model.
Enzyme activity assays also show Gd@C82(OH)22 not
only suppresses the expression of MMP’s but also significantly reduces
their activities. We then applied large-scale molecular-dynamics
simulations to illustrate the molecular mechanism by studying the
Gd@C82(OH)22–MMP-9 interactions in atomic detail.
Our data demonstrated that Gd@C82(OH)22 inhibits
MMP-9 mainly via an exocite interaction, whereas the well-known zinc
catalytic site only plays a minimal role. Steered by nonspecific
electrostatic, hydrophobic, and specific hydrogen-bonding interactions,
Gd@C82(OH)22 exhibits specific binding modes near
the ligand-specificity loop S1Ã¢€Â², thereby inhibiting MMP-9 activity.
Both the suppression of MMP expression and specific binding mode make
Gd@C82(OH)22 a potentially more effective
nanomedicine for pancreatic cancer than traditional medicines, which
usually target the proteolytic sites directly but fail in selective
inhibition. Our findings provide insights for de novo design of
nanomedicines for fatal diseases such as pancreatic cancer.
On Sat, Jul 19, 2014 at 11:23 PM, L. Stephen Coles M.D. Ph.D.
Tom: Do you have the full citation? — Steve Coles
At 01:31 AM 7/19/2014, Tom wrote:
Ã Ã Ã You’ve probably already read this but I thought I’d send
it anyway FYI.
It looks quite “cutting edge.”
Ã Ã Ã I trust your recent good news has
Yes.Ã More later. — SteveÃ Coles
L. Stephen Coles, M.D., Ph.D., Cofounder
Los Angeles Gerontology Research GroupE-mail: email@example.comE-mail: