ScienceDaily (Mar. 22, 2010) — Pancreatic cancer — known as the most fatal cancer with no known effective treatment — requires a radical new therapy. A promising approach may come in the form of tiny gold nanoparticles — loaded with a therapeutic agent to kill cancer — in a novel procedure called “nanoembolization,” said researchers at the Society of Interventional Radiology’s 35th Annual Scientific Meeting in Tampa, Fla.
“As current treatments for pancreatic cancer offer minimal benefit, entirely new approaches are needed. We’ve developed a radically different approach that might be able to overcome some of the obstacles that have hampered previous therapies for pancreatic cancer,” said Reed A. Omary, M.D., M.S., an interventional radiologist and professor of radiology and biomedical engineering and vice chair of research in the radiology department at Northwestern University in Chicago, Ill. Traditional attempts to treat this particularly horrible cancer include some combination of chemotherapy, radiation therapy, and/or surgery. However, none of these methods results in effective treatment.
Instead, Northwestern researchers constructed extremely tiny particles made out of gold — termed nanoparticles — with cancer-killing agents attached to them. These nanoparticles, which measure only 13 nanometers in diameter, are so small that 8,000 of them could be strung together and still occupy less than the width of a single human hair. In animal studies, the research team used an interventional radiology technique to inject the cancer-killing nanoparticles directly into the tumor. The investigators call this novel delivery technique “nanoembolization.” Omary said, “Using nanoembolization, we dramatically increased the concentration of the nanoparticles in the tumor by 55 times over traditional methods that use a vein (such as at the elbow). That’s a massive improvement — and a promising discovery for this dreadful disease.”
The pancreas is the organ located behind the stomach. It produces juices that help break down food and hormones that help control blood sugar levels. Pancreatic ductal adenocarcinoma is the most common type of pancreatic cancer and carries the worst prognosis of any cancer, even when diagnosed early. This aggressive cancer typically has a six-month survival rate at diagnosis. In 2009, it was estimated that more than 42,000 individuals, typically over the age of 60, were diagnosed with pancreatic cancer, making it the fourth-leading cause of cancer death in the United States. Because it is often found late and it spreads quickly, pancreatic cancer can be hard to treat.
“As current treatments offer minimal benefit, entirely new approaches are needed,” said Omary, in explaining the pre-clinical study. A major reason that current pancreatic cancer treatments do not work is that scar tissue develops around the cancer. This scar tissue blocks cancer-killing drugs from entering the tumor in the first place, said Omary.
“We used a catheter to deliver cancer-killing nanoparticles directly to the tumor. The catheter is placed into an artery near the groin and navigated through blood vessels to the site of the tumor, all without surgery. Once in the blood vessel that supplies the tumor, the catheter can deliver nanoparticles directly into the tumor. This method may offer a better way to overcome the scar tissue that blocks drugs from attacking the tumor,” he added. With this type of catheter delivery, more drug “can go directly where we want it: to the tumor itself,” said Omary. “This is not the case with injections through a vein, where the cancer-killing drug may not end up where it needs to be,” he explained.
The direct catheter injections also have the potential to reduce some of the side effects such as vomiting and hair loss that may be seen with typical chemotherapy. “Researchers have been using the same tool box for a long time without any benefit; it’s time for us to apply some high-tech tools to treat pancreatic cancer,” said Omary, the senior author of “Image-guided Nanoembolization as a Novel Local Therapy for Pancreatic Cancer: Feasibility in an Animal Model.”
“For decades, interventional radiology has offered innovative ways to treat cancer patients instead of traditional surgery, chemotherapy or radiation; after all, we invented the field of minimally invasive medicine. Interventional radiologists recognize that the greatest advances in medicine occur at the interface with other medical disciplines,” said Omary. “Nanoembolization is a terrific example of bringing together a diverse range of experts — in interventional radiology, chemistry and oncology — to develop a radically different method to treat the cancer with the most dismal survival rate,” he added.
Omary praised the efforts of all the Northwestern investigators including nanomedicine experts Chad A. Mirkin, Ph.D., director of the university’s International Institute for Nanotechnology and a member of President Obama’s Council of Advisors for Science and Technology, and C. Shad Thaxton, M.D., Ph.D., assistant professor of urology. Omary emphasizes that before this proposed new treatment is ready for patients, more studies will be needed to show safety and effectiveness.
Read more about…………..interventional radiologists
Interventional radiologists are board-certified physicians who specialize in minimally invasive, targeted treatments. They offer the most in-depth knowledge of the least invasive treatments available coupled with diagnostic and clinical experience across all specialties. They use X-rays, MRI and other imaging to advance a catheter in the body, usually in an artery, to treat at the source of the disease non-surgically. As the inventors of angioplasty and the catheter-delivered stent, which were first used in the legs to treat peripheral arterial disease, interventional radiologists pioneered minimally invasive modern medicine.
Today many conditions that once required surgery can be treated nonsurgically by interventional radiologists. Interventional radiology treatments offer less risk, less pain and less recovery time compared to open surgery.
Interventional Radiology Training
Interventional radiology is a recognized medical specialty by the American Board of Medical Specialties. Interventional radiologists are board-certified physicians with additional advanced training in minimally invasive, targeted treatments performed using imaging to guide them. Their board certification includes both Vascular and Interventional Radiology and Diagnostic Radiology which are administered by the American Board of Radiology.
Innovation and Patient Safety
Interventional radiologists’ unique blend of skills fosters innovation and enables them to quickly adapt their imaging expertise to pioneer nonsurgical treatments that are guided by imaging. They adapt a technique proven to work for one problem and apply it to another. When it comes to the best practices for safely performing minimally invasive treatments, interventional radiologists pioneered the procedures and the standards for safety and quality. Patient safety is incorporated into the development of these advances because interventional radiology and diagnostic radiology training programs include radiation safety, radiation physics, the biological effects of radiation and injury prevention.
The Society of Interventional Radiology (SIR) publishes guidelines for minimally invasive treatments, including criteria for adequate training for specific interventional procedures, as well as expected success and complication rates. These evidence-based guidelines are used by the FDA, hospitals and regulatory groups.
Patient Choices and Informed Consent
For many years, surgery was the only treatment available for many conditions. Today, interventional radiology treatments are first-line care for a wide variety of conditions. It is important to get a second opinion and know all of your treatment options before consenting to any procedure or surgery.
Minimally Invasive Interventional Radiology Treatments
- Abdominal aortic aneurysms
- Angioplasty & stent placement
- Cancer – Bone
- Cancer – Breast
- Cancer – Kidney
- Cancer – Liver
- Cancer – Lung
- Deep Vein Thrombosis
- Gastrostomy (feeding tubes)
- Hereditary Hemorrhagic Telanglectasia
- Hypertension and End-Stage Renal Disease
- Liver disease
- Needle biopsy
- Pelvic pain (chronic)
- Peripheral arterial disease
- Pulmonary Embolism
- Stroke and carotid artery disease
- Uterine Fibroids
- Varicoceles & Male Infertility
- Varicose Veins
- Venous access catheters
- Women and Vascular Disease
- Women’s Health
Read more about…………..interventional radiologists in the news – March 2010
Quick treatment crucial for dangerous blood clots
Date published: 3/7/2010
By Janet Marshall
BY HEATHER BRADY
Four and a half weeks after the birth of her first child, Faith Hilsinger found herself in the hospital again, this time in urgent need of help for a dangerous blockage of her pulmonary artery.
The blockage formed after a blood clot–called a deep vein thrombosis–broke free from her leg and shot up to her lungs.
Though Hilsinger hadn’t known the clot was forming in her veins, she knew right away when the pulmonary embolism, or blockage, hit.
“The pulmonary embolism felt like an ice pick got stuck between two ribs in my back and was twisted,” said Hilsinger, of Spotsylvania County. “That’s the only way I can describe how horrible it felt.”
While pulmonary embolisms can be fatal, Hilsinger made a full recovery after undergoing a relatively new procedure performed by Dr. John Statler, an interventional radiologist with Virginia Interventional and Vascular Associates in Fredericksburg.
‘SOMETHING WASN’T GOOD’
Hilsinger was recovering from a Caesarian section in August 2007 when she started experiencing what felt like a cramp in her leg. She had been sedentary for a couple of weeks as she tried to heal from her surgery. And being sedentary, especially after surgery, increases the risk of a clot.
Hilsinger said she called her obstetrician, who described typical blood clot symptoms–including red streaking marks, swelling and inflammation.
But “I didn’t seem to get any of them,” said Hilsinger, then 24.
When other symptoms appeared–back pain, trouble breathing, weakness in her legs and problems standing up one night–she attributed them to what felt like a pinched nerve in her back.
But the suffering intensified.
“In the five seconds it took to warm a bottle up in the microwave, I felt like I was going to collapse,” Hilsinger said.
What she was experiencing in that moment was the pulmonary embolism–a piece of the blood clot in her leg shooting up toward her heart and lodging in her lungs.
By then, her leg had begun to swell. Hilsinger visited a physician’s assistant at Reese Medical Associates, who sent her straight to the emergency department at Mary Washington Hospital.
“I knew right away something wasn’t good because there were two people in the waiting room, and I was admitted immediately,” Hilsinger said.
She said she was quickly hooked up to monitors and moved to a personal room.
“One of the nurses said: ‘Don’t even move in your bed. Don’t roll over, don’t cross your legs,'” Hilsinger said.
They didn’t want another piece of the clot to break off and travel toward her heart.
When a person suffers a pulmonary embolism stemming from a deep vein thrombosis, treatment options include medications and medical interventions.
Hilsinger said Statler, the interventional radiologist, put a filter into a large vein in her abdomen to prevent any more clots from traveling from her legs to her lungs.
The next day, he discussed with her the possibility of using a relatively new procedure, isolated pharmacomechanical thrombolysis (IPMT), to treat the clot in her leg.
“I was scared to death,” Hilsinger said. “All I could think of was I’m going to die from this [deep vein thrombosis]. This is going to kill me.”
Statler explained that the technique he wanted to use was less invasive and could bring quicker relief than the traditional method.
In the past, doctors would thread a long, thin tube into the clotted area of the vein using X-ray guidance. The tube had little holes in it, through which the doctors would disperse anti-clotting fluid.
The technique carried a dangerous risk–that part of the clot could break off and shoot up to the heart, forming an embolism during the procedure.
“That is potentially life-threatening, especially if you’re older,” Statler said.
But with the new technique, using a sophisticated catheter called the Trellis-8 system, two balloons inflate at either end of the tube, preventing the majority of the clot pieces from leaving the area.
“It would be tough to come up with something better than [the Trellis system],” Statler said.
‘MY ONLY OPTION’
Everything had happened so fast, and Hilsinger had a baby’s needs to consider. She wasn’t sure at first whether she wanted to undergo the procedure.
But with family members pitching in to care for her newborn, she decided to go through with it.
“I had help with the baby, so I could focus on me,” Hilsinger said. “That was one of my fears about going to the E.R. What’s going to happen to her if I’m stuck here?”
She realized, though, that she didn’t have much choice.
“I came to the conclusion that this was my only option,” Hilsinger said.
Not everyone with a deep vein thrombosis is a candidate for the Trellis procedure. Some people can be treated with anti-clotting medication alone.
But Hilsinger “had an incredible clot burden,” Statler said. “I mean, she had a clot basically from her toes to her abdomen in both legs.”
As Hilsinger described it, “No blood was flowing out of my legs, which was why the swelling happened so quickly.”
The procedure restored blood flow to Hilsinger’s legs. She was placed on blood thinners for nine months afterward, and she said it took three months for her body to fully absorb what was left of the clot.
AN IMPORTANT LESSON
As she recovered, Hilsinger said, she made sure to do a lot of walking. She said she took it slow but refused to sit around.
“I was bound and determined that I was never going to be in that situation again,” she said.
Hilsinger’s daughter, Riley, is 2 years old now, and Hilsinger is 23 weeks pregnant with her second child.
So far, she said, her pregnancy has been relatively uneventful, and she hopes it will stay that way. She feels she’s learned an important lesson because of her ordeal.
“Be aware,” she said. “If there’s any doubt in your mind, go to the doctor.”
Osteoporosis causes 1.5 million fractures. Riverside is doing work to repair and reduce the pain of these sorts of breaks. Vertebroplasty is a minimally invasive procedure used to alleviate pain. Cement is injected into the bone to stabilize the fracture.
AURORA, Colo. – A research project at the University of Colorado School of Medicine is examining new ways to reduce risks of heart attacks and diabetes for nearly a quarter of the U.S. population.
The project, which will measure the effect of an over-the-counter nutritional supplement, is led by Robert Eckel, MD, the former president of the American Heart Association.
The effort focuses on reducing health risks for people with what is called the metabolic syndrome. About 25 percent of Americans have it and they have twice the average risk for heart disease and five times the risk for diabetes.
The syndrome exists in someone who has three or more of these risk factors:
large waist circumference (greater than 35 inches in women and 40n inches in men)
high blood pressure (greater than 130/85 or onn treatment)
elevated blood sugar (glucose) concentration but withoutn diabetes
lipid disturbances including high triglyceridesn
lower levelsn of HDL, the “good” cholesterol
One of the key factors behind the higher health risks is a problem called oxidative stress. Oxidative stress causes problems in several ways. The body produces too much oxygen, which can cause damage to tissues. And it is hard for the human body to eliminate this excess oxygen or repair the damage it causes.
The study will try to determine if an over-the-counter supplement called Protandim helps reduce oxidative stress. Protandim is a nutraceutical, a supplement containing multiple nutrients.
“Many people suffer from the metabolic syndrome,” according to Eckel, a professor in the School of Medicine. “We are trying to learn whether a product that is relatively inexpensive and easy to obtain can help them.”
Participants in the study will be given Protandim or a placebo, then will switch to the other. Through blood samples, their oxidative stress will be tracked over three months. They will need to make five visits to the Clinical Translational Research Center at the University of Colorado Hospital on the Anschutz Medical Campus in Aurora. Those in the study will be financially compensated for their visits.
People interested in participating in the study should contact Professional Research Assistant Jamie Palmer at 303-724-5972 or Jamie.Palmer@ucdenver.edu
The Anschutz Medical Campus is a model for the type of interdisciplinary research in translational medicine that will take basic discovery “from the bench to the bedside.”
Faculty at the University of Colorado’s School of Medicine work to advance science and improve care. These faculty members include physicians, educators and scientists at University of Colorado Hospital, The Children’s Hospital, Denver Health, National Jewish Health, and the Denver Veterans Affairs Medical Center. Degrees offered by the UC Denver School of Medicine include doctor of medicine, doctor of physical therapy, and masters of physician assistant studies. The School is located on the University of Colorado’s Anschutz Medical Campus, one of four campuses in the University of Colorado system. For additional news and information, please visit the UC Denver newsroom online. Contact: Dan Meyers, 303.724.5377, email@example.com
Seattle Tops the List With Its Residents at Greatest Risk
MOUNTAIN VIEW, CA — (Marketwire) — 03/22/10 — Cybercrime, a threat that affects one in five online shoppers(1) and cost Americans $560 million in 2009 due to online fraud(2), may hit closer to home than many realize. Norton from Symantec (SYMC) teamed up with independent research firm Sperling’s BestPlaces to find and expose the nation’s top 10 cities most vulnerable to cybercrime.
The following are ranked the Norton Top 10 Riskiest Online Cities:
3.) Washington, D.C.
4.) San Francisco
5.) Raleigh, N.C.
9.) Austin, Texas
10.) Portland, Ore.
The rankings were determined through a combination of Symantec Security Response’s data on cyberattacks and potential malware infections, as well as third-party data about online behavior, such as accessing WiFi hotspots and online shopping.
- At the top of the rankings, Seattle claims the dubious distinction of America’s leading riskiest cybercrime city, placing near the top in categories such as cyberattacks and potential infections; online behavior that can expose people more to cybercrime, such as online shopping and banking online; and wireless Internet access.
- Boston and Washington, D.C. follow in second and third place. Both cities experience a very high level of cybercrime, perhaps due in part to their large number of WiFi hotpots.
- High-tech hubs San Francisco and Raleigh are ranked fourth and fifth. San Francisco tops the list for riskiest online behavior and highest number of WiFi hotspots per capita. Many of these cities are considered some of the most tech-savvy cities in the nation, proving that even skilled and experienced Internet users are at risk when it comes to cybercrime and online insecurity.
- Rounding out the top 10 are Atlanta, Minneapolis, Denver, Austin and Portland. According to the Norton research, Atlanta residents experience the most cyberattacks and potential infections. Minneapolis and Portland are near the top for risky online behavior, while Denver and Austin score high across the board.
“With more people than ever relying on the Internet to stay in touch, shop and pay their bills, feeling confident and secure in our information-driven world is vital,” said Marian Merritt, Norton Internet Safety Advocate. “This study highlights the cities most at risk of cybercrime and reminds individuals, families and businesses across the country of the hazards they face each time they go online. We’re here to educate consumers about how to protect themselves and ideally never fall victim to cybercrime.”
Of the 50 U.S. cities examined, Detroit came in as the least risky online city. Motor City’s residents were less likely to participate in risky online behavior compared to other cities in the study, and it also ranked low in cybercrime, access to the Internet, expenditures on computer equipment, and wireless Internet access. El Paso, Texas and Memphis, Tenn. came in second and third, respectively, on the list of least risky online cities.
“Despite people’s familiarity with technology and the Internet, this study shows that everyone is exposed to a certain level of risk when they are online,” said Bert Sperling, founder and researcher of Sperling’s Best Places. “No matter where you live — be it Seattle or Detroit — it’s important to be vigilant in everyday online behavior in order to protect yourself against cybercrime of all types.”
Top 3 Safety Tips from Norton
No matter where your city ranks on the list, people everywhere can benefit from online safety tips to help prevent becoming a victim of a cybercrime:
- Use legitimate security software that offers comprehensive protection against known and unknown online threats — There are a lot of security solutions to choose from, but comprehensive security solutions like Norton Internet Security and Norton 360 will help ensure you’re fully protected against malware, spyware, hackers, zero-day threats, and identity theft. Parents should also protect their kids too from online threats and inappropriate content by using OnlineFamily.Norton, a free family safety solution.
- Always keep your computer’s operating system and the software you run on it patched — Don’t ignore prompts to update your OS or applications with critical security fixes. Cybercriminals can get in through “holes” in unpatched computers.
- Stay educated — Visit the Norton site www.everyclickmatters.com and download the Norton Family Online Safety Guide to learn more about the realities of cybercrime and how to stay protected.
For more information, please visit www.NortonRiskiestOnlineCities.com.
To develop these rankings, researchers at Sperling’s BestPlaces analyzed data for each city including the number of cyberattacks and potential infections (data provided by Symantec Security Response), level of Internet access, expenditures on computer hardware and software, wireless hotspots, broadband connectivity, Internet usage and online purchases.
The Norton from Symantec Top 10 Riskiest Online Cities study analyzed 50 of the largest cities in the United States, by population defined by the U.S. Census Bureau.
Full survey content and additional details regarding methodology, criteria and sources are available upon request.
Complete Rankings – Cybercrime Cities
3. Washington, D.C.
4. San Francisco
5. Raleigh, N.C.
9. Austin, Texas
10. Portland, Ore.
12. Charlotte, N.C.
13. Las Vegas
14. San Diego
15. Colorado Springs, Colo.
16. Sacramento, Calif.
18. Oakland, Calif.
19. Nashville-Davidson, Tenn.
20. San Jose, Calif.
21. Columbus, Ohio
23. Kansas City, Mo.
24. New York
26. Albuquerque, N.M.
28. Omaha, Neb.
29. Virginia Beach, Va.
30. Los Angeles
31. Cincinnati, Ohio
33. St. Louis, Mo.
37. Oklahoma City
39. Jacksonville, Fla.
40. Tulsa, Okla.
41. San Antonio
44. Tucson, Ariz.
45. Long Beach, Calif.
46. Fort Worth, Texas
47. Fresno, Calif.
48. Memphis, Tenn.
49. El Paso, Texas
About Norton From Symantec
Symantec’s Norton products protect consumers from cybercrime with technologies like antivirus, anti-spyware and phishing protection — while also being light on system resources. The company also provides services such as online backup and PC tuneup, and is a trusted source for family online safety. Friend us on Facebook at www.facebook.com/norton and follow @NortonOnline on Twitter.
Symantec is a global leader in providing security, storage and systems management solutions to help consumers and organizations secure and manage their information-driven world. Our software and services protect against more risks at more points, more completely and efficiently, enabling confidence wherever information is used or stored. More information is available at www.symantec.com.
About Sperling’s BestPlaces
Bert Sperling has been helping people find their own “Best Place” to live, work and retire for more than 20 years. His firm, Sperling’s BestPlaces, puts facts in the hands of the public so they can make better decisions about best places to live, work, retire, play, or relocate. His bestselling books, Cities Ranked and Rated and Best Places to Raise Your Family, are published by John Wiley & Sons. More information about Bert and his work is available at www.bestplaces.net.
(2) Internet Crime Complaint Center http://www.ic3.gov/media/2010/100312.aspx
Biomimetic Signaling Gel Reduces Signs of Photoaging
Medscape.com, by Deborah Brauser, March 18, 2010 (Miami Beach, Florida) — A new topical gel containing a combination of energized microparticles of zinc and copper that produce biomimetic cell signaling (CYTOMIMIC) significantly improves the signs of clinical photoaging, including the appearance of under-eye and cheek wrinkles, pigmentation, and global lifting and firming, according to results from a randomized study chosen for oral presentation here at the American Academy of Dermatology 68th Annual Meeting.
“The principle of applying biomimetic electrical signals to the skin to stimulate rejuvenating effects is a very new and different way of approaching antiaging and skin care,” investigational team member Jeannette Chantalat, manager of research and development at Johnson & Johnson Consumer and Personal Products Worldwide, in Cincinnati, Ohio, told Medscape Dermatology.
“This is something we’ve been able to demonstrate now in several different studies, and it all boils down to this idea of creating signals for the skin in a very different way than any other topical ingredient,” she added.
New Technology Harnesses Bioelectricity in a Gel
CYTOMIMIC technology combines minerals into a complex that delivers “biological levels of electric signals similar to the skin’s natural bioelectricity,” Ms. Chantalat explained. “It’s basically harnessing the power of bioelectricity to help stimulate the skin’s own rejuvenation processes.”
She reported that in previous studies, this complex has “demonstrated anti-inflammatory activity and upregulation of collagen and elastin gene expression.” The studies also showed that it’s safe for topical use and has a low potential for eye irritation.
In this trial, the investigators sought to assess the bimineral complex in a topical gel with a moisturizer to examine its effect in reducing facial photoaging signs, “including in the delicate periorbital area.”
A total of 94 women between the ages of 40 and 65 years with mild to moderate photoaging were enrolled at 1 center in Texas and randomized to receive twice daily applications to the entire face and eye area, including the eyelids, with 1 of 2 combinations of the bimineral complex gel with an activating moisturizer (n = 30 and n = 33), or a placebo gel with an activating moisturizer (n = 31) for 12 weeks.
Digital photos and patient self-assessment questionnaires were used to evaluate efficacy and safety parameters at baseline and at weeks 2, 4, 8, and 12.
Results showed that both active treatment groups had statistically significant (P < .05) improvements in overall appearance, under-eye bags, under-eye wrinkles, cheek wrinkles, pigmentation, radiance, fine lines, and global lifting/firming, compared with the placebo group and with baseline assessment. These improvements were seen as early as week 2, and continued through to the end of the trial.
“We were especially happy to see the dramatic effects around the eyes, which is often a very difficult area to treat,” said Ms. Chantalat. She noted that they were also pleased with the improvements in the eyelids. “Many topicals can be irritating around the eye, so most people don’t look at treating that area.”
All of the products were well tolerated, and no treatment-related adverse events were reported.
Ms. Chantalat reported that the investigators would now like to look at using the bimineral complex for other areas of the body. “Because the technology is developed based on an understanding of how skin heals and uses bioelectricity, it is potentially transferable to other different tissues in the body.”
An Interesting Concept
“This was an intriguing study showing that, by using these bimineral products that create some electrical signals in the skin, we can reverse some of the signs of aging,” said session moderator Keyvan Nouri, MD, professor of dermatology and director of dermatologic surgery at the University of Miami School of Medicine in Florida.
“I think it’s a very interesting concept,” added Dr. Nouri, who was not involved in the study. “It’s been used previously in wound healing and in speeding healing. So it’s interesting to see that it can actually have some anti-aging and antiphotoaging effects too.”
This study was supported by Johnson & Johnson Consumer and Personal Products Worldwide, which employs Dr. Chantalat. Dr. Nouri has disclosed no relevant financial relationships.
American Academy of Dermatology (AAD) 68th Annual Meeting: Abstract P304. Presented March 7, 2010.
Breast-cancer sufferers could avoid the need for surgery in the future after doctors discovered a way of destroying tumours by freezing them.
Photograph by: Justin Sullivan, Getty Images
ScienceDaily.com, March 22, 2010 — Interventional radiologists have opened the door to an encouraging potential future treatment for the nearly 200,000 women who are diagnosed with breast cancer in the United States each year: image-guided, multiprobe cryotherapy. In the first reported study, researchers were able to successfully freeze breast cancer in patients who refused surgery; the women did not have to undergo surgery after treatment to ensure that tumors had been killed, note researchers at the Society of Interventional Radiology’s 35th Annual Scientific Meeting in Tampa, Fla.
“Minimally invasive cryotherapy opens the door for a potential new treatment for breast cancer and needs to be further tested. When used for local control and/or potential cure of breast cancer, it provided safe and effective breast conservation with minimal discomfort for a group of women who refused invasive surgery or had a local recurrence and needed additional management,” noted Peter J. Littrup, M.D., an interventional radiologist and director of imaging research and image-guided therapy for the Barbara Ann Karmanos Cancer Institute in Detroit, Mich. “This is the first reported study of successfully freezing breast cancer without having to undergo surgery afterward to prove that it was completely treated,” he added.
In the 13-patient study, no localized treatment recurrences were seen for up to five years, no significant complications were noted and women were pleased with the cosmetic outcomes, noted Littrup, who is also a professor of radiology, urology and radiation oncology at Wayne State University in Detroit. Cryotherapy was applied according to well-established freezing principles, and biopsies at the margins of the cryotherapy site immediately after the procedure and at the cryotherapy site in follow-up were all negative — showing no cancer, said Littrup.
In the United States, a woman is diagnosed with breast cancer every three minutes and one woman will die from the disease every 13 minutes. A woman has about a 13 percent lifetime risk of developing breast cancer, with women 50 years of age and older accounting for approximately 80 percent of all breast cancers. For these women, as well as the thousands of men diagnosed each year, breast cancer treatments can be highly effective but often require invasive treatment options such as surgery and chemotherapy. Surgery offers the best chance for a cure. Until long-term data are available, interventional treatments — such as cryotherapy, thermal ablation and laser therapy — are reserved for women who cannot have — or have refused — surgery.
In this study’s cryotherapy treatment, researchers used several needle-like cryoprobes that were evenly spaced and that were inserted through the skin to deliver extremely cold gas directly to the tumor to freeze it. This technique has been used for many years by surgeons in the operating room; however, in the last few years, the needles have become small enough to be used by interventional radiologists through a small nick in the skin, without the need for an operation. The “ice ball” that is created around the needle grows in size and destroys the frozen tumor cells. The major benefits of cryotherapy are its superb visualization of the ice treatment zone during the procedure, its low pain profile in an outpatient setting and its excellent healing with minimal scar, said Littrup. Breast imaging has markedly advanced by accurate improvements in breast magnetic resonance imaging (MRI), allowing for excellent treatment planning of tumor size and extent within the breast, as well as showing zones of destruction thoroughly covering the tumor after cryotherapy, he noted.
A major difference between this study and all prior uses of breast cryotherapy is the confirmation of sufficient deadly temperatures when using two or more cryoprobes, said Littrup. Prior breast cryotherapy studies had “inexplicably” used only a single cryoprobe and suggested that tumors larger than 1.5 centimeters could not be adequately treated, he explained.
“This is incongruent with more than 10 years of treating an entire prostate, which is approximately 5 centimeters, with more than six probes in order to generate well-defined sufficient deadly temperatures throughout the whole gland. We simply translated this concept to breast cancer in order to assure deadly temperatures well beyond all apparent tumor margins in order to generate successful use of cryotherapy in women,” said Littrup. “This emphasizes the important role of an interventional radiologist in pioneering image-guided therapy by appropriately using established treatment technology — let alone emerging ones — to deliver a sufficient treatment dose, rather than only relying on the organ-specific expertise of other subspecialized physicians,” said Littrup. “An interventional radiologist can better focus on the image-guidance similarities of nearly any treatment technology and thereby help lead the effort of improved cancer treatments for many organ sites,” added the co-author of “Cryotherapy for a Spectrum of Breast Cancer: US and CT-guidance.”
Surgeons and radiation oncologists have long tried to provide at least a 1-centimer margin of treatment surrounding all aspects of a localized breast cancer, and it was important to ensure a similar “surgical margin” of lethal temperatures beyond all tumor margins by cryotherapy in this study, said Littrup. “The well-visualized ice margin by ultrasound CT or MR is actually only the 0-degree Celsius line, or isotherm, which is not sufficiently lethal to cancer cells, but has unfortunately been confused with the actual treatment margin. We made sure that the lethal isotherm of approximately -30 degrees Celsius extended beyond all tumor margins,” said Littrup.
After breast MRI and thorough consultation, patient consents were obtained for institutional review board-approved breast cryotherapy. In 13 cryotherapy sessions, 25 breast cancer foci were treated in 13 patients, stages 1-4, using multiple 2.4-millimeter cryoprobes. Using only local anesthesia with mild sedation, ultrasound guidance alone was used in six patients; seven patients required both CT and ultrasound to better define ice margins. MR and/or clinical follow-up were available for up to 65 months after cryotherapy. Pretreatment breast tumor diameter was 1.7 + 1.2 centimeters (range, 0.5-5.8 centimeters) and an average of 3.3 cryoprobes produced ice diameters of 5.2 + 2.2 centimeters (range, 2-10 centimeters).
“With recent developments of powerful new cryotechnology, multiple directions for breast cryotherapy can be pursued, including translating the current, somewhat challenging, procedure done with ultrasound and/or CT guidance to a more consistent and reproducible MR-guided approach,” said Littrup. Cryotechnology promises to be more MR-compatible and would also allow accurate targeting of more difficult-to-see breast tumors. More importantly, larger studies in multiple centers needs to be done, following these basic cryobiology principles of sufficient lethal temperatures generated by multiple cryoprobes spaced evenly throughout a breast cancer region, he added.
New Omapatrilatlike Drug Impressive in Hypertension
Medscape.com, by Lisa Nainggolan, March 23, 2010 — A novel, first-in-class antihypertensive agent, which inhibits both the angiotensin II receptor and neprilysin, showed greater reductions in blood pressure than valsartan alone in a new study in more than 1200 patients reported at the American College of Cardiology 2010 Scientific Sessions and simultaneously published in the Lancet .
Lead author Dr Luis Miguel Ruilope (Hospital 12 de Octubre, Madrid, Spain) told heartwire : “This is a new compound with a dual effect that will help us to control blood pressure in a better way.” Given that it suppresses the angiotensin system and prolongs the life of natriuretic peptides, it may also have other ancillary effects, he said. The drug, LCZ696 (Novartis), was safe and effective in the trial, said Ruilope, and although further investigation is needed, he envisages that it could be useful in arterial hypertension, heart failure, and pulmonary hypertension, with particular benefit in diabetics and the elderly.
In an editorial accompanying the published study , Drs Bernard Waeber and Francois Feihl (Université de Lausanne, Switzerland) agree: there are “sufficient encouraging data [with LCZ696] to justify undertaking large clinical trials in various clinical disorders, notably hypertension, diabetes, and heart or renal failure.”
LCZ696, an Omapatrilatlike Drug Without the ACE Inhibition
Ruilope explained that LCZ696 increases the concentration of natriuretic peptides by inhibiting neprilysin (also known as neutral endopeptidase); prior to this agent, the most extensively studied inhibitor of neprilysin was omapatrilat (Bristol-Myers Squibb), a drug that was never marketed because it had an unacceptable side effect of angioedema.
But omapatrilat concomitantly inhibited three enzymes: angiotensin-converting enzyme, aminopeptidase P, and neprilysin, the researchers explain, whereas the new drug inhibits only two and substitutes angiotensin II blockade for ACE inhibition. Because angiotensin-receptor blockers have a lower risk of angioedema than do ACE inhibitors, it is hoped that LCZ696 will offer cardioprotective effects without the side effect of angioedema.
In the double-blind study, 1328 patients with mild to moderate hypertension from 18 countries were assigned to eight weeks of treatment in one of eight groups: 100 mg, 200 mg, or 400 mg of LCZ696; 80 mg, 160 mg or 320 mg of valsartan; 200 mg of AHU377, which represented the neprilysin-inhibitor moiety alone of LCZ696; or placebo.
The study of AHU377, which blocks neprilysin but not the angiotensin II inhibitor, illustrated that while this compound did reduce BP as a monotherapy, its effects were slight.
But “dual inhibition of the angiotensin II receptor and neprilysin have complementary effects,” say Ruilope et al. LCZ696 reduced blood pressure in a dose-dependent way; 200 mg of the study drug led to a significantly greater reduction in BP than did 160 mg of valsartan (-2.97 mm Hg diastolic; p=0.0023), and 400 mg of LCZ696 bettered 320 mg of valsartan (-2.70 mm Hg; p=0.0055).
And “in all study groups, the occurrence of adverse effects did not exceed those recorded with placebo,” note Waeber and Feihl in their editorial. “Crucially, no cases of angioneurotic edema occurred in the trial, suggesting that inhibition of neprilysin does not lead to bradykinin accumulation when the activity of angiotensin-converting enzyme is preserved. Such a possibility should be verified in a larger sample.”
Ruilope and colleagues do note some limitations of their study. First, although pulse pressure was assessed during the trial, central BP and aortic stiffness were not, “precluding a more thorough assessment of the antihypertensive properties of LCZ696,” they note.
Second, although the absence of angioedema in this study “is positive,” this “needs to be confirmed, particularly in black patients, because angioedema was more frequently reported by black patients” in the OCTAVE trial . Only 8% of patients in the current trial of LCZ696 were black, they note.
Future studies should identify hypertensive populations that would most benefit from LCZ696, with the current findings indicating it could be of benefit in a range of cardiovascular diseases, particularly in disorders in which vasoconstriction, volume overload, and neurohormonal activation play a part in pathophysiology, they conclude.
The study of LCZ696 was funded by Novartis. Ruilope has been an adviser and speaker for Novartis. Disclosures for the coauthors are listed in the paper. Waeber and Feihl report no conflicts of interest.
[ CLOSE WINDOW ]
- Ruilope LM, Dukat A, Böhm M, et al. Blood-pressure reduction with LCZ696, a novel, dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomized, double-blind, placebo-controlled, active comparator study. Lancet 2010; DOI:10.1016/S0140-6736(09)61966-8. Available at: http://www.thelancet.com.
- Waeber B and Feihl F. Blood-pressure reduction with LCZ696. Lancet 2010; DOI:10.1016/S0140-6736(10)60363-7. Available at: http://www.thelancet.com.
- Kostis JB, Packer M, Black HR, et al. Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs Enalapril (OCTAVE) trial. Am J Hypertens 2004; 17:103-111. Abstract
The Mayo Clinic, 2010 – More than two decades ago, before it was possible to measure DNA changes, Mayo Clinic scientists began to investigate the genetic basis of high blood pressure, AKA hypertension. Two decades later, they continue their own studies and also play a crucial role in a large network of investigations funded by the National Institutes of Health. The studies have uncovered that, rather than a single gene, your blood pressure is influenced by the interaction of multiple genes and environments. It is a complex field that requires huge, collaborative studies to find out who’s at risk for hypertension, who’s at risk for its complications, and which drug therapies best suit each patient.
A: You can thank your parents if you are playing genetic jeopardy with this “silent killer.”
Q: What is High Blood Pressure?
Stephen Turner, M.D.
The impact of hypertension on our health system is easy to grasp once you know that it is the most common reason an adult seeks health care. It is enormous—and it’s expanding along with our national girth. One of every three Americans has hypertension, but 30 percent of them don’t know it. That’s why it’s called the silent killer—many people don’t know they have it until it’s too late. It’s the single most important risk factor for stroke, the most common risk factor for heart disease and a leading cause of kidney disease.
Two decades ago Stephen Turner, M.D., was frustrated by the inability to predict who was going to get or experience its complications, and by not being able to prescribe the most effective medication for patients once they were diagnosed. When early clinical studies showed that inheritance plays a role in the quagmire of causes, Dr. Turner dedicated his career to understanding the genetic basis of essential hypertension (high blood pressure with no identifiable cause). He is now an internationally recognized expert in a field that includes nephrologists, cardiologists, endocrinologists, radiologists, geneticists and epidemiologists.
An Early and Enduring Endeavor in Clinical Research
In 1983, Dr. Turner, along with other Mayo Clinic investigators launched a multidisciplinary research collaboration between the University of Michigan and Mayo Clinic, called the Rochester Family Heart Study, which continues to this day.
The following year, Dr. Turner was awarded one of the first grants to examine the relationship between genetic variation and common disease. The study investigated the genetic basis of abnormalities in sodium transport in humans in an effort to uncover their role in the development and persistence of high blood pressure — a relevant study in light of the high salt diet common to modern societies. Resulting publications established that knowledge about the genetic effects on the ability of red cells to transport sodium holds one of the keys to predicting the probability of having hypertension, independent of the effects of gender, age and body weight.
Under the Rochester Family Heart Study, Dr. Turner and colleagues studied 600 families who had children in Rochester schools.
Bruce Johnson, Ph.D.
“We discovered that blood pressure was more similar between people who share genes than those who do not,” says Dr. Turner. “All of our work at that time was based on clinical similarities and differences. The next step was to sort out how much of the similarities were due to genetics, and how much to living together in similar environments. However, the technology was not yet available to measure DNA variation in large groups of subjects.”
Fortunately, the group had the foresight to save the blood samples from the studies. With today’s biotechnology, the whole genomes from the 4,000 study participants can be amplified to produce large amounts of genetic material, much of it from multiple generations. The genetic data is now being correlated with 20 years of blood pressure and other clinical and laboratory measurements—a unique and valuable resource for follow-up studies in genetic variation.
Dr. Turner’s mentorship has led to many studies including those by physiologist Bruce Johnson, Ph.D. and his colleagues Michael Joyner, M.D., Niki Dietz, M.D., Eric Snyder, M.D., and Thomas Olson, M.D. Dr. Johnson’s group examined cardiovascular responses to exercise in a group of young adults selected from the Rochester Family Heart Study.
“We had the participants exercise at two work intensities—a low level of exercise where no catecholamines are released, and heavy exercise where substantial amounts of epinephrine and norepinephrine are released,” says Dr. Johnson. “Catecholamines stimulate adrenergic receptors which play a role in the cardiovascular adaptations to exercise, including the regulation of blood pressure.”
Previous work by Dr. Turner and colleagues has found common variations in the genes that encode for the adrenergic receptors. In addition, this genetic variation caused some receptors to become less sensitive to catecholamine stimulation.
“This may help explain the range of cardiovascular responses observed in healthy adults,” says Dr. Johnson. “And it may also provide insight into which patients may benefit from exercise training as an intervention to treat hypertension.”
Gary Schwartz, M.D.
Another study that is putting the data to good use is an investigation into the genetics of low-renin hypertension initiated by Mayo nephrologist and hypertension specialist, Gary Schwartz, M.D., in 2003. It is the first study to identify a subset of people whose high blood pressure is based on the responsiveness of an important physiological system. The renin angiotensin system is a hormonal system involved in kidney function and blood pressure regulation. Blood pressure in people who have low activity of that hormonal system changes in response to salt in the diet.
“About 25 percent of people with essential hypertension have low-renin hypertension,” explains Dr. Schwartz. “We are identifying this subgroup of people in the Rochester Family Heart Study to investigate their genetic factors. That may help us identify those who will respond to dietary salt restriction or particular drugs. We hope that by studying a smaller, more homogenous subgroup, the genetic signal will be easier to find.”
Casting a Wider Net
Although Mayo Clinic initiated the low-renin study, the investigators were happy to share their protocol with long-time collaborators at Emory University, Atlanta, Ga., and pool results. As researchers delve into the complex mechanisms that regulate blood pressure, even within one individual, they are beginning to understand just how diverse the set of causes are for hypertension. For example, Dr. Schwartz has published studies demonstrating that a person’s blood pressure fluctuates considerably with time and activity. Given surprising new findings, such as that some people have a rise in blood pressure during sleep, the task of the researchers, the degree of collaboration, and the size of study samples needed to identify genetic influence, are all daunting.
To address the need, the National Institutes of Health initiated an extensive, collaborative program to identify genes that contribute to hypertension by studying family patterns. The Family Blood Pressure Program (FBPP) (http://www.sph.uth.tmc.edu/hgc/fbpp/) has been continually funded since 1995 and is now providing a publicly available resource to facilitate research into hypertension, its complications and responses to treatment.
FBPP incorporates four networks throughout the United States, including Hawaii. Each network includes multiple research sites and each site includes investigators from multiple disciplines. About 60,000 people, including multiple ethnic and racial groups, including Whites, Blacks, Hispanics, Asians and Pacific Islanders, are enrolled in a variety of FBPP studies.
“A high degree of collaboration is critical to enroll the huge numbers and variety of ethnic and racial groups necessary to characterize the genes that contribute to hypertension,” says Dr. Turner. “Blacks, for example, have severe high blood pressure three times as often as whites, get complications more often, and have different responses to drugs. We want to know if that is a result of genetic variation as we see in some other diseases.”
Mayo Clinic plays a critical role in the network to which it belongs—the Genetic Epidemiology Network of Arteriopathy (GENOA). In addition to recruiting 5,000 study participants, Mayo provides the network’s biochemistry laboratory. Dr. Turner is the primary investigator for GENOA at Mayo.
GENOA has completed sampling and extensive genetic typing on thousands of sibling pairs, including Blacks from Jackson, Miss., Hispanics from Starr County, Tex. and Whites from Rochester, Minn. In 1999, Dr. Turner was one of the GENOA investigators who published the first genome-wide scan for genes influencing blood pressure in the Rochester Family Heart Study and one of the first follow-up studies, which identified chromosome 2.
Heart, Brain and Kidney Complications: Who’s at Risk?
Iftikhar Kullo, M.D.
It is important to identify who, among those who have high blood pressure, are at risk of complications that cause heart, brain or kidney disease. The NIH is funding ancillary studies to map the genes that affect whether or not a person gets these complications.
With many DNA samples already measured, Dr. Turner’s group now uses an analytical pattern, called linkage analysis, to hunt down the genes by tracing patterns of heredity in families who have these various complications. This effort was buoyed, in 1998, by the addition of cardiologist Iftikhar Kullo, M.D., to the group. Dr. Kullo investigates novel methods of predicting cardiovascular disease, including genetic factors.
A 2001 GENOA study using genome-wide linkage analysis turned up evidence that there are multiple regions that influence variation in specific lipid levels that are associated with coronary heart disease (Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:971.)
“We looked at coronary arteries of study participants, did genome-wide linkage analyses of 11 lipid traits and compared results,” says Dr. Turner. “Mayo is a leader in the measurement of coronary artery calcification. We can now get high resolution CT scans to objectively quantify calcification in the heart. We hope that identification of genes that influence lipid metabolism will lead to a better understanding of what causes coronary artery disease and lead to the development of new therapies for the treatment and prevention of disease.”
Dr. Kullo was first author on a recently published linkage analysis study that identified a genomic region on chromosome 1, which exhibits pleiotropic (shared) genetic effects on several lipid traits (HDL cholesterol, triglycerides, and LDL particle size) in related people who have high blood pressure (Am J Hypertension 2005 Aug; 18(8):1084-90).
“How this genetic region influences the correlation of these lipid traits may influence the susceptibility of people who have high blood pressure to develop chronic heart disease,” says Dr. Kullo. “It is one more piece of this very large puzzle of trying to predict who is going to get the complication of cardiovascular disease from hypertension.”
Magnetic Resonance Imaging (MRI) is an important tool in a separate NIH-funded collaborative study that the Turner group is participating in called Genetics of Microangiopathic Brain Injury (GMBI). The study is revealing a remarkably strong genetic risk for cognitive impairment caused by damage of tiny vessels in the brain.
“We are looking at the genetics of leukoaraiosis, a condition that leads to changes in the subcortical white matter of the brain,” says Dr. Turner. “The white matter is supplied by arteries that penetrate deep into the brain. They have little collateral circulation and are particularly sensitive to small blood vessel damage. We’re using MRI to measure this brain shrinkage and what we found is that the heritability of brain shrinkage due to white matter change is remarkably strong. Heritability is measured on a scale of zero to one, one being totally genetic and its heritability is 0.7. The reason it’s clinically important is an increasing appreciation of the role of vascular disease in cognitive loss.”
The influence of Genomics on Hypertension
The kidneys are another target organ for complications from hypertension and one of the biggest problems for patients with the condition is ending up on dialysis. The NIH recently funded a new study to investigate chronic kidney disease and the Turner group is gearing up to lead the effort in Rochester and Jackson, MS.
Taking the Trial and Error out of Drug Therapies
Dr. Turner’s group is one of the first to study inheritance and drug response in the treatment of hypertension. Their research responds to the frustration of patients and their physicians in trying to identify the drug that is most likely to produce the best response in each patient. The field of pharmacogenomics tries to identify the genetic basis for why some people respond better to a given drug therapy than others.
“More than a half dozen drugs are available to treat high blood pressure but we have no clue how the drug will affect the patient until we try it,” says Dr. Turner. “The aim of genetic research is to replace the trial and error process with genetic tests that can identify predictors of response so that we can choose the best drug for a given patient.”
Dr. Turner’s group has undertaken two large studies in pharmacogenetics, both in collaboration with Emory University in order to conduct parallel studies in Blacks. They come under the umbrella of The Genetic Epidemiology of Responses to Anti-Hypertensives (GERA) study, a separate NIH-funded study.
The studies involved carefully monitoring the blood pressure of study participants who were taken off their usual medication and all given the same drug. The investigators searched for frequency in particular genes by screening participants for 50 candidate genes thought to affect blood pressure, and comparing results with the phenotype—the way they responded to the drug.
Publications resulting from the study of the diuretic drug hydrochlorothiazide, have shown that polymorphisms in six genes—the beta-3 subunit of G-proteins, angiotensin converting enzyme (ACE), angiotensinogen, angiotensin II receptor, endothelial nitric oxide synthase, and a protein kinese regulator of sodium transport by the kidney—all make contributions to blood pressure response as a result of treatment with the drug.
Polymorphisms are common sequence variations, which are present in the population at a frequency of greater than one percent. They are the result of insertion or deletion of one, two or several bases. (There are four bases: adenine (A), thymine (T), cytosine (C) and guanine (G), which are the building blocks of DNA.) A set of these tiny variations help to create your unique DNA pattern. Polymorphisms are important because they can alter the structure and function of the gene product, which can lead to disease or affect response to a drug. By conducting genome-wide association studies using polymorphisms, geneticists further the understanding of disease processes. The goal is to use the knowledge to develop genetic-based diagnostics and therapies.
In another study, Dr. Turner’s group found evidence of a gender specific effect on the blood pressure responses to the drug hydrochlorothiazide from a polymorphism in the gene that encodes angiotensin converting enzyme (ACE).
“Disease genes are logical candidates to influence the pharmacodynamics of antihypertensive drug response, and drug response genes are logical candidates to influence the development and progression of hypertension,” explains Dr. Turner. “Each of these studies helps us to better understand the genetic basis for drug response to hypertension.”
The Sobering Conclusion
There are many causes of essential hypertension. We know that obesity, diabetes, high cholesterol, inactivity and tobacco use are contributing factors. But how your body reacts to these environmental influences depends on the unique pattern of your genome. There is no single gene that is responsible for hypertension. The sobering conclusion of the last decade of research in this field is that it is a minefield of perplexing variations that has made identification of specific genes involved in hypertension causation a laborious and challenging task.
“Everyone is genetically unique so, to find these differences among people, the sample sizes need to be enormous,” says Dr. Schwartz. “The genetic contribution is made by multiple genes with each of them having a very small effect. The interaction with gene environment and gene-to-gene interaction makes it much more difficult to ferret out gene variation than we originally thought.”
It is becoming untenable for one institution to conduct meaningful genetics research into common conditions such as hypertension. Instead, broad, collaborative networks across multiple disciplines and institutions, such as FBPP, are the new paradigm for genetics research.
The good news is that you only have to collect DNA from a study participant once—their genetic data will be available for researchers indefinitely. Subsequent studies involving only clinical follow-up to determine the development of complications, such as heart attack or stroke, and to monitor the blood pressure and treatment changes, hold the promise of substantially increasing our understanding of the mechanisms that control blood pressure.
“We will be able to predict a predisposition to early death in the group of people that we have studied,” says Dr. Turner. “Moreover, in the coming years, as investigators collect and analyze large amounts of genetic information, we have the potential to revolutionize approaches to the prevention, evaluation, and treatment of hypertension and its associated target organ diseases.”