Navigation Links
Blood vessel mapping reveals 4 new 'ZIP codes'
Date:10/24/2011

HOUSTON - A research team led by scientists from The University of Texas MD Anderson Cancer Center have discovered four new "ZIP codes" in their quest to map the vast blood vessel network of the human body.

The study, published online the week of Oct. 24 in the Proceedings of the National Academy of Sciences, brings science one step closer to the goal of using the vascular system to personalize cancer therapy, as well as fight obesity, heart disease and other disorders. Researchers also found that some addresses are shared in vasculature across the board instead of always being organ-specific.

The study is part of ongoing research to identify specific and unique addresses, or ZIP codes, within the body's vascular system and use them to develop diagnostic, imaging and therapeutic strategies. Husband-and-wife research team Wadih Arap, M.D., Ph.D., and Renata Pasqualini, Ph.D., professors at the David H. Koch Center for Applied Research of Genitourinary Cancers at MD Anderson, pioneered the concept and were senior authors of the paper.

"By identifying vascular ZIP codes, we bring medicine closer to the ultimate goal of targeted therapies," Pasqualini said.

Innovative methods help investigation

This study supports the Arap-Pasqualini lab's ongoing research to show blood vessels are more than a uniform and ubiquitous "pipeline" that serves the circulatory system.

More than a decade ago, the group pioneered a screening technique that employs billions of viral particles, called phage, to discover, validate and use blood vessel diversity. The particles are packaged with small fragments of proteins called peptides that act as ligands. When injected into the body, they bind to specific receptors in the blood vessels and organs.

"This process is like a 'molecular mass mailing' to all addresses in the body," Arap said. "The peptides travel until they find a target and bind to it, then with our novel technology we recover and identify them. Knowing the characteristics of the peptides and where they attach can help us understand the vascular system's molecular makeup and develop therapies focusing on disease sites."

This new study was the first in which researchers evaluated the molecular repertoire of protein diversity in several patients, targeting multiple organs at once.

In three cancer patients, serial rounds of peptide collection were followed by biopsies from various tissues to determine where and how the peptides homed, which enabled the enrichment of targeting peptides for identifying ligand-receptors. After systemic delivery of a peptide library to the first patient, phage were recovered from organs, pooled and serially screened in two subsequent patients. Large-scale sequencing was then performed.

"This uncovered a new twist for the vascular map," Pasqualini said. "To this point, we had seen mainly addresses that were organ and tissue specific. Because of this synchronized method, we discovered some markers are vascular-associated at multiple sites."

Shared addresses surprise researchers

Analysis revealed four native ligand-receptors, three of which were previously unrecognized.

Two are shared among multiple tissues (integrin a4/annexin A4 and cathepsin B/apolipoprotein E3) and the other two have a restricted and specific distribution in normal tissue (prohibitin/annexin A2 in white fat tissue) or cancer (RAGE/leukocyte proteinase-3 in bone metastases).

The discovery of shared addresses especially intrigued researchers.

"No one knew about the novel aspect surrounding these particular proteins, and the fact that they can interact and come together to serve a common purpose," Pasqualini said. "There are likely to be many more."

A tissue-specific vascular-targeting system, comprising ANXA2 and prohibitin, was found as a ligand-receptor in human white adipose (fat) tissue vasculature. In earlier research, targeting of prohibitin with an apoptotic agent caused dramatic weight loss in obese rodents. The lab is applying to the Food and Drug Administration (FDA) to conduct a clinical trial for a new drug that will test this principle for weight loss in humans.

Moving the impact forward

This project establishes that large-scale study of the human vasculature can uncover many unidentified or unique molecular networks that can contribute to the treatment of many diseases.

"This endeavor and the applications of our findings are exciting," Arap said. "There are going to be many more receptors and many levels of diversity. We've just scratched the surface."

Translational applications, such as first-in-man clinical trials, have started within MD Anderson. The FDA has granted a safe-to-proceed status for the first vascular-targeted Investigational New Drug (IND). Three other drugs are in pre-IND stage, and several others are in pre-clinical laboratory phase.

"I believe these strategies to identify therapeutic targets on the vasculature are truly innovative both from a scientific and clinical perspective," said David Cheresh, Ph.D., associate director for Translational Research at the University of California, San Diego Cancer Center and noted authority on angiogenesis and cancer metastasis. "Identifying such targets will ultimately pave the way for the next generation of smart/targeted cancer therapies."

MD Anderson and some of its researchers, including Arap and Pasqualini, have equity positions in drug-development companies Alvos Therapeutics and Ablaris Therapeutics, which are subjected to certain restrictions under institutional policy. MD Anderson manages and monitors the terms of these arrangements in accordance with its conflict-of-interest policy.


'/>"/>

Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

Related medicine news :

1. E-counselling shows dramatic results in lowering blood pressure
2. Blood-pressure-lowering drug after stroke aids recovery, study finds
3. Inflammatory Bowel Disease Tied to Higher Risk of Post-Op Blood Clots
4. Hypertension, Not Blood Pressure Drugs, Linked to Birth Defects
5. New U of M start-up may save lives of victims of massive blood loss and trauma
6. Blood Type May Affect Survival After Heart Bypass
7. Stem cells from cord blood could help repair damaged heart muscle
8. Study Suggests Origins of Pregnancy-Linked High Blood Pressure
9. Experts find continuous glucose monitoring beneficial in maintaining target blood glucose levels
10. Restless legs syndrome may raise high blood pressure risk in middle-aged women
11. Restless Legs Syndrome May Boost Blood Pressure
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/9/2016)... ... February 09, 2016 , ... METTLER TOLEDO has ... personnel have a basic understanding of the techniques they use so they can ... help them reduce waste and rework to create a leaner overall lab experience. ...
(Date:2/9/2016)... ... 09, 2016 , ... United Methodist Communications collaborated with Chocolate ... animated video designed to prevent the next widespread Ebola outbreak from ... being distributed throughout Togo, Liberia, Sierra Leone, Nigeria, Côte d’Ivoire and other African ...
(Date:2/9/2016)... ... 09, 2016 , ... Shark Finds and Kevin Harrington, and the Product Managers of ... GRIP-DRY is a newly patented product that has solved some of the basic problems golfers ... early morning dew or right after a rain shower, might understand the struggle of placing ...
(Date:2/8/2016)... ... February 08, 2016 , ... The Federal ... federallabs.org . The site houses a wealth of federal resources that businesses ... the process called technology transfer (T2). As a network of over 300 federal ...
(Date:2/8/2016)... ... February 08, 2016 , ... ... Houma, LA, celebrates the beginning of a new charity campaign. As part of ... Appointed Special Advocates (CASA). In the belief that children deserve a voice, and ...
Breaking Medicine News(10 mins):
(Date:2/9/2016)... 9, 2016 Mast Therapeutics, Inc. (NYSE ... sickle cell disease and heart failure, today announced that it ... purchase common stock in an underwritten public offering.  The offering ... be no assurance as to whether or when the offering ... terms of the offering.   --> ...
(Date:2/9/2016)... Feb. 9, 2016 The new report "Global Diagnostic Ultrasound ... & Consulting group reveals that global diagnostic ultrasound devices market was ... to US$ 7,466.3 million by 2019 at a CAGR of 6.8% ... global ultrasound market has been analyzed for six geographies of ... Asia-Pacific , Latin America , ...
(Date:2/9/2016)... , Feb. 9, 2016 The leader ... that AcceleDent ® is the recipient of the ... category. An FDA-cleared, Class II medical device that speeds ... percent and relieves pain often associated with treatment, AcceleDent ... participated in the annual Orthotown survey of ...
Breaking Medicine Technology: