December 8th, 2010

Table of Contents:

Progress on the Cancer Front (Introduction to special issue)

News on Breast Cancer (New technology)

News on Colon Cancer (A promising discovery)

News on Lung Cancer (Transplant innovation)

Human Spirit (Reflection)

Progress on the Cancer Front

by American Senior Fitness Association

Senior health-fitness professionals routinely work with older adults for whom breakthroughs in cancer research may be of vital interest. Therefore, we are pleased to present the following news releases on advances in breast, colon, and lung cancer treatments describing important new initiatives under way at a major US health science center.

Located in Gainesville, Florida, the University of Florida (UF) 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, Florida, offering graduate education programs. Patient care activities, under the banner of 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 numerous community-based health-care facilities.

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News on Breast Cancer

by American Senior Fitness Association

With the snip of scissors during a recent ribbon-cutting ceremony at 4:30 p.m. Friday at the University of Florida Cancer & Genetics Research Complex, a new era in the treatment of breast cancer in Florida began.

The ceremony debued the Intrabeam system at Shands at UF medical center, an intraoperative radiation technology available at fewer than 20 treatment centers nationwide and the only Intrabeam system in the state of Florida. Rep. Debbie Wasserman Schultz, a breast cancer survivor and ardent advocate for women with breast cancer, helped cut the orange, blue and pink ribbon.

The great benefit of Intrabeam irradiation for patients is that it reduces or even eliminates the need for weeks of external radiation treatment following surgery for early stage breast cancers.

“The Intrabeam will dramatically shorten the duration of radiation treatment for many of our patients,” sai Stephen Grobmyer, M.D., a UF associate professor of surgery and director of the UF Breast Center. “Radiation therapy that would normally require three to six weeks of treatments can now be accomplished in 20 to 25 minutes during the surgery.”

Twenty years in the making, the Intrabeam system is a mobile irradiation device that can be used in the operating room to deliver precise doses of radiation directly to the tumor site. Because it uses low energy X-rays to deliver the radiation dose, it does not require a specialized, shielded room, as do standard, high-powered radiation technologies. Radiation using Intrabeam is delivered from a rod with a spherical tip, which is placed in the cavity left in the breast tissue following removal of the tumor. The tumor bed is then irradiated for a period of 20 to 30 minutes while the patient is under general anesthesia.

The FDA-approved Intrabeam procedure, known as targeted intraoperative radiotherapy, was shown as effective as whole breast radiotherapy but with fewer complications in a clinical trial known as TARGIT-A, launched in 2000.

“The TARGIT-A trial, which is a randomization of standard radiation compared to a one-time dose in the operative theater using Intrabeam, has demonstrated, after four years follow up, that the two are equivalent in their ability to prevent the breast cancer from coming back in the breast,” said Michael Alvarado, M.D., an assistant professor of surgery at the University of California at San Francisco and TARGIT-A investigator. “Not only is the one-time dose of radiation using Intrabeam just as effective as a full course of external radiation, it is more convenient for the patient and there is less risk involved in terms of damage to the heart, the lungs and the skin.”

Studies have shown that 70 percent of women with invasive breast cancer require radiation therapy to destroy remaining cancer cells. Grobmyer, who is a member of the UF Shands Cancer Center, estimates the majority of patients undergoing lumpectomy, a breast conserving surgery that removes the tumor but leaves healthy breast tissue intact, would be potential candidates for treatment with Intrabeam. With the Intrabeam technology, Grobmyer said many lumpectomy patients at the UF Breast Center will now complete their entire course of radiation during surgery, eliminating the need to undergo weeks of external radiation treatments.

“Studies suggest that the farther a woman lives from a treatment facility, the less likely she will be to receive radiation treatments,” Grobmyer said. “Some women will choose to have a mastectomy rather than breast conserving surgery because they aren’t able to commit to three to six weeks of radiation treatments, either because of physical disability or because they live too far away from the treatment facility. Intrabeam now makes lumpectomy a more viable option for many of these patients.”

While Intrabeam irradiation has been shown to be just as effective as external radiation therapy in preventing the recurrence of cancer at the tumor site, it may have an added cancer killing effect that external radiation can’t offer.

“Surgeons expect most, if not all, of the tumor can be removed, but in some cases microscopic parts of the tumor may remain within the tumor bed or attached to structures such as arteries or nerves that cannot be removed. Even under the best conditions, too often residual disease near the margin of the tumor resection remains,” said Paul Okunieff, M.D., chair of the UF department of radiation oncology and director of the UF Shands Cancer Center. “Historically, we would offer radiation after the patient has had time to heal from surgery, but with the Intrabeam system, with little to no added toxicity, radiation can be immediately delivered to the exactly correct location. Any remaining tumor cells are sterilized and have no time to regrow.”

Okunieff said the Intrabeam system has been proven to be effective in the treatment of brain and breast tumors, and it holds promise for the treatment of many other cancer types where the tumor may be attached to sensitive tissues that cannot be removed, such as in the treatment of head and neck, pancreatic and rectal tumors. Okunieff was one of the researchers who participated in the early design and engineering of the Intrabeam device, and he was the first to use it in patients during clinical trials to treat brain tumors.

A $346,000 grant from the Health Resources and Services Administration, an agency of the U.S. Department of Health and Human Services, helped pay for the technology. The grant was intended to broaden treatment options for Floridians, which will be even further expanded by UF’s participation in ongoing clinical trials of the Intrabeam to explore its effectiveness in treating more advanced and aggressive breast cancers.

“Being involved with studies with Intrabeam is an important part of what we do because it allows us to continually assess and refine the uses of the Intrabeam system,” Grobmyer said. “We’re in the era of personalized cancer therapy, tailored to the type and stage of cancer presented by each patient. The Intrabeam system is an important tool in this effort, and it provides excellent results, reduces side effects, and dramatically shortens the duration of treatment.”

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News on Colon Cancer

by American Senior Fitness Association

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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News on Lung Cancer

by American Senior Fitness Association

Eight years ago, he sat in his living room, tethered to oxygen, his lungs rapidly deteriorating from pulmonary fibrosis. If Tom Telford had not become Patient No. 199, he probably would have gone on this way, unable to breathe, until he died.

That year, 2002, Telford became the 199th patient to receive a lung transplant at Shands at the University of Florida. He can’t run a marathon and struggles walking up a flight of stairs, but Patient No. 199 is alive. But for many lung transplant recipients, a successful transplant does not always ensure years of survival.

“At five years post-transplant, only 50 percent of recipients survive,” said Telford, a semi-retired nuclear engineer who lives in Gainesville. “I was No. 199. I knew 195 to 205. I exercised with these people and got to know them. Now, many of those people are not alive. It is pretty depressing.”

To help change these statistics, the state of Florida has awarded a $1 million grant to UF to establish a lung transplant center and fund research projects focused on problems such as chronic rejection, the most common reason why patients die after a lung transplant. The center emerged in 2010 from the flagship lung transplant program.

“Of the solid organ transplants, the survival rate of lung transplants is unfortunately the lowest,” said Mark Brantly, M.D., division chief of pulmonary medicine in the UF College of Medicine and a director of research efforts for the new lung transplant center. “There are many challenges in transplanting lungs not the least of which is chronic rejection. We are looking to develop a multicollege research group that will help advance our knowledge about rejection and will develop new therapeutics to improve our patients’ lives.”

According to the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients, about half of lung transplant recipients are still alive after five years, and only about one-quarter of them make it to 10 years.

The funding has already been used to support five research projects involving researchers from the UF colleges of Medicine and Engineering. The projects include the following:

A study led by Thomas Beaver, M.D., will examine rehabilitation of donor lungs using what is known as perfusion technology. Only about one-quarter of potential donor lungs are able to be transplanted into patients, but studies have shown that attaching lungs to a machine that tricks the organs into thinking they are still inside the body and infusing them with medicine could rehabilitate them for transplant.

Maher Baz, M.D., director of the lung transplant center, will study whether an excess of cells known as T-helper cell 17 could play a role in triggering chronic rejection.

Frederick Kaye, M.D., and his team are studying tumors associated with lung transplants.

Studies led by Jay Patel, M.D., and CQ Xia, M.D., Ph.D., will examine whether lungs treated with an antioxidant protein prior to transplant could help stave off chronic rejection.

Chris Batich, Ph.D., and Gregory Schultz, Ph.D., are looking into the development of a device that could potentially remove antibodies associated with rejection from the blood of patients.

“This grant will allow us to put our three objectives into motion: education, clinical care and research in lung transplantation,” Baz said. “We are hoping this will allow us to advance lung transplant knowledge, which in turn will lead to more funding from varied sources that will advance knowledge further and ultimately help our patients.”

After his transplant in 2002, Telford set up a charitable trust to donate money to Baz’s research and UF’s transplant efforts. But after raising $62,000 during a tennis benefit in 2007, he teamed with John Ross, M.D., a professor emeritus of pediatrics in the College of Medicine, to take fundraising efforts a step further. The duo, along with other transplant recipients, lobbied state legislators for help. After three years, the help came through.

Aside from the research projects, the funds will also go toward the first steps toward developing an improved pediatric lung transplant program through Shands Transplant Center at Shands Children’s Hospital at UF.

“Shands is the best,” Telford said. “They have performed the most transplants, and it is the obvious place to develop this resource for the state of Florida."

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Human Spirit

by American Senior Fitness Association

The American journalist and author Mignon McLaughlin, who lived from 1913 to 1983, penned these inspirational words in 1960:

"People are made of flesh and blood and a miracle fiber called courage."

– Mignon McLaughlin

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