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Researchers have identified a protein that plays a key role in preventing skin cancer cells from dividing and multiplying.
Writing in the July 20 issue of Molecular Cell, a team at the University of Texas M.D. Anderson Cancer Center, reported that the protein IKKa prevented a vital "checkpoint" gene from shutting down and allowing cancer cells to spread.
The protein often is absent or only found at lower levels in a type of skin cancer cell.
IKKa is found at lower than normal levels in aggressive squamous cell carcinomas in both mice and humans. When operating normally, it allows the checkpoint gene 14-3-3o to respond to DNA damage in the cell. The gene usually creates a protein that blocks defective cells from dividing, allowing genetic errors to be repaired rather than copied.
Without IKKa proteins, the gene does not function optimally, and cells that multiply with damaged or abnormal genes are the root of cancer.
The interaction is part of the process of DNA methylation -- a process by which the work of a gene is chemically altered, but the gene itself is not damaged. Researchers look for ways to chemically turn the gene back on and restore its function.
The team inserted IKKa into deficient cells, which allowed the checkpoint gene to work again.
"What we've identified is a mechanism that promotes genetic instability in keratinocytes, a critical type of skin cell that makes up 90 percent of epidermal cells, during the development of human skin cancers," Yinling Hu, senior author of the paper and assistant professor in M.D. Anderson's department of carcinogenesis at the Science Park-Research Division in Smithville, Texas, said in a prepared statement. "Our finding opens a new avenue for identifying new therapeutic targets for battling cancer," Hu said.
The findings may have implications for a broad array of cancers, as the researchers noted that the checkpoint gene 14-3-3o is also shut dow n in cancerous epithelial cells. Epithelial cells are found in the outer layer of skin and in the linings of other body organs such as lungs, and the gastrointestinal, reproductive and urinary tracts.
HealthDay News, July 24, 2007
Natural Products Association launches testing program aimed at Increasing safety, quality and consumer confidence.
Melanoma remains a stubborn foe, with doctors reporting limited success in preventing the sometimes fatal skin cancer and even less success developing a cure.
"We'd like to reduce that death rate, but that's not happening," said Dr. Martin A. Weinstock, chairman of the American Cancer Society's Skin Cancer Advisory Committee. "We're not being effective in preventing melanoma. We've been making progress in early detection but not as much as we would like. And therapy for melanomas not detected early is basically poor."
But several advances announced in the last year -- from testing "sentinel" lymph nodes as a way to jump-start aggressive treatment, to new gene therapies that may one day beat back the cancer -- have given doctors a cautious sense of optimism.
Still, the experts add that these treatments need more testing, and prevention remains the best way to avoid the disease. So, the message remains the same -- protect yourself from the sun, and keep an eye on unusual skin growths.
"There are a lot of therapies that are promising," said Weinstock, professor of dermatology and community health at Brown University and chief of dermatology at the VA Medical Center in Providence, R.I. "But they're all possibilities. We just don't know if they're going to pan out yet."
Skin cancers in general are extremely survivable. The U.S. National Cancer Institute estimates that more than 1 million new cases of non-melanoma skin cancer will be diagnosed in 2007, claiming fewer than 2,000 lives.
Melanoma is another matter. It's rarer than basal cell or squamous cell skin cancer, with about 59,900 new cases expected to strike Americans this year. But it will kill an estimated 8,110 people, according to the cancer institute.
Melanoma remains frustratingly hard to prevent and cure, Weinstock said.
It begins in skin cells called melanocytes that produce melanin, the pigment that gives skin its natural color. Skin exposed to the sun causes melanocytes to produce more pigment, creating a sun tan. Sometimes, clusters of melanocytes and surrounding tissues form moles on the skin.
Melanoma occurs when those pigment cells become malignant. The first sign of trouble often is a change in the size, shape, color or feel of an existing mole, with most melanomas displaying a black or blue-black area. Melanoma also can appear as a new mole that is black or looks abnormal or ugly, according to the cancer institute.
If undetected or left untreated, melanoma can spread to other parts of the body, such as the liver, lungs or brain. The first sign that melanoma has spread, or metastasized, usually is the appearance of cancer cells in the body's lymph nodes. Part of the body's defense system, the nodes produce lymph, which travels throughout the body and filters out impurities.
In the past, doctors fighting melanoma would remove many or all of the body's lymph nodes to help prevent the spread of the cancer. But the experimental sentinel node biopsy technique allows doctors to remove only a few lymph nodes directly affected by the melanoma.
In the procedure, a radioactive substance is injected near the melanoma and its progress through the body is tracked. The first lymph nodes to take up the substance are called the sentinel lymph nodes.
Since the cancer is most likely to head to those lymph nodes first, only those nodes are surgically removed for testing. If positive, the rest of the lymph nodes are tested and removed. But if negative, the patient avoids what can be a painful procedure.
Sentinel node biopsy has been around for about two decades, but new studies have shown that its use can give patients a better fighting chance against metastasized melanoma.
A 2006 study headed by Dr. Donald L. Morton, who helped create the technique, found that patients whose lymph nodes tested positive and then had the rest of their nodes removed enjoyed a much higher five-year survival rate, compared with people who tested positive but delayed removal of their lymph nodes.
"The risk of dying from melanoma was almost one-half reduced if you had the lymph nodes removed versus waiting for them to grow to a detectable size," said Morton, medical director and chief of the melanoma program at John Wayne Cancer Institute at Saint John's Health Center, in Santa Monica, Calif.
Other scientists have found that boosting the immune system's ability to recognize and destroy cancer cells shows promise in treating melanoma.
In a recent study, National Cancer Institute researchers treated 17 patients with advanced, metastatic melanoma with white blood cells called T-lymphocytes that had been genetically engineered to better recognize the skin cancer. The result: Two of the patients went into a sustained remission.
Doctors believe this shows that such gene therapy can work, but much more work and many refinements remain ahead.
Until these tactics are improved upon, Weinstock recommends that people use the American Cancer Society's recommended "Slip, Slop, Slap" strategy for fighting skin cancer.
"The one major avoidable cause of melanoma is exposure to ultraviolet radiation from the sun," Weinstock said. "Slip on a shirt, slop on the sunscreen and slap on a hat."
HealthDay News, By Dennis Thompson, July 22, 2007
By Kimberly J. Heathman
Mixing in clinical trials, variables, replication and more, learn how to know when ingredient research has been properly cooked up.
The young woman in the American Cancer Society ad holds up a photo of a smiling woman. "My sister accidentally killed herself. She died of skin cancer," reads the headline.
The public-service announcement, financed by the sunscreen maker Neutrogena, is running in 15 women's magazines this summer. It warns readers that "left unchecked, skin cancer can be fatal," and urges them to "use sunscreen, cover up and watch for skin changes."
The woman in the picture is a model. And the ad's implicit message -- that those who die of skin cancer have themselves to blame -- has provoked a sharp response from some public-health doctors, who say the evidence simply does not support it. As the ad says, skin cancer is the most common form of cancer. But most skin cancer is not life-threatening: It represents less than 2 percent of all cancer deaths, an estimated 10,850 people this year. Almost all of those deaths are from melanoma, which makes up only 6 percent of all skin-cancer cases.
And the link between melanoma and sun exposure is not straightforward. Dr. Marianne Berwick, an epidemiologist at the University of New Mexico who studies skin cancer, led a study published in The Journal of the National Cancer Institute in 2005 finding that people who had a lot of sun exposure up to the time they got a diagnosis of melanoma actually had better survival rates than those who had little sun exposure. The researchers are conducting a large-scale follow-up aimed at clarifying the relationship between sun exposure and melanoma.
Until that is made clear, many doctors say, it is premature to suggest that people are endangering their lives by failing to use sunscreen.
"It's just not that simple," said Dr. Barry Kramer, associate director for disease prevention at the National Institutes of Health.
"We do have some pretty good evidence that sunscreen will reduce your risk of the less lethal forms of skin cancer," Kramer added. "There's very little evidence that sunscreens protect you against melanoma, yet you often hear that as the dominant message."
Dr. J. Leonard Lichtenfeld, deputy chief medical officer at the American Cancer Society, acknowledges that the advertisement is aggressive. "We have taken some license in taking that message and using it the way we've used it because that's the way to get the message to our target audience," he said.
The ad's creators settled on the approach with the help of focus groups, who told them: "To get the message through to me, you have to shock me and get my attention," he added.
"Our focus groups showed us that these young women as a group were oblivious to the risk and felt that skin cancer isn't a serious problem," Lichtenfeld said. "The issue is to try to prevent that sun exposure earlier in life so we reduce the risk for people later in life."
In an effort to spread awareness about sun safety, the cancer society has joined with Neutrogena, a division of Johnson & Johnson whose sunscreens carry the society's logo.
As part of the agreement, Neutrogena is paying for the public-service campaign, though its name is not mentioned in the advertisement.
The partnership benefited both parties, said Iris Grossman, director of communications for Johnson & Johnson. "We have the common goal of raising awareness," she said.
But this financial relationship raises red flags for some experts. "When people see an American Cancer Society public-service announcement, they expect it to reflect the best evidence," said Dr. Lisa Schwartz, co-director of the Outcomes Group at the Veterans Affairs hospital in White River Junction, Vt. "We don't want people who have a financial interest to be telling you the benefit of doing something."
Neutrogena did not influence the cancer society's message on skin cancer, Lichtenfeld said.
By Christie Aschwanden, New York Times News Service, July 17, 2007
The more moles a person has, the more likely their DNA has properties that help slow aging, according to a U.K. study of 1,800 twins.
People with more than 100 moles had longer telomeres than people with fewer than 25 moles, the study found. Telomeres -- bundles of DNA found at the end of chromosomes in all cells -- help keep chromosome ends from fraying and sticking to one another, BBC News reported.
Telomeres shorten as people age. The difference in telomere length between study volunteers with more than 100 moles and those with fewer than 25 moles was equivalent to six to seven years of aging, said the study, which appears in the journal Cancer Epidemiology Biomarkers and Prevention.
"The results of this study are very exciting as they show, for the first time, that moley people who have a slightly increased risk of melanoma may, on the other hand, have the benefit of a reduce rate of aging," said lead researcher Dr. Veronique Bataille of King's College London, BBC News reported.
"This could imply susceptibility to fewer age-related diseases, such as heart disease or osteoporosis, for example. Further studies are needed to confirm these findings," Bataille said.
HealthDay News, July 12, 2007
More and more professional athletes are realizing how the dangerous effects from the sun can disrupt their game. From baseball to hockey, running to skiing, skin cancer is leaving its mark on athletes in a range of sports. To spread awareness and help strike out skin cancer, the most common form of cancer in the United States, the American Academy of Dermatology (AAD) is urging athletes to Be Sun Smart.
“Thousands of athletes, both professional and amateur, are at high risk for developing skin cancer,” warns dermatologist Brian B. Adams, MD, MPH, FAAD, and chairperson of the AAD’s Sports Committee. “Outdoor athletes face double jeopardy because perspiring exacerbates their risk.”
Perspiration on the skin lowers the minimal erythema dose, the lowest ultraviolet (UV) light exposure needed to turn the skin barely pink. "You've already set yourself up for trouble if you are not using sunscreen when outdoors participating in sports," commented Dr. Adams. "When you perspire, you are even more susceptible to a burn, and with continued exposure, to wrinkles, age spots and maybe even skin cancer.”
Skin cancer has left its mark on runner Deena Kastor, one of America's top distance runners and an Olympic bronze medalist in the marathon. "I have 25 external stitches for basal cell carcinoma and early stages of melanoma," said Kastor. “I also have six internal stitches to tie off blood vessels the doctor cut through because the cancer runs deep."
Kastor encourages the public to take the necessary steps to prevent skin cancer. “I can only emphasize that it is never one thing that causes skin cancer,” said Kastor. “Maintaining healthy skin is a combination of using sunscreen, wearing clothing and hats that cover you in the sun, limiting exposure to the midday sun, eating foods high in anti-oxidants and visiting the dermatologist regularly.”
The AAD recommends seeking shade from 10 a.m. to 4 p.m., which according to Dr. Adams is, "exactly the time when most teams are outside practicing, from soccer players to long-distance runners to tennis players. These athletes are getting an enormous amount of exposure to UV light and it’s important that they follow some sun-safety precautions, including wearing sunscreen and protective clothes.”
Skin cancer also occurs in athletes who do not compete in the sun. During training-camp physicals in 2002, National Hockey League player Mark Cullen's health took a negative turn. His doctor detected a suspicious mole under his arm and it was discovered to be melanoma, the most deadly form of skin cancer.
"It was a shock," Cullen said. "Anytime you hear the word 'cancer', especially feeling that I was a young, healthy person, I was shocked. It was a scary time in my life and while I'm glad to have gone through it, I'm glad to be healthy right now."
It took three separate surgeries to remove Cullen’s growth, surrounding lymph nodes, and some skin. Luckily, Cullen did not have to undergo chemotherapy or radiation, as he initially believed. Almost three years later and with regular six-month checkups, Cullen is cancer-free.
"The skin cancer diagnosis helped me prioritize my life in general," Cullen said, "and made me realize what was important to me -- to take a step back and look at your life and where you're headed right now because you never know how long you're going to get."
More than 1 million new cases of skin cancer are diagnosed each year and one American dies of melanoma almost every hour (every 65 minutes). Of these cases, more than 108,000 are melanoma, a cancer that claims nearly 8,000 lives annually.
Dermatologists encourage all athletes to Be Sun Smart since sun exposure is the most preventable risk factor for skin cancer. Here’s how to do it:
- Generously apply sunscreen to all exposed skin using a Sun Protection Factor (SPF) of at least 15 that provides broad-spectrum protection from both ultraviolet A (UVA) and ultraviolet B (UVB) rays. Re-apply every two hours, even on cloudy days, and after swimming or sweating. Look for the AAD SEAL OF RECOGNITIO on products that meet these criteria.
- Wear protective clothing, such as a long-sleeved shirt, pants, a wide-brimmed hat and sunglasses, where possible.
- Seek shade when appropriate, remembering that the sun’s rays are strongest between 10 a.m. and 4 p.m.
- Use extra caution near water, snow and sand as they reflect the damaging rays of the sun which can increase your chance of sunburn.
- Protect children from sun exposure by applying sunscreen.
- Get vitamin D safely through a healthy diet that includes vitamin supplements. Don’t seek the sun.
- Avoid tanning beds. Ultraviolet light from the sun and tanning beds can cause skin cancer and wrinkling. If you want to look like you’ve been in the sun, consider using a sunless self-tanning product, but continue to use sunscreen with it.
- Check your birthday suit on your birthday. If you notice anything changing, growing, or bleeding on your skin, see a dermatologist. Skin cancer is very treatable when caught early.
For more information about skin cancer or the AAD’s sun-safety sports programs, please visit www.aad.org.
Patients who used the psoriasis drug Enbrel for more than a year had no more adverse effects than patients taking a placebo, a new study found.
And most patients showed an improvement in their psoriasis, according to the study. Enbrel had previously been shown to be safe and effective when used over a short period of time, but the question remained whether long-term use of the drug would be safe.
"This drug is safe for long-term use," said lead author Dr. Stephen Tyring, a clinical professor of dermatology at the University of Texas Health Science Center at Houston. "During 96 weeks of follow-up, both the safety and efficacy of the drug were very good."
Enbrel (etanercept) is a drug that blocks tumor necrosis factor, a pro-inflammatory cytokine. People with an immune disease, such as psoriasis, have too much tumor necrosis factor (TNF) in their bodies. Enbrel reduces the amount of TNF to normal levels, but it can also lower the ability of the immune system to fight infections.
In the trial, Tyring's team randomly assigned 618 people with psoriasis to 12 weeks of treatment with Enbrel or a placebo. The patents received 50 milligrams of Enbrel twice a week. After the initial 12 weeks of treatment, 591 patients from both groups continued to receive Enbrel for 84 weeks.
The study researchers found that people receiving Enbrel or a placebo had a similar number of adverse reactions, including serious infections. "There was not a problem with increased infections or any other adverse events in using the drug for the long term, and this is at the higher dosage of 100 milligrams a week," Trying said.
What's more, by the end of the trial, the psoriasis had improved at least 75 percent for 51.1 percent of the original Enbrel group and 51.6 percent of the original placebo group.
The findings are published in the June issue of the Archives of Dermatology.
Tyring noted that Enbrel is not usually used alone, as it was in this trial, but in combination with other drugs, such as creams, as well as with light therapy. "So, in real life, we see better results," he said.
The main drawback to long-term Enbrel treatment is cost, Tyring said. "Like all five biological treatments for psoriasis, Enbrel is expensive, and if the patient doesn't have insurance, it is difficult to keep using this dosage and perhaps even a lower dosage," he said.
According to the National Psoriasis Foundation, Enbrel can cost $10,000 to $25,000 a year or more, depending on the dose and how often it is taken.
One skin disease expert agreed that long-term use of Enbrel is safe and effective, even at the higher dose.
"Physicians would love to use the drug this way," said Dr. Jeffrey M. Weinberg, director of the clinical research center in the department of dermatology at St. Luke's-Roosevelt Hospital Center, in New York City. "The limiting factor is cost," he added.
Some patients do well on 50 milligrams a week, Weinberg said. "But many people do better at the higher dose, especially those who weigh more," he said. "About 40 percent of patients would benefit from the higher dose."
By Steven Reinberg, HealthDay News, June 19, 2007
The University of Michigan Medical School recently reported that retinol reduces the fine lines and wrinkles associated with natural aging.
Overall exposure to the sun's ultraviolet (UV) rays in childhood, not just sunburns, may be a major factor influencing a person's risk for skin cancer later in life, suggest initial results of research looking at the interaction of genes and UV exposure in 214 people with melanoma, the most deadly form of skin cancer.
Dr. Nancy Thomas, a dermatologist at the University of North Carolina, used satellite data to track average UV radiation in the towns and states where the patients lived at different times of their lives, the Associated Press reported.
She and her colleagues found that the patients who'd experienced the highest UV exposure by age 20 had the highest number of melanoma-related BRAF gene mutations. The same patients also had the most moles, another important risk factor for melanoma.
More research is needed, but Thomas suggested that rapidly growing skin on young people may be especially vulnerable to damage from UV rays, the AP reported.
In related news, the U.S. Food and Drug Administration is putting the finishing touches to new rules for sunscreen ratings. Currently, sun protection factor (SPF) ratings tell consumers only how well a sunscreen protects against UV-B rays that cause sunburn.
The agency wants the SPF ratings to also include how well sunscreens protect against UV-A rays that cause cancer and wrinkles, the AP reported. The proposed changes should be introduced within the next few weeks, but are subject to a public comment period before they take effect.
HealthDay News, June 11, 2007