Health for life

Resveratrol, a compound found commonly in grape skins and red wine, has been shown to have several beneficial effects on human health, including cardiovascular health and stroke prevention. Now, a University of Missouri researcher has discovered that the compound can make prostate tumor cells more susceptible to radiation treatment, increasing the chances of a full recovery from all types of prostate cancer, including aggressive tumors.


"Other studies have noted that resveratrol made tumor cells more susceptible to chemotherapy, and we wanted to see if it had the same effect for radiation therapy," said Michael Nicholl, an assistant professor of surgical oncology in the MU School of Medicine. "We found that when exposed to the compound, the tumor cells were more susceptible to radiation treatment, but that the effect was greater than just treating with both compounds separately."

Prostate tumor cells contain very low levels of two proteins, perforin and granzyme B, which can function together to kill cells. However, both proteins need to be highly "expressed" to kill tumor cells. In his study, when Nicholl introduced resveratrol into the prostate tumor cells, the activity of the two proteins increased greatly. Following radiation treatment, Nicholl found that up to 97 percent of the tumor cells died, which is a much higher percentage than treatment with radiation alone.

"It is critical that both proteins, perforin and granzyme B, are present in order to kill the tumor cells, and we found that the resveratrol helped to increase their activity in prostate tumor cells," Nicholl said. "Following the resveratrol-radiation treatment, we realized that we were able to kill many more tumor cells when compared with treating the tumor with radiation alone. Its important to note that this killed all types of prostate tumor cells, including aggressive tumor cells."

Resveratrol is present in grape skins and red wine and available over-the-counter in many health food sections at grocery stores. However, the dosage needed to have an effect on tumor cells is so great that many people would experience uncomfortable side effects.

"We dont need a large dose at the site of the tumor, but the body processes this compound so efficiently that a person needs to ingest a lot of resveratrol to make sure enough of it ends up at the tumor site. Because of that challenge, we have to look at different delivery methods for this compound to be effective," Nicholl said. "Its very attractive as a therapeutic agent since it is a natural compound and something that most of us have consumed in our lifetimes."

Nicholl said that the next step would be to test the procedure in an animal model before any clinical trials can be initiated. Nicholls studies were published in the Journal of Andrology and Cancer Science. The early-stage results of this research are promising. If additional studies, including animal studies, are successful within the next few years, MU officials will request authority from the federal government to begin human drug development (this is commonly erred to as the "investigative new drug" status). After this status has been granted, researchers may conduct human clinical trials with the hope of developing new treatments for cancer.

Researchers may soon be able to add yet another item to the list of exercises well-documented health benefits: A preliminary study suggests that when cancer survivors exercise for several weeks after they finish chemotherapy, their immune systems remodel themselves to become more effective, potentially fending off future incidents of cancer. The finding may help explain why exercise can significantly reduce the chances of secondary cancers in survivors or reduce the chances of cancer altogether in people who have never had the disease.

Laura Bilek, Graham Sharp, and Geoffrey Thiele, all of the University of Nebraska Medical Center, and Daniel Shackelford, Colin Quinn, and Carole Schneider, all of Rocky Mountain Cancer Rehabilitation Institute, analyzed T cells in the blood of cancer survivors before and after a 12-week exercise program. They found that a significant portion of these immune cells converted from a senescent form, which isnt as effective at combating disease, to a naïve form, ready to fight cancer and infections.

Their poster presentation entitled, "Effect of Exercise on T Cells in Cancer Survivors," will be discussed at The Integrative Biology of Exercise VI meeting being held October 10-13 at the Westin Westminster Hotel in Westminster, CO. This popular meeting is a collaborative effort between the American Physiological Society, the American College of Sports Medicine and the Canadian Society for Exercise Physiology. The conference is supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, an institute of the National Institutes of Health, GlaxoSmithKline, Inc., Stealth Peptides, Inc., and Seahorse Biosciences.

Exercise and Immunity

Study leader Laura Bilek explains that previous research had turned up a variety of positive associations between exercise and cancer -- notably, that exercise can reduce the risk of getting initial incidence of several different types of cancers, can often improve prognosis in cancer patients, and can reduce the risk of recurrence and secondary cancers survivors of some types of cancers. However, the mechanism behind these phenomena has been unknown.

Since other research has suggested that exercise can remodel the immune system, making it more effective at fighting disease in general, Bilek and her colleagues decided to investigate how exercise affects the immune system of cancer patients. Working with a group of 16 cancer survivors, all but one of who recently finished chemotherapy cancer treatment, the researchers focused on T cells, a type of immune cell that attacks a variety of infectious agents as well as cancer cells. After chemotherapy, previous research had shown that the majority of T cells become senescent, with a decreased ability to fight infections and cancers. However, Bilek says, rebuilding the population of responsive (naïve) T cells is critical for regaining normal immune function and cancer-fighting ability.

The researchers first took blood samples from each of the volunteers to examine how many senescent and naïve T cells each had. Then, these study subjects were all enrolled into 12-week exercise programs at the Rocky Mountain Cancer Rehabilitation Institute. All programs were individualized for the study participants, incorporating elements of cardiovascular exercise, strength and endurance training, and exercises for flexibility, posture, and balance, with extra emphasis in areas where participants were weak.

After the 12-week program, the researchers drew a second blood sample from each volunteer and ran the same T cell analysis.

Another Reason to Work Out Results showed that the ratio of senescent to naïve T cells changed favorably in the majority of participants, with most of the study subjects regaining greater numbers of the naïve variety.

"What were suggesting is that with exercise, you might be getting rid of T cells that arent helpful and making room for T cells that might be helpful," Bilek says.

She adds that this finding highlights the importance of exercise for all, including those with cancer and cancer survivors. These two populations might benefit especially from the heightened "cancer surveillance" -- the ability of the immune system to seek out and destroy budding cancers -- that this study suggests exercise brings, Bilek explains.

"Theres a litany of positive benefits from exercise," Bilek says. "If exercise indeed strengthens the immune system and potentially improves cancer surveillance, its one more thing we should educate patients about as a reason they should schedule regular activity throughout their day and make it a priority in their lives."

If youre having difficulty keeping your resolution to exercise 30 minutes a day, 5-days-a-week, then youre going to like this study.

Researches put young men through some very brief, but strenuous, workouts and found their sensitivity to insulin (and so their blood sugar levels) improved:

Extremely Short Duration High Intensity Interval Training Substantially Improves Insulin Action In Young Healthy Males, BMC Endocrine Disorders, January 2009

A total of 16 men, average age 21, underwent 6 sessions of exercise over 14 days.

A session of exercise consisted of:

• 30 seconds of cycling as fast as possible
  
• 4 minutes of rest
  
• The above repeated 4 to 6 times

An exercise session lasted 17 to 26 minutes, but only 2 to 3 minutes of that was actual exercise.

Compared to before training (baseline):

• Postprandial glucose levels declined 12% (measured by AUC: Area Under the Curve)
  
• Postprandial insulin levels declined 37% (AUC)
  
• Postprandial free fatty acid levels declined 26% (AUC)
  
• Insulin sensitivity improved 23% (measured by Cederholm index)
  
• Aerobic cycling performance improved 6%

The authors concluded:

"The efficacy of a high intensity exercise protocol, involving only ~250 kcal of work each week, to substantially improve insulin action in young sedentary subjects is remarkable. This novel time-efficient training paradigm can be used as a strategy to reduce metabolic risk factors in young and middle aged sedentary populations who otherwise would not adhere to time consuming traditional aerobic exercise regimes."

________