Re: [GRG] Nanomedicine and Pancreatic Cancer

Tom: Thank you. — Steve Coles
At 04:52 PM 7/19/2014, you wrote:
Dear Steve,
    Here it is…

http://ift.tt/1n4F9rz
    Hard copy: PNAS Seung-gu Kang, (2012): 109(38),
15431–15436.

Abstract:

    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 S1â€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.
Cheers,
Tom
On Sat, Jul 19, 2014 at 11:23 PM, L. Stephen Coles M.D. Ph.D.

wrote:

Tom: Do you have the full citation? — Steve Coles
At 01:31 AM 7/19/2014, Tom wrote:

Steve,
    You’ve probably already read this but I thought I’d send
it anyway FYI.
It looks quite “cutting edge.”
    I trust your recent good news has
continued.

Yes.  More later. — Steve  Coles

Best wishes,
Tom Coote

L. Stephen Coles, M.D., Ph.D., Cofounder
Los Angeles Gerontology Research GroupE-mail: scoles@grg.orgE-mail:
scoles@ucla.edu

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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