Healthy News for Healthy Nation

Moles. Researchers have uncovered a protein that stops the growth of melanoma, a cancer that develops from pigment-producing cells in the skin called melanocytes. (Credit: Michele Hogan)

One might call it a tale of two melanocytes. Given the same genetic mutation, why does one melanocyte shut down growth and become a relatively benign mole, while another rages out of control and develops into deadly melanoma?

In trying to tease out the answer to this simple question, Howard Hughes Medical Institute (HHMI) researchers have uncovered a protein that stops the growth of melanoma, a cancer that develops from pigment-producing cells in the skin called melanocytes. HHMI investigator Michael Green and colleagues at the University of Massachusetts Medical School reported their identification of the genetic underpinnings of a new way to thwart one of the deadliest forms of cancer in the February 8, 2008, issue of the journal Cell.

Green and his colleagues began by designing experiments that would help them determine what separates melanomas from ordinary moles at the genetic level. Moles, also known as nevi, and melanoma often result from the same genetic mutation, and the biological pathway that differentiates the two had been a mystery. The new study uncovers a relatively unknown protein that regulates the melanocyte’s “decision” to ward off cancer by either entering a programmed hibernation or committing suicide.

According to the American Cancer Society, 60,000 people in the United States developed melanoma in 2007, and more than 8,000 died of the disease. Melanoma is caused by the uncontrolled proliferation of melanocytes, whose pigment, melanin, protects the skin against the sun’s ultraviolet rays. Nevi, which are benign, are also caused by abnormal growth and differentiation of melanocytes.

While nevi are, by definition, non-cancerous, more than half the time the same mutation is at fault in melanoma and nevi: a single amino acid change in a protein called BRAF. BRAF is part of a signaling system that is important for cell growth and proliferation. The BRAF mutation found in nevi and melanoma increases the activity of the BRAF protein, prompting cells to multiply abnormally. In some melanocytes with this mutation, the proliferation cannot be stopped, and cancer develops.

But sometimes when the mutated BRAF gene is expressed in melanocytes, those cells go into a state of permanent hibernation via a process known as senescence. These cells form nevi, not melanoma. This, according to Green, indicates that the genetic checks and balances within those cells are working correctly. “The cell has sensed this oncogenic influence–activated BRAF–and that induces an anti-cancer mechanism to throw the cell into this frozen state,” he said. Green added that sometimes cells simply commit suicide instead of senescing.

Cancer results when something blocks this failsafe mechanism, said Green. “While this phenomenon was known, the components and the pathways involved were not,” he said.

Green, his postdoctoral fellow Narendra Wajapeyee, and their colleagues did a genome-wide search for the proteins involved. They used engineered retroviruses to insert short bits of RNA to selectively turn off individual genes in a series of melanocytes. Some of the cells progressed to cancer, while others did not. After testing thousands of genes, they found 17 that were required for activated BRAF to induce either senescence or suicide. Together, Green said, the proteins made by these genes make up the body’s melanoma defense pathway.

Green’s group found that three of those proteins are required for both the senescence and programmed cell death pathways. The identity of one of those proteins, insulin-like growth factor binding protein 7 (IGFBP7), surprised the researchers. Not much was known about IGFBP7, except that it was secreted, said Green. A secreted protein does not stay inside the cell that produces it, but instead is released from the cell and moves through the blood to other cells. Green said that a secreted protein’s role in the pathway caught them off guard, because “we would have thought this process would be purely intracellular.”

Green and his colleagues focused their attention on IGFBP7 because its presence suggested something intriguing: If one otherwise healthy melanocyte begins expressing BRAF, the IGFBP7 it produces can enter cells around it, prompting lots of melanocytes to “switch off,” rather than risking a tumor.

In the experiments reported in Cell, the researchers exposed human melanoma cells in culture to recombinant IGFBP7. The protein had the same genetic code as the human version, but was produced using genetically modified insect cells. The melanoma cells that were treated with IGFBP7 committed suicide– just as though their anti-cancer mechanism was working correctly.

The researchers also injected the protein into the bloodstream of mice on to which human melanoma tumors had been grafted. IGFBP7 entered the tumor cells and stopped their growth in the mice. “Melanoma cells [caused by BRAF mutations] shut off expression of this key regulator,” said Green. “Because of that, the cells escape from senescence and form a tumor.”

According to Green, the research also answers another controversy in the field: Are nevi dead-ends or are they precursors to melanoma” “If you go in and see a dermatologist, if they see a mole, they will generally… cut it off,” he said. “They don’t want to take the chance that it could be a precursor.”

However, Green thinks his results point in the other direction. Because IGFBP7 is a secreted protein, even if one activated BRAF-containing — but otherwise healthy — cell in the nevi stopped producing IGFBP7 and threatened to form a tumor, the IGFBP7 being secreted from the cells around it would kill it. “It’s an extremely powerful anti-cancer mechanism,” said Green.

The team’s findings are important not only from a research standpoint, but also for future clinical treatments, Green noted. Melanoma can be surgically removed if caught early, but in advanced cases there is really no treatment for it. Green said IGFBP7’s ability to target melanoma tumors throughout the body may make it a powerful tool for cancer therapy. “We’re really very excited about the prospects of trying to advance this as a melanoma treatment,” he said.

If this natural anti-cancer agent, called IGFBP7, can be produced and delivered to tumors, it might serve as a targeted chemotherapy for metastatic melanoma, a condition which is “basically untreatable” today, said  Green. It might also be used to treat other cancers with mutations in the oncogene known as BRAF.

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Slimming down is somewhat like boating. You set your course toward a destination (your goal weight), propel yourself with the right fuel (diet and exercise) and end up on an island paradise (in a bikini!). But the tiniest leak in your ship could sink your efforts. We’ve uncovered 10 sneaky ways your workout, your work habits and even your clothing can undermine your diet, and we devised easy fixes for each. Spot what’s holding you back, try our tips and set off toward your ideal body. Then slip into that swimsuit and enjoy!

Diet flub #1: You grocery shop on the fly
Like your boss and karaoke night, some things simply don’t go well together. The supermarket and an empty stomach are similarly mismatched. Shopping when you’re hungry makes you more likely to fill your basket with junk.

Fix it: Skip the checkout line and go online. Dieters who shopped at Web-based groceries bought fewer high-fat foods, a study from the University of Connecticut at Storrs finds. “It makes it easier to stick to your list,” says Amelia Lake, Ph.D., a research fellow at the Human Nutrition Research Centre at Newcastle University in Newcastle Upon Tyne, England. (Go to Self.com/health for a balanced list.) If you shop in person, stick to the store’s perimeter (typically the produce and dairy areas) to avoid impulse buys.

Diet flub #2: You work late
Overtime may help you nab a fatter paycheck, but it could foil your efforts to downsize your figure. Women who worked 40-plus hours per week were more likely to gain weight during the year than those who clocked out earlier, a study in the International Journal of Obesity reports. Stress and fatigue may make desk jockeys more apt to eat fast food and less inclined to exercise. “Women’s bodies are wired to hang on to fat, especially in the abdomen, when they experience chronic stress,” says Kathleen Hall, Ph.D., founder of The Stress Institute in Atlanta.

Fix it: Take mood-lifting breaks. “Pinpoint when during the day you’re most likely to hit a slump,” Hall says. “Then engage in something playful or soothing during that time — doing so produces feel-good endorphins to battle stress.” Put on headphones and download a new song, or recap last night’s reality-TV antics with a friend. Physically active downtime is especially effective, Hall says; stretch, toss a foam ball with an officemate or pump out a set of biceps curls using a dumbbell stashed under your desk.

Diet flub #3: You celebrate workouts with M&M’s
After a tough hour at the gym, do you (A) grab fresh fruit, (B) feel too great to eat or (C) reward yourself with a huge dinner (“I’ll have the Fiesta Nachos, please!”)? If you answered C, you’re not alone. Women ate about 120 more calories following intense exercise than after a lighter workout that burned the same calories, a study from the University of Ottawa reveals. The splurge may feel justified because the workout seemed so difficult.

Fix it: Stow a healthy snack in your gym bag so you don’t overdo your next meal. Mix ¼ cup of dried cranberries with 2 tablespoons of unshelled sunflower seeds in a resealable plastic bag. The mix packs protein and carbs to satisfy your hunger, and cranberries contain antioxidants that help quell postworkout inflammation, says Leslie Bonci, R.D., director of sports medicine nutrition at the University of Pittsburgh Medical Center.

Diet flub #4: You don’t ever count calories
You may think you’re vigilant about monitoring portions, but mindless bites can equal hundreds of unaccounted-for calories.

Fix it: If dieting were a poker game, logging your food intake would be your ace in the hole. But few women have the discipline (or the time) to record every morsel. Fortunately, simply thinking about your most recent meal can keep overeating in check, a study from the University of Birmingham in England suggests. When women were asked to write down what they had for lunch before they were offered cookies later in the day, they ate fewer treats than those who weren’t asked to remember their meal. “Recalling what you ate may remind you of how filling that food was,” says lead researcher Suzanne Higgs, Ph.D.

Diet flub #5: You’re an e-mail addict
The number of calories you burn e-mailing a coworker? Five. The number it takes to walk over to her? Eleven. Multiply that by how often this scenario plays out in a week (roughly a bazillion), and you see how tech squelches your activity level.

Fix it: Slip movement into your entire day, not only your gym time. Stand up when you’re talking on the phone, and deliver at least five messages a day in person. You can torch about 100 calories daily this way, says James Levine, M.D., an endocrinologist at the Mayo Clinic in Rochester, Minnesota. That’s enough to burn off nearly a pound a month!

CONTINUED: Diet flub #6

When your body grows accustomed to performing the same exercise over and over, it starts to get better at it. The result? Each move requires less effort, so you burn fewer calories.

Fix it: Step out of your comfort zone. For starters, ramp up your cardio with intervals (short bursts of high-speed effort. Volunteers who interspersed hour-long bike rides with intervals (four minutes at high intensity followed by two minutes of rest) burned 36 percent more fat than when they cycled at a steady, moderate intensity, a study in the Journal of Applied Physiology indicates. Vary the type of exercise you do for even better results. If you lift weights, try kickboxing; if you’re a cardio queen, pick up weights. Already burning and firming? Join a sports team. New activities sizzle more calories by activating different muscle groups.

Diet flub #7: You prefer comfy clothing
Forgiving styles, such as flowy tops and unstructured dresses, make it easy to miss cues that extra pounds are creeping on.

Fix it: Keep tabs on your tush by zipping up your favorite pair of denims every Friday. “I tell my clients all the time, ‘Jeans don’t lie,’ ” says Jim Karas, a trainer in Chicago and author of “The Cardio-Free Diet” (Simon Spotlight Entertainment). “Wear your jeans on the weekend; most people tend to eat more on those two days,” Karas says. Once you’ve dropped a size, give away your larger clothes to ensure you won’t drift into them again.

Diet flub #8: You taste while you cook
You can slice and dice with the best of them, so you can whip up a nutritious, light meal instead of dialing for oil-drenched takeout. But a spoonful here, a bite there and that glass of wine you sip while you’re stirring can quickly add up until you’ve consumed a meal’s worth of calories before dinner even hits the table.

Fix it: To keep your mouth busy, fix yourself a bowl of chopped veggies to munch on, or chew a piece of gum — it’s no fun sneaking samples of stew with spearmint breath. You might also invite a pal into the kitchen with you. “My clients nibble more when they’re preparing dinner alone because they’re not occupied by talking to someone,” says Monique Ryan, R.D., of Chicago. Cooking for one? Plug in your iPod and sing along.

Diet flub #9: Your kitchen is packed
If your fridge resembles a Trader Joe’s display case, then you’ll be constantly tempted to nosh. Dieters who were allowed to eat whatever they wanted for snacks took in more snack calories each week than those who were limited to one type, a study in the journal Eating Behaviors notes. Repeat eaters got tired of the flavor and craved it less. The same concept applies whether you’re faced with unlimited options at a buffet, a restaurant or your own stuffed pantry. The more choices you have, the bigger your appetite will seem.

Fix it: Pick one splurge item to keep in the house at a time — chocolate, ice cream sandwiches or your favorite cheese — and have a little each day to satisfy your taste buds. Don’t buy another treat until you’ve finished it. (But don’t down it all at one sitting.) When you’re eating out, skip buffets, forget the enormous menu and order from the specials board; you’ll have fewer options, and the ingredients will probably be fresher anyway.

Diet flub #10: You slim down solo
It’s tempting to keep your 10-pound goal a secret (and wow everybody later with your results), but coming clean about your diet to pals increases your odds of success, according to an analysis of 46 studies by researchers at Tufts-New England Medical Center in Boston. People with social support lost 6 percent more weight than those who dropped pounds on their own.

Fix it: Tell roommates, family and coworkers that you’re eating healthfully. “They can provide encouragement, serve as role models or at least avoid acting as a bad influence,” says lead author Michael Dansinger, M.D. “It also adds accountability.” Pretty soon, the news will be everywhere: You’ve lost the weight for good.

Copyright © 2007 CondéNet. All rights reserved.

(WebMD) A new survey shows that one in 33 U.S. teens has tried meth, nearly a quarter say it would be easy to get meth, and some see benefits to meth use.

The survey included about 2,600 students aged 12-17 at 43 public, private, and parochial junior and senior high schools nationwide. The margin of error is on average +/- 2 percentage points.

During class last spring, the students completed the confidential surveys about methamphetamine (meth) use.

The results show that most teens haven’t tried meth. But many say they could get meth pretty easily if they tried.

• Nearly a quarter (24 percent) say it would be “very” or “somewhat” easy for them to get meth.
• 1 in 10 said they have ever been offered meth.
• Students who admit to ever using meth say they first tried meth at age 12, on average.

The survey also shows that about one in six students say they have a friend or family member who has used meth or been treated for meth use.

Most students reported strongly disapproving of using meth even once or twice and indicated that they consider meth use to be risky, even if only used once or twice.

But some students actually saw benefits to meth use.

Almost a quarter (24 percent) say meth “makes you feel euphoric or very happy.” Nearly as many (23 percent) said meth helps people lose weight, and 22 percent said meth “helps you deal with boredom.”

Few teens said they talked to their parents about meth.

Earlier this year, other researchers reported that crystal meth is more widely used among young adults in the U.S. than previously thought.

Crystal meth is smoked. Meth can be injected, snorted, or taken as a pill, and meth also goes by other names, including crank, speed, chalk, white cross, fire, and glass.

GFK Roper Public Affairs & Media conducted the meth survey for the Meth Project, which seeks to curb meth use.

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Janet McGrath, a 34-year-old graphics designer in Las Vegas, underwent treatment for clinical depression for six months before she began to accept the reality that her face would probably bear ugly acne scars for life. Happily, another realization soon followed: with the right kind of acne scar treatment, she could reclaim large parts of her face. “In the past year, my face has gone from looking like the surface of the moon to a dirt track,” is the way Janet describes it. What she probably means is that the ugly pockmarks have given way to skin that is a little rough and uneven.

Scars outside and within
The problem of acne scarring is a widespread one that often proves no less thorny than the actual acne outbreak. While plenty of acne patients are relieved that their acne outbreaks appear to be under control, they cannot come to terms with the fact that the unsightly scars remain as a reminder of their suffering. Typically, the milder forms of acne do not cause scarring, as most of us know. At worst, the scarring may be temporary. However, those who suffer from graver forms of acne such as cystic acne are likely to be left with unsightly scars that also have a deep-rooted mental effect.

Types of acne scars
According to dermatologist Dr Andrew Waite, many of his patients come to him for treatment of “post-inflammatory pigmentation”, which is the condition that follows the healing of an acne lesion. He adds that acne scars may be divided into two categories – keloids, which cause an overgrowth of irregular-shaped tissue at the site of a healed lesion and which may be hereditary in nature; and ice-pick scars, which are commoner than keloids, are linear or circular in shape, and are the result of loss of tissue from the injured spot. Soft tissue scars and depressed fibrotic scars are variations of ice-pick scars.

Treatment of acne scars
As with all things acne, the Acne Treatment for scars is not a straightforward affair. Depending on the intensity of the scars, your dermatologist may prescribe anything from topical lotions to LASER therapy, or even that painful process known as dermabrasion. Skin grafts and filling agents like collagen are also used on occasion. Skin grafts from behind the ears – using a technique known as punch grafting – are particularly helpful for stubborn ice-pick scars.

Very severe scars may require dermabrasion, a procedure in which the stratum corneum is removed by abrasion. As Dr Waite says, the procedure is painful and usually requires a general anesthetic. Post-operation, the skin is red and raw and takes several months to heal. And dermabrasion is not too successful when it comes to sunken scars; it works better when the scar is raised above the surrounding skin.

Those who opt for LASER therapy for acne scarring will experience a rawness of the skin similar to that caused by dermabrasion. This is because LASER therapy involves the use of carbon dioxide to carefully remove skin layer by layer. Yet another process is peeling, which once again involves the removal of the epidermal layer, and is ideal for superficial scars.

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