Topic: Research

The Immune System

Monday, October 31st, 2011 by American Senior Fitness Association   View This Issue of Experience!

Cancer patients, as well as many others with suppressed immune systems, often have extra trouble fighting off life-threatening infections. Now there is new hope for improving the immune response of these patients, thanks to recent research findings described in this University of Florida news release:

University of Florida researchers have identified two key steps required to activate the body’s innate immune system, its first line of defense against infection.

The discoveries offer insight into why some trauma patients survive their initial injuries but die from seemingly less serious causes soon afterward.

“We’re able to bring them through the trauma with an 80 percent or higher success rate, and then after a few weeks in the hospital they succumb to secondary infections, like pneumonia and urinary tract infections,” said Matthew Delano, M.D., Ph.D., a UF surgical resident.

Researchers, including Delano and Lyle Moldawer, Ph.D., a professor and vice chairman of research in UF’s department of surgery, say understanding the chemical signals that help direct immunity may lead to improved therapies for patients with suppressed immune systems, such as those with critical injuries, HIV and cancer, who need extra help fighting infections.

In an article published in the July issue of the Journal of Experimental Medicine, the scientists describe how B cells, a specific type of white blood cell, release a chemical called CXCL10 to trigger inflammation and the deployment of cells designed to fight any pathogens or foreign matter.

Previously, B cells were thought to be involved only in the body’s adaptive immune response, which recognizes invaders, proliferates and responds more effectively to subsequent encounters. The innate immune response is more generic and wasn’t thought to convey any long-lasting immunity to specific threats.

“What we showed, which is actually quite revolutionary, is that B cells modulate the early innate immune response,” Moldawer said.

A review of the paper appeared in the August issue of Nature Reviews Immunology.

In a separate study published in the July 15 issue of the Journal of Immunology, researchers identified a protein called stromal cell-derived factor 1, known as SDF-1, that directs the release of neutrophils, another type of white blood cell, from the bone marrow to the site of infection. Neutrophils will attack any pathogen and are one of the body’s first weapons used to fight infection.

Bone marrow usually makes SDF-1, but stops production when an infection begins. Tissues at the infection site start making the protein instead, and neutrophils migrate to the areas with the highest concentrations of SDF-1. Once there, they battle the invading pathogens.

“If we block this increase (in SDF-1 in the infected area), then we don’t see a mobilization,” Moldawer said. “The neutrophils are not recruited to the site of infection and the infection can’t be controlled.”

Moldawer said SDF-1 also speeds neutrophils’ development from stem cells and increases their “bacteria-killing properties.”

The identification of SDF-1 and of CXCL10 in activating the body’s innate immune response could pave the way for medicines that stimulate innate immunity in immune-suppressed patients.

Scientists from the University of California,-Los Angeles, Yale University, Duke University Medical Center, Osaka University, Merck Research Laboratories and the University of Virginia also helped with the studies.

“The next step is to ask whether giving SDF-1 can improve outcomes in patients that have reduced numbers of inflammatory cells due to chemotherapy, malnutrition, etc.,” Moldawer said.

The researchers will ask the same question about CXCL10.

Richard Hotchkiss, M.D., a professor at Washington University School of Medicine in St. Louis, applauded the researchers’ efforts to find new approaches to fighting infection and preventing and battling sepsis. Sepsis is a serious complication of infection in which the immune system becomes overactive and disrupts normal blood flow. The condition can lead to organ failure. Hotchkiss was not involved in the research.

“Using drugs which can up- or downregulate host immunity would be a nice accompanying approach to sepsis,” he said. “Rather than just focusing on antibiotics, we should be focusing on drugs which can improve patient immunity and their ability to fight off new, secondary infections.”

The University of Florida Health Science Center – the most comprehensive academic health center in the Southeast – is dedicated to high-quality programs of education, research, patient care and public service. The Health Science Center encompasses the colleges of Dentistry, Public Health and Health Professions, Medicine, Nursing, Pharmacy and Veterinary Medicine, as well as the Veterinary Hospitals and an academic campus in Jacksonville offering graduate education programs in dentistry, medicine, nursing and pharmacy. Patient care activities, under the banner UF&Shands, are provided through teaching hospitals and a network of clinics in Gainesville and Jacksonville. The Health Science Center also has a statewide presence through satellite medical, dental and nursing clinics staffed by UF health professionals; and affiliations with community-based health-care facilities stretching from Hialeah and Miami to the Florida Panhandle.

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Short-Term Memory Loss and Alzheimer’s

Friday, September 30th, 2011 by American Senior Fitness Association   View This Issue of Experience!

A study of screening tests for Alzheimer’s disease was recently published in the Archives of General Psychiatry and discussed by MedlinePlus, a publication of the National Institutes of Health (NIH). Somewhat surprisingly, the Spanish researchers who conducted the investigation found short-term memory loss to be a stronger predictor of Alzheimer’s disease than variables known as "biomarkers" (for example, changes in the composition of cerebrospinal fluid or in brain volume).

Short-term memory loss is an important indication of mild cognitive impairment (MCI). Persons with MCI may find it difficult to recall what they did the day before, may frequently lose their train of thought, and/or may feel challenged when trying to find their way around places that are actually familiar to them. These traits may also be accompanied by depression, anxiety, or uncharacteristic irritation and aggression. MCI does not necessarily progress to the development of Alzheimer’s disease, and persons with MCI often can function in a satisfactory manner despite some minor degree of memory loss.

The study involved more than 500 subjects, as follows:

  • 116 with MCI who developed Alzheimer’s within two years;
  • 201 with MCI who did not develop Alzheimer’s;
  • 197 with no cognitive problems.
  • The methods undertaken included:

  • Conducting measures of delayed memory;
  • Analyzing cerebrospinal fluid samples collected at baseline and then annually for two years;
  • Analyzing blood samples collected at baseline for genes associated with Alzheimer’s disease;
  • Assessing brain volume and cortical thickness through the use of magnetic resonance imaging.
  • Findings included the following:

  • The presence of MCI at baseline was a stronger predictor of Alzheimer’s disease than were most of the biomarkers;
  • Two measures of delayed memory — as well as the cortical thickness of the left middle temporal lobe — were linked with a higher risk of MCI developing into Alzheimer’s disease.
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    Stroke Prevention

    Friday, September 30th, 2011 by American Senior Fitness Association   View This Issue of Experience!

    Here’s more important news on the subject of avoiding stroke: Researchers have discovered that aggressive medical therapy could help prevent stroke, perhaps even more effectively than surgery involving balloon angioplasty and stent insertion. For details, see the following news release from the University of Florida Health Science Center in Gainesville.

    To prevent a common type of stroke, intensive medical therapy could be better by itself than in combination with surgery that props open affected arteries. But it remains to be seen whether the apparent advantage will prove true over the long term.

    The findings, from a national clinical trial conducted by University of Florida researchers and colleagues, were published online in The New England Journal of Medicine on Wednesday, Sept. 7.

    Against expectations, the short-term risk of stroke and related death was twice as high in some cases for patients whose diseased arteries were widened via balloon angioplasty and stent insertion, compared with patients who received medical therapy alone. Although the 30-day risk of stroke for the stenting patients is concerning, long-term results could be more favorable, the researchers said.

    “Five years from now, who will be doing better — the patients who are being medically managed, or those who received a stent?” said study co-author Michael F. Waters, M.D., Ph.D., director of the Shands at UF Stroke Program, who along with Brian L. Hoh, M.D., the William Merz associate professor of neurological surgery in the College of Medicine, led the UF portion of the trial.

    The study will have a substantial impact on clinical practice and research, the researchers said, because it is the first randomized stroke trial to pit stenting against nonsurgical treatment for symptomatic intracranial atherosclerosis, a type of stroke caused by artery blockage in the brain. Early results clearly show that intensive medical management is key to improving health, the researchers said.

    “This study provides an answer to a longstanding question by physicians — what to do to prevent a devastating second stroke in a high-risk population. Although technological advances have brought intracranial stenting into practice, we have now learned that when tested in a large group this particular device did not lead to a better health outcome,” said Walter Koroshetz, M.D., deputy director of the NIH National Institute of Neurological Disorders and Stroke, which funded the clinical trial.
    Every 40 seconds, someone in the U.S. has a stroke. Stroke is the fourth leading cause of death and a leading cause of disability in the U.S. Almost 800,000 people a year have a new or recurring stroke, according to the American Heart Association. With higher than average rates of stroke and related deaths, parts of the southeastern U.S. are together termed the “Stroke Belt.”

    Patients with the type of stroke known as symptomatic intracranial atherosclerosis do not respond well to existing treatments. One-quarter of those patients have another stroke within 12 months, and the risk of additional strokes continues in subsequent years. Doctors are unsure what the best course of treatment is.
    To find out, the UF researchers and colleagues launched a clinical trial, nicknamed SAMMPRIS, at 50 sites around the country, including at the Medical University of South Carolina, the lead site. The study recruited 451 participants age 30 to 80 who had at least 70 percent narrowing in the arteries in the brain, and had experienced symptoms within the previous 30 days. UF recruited the second-highest number of patients among all sites, through its stroke program, which has been designated a Comprehensive Stroke Center by the Agency for Health Care Administration.

    Patients in one group were randomly assigned to receive intensive management involving smoking cessation and medications for blood pressure, cholesterol, diabetes and blood-clot prevention. A second group of patients had that same medical treatment but also had balloon angioplasty and stent implantation into the affected brain artery to improve blood flow.

    Almost 15 percent of patients who received stents had a stroke or died within 30 days of enrolling in the study, compared with just under 6 percent of patients in the medical therapy group. The stark difference between the groups persisted almost a year, by which time about 21 percent of patients who had received stents had had negative effects, compared with 12 percent in the medical group.

    The researchers initially thought that patients who received stents would have fared better, given the successful use of similar procedures in clinical practice at the Shands at UF Stroke Program and other medical centers.

    But the striking difference between the two patient groups prompted the study’s independent safety monitoring body to call off new recruitment. The researchers will, however, continue to monitor previously enrolled patients for the next two years.

    It’s not unusual for surgical patients to have more complications at first, the researchers said. That’s because the invasiveness of surgery poses an inherent risk regardless of the illness being treated.

    “The real question is, is there a benefit to patients over the long term,” said study co-author and co-principal investigator Hoh, who is an associate professor of radiology and neuroscience in the UF College of Medicine. “If you think about it, when people are concerned about stroke, it’s not just their first month that matters, so we’re waiting to see what the longer-term results will be.”

    Over time, improvement of stent design and honing of surgical techniques could help improve outcomes for patients.
    “This is certainly not the final say on managing this disease,” Waters said. “This is another piece of the puzzle that helps to guide our hand.”

    The University of Florida Health Science Center – the most comprehensive academic health center in the Southeast – is dedicated to high-quality programs of education, research, patient care and public service. The Health Science Center encompasses the colleges of Dentistry, Public Health and Health Professions, Medicine, Nursing, Pharmacy and Veterinary Medicine, as well as the Veterinary Hospitals and an academic campus in Jacksonville offering graduate education programs in dentistry, medicine, nursing and pharmacy. Patient care activities, under the banner UF&Shands, are provided through teaching hospitals and a network of clinics in Gainesville and Jacksonville. The Health Science Center also has a statewide presence through satellite medical, dental and nursing clinics staffed by UF health professionals; and affiliations with community-based health-care facilities stretching from Hialeah and Miami to the Florida Panhandle.

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    Research and Practical Health Care

    Friday, May 6th, 2011 by American Senior Fitness Association   View This Issue of Experience!

    The great universities of the world produce important research findings and provide practical medical care as well. Below are three current news releases from the University of Florida that demonstrate such centers’ value — and that will be of great interest to those involved in older adult health and fitness.

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    Exercise Cuts Older Adult Health Costs

    Friday, May 6th, 2011 by American Senior Fitness Association   View This Issue of Experience!

    While most senior health-fitness professionals already advocate insurance coverage of structured physical exercise programming for older adults, the following news release strongly reinforces that position:

    Structured exercise and physical activity programs should be covered by insurance as a way to promote health and reduce health care costs, especially among high health-risk populations such as those who have diabetes.

    So says Marco Pahor, M.D., director of the University of Florida Institute on Aging, in an editorial Wednesday, May 4, in the Journal of the American Medical Association. Pahor’s paper accompanies an analysis of multiple clinical trials that examined the effect of exercise and physical activity on the control of blood glucose levels.

    “Cumulative work over the past few decades provides solid evidence for public policymakers to consider structured physical activity and exercise programs as worthy of insurance reimbursement,” Pahor said.

    A host of studies have linked exercise programs with improved health measures related to blood pressure, lipid levels — including cholesterol and triglycerides — cardiovascular events, cognition, physical performance, premature death and quality of life. People who take part in programs that contain both aerobic and resistance training are likely to get the greatest benefit, compared with people who do only resistance exercises.

    The study that Pahor’s editorial accompanied, conducted by Daniel Umpierre, M.Sc., of the Hospital de Clinicas de Porto Alegre, Brazil, and colleagues, compared the association between physical activity advice and structured exercise programs, respectively, and markers of diabetes.

    Analyses of interventions to promote physical exercise in adults have found that compared with no intervention, exercise programs are cost-effective and have the potential to improve survival rates and health-related quality of life.

    Some insurance providers already include a fitness benefit for members, such as monthly membership at certain fitness centers or access to personal trainers or exercise classes at reduced cost. Use of such health plan-sponsored club benefits by older adults has been linked to slower increases in total health care costs.

    In one study, older adults who visited a health club two or more times a week over two years incurred $1,252 less in health care costs in the second year than those who visited a health club less than once a week. Programs among people with lower incomes can also pay off, because people in that group are otherwise more likely to forego health-promoting physical activity because of economic constraints or safety concerns.

    “People are willing to invest in improved health, but if you have a fixed amount of resources then you want to choose where you get the most health for the dollar,” said Erik Groessl, an assistant professor of family and preventive medicine at the University of California, San Diego, and director of the UCSD Health Services Research Center. Groessl was not involved in the current analysis.

    Group training or walking programs, for example, can be cost-effective, sustainable forms of physical activity that don’t require expensive health care professionals or equipment. But more costly interventions that yield dramatic results might also be worth the expense.

    With respect to type 2 diabetes, Medicare reimburses for approved self-management education and medical nutrition therapy programs. But no specific reimbursement is given for any physical activity or exercise program, despite evidence that such programs can help improve health and cut costs.

    Questions remain as to what format reimbursable exercise and physical activity programs should take, what population group should be targeted, and at what stage of life or health status would a lifestyle intervention be most cost-effective to implement.

    Various studies, including the UF Institute on Aging Lifestyle Interventions and Independence for Elders, or LIFE study, are aimed at answering those questions through randomized controlled trials that can provide data about the efficacy and cost-effectiveness of structured activity programs with respect to a range of health outcomes. Funded by the National Institute on Aging, the LIFE study is the largest of its kind to examine physical activity and health education as a way to prevent mobility disability among older adults, and accounts for the largest federal award to the University of Florida.

    The institute will break ground on May 26 for a 40,000-square-foot complex within UF’s new $45 million, 120,000-square-foot Clinical and Translational Research Building, which will serve as headquarters for this research and others aimed at speeding scientific discoveries to patients.

    “There is a lot of evidence that physical activity works, and I think it’s time to start putting it into practice more widely,” Groessl said.

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    Listen to the Quiet Protein

    Friday, May 6th, 2011 by American Senior Fitness Association   View This Issue of Experience!

    As noted in the article below, lung cancer strikes both cigarette smokers and nonsmokers. For new hope in the fight against this form of cancer, read on:

    When a movie character says, “It’s too quiet,” that’s usually a sign something bad may happen.

    Now, University of Florida researchers have discovered that when variations of a certain protein in our cells are too quiet, it may add to the risk that someone will develop lung cancer. When scientists restored the protein to its normal, active self, its cancer-inhibiting properties reappeared.

    These discoveries, published in two reports in the online version of Oncogene, provide evidence that drugs can potentially suppress tumor growth by restoring cellular processes rather than inhibiting cancer-causing genes known as oncogenes.

    “It’s a well-accepted fact that you can inhibit things, particularly oncogenes,
    that drive cancer. Oncogenes are the cancer’s gas pedal,” said principal investigator David Reisman, M.D., Ph.D., a UF associate professor of medicine and a member of the UF Shands Cancer Center. “What we’ve done is demonstrate the feasibility of reconstituting the cancer brake.”

    The protein, known as Brahma, or BRM, is involved in the regulation of cellular functions like gene expression, DNA repair, cell adhesion and telling cells whether to divide and grow or stop dividing and die. Other studies have found
    “silenced” BRM is present in 10 to 20 percent of all solid tumors. Reisman knew from his own research in mouse models that silencing the BRM gene alone did not cause tumor growth, but when carcinogens were introduced, 10 times as many tumors appeared compared with mice with normal BRM expression.

    “The gene was not a tumor suppressor in the classical definition but a tumor susceptibility gene, and when the expression is lost, it primes you to other events that potentiate the development of tumors, such as tobacco carcinogens,” Reisman said.

    More people die of lung cancer every year than of cancers of the breast, colon, prostate or lymphoma combined, according to the National Cancer Institute. However, only 10 percent of smokers develop lung cancer and as many as 15 percent of those diagnosed with lung cancer have never smoked.

    Reisman’s work suggests the presence of two variations within the BRM gene — known as polymorphisms — could potentially be biomarkers for lung cancer and assist doctors in identifying individuals at higher risk, which could lead to more cost-effective screening practices and lifesaving early detection.

    Study investigators sequenced the genes of 160 people and learned that roughly 20 percent carry the gene variants. With collaborator Geoffrey Liu, M.D., a research scientist at the Ontario Cancer Institute at the University of Toronto,
    the team then verified the presence of the silenced BRM variants in human lung tumors.

    Reisman and Lui also conducted case control studies on 1,199 people who were
    matched for age, gender and smoking history but in whom 484 individuals had lung cancer and 715 were healthy and cancer free.

    “We found these polymorphic sites were greatly enriched in the population that had developed lung cancer,” Reisman said. “The chance that you would develop lung cancer if you had both polymorphic sites was 220 percent higher. Our analysis demonstrated those odds to be independent of smoking history, sex, race and cancer type.”

    Reisman’s team also studied whether it would be possible to restore the normal expression of the BRM protein. Certain compounds, called histone deacetylase — or HDAC — inhibitors, had been demonstrated by other researchers to reactivate the BRM gene, but did not restore the normal, cancer-suppressing function of the BRM protein.

    By introducing the healthy protein alongside the reactivated gene, the researchers were able to stop the growth of cancer cells. That makes the process a potential target for drug therapies to use in suppressing many tumor types.

    “We know there are a lot of genes that are silenced in cancer, and it’s believed that gene silencing is necessary in order for the cancer to grow and thrive. This research demonstrates — and is really the first example of — an approach that’s led to the reactivation of a specific tumor-suppressing gene,” said Aubrey Thompson, Ph.D., a professor of cancer biology at Mayo Clinic Comprehensive Cancer Center in Jacksonville, Fla., who was not involved in the research.

    “That’s a really big deal,” he said. “It’s an approach that is widely applicable to a lot of genes and a lot of different types of cancer. I think it’s going to be met with a great deal of enthusiasm and interest from researchers in human cancer therapy.”

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    Need Weed?

    Friday, April 15th, 2011 by American Senior Fitness Association   View This Issue of Experience!

    It’s a poorly kept secret that many senior citizens have both longstanding and ongoing experience in the use of marijuana. But did you know that physical exercise might curb the urge to partake? Jim Evans explains below.


    DEAR JIM: I’ve been smoking “weed” most of my life – since I was about 20. I’m 73 now and I still smoke 3-4 joints a day. I’ve thought about quitting from time to time, but it helps me relax and it’s pretty much of a habit now anyway. As you can probably guess, I’m pretty laid back after all these years, but I have been experiencing an increasing number of panic attacks as I grow older. I know there isn’t any
    way to treat my dependence with medication, and I really don’t want to quit anyway, but I’m wondering if some kind of physical activity might help me to cut back a little. POTHEAD FROM POMONA

    DEAR POTHEAD: Until recently I couldn’t really say whether exercise might be a factor in curbing marijuana use or not. However, a recent study by Vanderbilt University Medical Center seems to indicate that exercise might actually curb both marijuana use and cravings.

    The study, published earlier this year in the journal PLoS ONE , found that, after just a few sessions of running on treadmill, participants who were admittedly “cannabis-dependent” but did not want treatment to stop smoking pot, experienced a significant decrease in both cravings and daily use.

    In fact, their craving for and use of cannabis was cut by more than 50 percent after exercising on a treadmill for 30-minute sessions over a two-week period. Researchers measured the amount of exercise needed for each individual to reach 60-70 percent of their maximum heart rate respectively, creating a personalized exercise treadmill program for each participant.

    “This is 10 sessions but it actually went down after the first five. The maximum reduction was already there within the first week,” said co-author Peter Martin, M.D., director of the Vanderbilt Addiction Center.>

    “There is no way currently to treat cannabis dependence with medication, so this is big considering the magnitude of the cannabis problem in the U.S. And this is the first time it has ever been demonstrated that exercise can reduce cannabis use in people who don’t want to stop.”

    The importance of this study – and future studies – will only continue to grow with the new knowledge of the role of physical activity in health and disease, according to co-author Maciej (Mac) Buchowski, Ph.D, Research Professor of Medicine and director of the Vanderbilt Energy Balance Laboratory.

    “It shows that exercise can really change the way the brain works and the way the brain responds to the world around us,” added Martin. “And this is vital to health and has implications for all of medicine.”

    More research will need to be done to substantiate these findings, but it certainly sounds promising. In the meantime, you might start walking for 30 minutes a day – on a treadmill or otherwise – and gradually increase the pace and see what happens. You can do your own personal experiment to see if it helps you to cut back on your pot smoking. If not, at least you’ll be in better shape.

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    Looking Back — And Forward — With Smiles

    Thursday, March 24th, 2011 by American Senior Fitness Association   View This Issue of Experience!

    During the first quarter of 2011, SFA has begun a number of exciting initiatives including the preparatory stages of two new professional education courses. As these events unfold, look for detailed announcements in Experience! Below are just a few highlights from 2010:

  • SFA president Janie Clark continued to champion older adult quality of life in her role as an effective advocate for optimal senior fitness programming. She served on the National AFib Support Team, which was sponsored by the pharmaceutical corporation sanofi-aventis to promote a better understanding of atrial fibrillation among laypersons, medical personnel, and health-fitness professionals. She appeared on Retirement Living Television and wrote for EP Lab Digest, the news and clinical update publication for electrophysiology professionals. She also gave interviews for articles in Club Industry magazine, the Chicago Tribune, American Fitness magazine (published by AFAA, the Aerobics and Fitness Association of America), and numerous other media outlets.
  • SFA launched a popular newsletter and website series "Who’s Who in Senior Fitness" which profiles individuals who’ve made key contributions to the field. Upcoming issues of Experience! will feature Kay Van Norman, Jim Evans, and more.
  • The Association signed on to exciting new corporate partnership and distributorship agreements.
  • SFA members achieved numerous worthwhile accomplishments, many of which were documented in Experience! You can access past issues by visiting SFA’s website.
  • SFA’s latest professional education program, Brain Fitness for Older Adults, continued to earn stellar expert reviews, such as the following statement by neuroscientist Dr. Ryan McKim, PsyD: "Drawing on recent neuroscientific research, SFA has designed a thoughtful and progressive training program for senior fitness professionals interested in integrating cognitive fitness into their existing physical activity programs. Recent advances in neuroscience are drawing long overdue attention to the importance of cognitive health. SFA has designed an impressive and well-researched training program for senior fitness professionals."
  • Educational participants gained vital knowledge and expertise from their SFA courses. Below are some commentaries from students who completed their work during the past few months.
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    News on Colon Cancer

    Wednesday, December 8th, 2010 by American Senior Fitness Association   View This Issue of Experience!

    A chemical compound made from a type of bacteria discovered in the Florida Keys by a University of Florida pharmacy researcher has shown effectiveness in fighting colon cancer in preclinical experiments.

    Writing online in the Journal of Pharmacology and Experimental Therapeutics, scientists say the compound — known as largazole because it was first found near Key Largo — inhibits human cancer cell growth in cultures and rodent models by attacking a class of enzymes involved in the packaging and structure of DNA.

    More study is needed, but scientists hope that the discovery will lead to new treatments for the roughly 50,000 people struck with colorectal cancer each year in the United States. Researchers are enthusiastic because in addition to having the marine bacteria as a natural source of the chemical, they have been able to synthetically produce the active chemical compound extracted from the bacteria.

    “It is challenging to develop natural marine products into drug therapies due to what is termed the ‘the supply problem,’” said Hendrik Luesch, Ph.D., an associate professor of medicinal chemistry in the UF College of Pharmacy. “We have solved the supply problem for largazole because it has a relatively simple structure, which has made it easy to reproduce in the lab.”

    The Luesch lab discovered largazole while investigating samples of bacteria from the Florida Keys, publishing the finding in 2008.

    Known as cyanobacteria, the microbes have evolved to fend off predators or cope with harsh conditions in a marine environment, employing toxins to aid their own survival. The toxins are the compounds chemists such as Luesch wish to isolate and understand in a quest to create drugs that similarly fend off invading cancers in the body.

    Since the discovery, Luesch’s lab determined the compound inhibits enzymes known as histone deacetylases, or HDACs, which are linked to many diseases and are increasingly viewed as promising for cancer therapy.

    Jiyong Hong, Ph.D., an assistant professor of chemistry at Duke University, teamed with the UF researchers to chemically reproduce the compound for further preclinical testing, which indicates it is a potent inhibitor of cancer cells that has the right properties to reach its intended target without the toxic side effects of many cancer drugs.

    “Knowing HDAC is the target that makes largazole effective means we can predict good drug properties because there are already two anticancer products on the market that work this way,” said Luesch, who is a member of the UF Shands Cancer Center.

    Three important aspects make this marine compound more promising than other natural products as an effective cancer-fighting drug, Luesch said — availability of supply, knowing its mode of action and the fact that its cellular target is already a proven anticancer target known to result in the necessary selectivity for cancer cells over normal cells.

    Luesch presented the findings Sept. 9 at the Marine Drug Discovery Symposium in Pohang, South Korea, and in mid-October at the Marine Natural Products Symposium in Phuket, Thailand. The research was featured on the cover of November’s Journal of Pharmacology and Experimental Therapeutics.

    He completed his initial preclinical studies that demonstrated largazole’s effectiveness in inhibiting the growth of more than one type of colon cancer cell through the 2009 American Recovery and Reinvestment Act stimulus funding from the National Cancer Institute.

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