Modified Collagen Could Yield Important Medical Applications

Collagen often pops up in beauty products and supermodel lips. But by mating collagen with a molecular hitchhiker, materials scientists at Johns Hopkins hope to create some important medical advances. The researchers have found a simple new way to modify collagen, paving the way for better infection-fighting bandages and a treatment to block the formation of unwanted scar tissue. In addition, tissue engineers may be able to use modified collagen in the lab to help control the formation of tiny new blood vessels that can be used to promote the integration of tissue implants in patients.

The research focuses on the human body's most common protein. Collagen promotes blood clotting and provides the sponge-like scaffold upon which cells build nerves, bones and skin. Because it is non-toxic, dissolves naturally over time and rarely triggers rejection, collagen is commonly used in cosmetics, drug delivery systems and biocompatible coatings.

"This new modified collagen opens the door to new medical treatments, because it is easy to attach bioactive agents to certain peptides," says Michael (Seungju) Yu, an assistant professor in the Department of Materials Science and Engineering of Johns Hopkins University.

"When the peptides bind with collagen, these attached agents can dramatically change the way collagen behaves in the body. For example, collagen normally attracts cells to close up a wound and form scar tissue, which can lead to dangerous clots inside a blood vessel or at certain injury sites, where scar tissue can interfere with the formation of new nerve connections. However, in our lab experiments, the modified collagen followed a different course. It actually repelled cells instead of attracting them. When we added human cells to a lab dish, the cells migrated toward an untreated collagen film but avoided the modified collagen sample. This form of collagen could stop the formation of blood clots and scar tissue", Yu explains.

Still other medical uses are possible. A growth factor joined to collagen could encourage new cells to multiply. An antibiotic attached to collagen could help a collagen-based bandage fight infections over a long period of time. Modified collagen could also release helpful medications while serving as a coating for surgical tools and implants.

"With this process," Yu said, "we can make the collagen that's already found in the human body behave in new ways, including some ways that are not found in nature. Modified collagen can give us great new tool for treating injuries and illnesses."

Yu's research is supported by grants from the National Science Foundation and the National Institutes of Health.


Dual-Drug Therapy Targets Colon Cancer Gene

Johns Hopkins Kimmel Cancer Center scientists have found that interferon, used for 30 years to treat blood cancers, multiple sclerosis and hepatitis, selectively kills colon cancer cells when combined with another standard chemotherapy agent. New studies suggest that the combination tactic, which targets a common gene pathway in colon cancer cells, could be more potent than either drug alone, and has fewer side effects.

"Instead of killing a tree by chopping it down, this approach focuses on cutting off the diseased branch, leaving the rest of the tree relatively unscathed," says Betsy Barnes, Ph.D., assistant professor of oncology and lead researcher.

By itself, interferon's cell-killing activity is non-specific in targeting a variety of cells and cell-based gene activity, causing serious side effects such as heart failure and low blood counts, in addition to killing cancer cells. But scientists found one factor in interferon's makeup that could have cancer-killing qualities, but with fewer side effects since it activates fewer genes.

The team found that IRF5 (Interferon Regulatory Factor-5), which works as a tumor suppressor to halt cancer cell growth, is turned off by many cancers, but low levels of the suppressor protein are found in most colon cancers. To boost IRF5 levels, the investigators combined interferon with a chemotherapy drug called irinotecan (CPT-11), a drug that damages DNA in rapidly dividing cells, rendering them unable to divide.

To demonstrate their theory that IRF5 is a key ingredient in the dual-drug therapy, the scientists tested various combinations of the drugs in colon cancer cell lines, with or without IRF5. Irinotecan alone causes 65 percent cell death in lines with IRF5 proteins present. Knock out IRF5 proteins and cell deaths drop to 37 percent. When the investigators combined irinotecan and interferon, more than 80 percent of colon cancer cells with IRF5 proteins died.

"Not only does the combination of these drugs involve fewer gene activations, it may allow use of smaller amounts of both drugs and limit side effects," says Betsy Barnes, Ph.D., assistant professor of oncology and lead researcher.

It is not clear whether the combination therapy would work in other cancers, since IRF5 is absent in a number of blood cancers. But since colon cancer is the third deadliest cancer in the United States, Barnes and her team will conduct further tests in genetically modified mice and potentially create a new strategy to treat the disease.

Colon cancer strikes more than 100,000 people in the United States annually and kills more than 56,000.

Funding for this research was provided by the American Cancer Society and a Flight Attendant Medical Research Institute Young Clinical Scientist Award.

On the web: www.hopkinskimmelcancercenter.org

A Friendly Reminder for HIV Patients

A pocket-size device giving electronic-voice reminders to "take your medicine" proves to be a success for people living with HIV whose memory is slightly impaired by the virus.

Researchers at Johns Hopkins report that the device, dubbed "Jerry" by most users, is a portable gadget programmed to ease the task of taking medicines in multiple doses every day on time. HIV-infected patients, particularly those suffering from mild memory loss from the disease, benefit highly from Jerry's friendly reminders, according to a study published in the Sept. 15 issue of the journal Clinical Infectious Diseases.

Like an alarm clock, Jerry, more properly known as Disease Management Assistance System (DMAS), flashes a light and verbally tells the patient the exact dosage and medication to take at the correct time. DMAS is rechargeable and weighs about as much as a cell phone. Its computer programming keeps track of the patient's compliance, allowing the doctor to download and print a report for monitoring the patient's adherence to the medication schedule.

"One of the biggest reasons HIV patients cite for not taking their medication is just plain forgetfulness," says Adriana Andrade, M.D., M.P.H., assistant professor at Division of Infectious Diseases. "We thought a verbal reminder would be the best possible solution."

"On average, HIV-infected, treatment-naïve patients today take roughly two pills once a day, a significant decrease from a few years ago, when patients had to juggle dozens of medications per week," says Andrade. "But with all the regimens, patients must adhere to their medication faithfully because the virus easily develops a resistance, more so than most infectious diseases."

Fifty-eight of 64 patients completed the four-month study. Half of the patients were given a Jerry device and attended adherence counseling sessions, while the other half received only counseling. Those with Jerry took their medication 80 percent of the time, while those without did so only 65 percent of the time.

"Hopefully, other devices like the DMAS will be further evaluated in similar studies, while incorporating the recent technologies of the two-way pager, cell phones or special alarm clocks," says Andrade.

The DMAS used in this study was manufactured by Adherence Technologies.

Funding was provided by grants from the National Institutes of Health, the Johns Hopkins Hospital General Clinical Research Center and Merck Laboratories.

On the web: www.hopkins-aids.edu


Hopkins Center for Integrative Medicine Offers News Alternative Programs for Patients

Johns Hopkins will now offer selected, evidence-based alternative medicine services, including acupuncture, a mind-body program and a consultation service, through the Johns Hopkins Center for Integrative Medicine (CIM). The program is designed to fill a void for those who wish to explore proven alternative therapies not offered by conventional health care providers.

"There is a high degree of interest in alternative and integrative medicine among Americans, who alone spend more than $27 billion a year on this type of health care," says Adrian Dobs, M.D., director of CIM and the Hopkins Clinical Trials Unit. "We developed CIM to scientifically test and review alternative approaches to medicine in order to ascertain what is beneficial, effective and safe and what is not. This is why we can now enthusiastically offer acupuncture and mind-body programs, which have been found effective for many patients."

CIM was established five years ago with a $7.8 million grant from the National Institutes of Health and a mandate to study alternative therapies for cancer with the same scientific rigor Hopkins employs in its other clinical trials. A grant from the Sidney Kimmel Foundation for Cancer Research is funding a new, complementary and integrative medicine program for oncology patients. For example, increasingly, research is showing that acupuncture is beneficial for relieving certain types of pain and side effects of some cancer treatments. The 1997 NIH Consensus Statement on Acupuncture supports its use for combating nausea, vomiting and fatigue from chemotherapy and radiation therapy. The World Health Organization recognizes that acupuncture may help more than 140 different medical problems.

Mind-body courses of varying lengths are designed to help patients cope with their emotional responses to cancer, as well the symptoms of the disease. Patients are taught how to use guided imagery, relaxation, breathing techniques and meditation to enhance treatment and control pain.

"Our programs focus on improving coping skills and developing a personal plan to enhance the effectiveness of these patients' chemotherapy and radiation treatments while minimizing the side effects," says Dobs.

Also offered is a consulting service to give patients and their providers help in sorting through various complementary therapies to determine which approaches work best for them as well as to ensure that any herbal or nontraditional drugs being taken are compatible with other medical drugs.


PSA Remains Best Indicator of Prostate Cancer Progression

Despite recent claims by some urologists that measuring the blood protein prostate-specific antigen (PSA) may not be effective in predicting risk of prostate cancer, a Johns Hopkins study of more than 2,000 men confirms that
PSA remains the best measure of the likelihood of cancer recurrence after surgery.

Results of the study demonstrated that men with high PSA levels prior to prostate removal surgery were significantly more likely to have advanced clinical stages of cancer, evidence of higher grade cancers in surgically removed
tissue, and spread of cancer cells beyond the prostate. In addition, increasing PSA was significantly associated with increased risk of cancer recurrence after surgery, even in men with lower PSA levels prior to surgery.

PSA is a protein produced by cells of the prostate gland. Prostate cancer can increase PSA, so the higher the PSA level, the greater the likelihood that a patient has prostate cancer. Also, higher PSA values generally reflect larger, more aggressive cancers.

For the study, 2,312 men who had prostate removal surgery at Johns Hopkins between 1992 and 2004. All operations were performed by Patrick C. Walsh, M.D., professor
and former chair of urology.

"From our study and others, it is clear that a single PSA value is an extremely useful measure of a patient's risk of progression after surgery," says Dr. Walsh. "However, looking at how quickly the PSA increases over time is likely to be even more informative than a single value."

The study was supported by the National Institutes of Health, the Department of Defense and the American Foundation for Urological Disease/American Urological Association.

Hopkins Physicians Conduct Study in Sahara Desert

Brian Krabak, M.D., and Brandee Waite, M.D., sports medicine and rehabilitation specialists from the Johns Hopkins Department of Orthopedics will once more lead the medical team of a race across the desert.

Chosen in March of this year to lead the medical team at the Gobi Desert race organized by RacingThePlanet®, the physicians will now face a new challenge. They not only will lead an international team of volunteers and medical doctors, but also use the opportunity to conduct a study on how highly demanded athletes behave during the race.

"We will measure from heart rate to perspiration and determine the limits of these elite athletes," says Dr. Krabak.

Again, as Dr. Waite says, one of the biggest challenges will be to make the tough decision of whether an injured athlete should compete and risk further injury; not a simple decision in the face of athletes' "burning desire to continue".

Part of the 4 Deserts™ race (Atacama in Chile, Gobi in China, Sahara in Egypt and Artarctica) the race now shifts to Egypt with a 250 kilometer race planned across the hottest place on Earth. The third leg of the 4 Deserts™ series, will take place September 25th – October 1st in the great Sahara Desert of Egypt.

The race will feature 100 competitors from more than 20 nations around the world with equal numbers coming from Asia, North America and Europe. The Sahara Race is a seven-day competition, divided into six-stages. Beginning on the morning of September 25th, competitors will have to make their way through multiple checkpoints until reaching five campsites established daily. Each stage is roughly a marathon (42 kilometers in length) but there is also one 80 kilometer stage held over two days during which competitors race through the night guided by bright green glow sticks. Only a ration of water and a place in a tent is provided daily. Competitors must carry all their own food and gear for the duration of the race which adds to the immense effort of making it to the finishing line.

The race will be in a pristine and little traveled area of the secluded Sahara Desert in Egypt. Competitors will follow a course from the Farafra Oasis to the Bahariya Oasis crossing the spectacular Black and White Deserts. In the White Desert, often referred to as the "ghost town," natural chalk sculptures formed over thousands of years by wind erosion rise up out of the desert to provide spectacular scenery. The terrain throughout the race will vary from sand dunes to dried river beds to rocky plateaus. Competitors will also be treated to several natural sulfur springs along the way before making their way back to Cairo to finish at the ancient Giza Pyramids.

The field will be exceptionally diverse with individuals ranging in age from 21-year-old Han Jang of Korea to 73-year-old Laurie Brophy of Wales in the United Kingdom. Also among the competitors will be Kyung Tae Song from Korea, who is blind and will enter the race aided by his guide. Competitors represent many professions including investment banking, law, venture capital, medicine and academia, among others.

Johns Hopkins Medicine International will keep a journal at the www.jhintl.net website, as well as in the Korean ( www.hopkinskorea.com) and Spanish ( www.saludhopkins.com) websites.

There's also the possibility of a video journal, as the Johns Hopkins Office of Telemedicine will make satellite transmission available from the different checkpoints of the race.


Former patient of Johns Hopkins Medicine International Writes a Book that Praises the Vasculitis Center

Laura Becker, former patient of Johns Hopkins Medicine International and the Johns Hopkins Vasculitis Center visited the hospital on the first week of September to share her new book "Caminar com el Alma" ("Walking with the Soul" in English) with doctors and the staff of Johns Hopkins Medicine International.

The book, a summary of her journey through managing a life of pain, physical (she was diagnosed with vasculitis, an autoimmune disease, in 1997), and emotional (she had just gone through a divorce) also describes many alternative treatments she tested.

Laura also praises the Johns Hopkins Hospital, where she was treated from 1998 to 2002, the Vasculitis Center (which had been inaugurated a short time after she was diagnosed), former Hopkins physician Dr. Hossein Nousari and the whole staff of the Vasculitis Center and from the Office of International Services (today Johns Hopkins Medicine International).

"Although the book is written in Spanish", says Becker, "I am sure people will be interested to know about my story. I met many people whose Spanish is the first or second language at Hopkins. Maybe I'll have it translated to English soon."

Copies of the book were donated to the Johns Hopkins archives and Johns Hopkins Medicine International.