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Researchers Creating Ways to Alert Immune System to Recognize Cancer Cells

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Cancer cells can bypass the immune system by pretending to be harmless. But researchers at the University of North Carolina at Chapel Hill’s Eshelman School of Pharmacy, led by Moo J. Cho, Ph.D., an associate professor of molecular pharmaceutics, are creating a way to expose these cancer cells and alert the immune system to recognize and attack the tumor.

“It’s like planting a big red flag on the tumor to attract the attention of the body’s immune system, which normally ignores cancerous cells,” Cho said. “It’s a great idea. We just don’t know how to do it yet.”

The Natinal Cancer Institute has awarded Dr. Cho, a member of UNC’s Lineberger Comprehensive Cancer Center. The goal of the research is to develop a unique way to intravenously administer a nucleic acid derived from bacteria and deliver it to a tumor. While it is possible to inject some tumors directly, many are relatively inaccessible and can be better reached through the body’s own pathways, Cho said.

The bacteria’s nucleic acid would normally be excreted very rapidly from the body when delivered via IV. Cho plans to add a molecule to the nucleic acid that will allow it to latch on to a class of proteins called IgG immunoglobulin that occur naturally in the body.

“We will ask the IgG antibodies to carry the bacteria-derived nucleic acid as a guest throughout the body,” Cho said. “This will allow the nucleic acid to circulate for days, which is different from how antibodies have been used in classical targeted delivery.”

Cho believes that eventually enough nucleic acid will be carried to the tumor to attract the attention of nearby immune cells, which recognize the nucleic acids as an invading pathogen, triggering an anti-tumor immune response. This approach differs from the classical method of actively targeting a tumor based on specific markers.

“Rapidly growing solid tumors are surrounded by imperfect, almost chaotic, blood flow,” Cho said. “The tissue is very leaky. Because of this unusual permeability, the antibody-nucleic acid complex should become lodged in the tumor periphery. This should mimic a local infection, which the body will work to eliminate.”

Infecting a tumor so that the body can see it and kill it is one element of immunotherapy, a cancer-treatment option that has been used since the late nineteenth century but has fallen out of favor since the development of radiation therapy and chemotherapy. Radiation and chemotherapy are well understood and relatively predictable, but they can kill healthy cells as well as cancerous ones, suppress the immune system, and come with unpleasant and often dangerous side effects.

“You can use a sledgehammer to kill a fly,” Cho said. “But I prefer to try a lighter touch.”

Breast Cancer Radiation Treatment Time Reduced from Seven Weeks to One

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A recent study presented at the American Society for Therapeutic Radiology and Oncology meeting, claims that accelerated partial breast irradiation (APBI) using a newer type of irradiation therapy called balloon brachytherapy reduces radiation therapy from six or seven weeks to one, and is as effective in keeping breast cancer from coming back as the standard external beam radiation treatment.

“Not only does it make radiation treatment much more convenient, it may actually increase the rate of breast conservation, since some women choose mastectomy because they live too far from a radiation center and cannot afford the time and expense of six to seven weeks of living or traveling to the center,” Peter Beitsch, M.D., lead author of the study and a surgical oncologist at Medical City Dallas Hospital in Dallas, said. “Also, there are many women who for a host of reasons don’t receive the necessary postoperative radiation and the shortened course should hopefully allow more women to receive the therapy that they need.”

Many women have a lumpectomy followed by radiation therapy, which enables them to keep their breast after treatment, a process that can last some six or seven weeks. Brachytherapy treats only the area surrounding the tumor, instead of the whole breast. After removal of the tumor, a small balloon is inserted into the cavity. The balloon is attached to a catheter which delivers high doses of radiation via tiny radioactive seeds into the lumpectomy cavity.

The American Society of Breast Surgeons (ASBS) MammoSite RTS Registry Trial evaluated data from more than 1,400 women with early stage breast cancer who were treated with balloon brachytherapy using the MammoSite Radiation Therapy System, one type of breast brachytherapy. In this study, 400 women were followed for nearly four years and results show that women with early-stage breast cancer who are treated with APBI using this type of balloon brachytherapy had the same chance of the cancer returning as those who had the standard radiation treatment.

The study was presented September 22, 2008, at the American Society for Therapeutic Radiology and Oncology’s 50th Annual Meeting in Boston, MA.

Source: American Society for Therapeutic Radiology and Oncology (ASTRO), September, 2008

Frequency of Eating Candy, Not Amount, Increases Risk of Cavities

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According to Temple University pediatric dentist Mark Helpin it’s the frequency of eating candy, not the amount, that increases the risk of cavities. So when her daughters go trick or treating, Megan Chiplock lets them eat as much as they want.

“We let them go at it, gorge themselves, and maybe for a few days after if they want a piece here and there,” she says. “But they really get their fill on Halloween night, and [then] it’s sort of out of their system.” “The frequency of eating candy, and other refined carbohydrates, and their stickiness, are big factors in creating the risk of caries (cavities),” adds. Mark Helpin.

The pH balance in the mouth can be changed by eating carbohydrates. The resulting increase in acidity can increase the risk of cavities, and each time someone eats candy it can take an hour for the acid environment in the mouth to dissipate.

“So, if I eat a piece of candy now, the pH in my mouth will become acidic, and it will take 30-60 minutes for it to become normal,” said Helpin. “If I keep eating candy throughout the day, there is acid in my mouth for a much longer period of time. The longer teeth are in an acid environment, the greater the risk they will become decayed.”

There are several ways that parents can allow kids to enjoy the holiday, and still minimize the risk, says Helpin, the acting chair of Pediatric Dentistry at Temple’s Maurice H. Kornberg School of Dentistry. “Parents can let kids eat a bunch [of candy] now and a bunch later. But don’t let them have one piece now, then an hour later let them have another piece,” he said, adding that candy can also be dispensed as a dessert or snack. Treats as dessert at mealtimes? Good idea, says Helpin, because the production of saliva increases and that helps wash away oral acidity. Brushing teeth immediately after eating candy is recommended by Helpin, or at least rinsing out the mouth with water 3 or 4 times after eating, again to reduce acidity in the mouth.

Helpin warns that substituting small bags of chips or pretzels for candy doesn’t solve the cavity problem, either. “Chips and pretzels are also carbohydrates and they also will create an acid environment that can create cavities,” he says. “These treats and snacks get stuck on your teeth, and that’s the stickiness factor,” he said.

At trick or treat time, Helpin avoids sticky candies in favor of sugar-free varieties. Ultimately, “it’s not realistic to think you can tell your child you can’t have candy, cookies, cakes, or other treats,” says Helpin. “Those are the things most people enjoy—and we want our kids to enjoy life.”

Pregnant Moms: Eat Your Fish, It’s Good For Baby, So Is Longer Breastfeeding

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A study of Danish mothers and infants finds that infants benefit from physical and cognitive development when the mother eats fish when pregnant. Longer breastfeeding also benefits baby.

Fears of mercury levels in fish have led to American women being advised to keep their fish consumption to a minimum, but this study recommends that pregnant women eat low-mercury fish—cod, plaice, salmon, herring and mackerel—at least three times a week. Additionally, the study reinforces existing evidence that breastfeeding is beneficial to an infant’s development.

“These results, together with findings from other studies of women in the U.S. and the United Kingdom, provide additional evidence that moderate maternal fish intake during pregnancy does not harm child development and may on balance be beneficial,” said Assistant Professor Emily Oken, lead author of the study.

Researchers from the Department of Ambulatory Care and Prevention of Harvard Medical School and Harvard Pilgrim Health Care and the Maternal Nutrition Group from the Department of Epidemiology at Statens Serum Institut in Copenhagen, Denmark, conducted the study. It was published in the September issue of American Journal of Clinical Nutrition and confirmed that the omega-3 fatty acids in fish, and breast milk compounds benefit infant development.

The study reviewed 25,446 children born to pregnant women enrolled from 1997—2002 in the Danish Birth Cohort. Participants were asked about child development markers at 6 and 9 months postpartum, and breastfeeding at 6 months postpartum. Prenatal diet, including amounts and types of fish consumed weekly, was assessed by a detailed food frequency questionnaire administered when they were six months pregnant.

Mothers were asked about their infants’ specific physical and cognitive development markers at 6 months, eg. holding up his/her head, sitting with a straight back, sitting unsupported, responding to sound or voices, imitating sounds, or crawling. More advanced markers were checked at 18 months – could the child hold up his/her head, sit with a straight back, sit unsupported, respond to sound or voices, imitate sounds, or crawl.

The children whose mothers ate the most fish during pregnancy were more likely to have better motor and cognitive skills. For example, among mothers who ate the least fish, 5.7% of their children had the lowest developmental scores at 18 months, compared with only 3.7% of children whose mothers had the highest fish intake. Compared with women who ate the least fish, women with the highest fish intake (about 60 grams—2 ounces—per day on average) had children 25% more likely to have higher developmental scores at 6 months and almost 30% more likely to have higher scores at 18 months.

Longer duration of breastfeeding was also associated with better infant development, especially at 18 months. Breastmilk also contains omega-3 fatty acids. The benefit of fish consumption was similar among infants breastfed for shorter or longer durations.

“In previous work in a population of U.S. women, we similarly found that higher prenatal fish consumption was associated with an overall benefit for child cognitive development, but that higher mercury levels attenuated this benefit,” says Dr. Oken. “Therefore, women should continue to eat fish—especially during pregnancy—but should choose fish types likely to be lower in mercury.” Information on mercury levels in commonly consumed fish is available at the U.S. Food and Drug Administration website.

Source: American Journal of Clinical Nutrition, September, 2008

Simple Blood Test May Identify People At Risk Of Developing Alzheimer’s Disease

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A 20-year study by researchers at Columbia University Medical Center has found that a simple blood test may identify people at risk of developing Alzheimer’s Disease. These ground-breaking findings could change the way the disease is treated or someday prevent it.

The findings indicate that people with elevated levels of a certain peptide in the blood plasma, Amyloid Beta 42 (Aß42), are at increased risk of developing Alzheimer’s disease. Conversely, a decline of Aß42 in the bloodstream may signal the compartmentalization or “traffic jam” of Aß42 in the brain, which occurs in the brains of people with Alzheimer’s.

“To date, Aß42 levels have measured most reliably in the cerebrospinal fluid, which is more difficult to collect than blood,” said Nicole Schupf, Ph.D., Dr.P.H., associate professor of clinical epidemiology at Columbia University Medical Center and lead author of the paper. “Blood draws can be done with relative ease and greater frequency than spinal taps, which is typically the way cerebrospinal fluid is collected.”

The study showed researchers that plasma levels of Aß42 appear to increase before the onset of Alzheimer’s disease and decline shortly after the onset of dementia. They deduce that Aß42 trapped in the brain could account for the decrease in levels post-dementia. Richard Mayeux, M.D., M.S., professor of neurology, psychiatry, and epidemiology, and co-director of the Taub Institute of Research on Alzheimer’s Disease and the Aging Brain at CUMC, led the Northern Manhattan study, and compares findings finding to something similar seen in heart attack patients, who typically have elevated lipid levels in their bloodstream prior to a heart attack, but decreased post-heart attack lipid levels.

Dr. Mayeux, the senior author of this paper, reported that, using more specific antibodies developed by the Ravetch Laboratory at Rockefeller University, the research team isolated the most harmful form of amyloid compound, the protofibrillar form of Aß. While the cognitive impairments of Alzheimer’s can be monitored throughout the disease course, clinicians have had no reliable way to monitor the pathologic progression of the disease.

Being able to reliably measure Aß levels in the blood could provide clinicians with a tool that forecasts the onset of Alzheimer’s much earlier. Earlier detection would of course be an important step in combating the disease, researchers said.

Source: Proceedings of the National Academy of Sciences, Sept. 8, 2008

Too Few Americans Being Vaccinated Against Serious Diseases

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The Center for Disease Control warns that far too few Americans are being vaccinated against serious, even deadly diseases.

“There’s always been an emphasis in pediatrics on prevention, and immunizations are a big part of that, but adult medicine has not caught up,” says William Sutker, M.D., infectious disease specialist on the medical staff at Baylor University Medical Center at Dallas. Confirming this observation, a study by the Centers for Disease Control (CDC) found that less than five percent of American adults are up-to-date on all of their immunizations.

“I think people don’t realize the number of deaths that occur because of infectious diseases every year,” says Dr. Sutker. It is estimated only 50% of adults over 50 with diabetes or heart disease should receive flu or pneumonia vaccines. “I think the flu and pneumonia vaccine are grossly underutilized,” adds Dr. Sutker.

“All adults over 60 also should be vaccinated against shingles, but just two-percent currently are. And now there’s yet another concern—whooping cough. Because adults haven’t been immunized against whooping cough in years, the illness is now starting to show up in adults and so that’s why there’s been a new emphasis trying to immunize adults again,” says Dr. Sutker.

The whooping cough vaccine is given in combination with the diphtheria and tetanus booster— which should be administered every 10 years. Experts say the results of this CDC study prove not nearly enough emphasis is put on adult immunizations, which can be lifesaving.

“So although it seems we’re more concerned with heart disease and cancer, I think the public needs to know that infectious diseases are still out there and are a potential cause of problems,” says Dr. Sutker.

For more information about vaccinations, talk to your family physician.

Source: Baylor Healthcare Systems

Mental Abilities Weaken Long Before Death, Despite Absence of Dementia

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A new study finds that a decline in older people’s’ mental abilities starts years before death, even if they do not have dementia.

“These changes are different and separate from the changes in thinking skills that occur as people get older,” said study author Valgeir Thorvaldsson, MSc, of Göteberg University in Sweden. “We found accelerated changes in people’s mental skills that indicated a terminal decline phase years before death.”

Perceptual speed starts deteriorating some 15 years before death, spatial ability starts failing nearly 8 years before death, and verbal ability about 6.5 years before death. These findings came out of a study using 288 people without dementia, who were monitored from age 70 to death, with an average age at death of 84. Their mental skills were checked up to 12 times over a 30-year period, to ensure they did not have dementia.

Said Thorvaldsson: “Cardiovascular conditions such as heart disease or dementia that is too early to be detected could be factors,” he said. “Increased health problems and frailty in old age often lead to inactivity, and this lack of exercise and mental stimulation could accelerate mental decline.”

Thorvaldsson also noted that verbal abilities declined sharply in the terminal phase and did not decline significantly due to age only. “This indicates that people remain stable in their verbal abilities unless they are experiencing disease processes that also increase their mortality risk,” he said. “A change in verbal ability might therefore be considered a critical marker for degeneration in health in older people.”

Source: Neurology, the medical journal of the American Academy of Neurology, August 27, 2008, online edition.

Researchers Determine What Causes Baggy Eyelids

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Fat expansion in the eye socket is the reason baggy eyelids come with aging, according to a UCLA research team, who advise patients looking for a cure that fat excision should be the main target of treatment for this condition.

The study is the first to examine the anatomy of multiple subjects to determine what happens to the lower eyelid with age. The effects of age on the face were also measured using high-resolution magnetic resonance imaging.

“A common treatment performed in the past and present is surgical excision of fat to treat a ‘herniation of fat’ —meaning that the amount of fat in the eye socket does not change but the cover that holds the fat in place, the orbital septum, is weakened or broken and fat slips out,” said lead author Dr. Sean Darcy, a research associate in the division of plastic and reconstructive surgery at the David Geffen School of Medicine at UCLA and a plastic surgery resident at the University of California, Irvine.

“This orbital septum weakening or herniation-of-fat theory is what most plastic surgeons have been taught. However, our study showed there is actually an increase in fat with age, and it is more likely that the fat increase causes the baggy eyelids rather than a weakened ligament,” Darcy said. “There have been no studies to show that the orbital septum weakens.”

40 people participated in the study, (17 males, 23 females) between the ages of 12 and 80 years, and the evidence showed that the lower eyelid tissue increased with age and that the largest contributor to this size increase was fat increase. The American Society of Plastic Surgeons reported that in 2007 close to 241,000 Americans had eyelid surgery, one of the top four cosmetic procedures. Many plastic surgeons treating baggy eyelids do not remove fat but reposition it, or tighten the ligament holding the eyeball in place. Meanwhile, there is no data sowing that these structures change with age.

“Our findings may change the way some plastic surgeons treat baggy eyes,” said study co-author Dr. Timothy Miller, professor and chief of plastic surgery at the Geffen School. “Our study showed that a component of a patient’s blepharoplasty procedure should almost routinely involve fat excision rather than these procedures.”

Blepharoplasty refers to surgical rejuvenation of the upper or lower eyelids, or both, depending on the extent of aging or disease. The procedure is usually performed on the lower eyelid because the most common complaint patients have is that their eyes appear tired, puffy or baggy. The surgeon makes external incisions along the natural skin lines of the eyelid to remove the excess fat and improve the contour of the lower eyelid.

“Although baggy lower eyelids are a significant result of aging and fat expansion, there are other factors that can contribute too,” Miller said. “We recommend that surgeons evaluate each component and address them accordingly in an individualized approach to blepharoplasty.”

Source: Journal of Plastic and Reconstructive Surgery, September, 2008

Hormone Replacement Therapy (HRT) Improves Sleep, Sexuality and Joint Pain in Older Women

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The British Medical Journal has just published the findings of new study by the WISDOM research team (Women’s International Study of long Duration Oestrogen after Menopause) which finds that HRT therapy can achieve major improvements in quality of life.

The average age of the 2,130 post-menopausal women used for the study was 13 years after menopause (although most of them did not have menopausal symptoms). Participants lived in the UK, Australia and New Zealand, and the study measured the impact on their quality of life of combined oestrogen and progestogen hormone therapy.

“Our results show that hot flushes, night sweats, sleeplessness and joint pains were less common in women on HRT in this age group. Sexuality was also improved,” says Professor Alastair MacLennan, leader of the Australian arm of WISDOM and head of Obstetrics & Gynaecology at the University of Adelaide, Australia. Overall, quality of life measures improved. Even when women did not have hot flushes and were well past menopause, there was a small but measurable improvement in quality of life and a noted improvement in sleep, sexuality and joint pains. HRT users also had more breast tenderness and discharge compared to those on a placebo,” he says.

Dr. Beverley Lawton, Head of WISDOM New Zealand, says: “These new data should be added to the risk/benefit equation for HRT. The quality of life benefits of HRT may be greater in women with more severe symptoms near menopause. New research suggests that HRT taken from near menopause avoids the cardiovascular risks seen when HRT is initiated many years after menopause.”

Professor MacLennan says studies such as those conducted by WISDOM “enable the risks of HRT to be reduced and its benefits maximized when the treatment is individualized to each woman”.
“Early start-up side effects can usually be alleviated by adjusting the treatment,” he says. “For most women with significant menopause symptoms the benefits of HRT outweigh the risks.

The latest analyses of the main long-term randomized control trial of HRT (The Women’s Health Initiative) show that breast cancer is not increased by oestrogen-only HRT and is only increased in women using combined oestrogen and progestogen HRT after seven years of use. This increased risk is less than 0.1% per year of use.

“If a woman feels that HRT is needed for quality of life, then doctors can find the safest regimen for her. She can try going off HRT every 4-5 years, and can then make an informed choice about whether she takes and continues HRT.”

Source: British Medical Journal, Augst 22, 2008 (BMJ 2008;337:a1190)

BMP-7 Protein Produces “Good” Fat that Helps Fight Obesity

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Researchers have found that a bone growth protein, known as BMP-7, also aids the growth of brown (or “good”) fat that helps fight obesity.

“Obesity is occurring at epidemic rates in the U.S. and worldwide and that impacts the risk and prognosis of many diseases,” said Yu-Hua Tseng, Ph.D. an Assistant Investigator in the Joslin Section on Obesity and Hormone Action and lead author of the paper published in the August 21 issue of Nature. “We hope this study can be translated into applications to help treat or prevent obesity.”

Dr. Teng cited obesity as a major risk factor for type 2 diabetes, and its close relationship to the metabolic syndrome, a group of medical problems associated with insulin resistance that can increase the risk of atherosclerosis.

Dr. Teng states that there are 2 main types of fat cells, white and brown. In laboratory studies of mouse cells, she and her colleagues found that a bone-producing protein called BMP-7 drives precursor cells giving rise to mature brown fat cells.

“White fat cells are the ‘conventional’ form of fat designed to store energy. By contrast, the main role of brown fat is to burn calories by generating heat. Brown fat cells largely disappear by adulthood in humans, but their precursors still remain in the body,” Tseng explained.

An earlier (2005) Joslin study by Dr. Teng and colleagues discovered genes that control the creation of the precursor cells of brown fat. A later (2007) Joslin study by C. Ronald Kahn, M.D., head of the Joslin Section on Obesity and Hormone Action and also a co-author of the current Nature study, found clusters of brown fat cells dispersed between bundles of muscle fibers in an obesity-resistant strain of mice.

The study identified BMP-7 as the protein capable of inducing the formation and function of brown fat cells.Delivery of BMP-7 into mice using adenovirus as a vector resulted in an increase in the development of brown fat tissue. In one of the experiments, the mice that developed brown fat tissue gained less weight than those that did not. In another experiment, mice that received injections of progenitor cells—similar to stem cells—that had been pre-treated with BMP-7 also developed additional brown fat tissue.

The purpose of the study was to determine what controls the development of fat depots, a central question in adipocyte biology. BMPs are a family of proteins known to regulate organ formation during embryonic development. Dr. Teng and associates suggested that different members of BMPs determine brown versus white fat cell fate. Scientists hope that improved knowledge of fat development will lead to new drugs or therapeutic approaches to fight obesity.

“Diet and exercise are still the best approaches for weight reduction in the general population,” Tseng said. “However, for people who are genetically predisposed to obesity, these approaches may have very little effect.” As we learn more about the controls of brown fat development, medical interventions to increase energy expenditure by brown fat inducing agents, such as BMP-7, may provide hope to these individuals in losing weight and preventing the metabolic disorders associated with obesity,” she said.

Source: Nature, August 21, 2008