Researcher Jane Armer

Yaowarat Matchim, a former nursing doctoral student; Jane Armer, professor of nursing; and Bob Stewart, professor emeritus of education and adjunct faculty in nursing, found that breast cancer survivors’ health improved after they learned Mindfulness-Based Stress Reduction (MBSR), a type of mindfulness training that incorporates meditation, yoga and physical awareness.

“MBSR is another tool to enhance the lives of breast cancer survivors,” Armer said. “Patients often are given a variety of options to reduce stress, but they should choose what works for them according to their lifestyles and belief systems.”

Researcher Yaowarat Matchim

“Mindfulness-based meditation, ideally, should be practiced every day or at least on a routine schedule,” Armer said. “MBSR teaches patients new ways of thinking that will give them short- and long-term benefits.”

Armer says the non-pharmaceutical approach works best as a complement to other treatment options such as chemotherapy, radiation and surgery.

“Post diagnosis, breast cancer patients often feel like they have no control over their lives,” Armer said. “Knowing that they can control something—such as meditation—and that it will improve their health, gives them hope that life will be normal again.”

The study, “Effects of Mindfulness-Based Stress Reduction (MBSR) on Health Among Breast Cancer Survivors,” was published in the Western Journal of Nursing Research.

Material adapted from University of Missouri-Columbia.

“Weight loss and reduced insulin levels are required for breast cancer prevention, but [these levels] are difficult to achieve and maintain with conventional dietary approaches,” said Michelle Harvie, Ph.D., SRD, a research dietician at the Genesis Prevention Center, who presented the findings at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.

Harvie and her colleagues compared three diets during four months for effects on weight loss and blood markers of breast cancer risk among 115 women with a family history of breast cancer. They randomly assigned patients to one of the following diets: a calorie-restricted, low-carbohydrate diet for two days per week; an “ad lib” low-carbohydrate diet in which patients were permitted to eat unlimited protein and healthy fats, such as lean meats, olives and nuts, also for two days per week; and a standard, calorie-restricted daily Mediterranean diet for seven days per week.

Data revealed that both intermittent and low-carbohydrate diets were superior to the standard, daily Mediterranean diet in reducing weight, body fat and insulin resistance. Mean reduction in weight and body fat was roughly 4 kilograms (about 9 pounds) with the intermittent approaches compared with 2.4 kilograms (about 5 pounds) with the standard dietary approach. Insulin resistance reduced by 22 percent with the restricted low-carbohydrate diet and by 14 percent with the “ad lib” low-carbohydrate diet compared with 4 percent with the standard Mediterranean diet.

“It is interesting that the diet that only restricts carbohydrates but allows protein and fats is as effective as the calorie-restricted, low-carbohydrate diet,” Harvie said.

She and her colleagues plan to further study carbohydrate intake and breast cancer.

Material adapted from American Association for Cancer Research (AACR).

“The findings add to the body of evidence indicating that obesity, in general, increases a patient’s chance for having a worse prognosis,” said lead researcher Sao Jiralerspong, M.D., Ph.D., an assistant professor of medicine at Baylor College of Medicine.

“Obesity is a probable risk factor for worse breast cancer outcomes, and ours is the latest study to suggest it has an effect on treatment outcome as well,” Jiralerspong said.

Using data from the Lester and Sue Smith Breast Center at Baylor, Jiralerspong and colleagues examined the link between weight and treatment modality in 4,368 patients treated between 1970 and 1995. For the group as a whole, data revealed that overweight patients had similar outcomes to normal-weight patients, but obese patients had an increased risk for worse TTR, DFS and OS.

Among patients who received no adjuvant chemotherapy or endocrine therapy, there was a trend for worse survival outcomes in obese patients compared with normal-weight patients.

Obese patients who received chemotherapy fared significantly worse compared with normal-weight patients, “with the magnitude of this effect approaching that of the degree of benefit expected from chemotherapy,” Jiralerspong said.

In contrast, overweight patients who received endocrine therapy, predominantly tamoxifen, fared significantly better compared with normal-weight patients.

“Finding that overweight patients have a better outcome than normal-weight patients after tamoxifen treatment is surprising. We are examining the possible reasons for this,” Jiralerspong said.

He said that obesity could contribute to worse outcomes because of biological factors associated with excess weight, such as higher blood insulin and estrogen levels, inflammation and growth factors secreted by fat cells. But Jiralerspong also added that more research is needed to understand the effect of body mass on adjuvant treatment because of the unexpected findings and because additional agents are in use today compared with the time period studied.

The study was funded by the Lester and Sue Smith Breast Center at Baylor College of Medicine.

Material adapted from American Association for Cancer Research (AACR).

The study results were reported at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.

Researchers evaluated health care data from a region of 1.5 million people living in Southwestern Sweden to provide a comprehensive picture of cancer risk.

“We are looking at everybody, and we found that diabetes in adult women and obesity in women aged 60 and older significantly increased breast cancer risk,” said Håkan Olsson, M.D., professor in the departments of oncology and cancer epidemiology at Lund University. “This is useful information for women who want to know their risk and who can take steps to lower it.”

He and his colleagues examined records of 2,724 patients up to 10 years before they developed cancer and 20,542 patients who never developed the disease. They found that obesity in women after age 60 increased risk for developing breast cancer by 55 percent. “At the most, 15 out of 100 obese women would get breast cancer compared with slightly less than 10 out of 100 in the general population,” Olsson said.

Women with diabetes had a 37 percent increased risk for developing breast cancer if their diabetes had been diagnosed up to four years before cancer was diagnosed.

Women with abnormally low levels of blood lipids (mostly cholesterol) had a 25 percent greater risk for developing breast cancer, while high levels of blood lipids appeared to be associated with a lower risk for breast cancer. The mechanisms behind these effects are unclear, and the finding needs to be replicated in a different population-based study, Olsson said.

Researchers also looked at the national drug prescription registry to examine the link between risk for all cancers and use of two diabetes drugs, glargine and metformin. In this study, investigators found that glargine use, which had been associated with increased cancer development in previous European studies, almost doubled the risk for development of any cancer, while metformin was linked to an 8 percent lower risk for cancer in patients with diabetes.

Olsson said more research is needed to clarify the specific cancers at increased risk. The number of patients in this study who developed breast cancer using these medications was too small to make any link to breast cancer risk, specifically, he said.

The study was funded by Sweden’s Southern Health Care Region.

Material adapted from American Association for Cancer Research (AACR).

“Coffee has already been shown to be protective against diabetes due to its effect on insulin,” said Giovannucci, a senior researcher on the study. “So we hypothesized that we’d see a reduction in some cancers as well.”

Giovannucci, along with Youjin Je, a doctoral candidate in his lab, and colleagues observed cumulative coffee intake in relation to endometrial cancer (i.e., cancer that starts in the uterus) in 67,470 women who enrolled in the Nurses’ Health Study. During the course of 26 years of follow-up, researchers documented 672 cases of endometrial cancer.

Drinking more than four cups of coffee per day was linked with a 25 percent reduced risk for endometrial cancer. Drinking between two and three cups per day was linked with a 7 percent reduced risk. A similar link was seen in decaffeinated coffee, where drinking more than two cups per day was linked with a 22 percent reduced risk for endometrial cancer.

Giovannucci said he hopes this study will lead to further inquiries about the effect of coffee on cancer because in this and similar studies, coffee intake is self-selected and not randomized.

“Coffee has long been linked with smoking, and if you drink coffee and smoke, the positive effects of coffee are going to be more than outweighed by the negative effects of smoking,” said Giovannucci. “However, laboratory testing has found that coffee has much more antioxidants than most vegetables and fruits.”

Material adapted from American Association for Cancer Research (AACR).

“Cancer-related fatigue is the symptom that most limits quality of life and is most common in patients that survive cancerous processes,” explained Manuel Arroyo, researcher from the University of Granada and lead author of a study that links psychological disorders and physical pain episodes with fatigue after treating a breast tumor.

More than 66% of breast cancer survivors suffer tiredness following recovery, caused directly by the disease, physical deterioration or the treatment received. Therefore, understanding the factors related with fatigue and how they can be alleviated optimizes survivors’ recovery.

Fifty-nine female patients treated for breast cancer were followed-up one year after having clinically overcome the disease. The researchers assessed their psychological and physical condition as well as different aspects linked to the typical medical symptoms following a cancerous process (tiredness, pain, limited movement, depression, etc.).

A statistical procedure (resampling) allowed inferences to be made similar to those that would be obtained from larger samples. “This method means that the data were more reliable and eliminated the problem of having a reduced sample size,” explained Arroyo. “It is difficult to find volunteers because patients are not often very willing to participate in research after having been through such harsh treatment.”

The results show that the patients most affected by tiredness following treatment also suffer episodes of depression and body image deterioration, neck and shoulder pain, and limited arm movement, possibly due to the surgical intervention.

Effects of survival
Following breast cancer treatment, patients present with physical and psychological symptoms that influence their health.

Previous studies have already observed self-esteem- and body image-related disorders following the cancerous process. But for the first time, a team of researchers has associated sensory hypersensitivity, limited movement and certain psychological conditions with fatigue observed following cancer treatment.

“These findings should motivate patient support programs which improve their psychological condition and offer resources that can reduce pain,” pointed out Arroyo, who further stressed that “if fatigue is not treated, patients can suffer it for years, having a serious physical, emotional, social and economic impact.”

Material adapted from Plataforma SINC.

Reference
Cantarero Villanueva, Antarero Villanueva, C- Fernández Lao, C. Fernández de las Peñas, L. Díaz Rodríguez, E. Sánchez Cantalejo, M. Arroyo Morales. “Associations among musculoskeletal impairments, depression, body image and fatigue in breast cancer survivors within the first year after treatment”. European Journal of Cancer Care 20 (2011): 632-636, septiembre de 2011.

Conversely, black tea consumption was shown to reduce lung cancer risk in nonsmoking women, while higher BMI and increased fruit consumption were associated with a lower risk of lung cancer in both men and women.

Lung Cancer Risk Factors
“Heavy drinking has multiple harmful effects, including cardiovascular complications and increased risk for lung cancer, said Stanton Siu, MD, FCCP, Kaiser Permanente, Oakland, California. “We did not see a relationship between moderate drinking and lung cancer development. So it appears probable that most middle-aged and older moderate drinkers have coronary artery protection and no increased risk of lung cancer risk.”

Dr. Siu and his research team studied 126,293 people who provided baseline data from 1978 to1985 and followed them until 2008 to determine their risk for developing lung cancer in relation to cigarette smoking, alcohol consumption, gender, ethnicity, BMI, and level of education. Of the 1,852 people who developed lung cancer during this time, results showed that cigarette smoking remained a strong predictor of all types of lung cancer; however, heavy alcohol consumption (> 3 alcoholic drinks per day) also increased lung cancer risk, with a slightly higher risk related to heavy beer consumption as opposed to wine and liquor.

“Genetic variations among different ethnic groups could explain the elevated risk for lung cancer. Environmental exposures, occupation, and diet can also influence lung cancer risk,” said Dr. Siu.

Reduced Risk of Lung Cancer
Although researchers found several factors that increased lung cancer risk, other factors were found to be related to reduced risk of the disease. Dr. Siu and team found an inverse relationship between BMI and lung cancer risk, where higher BMI levels were associated with a lower risk for lung cancer. A similar relationship was seen in those who graduated from college.

“Explanations are not evident, but people with more education probably have a generally healthy lifestyle,” said Dr. Siu. “The BMI-cancer association was independent of smoking, and we speculate that nutritional factors may be involved.”

In a separate study also presented at CHEST, researchers from the Czech Republic investigated the relationship between smoking exposure, diet, and exercise, and the risk of lung cancer. They found that consumption of black tea had a protective effect on nonsmoking women, while fruit had a protective effect for both men and women.

“Smoking remains the primary risk factor for lung cancer, yet we can’t ignore other environmental or lifestyle factors that may impact one’s health,” said David Gutterman, MD, FCCP, President of the American College of Chest Physicians. “Quitting smoking or never starting can help to reduce lung cancer risk, as can living an overall active and healthy lifestyle.”

Material adapted from American College of Chest Physicians.

Researcher Thordis Thorsteinsdottir

The results are based on a survey of 833 men admitted to 12 different urology clinics, corresponding to 86% of all eligible men operated on at these centers between 1 September 2008 and 31 August 2009. The men were asked questions about their mental health before and three months after surgery.

One in four thought about death
“Our results show that 73% of the men had sudden involuntary negative intrusive thoughts about their cancer at some point before surgery, and almost 60% still had these thoughts three months after surgery,” says Thordis Thorsteinsdottir, in whose thesis the results are reported. “One in four thought about their own death at least once a week.”

Lower perceived quality of life
Her thesis shows that men who do not expect to be cured by the treatment have negative intrusive thoughts more often.

“Men who often think these thoughts about their prostate cancer before surgery are more likely to have low or moderate perceived quality of life three months afterwards,” says Thorsteinsdottir.

New method can reduce intrusive thoughts
Her thesis discusses a method which can reduce these intrusive thoughts. Known as expressive writing, the method has been tested on other cancer patients with good results and involves getting the men affected to spend 20 minutes writing down their feelings on at least three occasions after getting their cancer diagnosis.

Easier to talk
The idea is that this helps the men to put their intrusive thoughts into words. It is then easier to talk to friends and family, which reduces their negative thoughts and so improves their mental health.

“Health professionals could be better at communicating with men who have had a cancer diagnosis,” says Thorsteinsdottir. “If every man was asked ‘What do you think about your cancer and your future?’ and we then took the time to listen, we might be in a better position to help them handle this new situation and prevent drastic actions such as suicide.”

Covers 4,000 men
The thesis is the first from a study which, once data collection is complete, will cover 4,000 men with prostate cancer from 13 urology clinics in Sweden. The study is being led by Eva Haglind from the Sahlgrenska Academy.

The thesis has been successfully defended.

Material adapted from University of Gothenburg.

Ann Bettencourt, professor of psychological sciences at MU, studied who is most likely to experience distress following breast cancer diagnosis and when depressive symptoms tend to occur throughout the course of treatment. Bettencourt found evidence that single women and women with children in the home were more likely to be depressed during the year following treatment.

“Many women receive strong support following their initial diagnoses of and treatment for cancer, but then the social support can wane,” Bettencourt said. “Our findings suggest that both single women and mothers with children in the home may need additional support across the entire year following breast cancer diagnosis and treatment.”

The research also links depression levels with income and age. Women with different incomes tend to have similar levels of elevated depression during treatment, but those symptoms decrease among women with higher incomes in the year following treatment. Younger breast cancer survivors experience more depression during treatment than older patients, but report levels similar to those of older women after treatment is complete.

Bettencourt says identifying risk factors for depression among breast cancer patients is an important part of a woman’s prognosis. In a separate study, she links depression with both intentions to adhere to treatment plans and lack of adherence to medication regimens. The research shows that more depressed breast cancer survivors have less favorable attitudes toward and perceptions of treatment regimens and thus are less likely to adhere to them.

“Depression can interfere with patients’ willingness to adhere to medication regimens,” Bettencourt said. “Deviating from the prescribed course of treatment may complicate patient outcomes and threaten prognosis.”

Material adapted from University of Missouri-Columbia.

Reference
The studies, “Predictors of Depressive Symptoms Among Breast Cancer Patients During the First Year Post Diagnosis,” and “Depression and Medication Adherence Among Breast Cancer Survivors: Bridging the Gap with the Theory of Planned Behavior,” were published in Psychology and Health.

“In many studies, higher consumption of alcohol has been associated with an increased risk of breast cancer. However, the effect of low levels of drinking as is common in the United States has not been well quantified,” according to background information in the article. “In addition, the role of drinking patterns (i.e., frequency of drinking and ‘binge’ drinking) and consumption at different times of adult life are not well understood.”

Researchers examined the association of breast cancer with alcohol consumption during adult life, including quantity, frequency, and age at consumption. The study included 105,986 women enrolled in the Nurses’ Health Study who were followed up from 1980 until 2008 with an early adult alcohol assessment and 8 updated alcohol assessments. The primary outcome the researchers measured was the risk of developing invasive breast cancer.

During the follow-up period, there were 7,690 cases of invasive breast cancer diagnosed among the study participants. Analyses of data indicated that a low level of alcohol consumption (5.0 to 9.9 grams per day, equivalent to 3-6 glasses of wine per week) was modestly but statistically significantly associated with a 15 percent increased risk of breast cancer. In addition, women who consumed at least 30 grams of alcohol daily on average (at least 2 drinks per day) had a 51 percent increased risk of breast cancer compared with women who never consumed alcohol.
The researchers also found that when examined separately, alcohol consumption levels at ages 18 to 40 years and after age 40 years were both strongly associated with breast cancer risk. The association with drinking in early adult life still persisted even after controlling for alcohol intake after age 40 years.

Binge drinking, but not frequency of drinking, was also associated with breast cancer risk after controlling for cumulative alcohol intake.

The authors add that although the exact mechanism for the association between alcohol consumption and breast cancer is not known, one probable explanation may involve alcohol’s effects on circulating estrogen levels.

“In summary, our study provides a comprehensive assessment of the relationship between alcohol intake and breast cancer risk in terms of timing, frequency, quantity, and types of alcohol in a large prospective cohort with detailed information on breast cancer risk factors,” the researchers write. “Our results highlight the importance of considering lifetime exposure when evaluating the effect of alcohol, and probably other dietary factors, on the carcinogenesis process. However, an individual will need to weigh the modest risks of light to moderate alcohol use on breast cancer development against the beneficial effects on cardiovascular disease to make the best personal choice regarding alcohol consumption.”

Material adapted from JAMA.

Reference
JAMA. 2011;306[17]:1884-1890.

“Lifetime risk of prostate cancer in the United States is currently estimated to be 16 percent. Although most cases are found at an early, curable stage, treatment is costly and urinary, sexual, and bowel-related adverse effects are common,” according to background information in the article. There has been considerable preclinical and epidemiological evidence that selenium and vitamin E may reduce prostate cancer risk. “The initial report [published December 2008] of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer.”

Researchers examined the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. SELECT included a total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico who were randomized between August 2001 and June 2004. Eligibility criteria included a prostate-specific antigen (PSA) measure below a certain level, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for other men. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8,752 to receive selenium (200 micrograms/day); 8,737, vitamin E (400 IU/day); 8,702, both agents; and 8,696, placebo, with a planned follow-up of a minimum of 7 years and maximum of 12 years. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011.

Since the initial report, a total of 521 additional prostate cancers have been diagnosed: 113 in the placebo group, 147 in the vitamin E group, 143 in the selenium group, and 118 in the combination group. The researchers found that the rate of prostate cancer detection was greater in all treatment groups when compared with placebo but was statistically significant only in the vitamin E alone group (a 17 percent increased rate of prostate cancer detection). Compared with the placebo group, in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer, as did 575 in the selenium group and 555 in the selenium plus vitamin E group. The difference in rates of prostate cancer between vitamin E and placebo became apparent during the participants’ third year in the trial. The elevated risk estimate for vitamin E was consistent across both low- and high-grade disease.

“In this article, we report an observation of important public health concern that has emerged with continued follow-up of SELECT participants,” the authors write. “Given that more than 50 percent of individuals 60 years or older are taking supplements containing vitamin E and that 23 percent of them are taking at least 400 IU/d despite a recommended daily dietary allowance of only 22.4 IU for adult men, the implications of our observations are substantial.”

The researchers note that the fact that the increased risk of prostate cancer in the vitamin E group of this trial was only apparent after extended follow-up suggests that health effects from these agents may continue even after the intervention is stopped, emphasizing the need for long-term follow-up. They add that the findings of this and other studies illustrate the importance of large-scale, population-based, randomized trials in accurately assessing the benefits and harms of micronutrients as dietary supplements.

“The observed 17 percent increase in prostate cancer incidence demonstrates the potential for seemingly innocuous yet biologically active substances such as vitamins to cause harm. The lack of benefit from dietary supplementation with vitamin E or other agents with respect to preventing common health conditions and cancers or improving overall survival, and their potential harm, underscore the need for consumers to be skeptical of health claims for unregulated over-the-counter products in the absence of strong evidence of benefit demonstrated in clinical trials.”

Material adapted from JAMA.

Reference
JAMA. 2011;306[14]:1549-1556.

“We found that after diagnosis, black and Hispanic breast cancer patients reported higher levels of stress than whites, and that stress was associated with tumor aggressiveness,” said Garth H. Rauscher, Ph.D., associate professor of epidemiology in the division of epidemiology and biostatistics at the School of Public Health, University of Illinois at Chicago.

Rauscher and colleagues studied patient-reported perceptions of fear, anxiety and isolation, together referred to as psychosocial stress, and associations with breast cancer aggressiveness. He cautioned that patients’ stress levels were examined two to three months post-diagnosis.

The study included 989 breast cancer patients who were recently diagnosed; of those, 411 were non-Hispanic black, 397 were non-Hispanic white, and 181 were Hispanic. Results showed that psychosocial stress scores were higher for both black and Hispanic patients compared to white patients.

“Those who reported higher levels of stress tended to have more aggressive tumors. However, what we don’t know is if we had asked them the same question a year or five years before diagnosis, would we have seen the same association between stress and breast cancer aggressiveness?

“It’s not clear what’s driving this association. It may be that the level of stress in these patients’ lives influenced tumor aggressiveness. It may be that being diagnosed with a more aggressive tumor, with a more worrisome diagnosis and more stressful treatments, influenced reports of stress. It may be that both of these are playing a role in the association. We don’t know the answer to that question,” Rauscher said.

Material adapted from American Association for Cancer Research.

“However,” the authors write, “some epidemiologic data, mainly from case-control studies, suggest an association between analgesic use and an increased risk of RCC.”

Eunyoung Cho, Sc.D., from Harvard Medical School and Brigham and Women’s Hospital, Boston, and colleagues examined the relationship between analgesic use and RCC risk. They used data from the Nurses’ Health Study and the Health Professionals Follow-up Study, both prospective cohort studies. Beginning in 1990 in the Nurses’ Health Study and 1986 in the Health Professionals Follow-up Study, and every two years thereafter, use of aspirin, other NSAIDs and acetaminophen was determined. Follow-up was 16 years and 20 years, respectively. The researchers evaluated the baseline and duration of use of analgesics. They also assessed other risk factors for RCC, such as body weight, smoking, recreational physical activity and history of hypertension.

Among the 77,525 women and 49,403 men included in the study, the researchers documented 333 RCC cases. No association was found between aspirin and acetaminophen use and RCC risk. An association was found between regular use of nonaspirin NSAIDs and an increased risk of RCC, with a 51 percent increase in the relative risk. The researchers noticed a dose-response relationship between duration of nonaspirin NSAID use and RCC risk; there was a 19 percent decrease in relative risk for use less than four years, a 36 percent increase in relative risk for use of analgesics for four years to less than 10 years and nearly three times the relative risk for use for 10 or more years.

“In these large prospective studies of women and men, we found that use of nonaspirin NSAIDs was associated with an elevated risk of RCC, especially among those who took them for a long duration,” write the authors, who add that aspirin and acetaminophen were not associated with RCC risk. “Risks and benefits should be considered in deciding whether to use analgesics; if our findings are confirmed, an increased risk of RCC should also be considered.”

Material adapted from JAMA.

Reference
Arch Intern Med. 2011;171[16]:1487-1493.

In findings published on-line on Sept. 11, 2011, in Nature Medicine, the UAB team shows that malignant glioma cells release a tremendous amount of a neurotransmitter called glutamate into healthy neurons surrounding the tumor site. Neurons normally use glutamate to communicate with one another, but not in the staggering amounts released by the glioma cells.

“These tumor cells produce an enormous amount of glutamate, 100-fold beyond normal,” said Harald Sontheimer, Ph.D., professor of neurobiology at UAB and lead investigator. “This leads to a state of hyper-excitability that overwhelms healthy neurons and leads to their death.”

Sontheimer says the death of neurons in proximity to the glioma gives the malignant cell room to grow and expand into the space previously occupied by the neurons.

“The brain is a dense, closely packed space,” said Sontheimer, who directs the UAB Center for Glial Biology in Medicine. “For the glioma to grow, it has to make room for itself, which it does by clearing out surrounding neurons with this blast of glutamate.”

Excess glutamate can also cause abnormal electrical activity in the brain, which is the basis for epileptic seizures. Sontheimer’s team found that mice with human glial cells developed abnormal brain activity and behavioral signs consistent with seizures.

The good news, Sontheimer says, is that sulfasalazine, a drug used to treat Crohn’s disease, irritable bowel disease and some types of arthritis, seems to inhibit the glioma from releasing the large amount of glutamate. In mice, sulfasalazine stopped the release of glutamate and prohibited seizures.

Without the abnormal glutamate release, the nearby neurons are unaffected by the glioma, and its growth is compromised. Sontheimer says evidence suggests that tumor cells that cannot grow tend to die.

But sulfasalazine, as formulated to treat Crohn’s disease and other conditions, is not an efficient way to treat gliomas; because it is designed to break apart in the intestines, only about 20 percent of the drug gets into the blood stream where it can be carried to a glioma site in the brain. Sontheimer says, however, that the drug could be re-formulated to make it more efficient and effective.

“The drug could be re-designed so that it does not cleave apart in the intestine, keeping more of it in the blood stream for a longer period of time,” he said.

Sontheimer thinks a clinical trial of sulfasalazine in humans is warranted, and sulfasalazine should be considered an adjutant therapy to inhibit seizures in patients with glioma in the meantime.

“While we are waiting for the development of a new drug, the existing one will work to some degree. It’s nice to have a sharp knife, but a dull one will work,” Sontheimer said.

Sontheimer says the drug might be especially valuable in the early stages of the glioma, when the tumor is small, potentially to slow the progression of the disease and provide for a better quality of life.

About 18,000 Americans develop gliomas each year, and about half will die within 12 months of diagnosis, according to the Society for Neuroscience.

The study was funded by the National Institutes of Health, the UAB Brain Tumor SPORE grant, the Neuroscience Blueprint Core grant and the National Coalition for Cancer Research.

Material adapted from University of Alabama at Birmingham.

Music and music therapy are used in a wide range of clinical settings. Treatments range from patients listening to pre-recorded music, to music therapists engaging patients in music experiences to improve psychological and physical well-being. In their review, researchers focused on trials with patients with any kind of cancer who were offered music or music therapy sessions.

The researchers analyzed evidence from 1,891 patients taking part in 30 trials. Thirteen trials used trained music therapists, while in the remaining 17 trials, patients listened to pre-recorded music. How long and how often patients participated in music sessions varied greatly among trials.

The results show that, compared to standard treatments, music reduced anxiety considerably based on clinical anxiety scores. Some trials reported much larger beneficial effects than others. The results also suggest that music therapy may increase patients’ quality of life. There was some benefit in music for mood and pain, although not depression. Smaller beneficial effects were seen for heart rate, respiratory rate and blood pressure.

“The evidence suggests that music interventions may be useful as a complementary treatment to people with cancer,” said Bradt, a board-certified music therapist with expertise in medical music therapy. “Music interventions provided by trained music therapists as well as listening to pre-recorded music both have shown positive outcomes in this review, but at this time there is not enough evidence to determine if one intervention is more effective than the other.”

Bradt added, “It should be noted, however, that when patients can’t be blinded to an intervention, there is an opportunity for bias when they are asked to report on subjective measures like anxiety, pain, mood and quality of life.”

The researchers point out that the quality of evidence for some outcomes was low because of the small numbers of trials that have been carried out. Further trials could help increase certainty in the findings and improve understanding of music’s impact on distress, body image and other aspects, for which research is currently too scarce to draw any conclusions.

Bradt was the lead author of four previous Cochrane reviews on music interventions with medical patients. She is an associate professor in the Department of Creative Arts Therapies at Drexel.

Material adapted from Drexel University.

Reference
Bradt J, Dileo C, Grocke D, Magill L. Music interventions for improving psychological and physical outcomes in cancer patients. Cochrane Database of Systematic Reviews 2011, Issue 8. Art. No.: CD006911. DOI: 10.1002/14651858.CD006911.pub2.

The disease-specific survival rate for advanced-stage melanoma is poor, so detecting the cancer in an earlier stage is the best means to ensure a favorable prognosis, according to background information in the article. Previous research has demonstrated that patients find most melanomas, and that those lesions tend to be thicker than physician-detected lesions. “Working on the premise that physician-based screening and patient self-screening are vital in the detection of early melanoma,” explain the authors, “we compared melanoma characteristics in patients new to our practice vs. established patients in the pigmented lesions clinic (PLC) at Memorial Sloan-Kettering Cancer Center” (MSKCC) in New York City.

Ivanka Kovalyshyn, D.O., from MSKCC, and colleagues conducted a retrospective review of patient records and biopsy logs from two MSKCC pigmented lesion specialists from January 1998 through December 2008. The institution’s PLC serves patients at high risk for developing melanoma, so each patient visit involves a total body skin examination, and patients are given brochures instructing them how to perform skin self-examination (SSE). Researchers divided the group into “established” patients, who had been treated at MSKCC’s PLC for three months or more, and “new” patients who were new to the practice.

A total of 527 melanomas were identified in 394 patients. Among the established group, lesions tended to be thinner, more often detected in the in situ phase and less likely to exhibit negative prognostic attributes. Physicians detected 82 percent of melanomas in established patients and 63 percent in new patients. The overall patient-detection rate was 18 percent, and most lesions found by patients were detected because of change in appearance.

“Although we recognized that high-risk patients may have more frequent physician skin examinations and may be more vigilant in performing SSE, we strongly believe that the PLC setting contributes to earlier detection of melanoma in our cohort,” the authors write. They do note that the patient’s role in melanoma recognition is important as well. “Therefore,” they conclude, “it is crucial to emphasize that a combined strategy of physician detection and patient participation must continue to be implemented to ensure early melanoma diagnosis.”

Material adapted from JAMA.

Reference
Arch Dermatol. Published July 18, 2011. doi:10.1001/archdermatol.2011.181.

Latinos’ annual age-adjusted incidence of melanoma is 4.5 per 100,000, which represents an increase of 28.6 percent since 1992. Further, when melanoma is diagnosed, it tends to be thicker among Latinos than among non-Latino white individuals. Acculturation, defined as use of the English language and length of residence in the United States, may affect this population’s efforts to avoid sun-related health problems, note the authors: “Acculturated Latinos might have increased exposure to sun safety information via health care access, education, and expanded social networks but display decreased engagement in some sun-safe behaviors.”

Valentina A. Andreeva, Ph.D., from the University of Paris XIII in Bobigny, France, who conducted research at the University of Southern California, and colleagues examined cross-sectional data from the National Cancer Institute’s 2005 Health Information National Trends Survey. Four-hundred ninety-six Latino respondents answered questions about sun-safe behaviors: wearing sunscreen, long-sleeved shirts and long pants and staying in shade when outside for at least one hour on warm, sunny days. Acculturation was determined by preferred language for the interview, perceived comfort with the English language and, for foreign-born respondents, age at U.S. arrival and duration of U.S. residence. Researchers also asked about health care access, educational level and social support from community organizations, family or friends, neighbors and religious institutions.

There was a positive association between acculturation and sunscreen use and a negative association between acculturation and use of sun-protective clothing, with these associations mediated by educational level. However, the indirect effects of acculturation, education level, perceived health status and social networks appeared to significantly affect this behavior. The researchers found that the direct negative association between acculturation and use of shade was significant, and that education level combined with acculturation to mediate the use of sun-protective clothing.

The authors noted that social networks appeared to have the most overall influence on sun-safe behaviors, that health care access did not display any associations mediated by other factors and that research should focus on sun-safe behaviors other than sunscreen use, for which most of the hypothesized mediators were supported. “In conclusion, sun safety practice is critical for the prevention of skin cancer regardless of skin type, but no ethnoracial group appears to meet current primary prevention recommendations,” the researchers state. “Our results, denoting variability in the mediation mechanisms for different sun-safe behaviors, could guide primary prevention program development for Latinos and future public health research.”

Material adapted from JAMA.

Reference
Arch Dermatol. 2011;147[7]:814-819.

“This was very surprising, because when you look at the differences in reductions by state they are huge,” said Jemal.

Although colorectal cancer remains the third leading cause of cancer mortality for men and women, rates have been declining nationwide for several decades. The researchers analyzed the temporal trend in age-standardized colorectal cancer death rates for each state from 1990 to 2007.

Overall, states in the South had a lower reduction in mortality than states in the North. The researchers found a strong correlation between higher rates of screening and higher reductions in rates of mortality by state. They speculate that economic disparities may be playing a role in rates of screening. In Mississippi, 18.8 percent of people do not have health insurance, compared with 5.4 percent in Massachusetts. More than 20 percent of the population of Mississippi lives below the poverty line, compared with a national average of 13 percent.

Elizabeth Jacobs, Ph.D., an associate professor of epidemiology and biostatistics at the University of Arizona, said the report shows a significant change in historical trends.

“It used to be that the highest rates of colorectal cancer mortality were in the northeastern part of the United States, but now we’ve really seen a switch,” said Jacobs, an editorial board member of Cancer Epidemiology, Biomarkers & Prevention. “It shows the importance of access to screening.”

Material adapted from American Association for Cancer Research (AACR).

“This provides some initial evidence that we need to look at the effects of exercise interventions, not only to ease symptoms but also to impact progression and survival,” said Lee W. Jones, PhD, associate professor in the Duke Cancer Institute and senior author of the study.

Although the study was not designed to test whether regular exercise actually causes longer survival among brain cancer patients, it established a strong correlation that could give doctors and patients a more accurate prognosis of long-term survival.

The study enrolled 243 patients at the Preston Robert Tisch Brain Tumor Center at Duke with advanced recurrent gliomas, lethal brain malignancies that typically result in a median life expectancy of less than six months.

The patients who reported participating in regular, brisk exercise – the equivalent of an energetic walk five days a week for 30 minutes – had significantly prolonged survival, living a median 21.84 months vs. 13.03 months for the most sedentary patients.

The self-reported exercise behavior offered an important additional means of predicting survival among the glioma patients beyond other measures traditionally used for prognosis, including a six-minute walk test.

Jones said the walk test is a good way to gauge the functional capacity of people with heart failure or other cardiac or pulmonary disorders, but it may not be informative for brain cancer patients who frequently suffer dizzy spells and other neurological problems that hamper walking.

Jose Cortes, a Duke patient who has battled inoperable anaplastic astrocytoma since 2009, has been an avid proponent of the power of exercise during his treatment.

“I exercised regularly prior to my illness and I wanted to stay as active as possible,” Cortes said. “But it was impossible for me to do things that I could do easily before. My first goals in physical therapy were to put on my shoes without tipping over and keep my equilibrium while walking and talking or walking and turning my head.”

As he met and surpassed his early goals, he began walking for 30 minutes a day and last year joined a Zumba fitness-dance class at his local YMCA.

“I wanted to be able to exercise because it makes me feel alive again,” Cortes said. He cautioned that exercise is no cure – his cancer has responded well to chemotherapy – but he said being active helps both physically and mentally.

“Exercise is a very good way to overcome the side effects of your disease,” he said. “You can feel more positive about your life even if you are in a terminal state. The most important thing is to just do it at your own pace and do your best.”

The Duke study demonstrates that if doctors know about their patients’ exercise regimens, they will have a better way to assess long-term outcomes. Jones said an accurate prognosis is important to determine the overall health of patients, potential tolerance for certain types of treatment, and eligibility for clinical trials.

Jones said a major goal of his research is to discover why exercise may lead to improvements in survival following a cancer diagnosis.

“Discovering these mechanisms could provide new insights into cancer progression,” Lee said. “It could also lead to novel studies where exercise is combined with certain cancer therapies to see if both interventions together are more effective at inhibiting cancer recurrence or progression, not just minimizing the adverse side effects of the cancer therapies.”

Jones conducted the study with colleagues in the Preston Robert Tisch Brain Tumor Center at Duke. Authors include Emily Ruden; David A. Reardon, M.D.; April D. Coan; James E. Herndon II, PhD; Whitney E. Hornsby; Miranda West; Diane R. Fels, PhD; Annick Desjardins, M.D.; James J. Vredenburgh, M.D.; Emily Waner; Allan H. Friedman, M.D.; Henry S. Friedman, M.D.; and Katherine B. Peters, M.D., PhD.

Material adapted from Duke University Medical Center.

Researcher Sven Wilson

Similar to studies of other types of cancers, the researchers did find that married people were diagnosed at earlier stages of colon cancer and sought more aggressive treatment. The researchers took those and other factors into account before calculating the benefit of marriage on survival odds.

“Controlling for the stage that the cancer was detected is key,” said Sven Wilson, a study coauthor and professor at Brigham Young University. “Without that, it’s hard to know whether the analysis is just picking up a diagnosis effect.”

Colon cancer is the fourth most common type of cancer in the United States for both men and women. Curiously, the marriage benefit seen in the new study was nearly identical for both men and women.

So what is driving the different survival rates?
Marriage is a self-selected group, and Wilson is careful to note that the selection process makes it difficult to sort out the root cause. One intuitive idea is that spouses serve as an important informal caregiver during a critical time, and that extra support may translate into better disease management and, hence, better outcomes.

Material adapted from Brigham Young University.

Stacey A. Kenfield, Sc.D., of the Harvard School of Public Health, Boston, and colleagues conducted a study to assess the relation of cigarette smoking and smoking cessation with overall, prostate cancer-specific, and cardiovascular disease (CVD) mortality and biochemical recurrence among men with prostate cancer. The study included 5,366 men diagnosed with prostate cancer between 1986 and 2006 in the Health Professionals Follow-Up Study.

Among the men diagnosed with prostate cancer, there were 1,630 deaths, 524 (32 percent) due to prostate cancer and 416 (26 percent) to CVD, and 878 biochemical recurrences. Analysis indicated that compared with never smokers, current smokers had an increased risk of dying from prostate cancer, CVD, and all-cause mortality and an increased risk of biochemical recurrence. A greater number of pack-years was associated with an increased risk of prostate cancer mortality, CVD mortality, and total mortality but not biochemical recurrence. Compared with current smokers, men who had quit smoking for 10 or more years had prostate cancer mortality risks similar to those who had never smoked.

The authors write that a direct effect of smoking on prostate cancer progression is biologically plausible, including tumor promotion through carcinogens from tobacco smoke; increased plasma levels of total and free testosterone, an androgen involved in the development and progression of prostate cancer in some smokers, with some studies reporting a dose-dependent association; epigenetic effects, including aberrant methylation profiles among current smokers, which correlate with aggressive disease; and nicotine-induced angiogenesis [formation of new blood vessels], capillary growth, and tumor growth and proliferation.

“In summary, smoking at the time of diagnosis was associated with substantially increased overall mortality and prostate cancer mortality and recurrence. Ten-year quitters had risks similar to never smokers. These results provide further support that smoking may increase risk of death from prostate cancer,” the authors conclude.

Material adapted from JAMA.

Reference
JAMA. 2011;305[24]2548-2555.

“Currently, it is well documented that the practice of health care in America varies widely across both institutions and demographic populations,” they write. “This is true across specialties and disease sites.” These discrepancies may stem from physicians’ lack of knowledge about appropriate care, disagreement with generally accepted standards of care, or both.

Caprice C. Greenberg, M.D., M.P.H., from Brigham and Women’s Hospital, Boston, and colleagues studied National Surveillance, Epidemiology, and End Results data on surgical treatment for five cancers: breast, colon, gastric, rectal, and thyroid. They limited the field to patients ages 65 years and older who were Medicare beneficiaries and were diagnosed with one of those five cancers between January 2000 and December 2005. The researchers analyzed the surgical treatment of these patients for concordance with national cancer-care guidelines classified by the strength of supporting evidence. Specifically, researchers looked at surgical management of the primary tumor, evaluation and treatment of nodes susceptible to cancer, and referral for adjuvant treatment.

The authors identified 11 guidelines for surgical oncology care and determined whether these guidelines were graded by the National Comprehensive Cancer Network (NCCN) as having a high level of evidence or universal consensus but less evidence. For seven of the 11 guidelines, more than 90 percent of hospitals were in concordance, including all guidelines relating to adjuvant therapy. The proportion of hospitals treating 100 percent of their patients in accordance with the guidelines varied; concordance with guidelines was greatest for adjuvant care. patients who were younger, healthier, wealthier, white, had less-aggressive cancers and lived in the Midwest were the most likely to receive appropriate care.

The guidelines most likely to be followed were those which received a high NCCN evidence rating. The authors suggested that the relationship between evidence level and clinical acceptance should be studied further. Additionally, they note, guidelines relating to adjuvant therapy had a high level of concordance. The researchers conclude, “It is critical that surgeons focus on generation of the data necessary to inform clinical decision making and promote high-quality surgical care.”

Material adapted from JAMA.

Reference
Arch Surg. 2011; doi:10.1001/archsurg.2011.141.

“This shows that something as simple as a change in diet can have an impact on cancer risk,” said lead researcher Gerald Krystal, Ph.D., a distinguished scientist at the British Columbia Cancer Research Centre.

Cancer Research editor-in-chief George Prendergast, Ph.D., CEO of the Lankenau Institute for Medical Research, agreed. “Many cancer patients are interested in making changes in areas that they can control, and this study definitely lends credence to the idea that a change in diet can be beneficial,” said Prendergast, who was not involved with the study.

Krystal and his colleagues implanted various strains of mice with human tumor cells or with mouse tumor cells and assigned them to one of two diets. The first diet, a typical Western diet, contained about 55 percent carbohydrate, 23 percent protein and 22 percent fat. The second, which is somewhat like a South Beach diet but higher in protein, contained 15 percent carbohydrate, 58 percent protein and 26 percent fat. They found that the tumor cells grew consistently slower on the second diet.

As well, mice genetically predisposed to breast cancer were put on these two diets and almost half of them on the Western diet developed breast cancer within their first year of life while none on the low-carbohydrate, high-protein diet did. Interestingly, only one on the Western diet reached a normal life span (approximately 2 years) with 70 percent of them dying from cancer while only 30 percent of those on the low-carbohydrate diet developed cancer and more than half these mice reached or exceeded their normal life span.

Krystal and colleagues also tested the effect of an mTOR inhibitor, which inhibits cell growth, and a COX-2 inhibitor, which reduces inflammation, on tumor development, and found these agents had an additive effect in the mice fed the low-carbohydrate, high-protein diet.

When asked to speculate on the biological mechanism, Krystal said that tumor cells, unlike normal cells, need significantly more glucose to grow and thrive. Restricting carbohydrate intake can significantly limit blood glucose and insulin, a hormone that has been shown in many independent studies to promote tumor growth in both humans and mice.

Furthermore, a low-carbohydrate, high-protein diet has the potential to both boost the ability of the immune system to kill cancer cells and prevent obesity, which leads to chronic inflammation and cancer.

Material adapted from American Association for Cancer Research.

“Scientists have known for years that Tai Chi positively impacts physical and emotional health, but this small study also uncovered evidence that it might help cognitive functioning as well,” said Stephanie Reid-Arndt, assistant professor and chair of the Department of Health Psychology in the School of Health Professions. “We know this activity can help people with their quality of life in general, and with this new study, we are encouraged about how Tai Chi could also help those who have received chemotherapy. I also hope this encourages more people to think about Tai Chi positively on a broader scale in their lives.”

Stephanie Reid-Arndt, an MU health psychologist, has found evidence that an ancient Chinese martial art might help people who had chemotherapy and are suffering from cognitive declines. (Credit: University of Missouri)

The MU pilot study followed a group of women with a history of chemotherapy. The women participated in a 60-minute Tai Chi class two times a week for 10 weeks. The women were tested on memory, language, attention, stress, mood, and fatigue before and after the 10-week sessions. According to Reid-Arndt, the results of the tests indicated that the women had made significant improvements in their psychological health and cognitive abilities.

“Tai Chi really helps individuals focus their attention, and this study also demonstrates how good Tai Chi could be for anyone, whether or not they have undergone treatment for cancer,” Reid-Arndt said. “Due to the small size of this study, we really need to test a larger group of individuals to gain a better understanding of the specific benefits of this activity for patients who have been treated with chemotherapy and how significant these improvements might be.”

Material adapted from University of Missouri-Columbia.

In particular, overweight or obese women with a history of estrogen receptor-positive breast cancer, but not those with estrogen receptor-negative cancer, had a higher risk of dying of their disease, said the study’s lead author, Christina Dieli-Conwright, PhD.

“This relationship between dying and being obese or overweight may depend on whether the type of breast cancer is hormonally dependent,” said Dieli-Conwright, assistant research professor at City of Hope National Medical Center in Duarte, Calif.

The research involved participants of the large California Teachers Study who, between 1995 and 2006, received a diagnosis of invasive breast cancer — cancer that has spread beyond the breast ducts. Of the 3,995 women studied, 262 died of breast cancer through 2007, the authors reported in their abstract.

They defined obesity as a body mass index (BMI, in kg/m2) of 30 or higher. The authors obtained BMI, a measure of height and weight, from questionnaires showing each participant’s self-reported height and weight at baseline and at age 18. Baseline was the beginning of the study and was near, but necessarily at, diagnosis, according to Dieli-Conwright.

Women who were obese at baseline had a 69 percent higher risk of dying of their breast cancer than did nonobese women, Dieli-Conwright said. This same increased mortality, or death, risk was present in women who were overweight (BMI of 25 to 29) at age 18.

The researchers also analyzed the mortality risk by estrogen receptor status (whether the hormone estrogen fuels the breast cancer). They found that the higher the BMI, the greater the risk of dying of breast cancer for women with estrogen-dependent cancer. They saw no such link in women with estrogen-negative breast cancer. Women who are obese or overweight tend to have higher levels of circulating estrogen, which likely explains this difference, Dieli-Conwright said.

Their findings add to the growing scientific evidence that obesity raises the risk of both developing breast cancer and dying of it.

“What we know now is that there is a strong link between dying from breast cancer and being obese,” Dieli-Conwright said. “And it’s not just your BMI near the time you’re diagnosed that’s important.”

She continued, “With the obesity epidemic on the rise, weight management programs using exercise and diet are vital in cancer prevention and survivorship.”

Material adapted from Endocrine Society.

“We were surprised to see how prevalent these symptoms still are,” said study co-investigator Lynne Wagner, an associate professor of medical social sciences at Northwestern University Feinberg School of Medicine and a clinical health psychologist at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “This is one of the first looks at what’s really happening for survivors in terms of symptoms and treatment among community-based treatment settings across the U.S.”

The persistent pain in survivors who are cancer-free and no longer receiving any treatment is particularly puzzling, Wagner noted, because good treatment exists. “It seems we haven’t come a long way in managing pain despite a lot of medical advances, ” she said. “This is eye opening. It tells us we need to be better in clinical practice about managing our survivors’ pain.”

Wagner will present the findings June 4 at the 2011 American Society of Clinical Oncology Annual Meeting in Chicago. Sunday is National Cancer Survivors Day.

Cancer survivors seem to slip through the cracks in healthcare in terms of getting treatment for their pain and other symptoms.

“We don’t have a great system to provide care to cancer survivors,” Wagner said. “Cancer survivors are left trying to put the pieces together to find optimal care. They ideally need to see someone who is knowledgeable about the long-term affects of treatment.” She pointed to the example of the STAR (Survivors Taking Action & Responsibility) Survivorship Program at Lurie Cancer Center, a comprehensive long-term follow-up program for survivors of pediatric cancer.

The study included a sample of 248 survivors of breast, colorectal, lung, and prostate cancer. The survivors were primarily female and white, and most were more than five years post-diagnosis. They also had been treated in community settings — where 80 percent of people with cancer are treated in the United States — as opposed to academic medical centers. This group best represents the typical experience of cancer survivors around the country, Wagner said.

The most common symptoms reported by survivors were fatigue (16 percent), disturbed sleep (15 percent), cognitive difficulties (13 percent), and pain (13 percent.)

Survivors need education programs for transitioning from treatment to life as a cancer survivor, and this education should include skills for managing these difficult and chronic symptoms, Wagner said. Medical providers also need to be educated about survivors’ lingering symptoms.

“It is acceptable for someone actively going through cancer treatment to have pain medications, but when they transition to being survivors, that acceptance goes away,” Wagner said. “If they ask for pain medication again, doctors may worry that they are getting addicted.”

The study also pointed out the need to develop better ways to address sleep problems, fatigue, and lasting difficulties with memory and concentration. Non-drug interventions for improving sleep are effective, Wagner said, and researchers need to tailor these for cancer survivors.

Exercise is the most effective weapon against cancer-related fatigue, but it’s challenging to adhere to an exercise regime when you don’t feel well. “We need to see how we can be more effective in promoting physical activity among survivors,” Wagner said.

Researchers also documented any treatment interventions for study participants’ symptoms and then repeated an assessment of the symptoms four weeks later.

“We generally found the same severity of these symptoms one month later, suggesting they tend to be chronic,” Wagner said.

The study stemmed from a 2002 National Cancer Institute meeting on pain, fatigue and depression in cancer. Participants concluded more research was needed on the prevalence of these symptoms.

Material adapted from Northwestern University.

Unprotected sun exposure is the most preventable risk factor for skin cancer. More than 3.5 million new cases of skin cancer will be diagnosed in the United States this year, affecting 2 million people. At current rates, one in five Americans will develop skin cancer in his or her lifetime. Approximately 75 percent of skin cancer deaths are from melanoma, and the incidence of melanoma has been rising for at least 30 years.

“Scientific evidence supports the benefits of sunscreen usage to minimize short and long-term damage to the skin from UV radiation and outweighs any unproven claims of toxicity or human health hazard,” said Ronald L. Moy, MD, FAAD, president of the Academy. “To reduce the risk of skin cancer and premature aging, dermatologists continue to recommend generously applying a water-resistant, broad-spectrum sunscreen – that protects against both types of ultraviolet radiation (UVA and UVB) – with an SPF 30 or higher, in conjunction with other sun-safe practices such as limiting sun exposure, seeking shade, and wearing sun-protective clothing, hats and sunglasses.”

Sunscreen products contain one or more active drug ingredients – compounds that absorb, scatter or reflect UV light – and are regulated as over-the-counter (OTC) drugs by the U.S. Food and Drug Administration (FDA). The FDA has several safety and effectiveness regulations in place that govern the manufacture and marketing of all sunscreen products, including safety data on its ingredients. However, recent media reports have questioned the health risks of some sunscreen ingredients, specifically oxybenzone and retinyl palmitate, as well as the use of nanotechnology in sunscreen.

Oxybenzone is one of the few FDA-approved ingredients that provides effective broad-spectrum protection from UV radiation, and has been approved for use since 1978. “Contrary to recent reports, available scientific literature and decades of public use does not support a link between oxybenzone in sunscreen and hormonal alterations, or other significant health issues in humans,” stated Dr. Moy. “The FDA has approved oxybenzone in sunscreen for use on children older than six months, and dermatologists continue to encourage protecting children by playing in the shade, wearing protective clothing and applying broad-spectrum sunscreen.”

Retinyl palmitate is a form of vitamin A (retinol), but is not an active drug ingredient in sunscreen. When used in sunscreen, retinyl palmitate serves cosmetic purposes as an antioxidant to improve product performance against the aging effects of UV exposure, or to enhance product aesthetic qualities. Despite recent concerns from in vitro (test tube) studies and one unpublished report using mice, “topical and oral retinoids are widely prescribed to treat a number of skin diseases, such as acne and psoriasis, and there is no published evidence to suggest either increase the risk of skin cancer in these patients,” said Dr. Moy. “In fact, oral retinoids are used to prevent skin cancers in high-risk patients such as those who have undergone organ transplantation.” Dr. Moy also added that “unlike more potent prescription forms of vitamin A, there is no evidence to suggest that use of sunscreen with retinyl palmitate poses comparable risks.”

The broad-spectrum sunscreen active ingredients titanium dioxide and zinc oxide leave a white residue on the skin following application when used in a larger particle form. However, when these active ingredients are converted into nanoparticles – smaller, lighter molecules – they appear to vanish on the skin, do not leave a residue, and retain and enhance their ability to block UVA and UVB light.

“While widespread use of nanotechnology in medicine is currently under evaluation, one of the main benefits of nanoparticles in sunscreens is that the small molecules can provide more protection and more even coverage on the skin’s surface than larger particles,” said Dr. Moy. “Considerable research on the use of nanoparticles on healthy, undamaged skin has shown that the stratum corneum – the outermost layer of the skin – is an effective barrier to preventing the entry of nanoparticles into the deeper layers of the skin. Titanium dioxide and zinc oxide have a long history of safe use in sunscreens and offer good options for broad-spectrum UV protection.”

There has also been concern that sunscreen use prevents the synthesis of vitamin D by the skin. Vitamin D is an essential nutrient that is vital for strong bones and a healthy immune system. The Academy recommends that an adequate amount of vitamin D should be safely obtained from a healthy diet that includes foods naturally rich in vitamin D (e.g., dairy products and fish), foods/beverages fortified with vitamin D (e.g., fortified milk and fortified cereals), and/or vitamin D supplements — and not from UV exposure. The Academy recently updated its position statement on vitamin D based on the published review of the increasing body of scientific literature on this vitamin conducted by the National Academy of Sciences Institute of Medicine (IOM).

“Unprotected UV exposure to the sun or indoor tanning devices is a known risk factor for the development of skin cancer. Since sun exposure is responsible for vitamin D production in the skin, wearing sunscreen can decrease the skin’s production of vitamin D, but alternative and safer options are available to obtain your vitamin D,” states Dr. Moy. “Individuals who properly and consistently wear sunscreen or use other UV protective measures, and are concerned about their vitamin D, should discuss obtaining sufficient vitamin D from foods and/or vitamin supplements with their doctor.”

The FDA is continuing to work on addressing requirements for UVA coverage in sunscreens and considering sunscreen labeling changes to help the public make knowledgeable decisions about protecting themselves from the dangers of sun exposure. “Dermatologists recommend the use of broad-spectrum sunscreen products to protect against UVA and UVB rays and we rely on the FDA to confirm the safety of the products,” said Dr. Moy. The American Academy of Dermatology currently awaits the FDA’s final ruling to provide the most current information.

“Despite any concerns over the use of sunscreen, they are an important component of a daily protection plan, as dermatologists understand the limitations of clothing and minimizing sun exposure. There are many sunscreen products available that meet the Academy’s recommendations, and consumers need to be comfortable with their choice of product in order to use it routinely”, Dr. Moy added. “Since allergic and other reactions can occur, individuals should read the product’s labeling carefully, use as directed, and seek the advice of their dermatologist in using sunscreens and any product applied to the skin. The American Academy of Dermatology will continue to monitor scientific evidence related to sunscreen ingredients and their effectiveness to help guide patients and the public.”

Material adapted from American Academy of Dermatology (AAD).

Richman said the evidence adds to the growing body of literature that suggests walking regularly may prevent a variety of adverse health problems, including cardiovascular disease and certain types of cancer. “Walking is something everyone can and should do to improve their health,” she said.

Richman and colleagues observed 1,455 men who were diagnosed with prostate cancer that had not spread beyond the prostate. These patients reported their physical activity by questionnaire about 27 months after their diagnosis and prior to any evidence of recurrence or second treatment.

Researchers recorded 117 events, including biochemical recurrences (elevations in PSA), secondary treatments, bone metastasis, and prostate cancer-specific death. They found that men who walked briskly for at least three hours a week had a 57 percent lower rate of progression of disease than men who walked at an easy pace for less than three hours a week.

“The benefit from walking truly depended on how quickly you walked. Walking at an easy pace did not seem to have any benefit,” said Richman.

This collaborative group also recently reported in a separate cohort of men with prostate cancer that vigorous physical activity after diagnosis was associated with a reduced risk of prostate cancer-specific death.

Prostate cancer is the second leading cause of cancer death among men and more than 2.2 million men in the United States currently live with the disease. In 2010, there were 217,000 new cases.

Stephen M. Schwartz, Ph.D., a full member at the Fred Hutchinson Cancer Research Center and a senior editor of Cancer Research, said this study is important because research on the role of physical activity in prostate cancer has been relatively sparse.

“We have had some studies that show a reduced risk of developing prostate cancer, but this is strong evidence of a benefit after someone is diagnosed,” said Schwartz.

Material adapted from American Association for Cancer Research (AACR).

The findings, to be presented next month in an oral session at the 47th annual meeting of the American Society of Clinical Oncology by Lorenzo Cohen, Ph.D., professor and director of the Integrative Medicine Program at MD Anderson, are the latest in an ongoing effort to scientifically validate the age-old belief that mind-body interventions have a beneficial impact on the health of cancer patients. The research was conducted in collaboration with India’s largest yoga research institution, Swami Vivekananda Yoga Anusandhana Samsthana in Bangalore, India.

The study assessed, for the first time, yoga benefits to cancer patients by comparing their experience with patients in an active control group who integrated simple, generic stretching exercises into their lives. “The combination of mind and body practices that are part of yoga clearly have tremendous potential to help patients manage the psychosocial and physical distress associated with treatment and life after cancer, beyond the benefits of simple stretching,” said Cohen.

To conduct the study, 163 women with breast cancer (stage 0-3) averaging 52 years of age were randomized to one of three groups: 1) yoga; 2) simple stretching; or 3) no instruction in yoga or stretching. Participants in the yoga and stretching groups attended sessions specifically tailored to breast cancer patients for one hour three days a week throughout their six weeks of radiation treatment.

Participants were asked to report on their quality of life, including fatigue, daily functioning, benefit finding, depression and spirituality. Saliva samples were collected and electrocardiogram tests were administered at baseline, end of treatment, and at one, three and six months post-treatment.

After completing radiation treatment, only the women in the yoga and stretching groups reported a reduction in fatigue. At one, three and six months after radiation therapy, women who practiced yoga during the treatment period reported greater benefits to physical functioning and general health. They were more likely to perceive positive life changes from their cancer experience than either other group.

Women who practiced yoga also had the steepest decline in their cortisol across the day, indicating that yoga had the ability to regulate this stress hormone. This is particularly important because higher stress hormone levels throughout the day, known as a blunted circadian cortisol rhythm, have been linked to worse outcomes in breast cancer.

According to Cohen, developing a yoga practice also helps patients after completing cancer treatment. “The transition from active therapy back to everyday life can be very stressful as patients no longer receive the same level of medical care and attention. Teaching patients a mind-body technique like yoga as a coping skill can make the transition less difficult.”

Through a grant from the National Cancer Institute – the largest ever awarded for the study of yoga in cancer – Cohen and his team will next conduct a Phase III clinical trial in women with breast cancer to further determine the mechanisms of yoga that lead to improvement in physical functioning, quality of life, and biological outcomes during and after radiation treatment. A secondary aim of the trial, but one of great importance, stressed Cohen, is assessing cost efficiency analysis for the hospital, health care usage costs in general, and examining work productivity of patients.

MD Anderson recognizes the growing body of research indicating that relaxation-based interventions can contribute to the well-being of people with cancer. Through the Integrative Medicine Program, complementary therapies, such as yoga, are offered at MD Anderson’s Integrative Medicine Center, and are used in concert with mainstream care to manage symptoms, relieve stress, enhance quality of life, and improve outcomes for patients and their caregivers. MD Anderson’s Integrative Medicine faculty also conduct research in the biological and behavioral effects of mind-body based interventions; the anti-cancer potential of natural compounds; and, acupuncture to treat common cancer treatment-related side effects.

In addition to Cohen, other MD Anderson researchers contributing to this study include: Kavita Chandwani, M.D., former senior research coordinator and yoga teacher; Robin Haddad, M.P.H. , research coordinator, George Perkins, M.D. in the Department of Radiation Oncology; Amy Spelman, Ph.D., Kayla Johnson, B.S. and Adoneca Fortier, B.S., all staff in the Integrative Medicine Program; Banu Arun, M.D., in the Department of Breast Medical Oncology; and Qi Wei, M.S., Sr. Statistical Analyst. Clemens Kirschbaum, Ph.D. contributed from the Technical University of Dresden, Dresden, Germany. Collaborators from SVYASA include NV Raghuram, B.E.; R. Nagarathna, M.D., and HR Nagendra, Ph.D., founder.

Material adapted from University of Texas M. D. Anderson Cancer Center.

“To our knowledge, this study is the first one providing experimental evidence that a high-rate intermittent lack of oxygen, or hypoxia, mimicking the one experienced by OSA patients enhances tumor growth,” said Ramon Farre, PhD, professor of physiology at the University of Barcelona School of Medicine Biophysics and Bioengineering Lab.

Recurrent hypoxia is one of the hallmarks of OSA, which may affect around 5 percent of Americans. OSA has been associated with an increased risk of cardiovascular disease, including high blood pressure, as well as daytime sleepiness and a lower quality of life.

“Although earlier studies in animals have shown that lack of oxygen, or hypoxia, plays an important role in regulating the various stages of tumor formation and progression, the results obtained from human studies including large groups of OSA patients are not easy to interpret because there are other contributing conditions, most notably obesity,” Dr. Farre added. “This well-controlled mouse model study allowed us to ensure that the only variable under study was intermittent hypoxia.”

In this study, mice injected with melanoma tumor cells were divided among two groups. In the first group, mice were exposed to intermittent hypoxia, where oxygen was restricted for 20-second periods at a rate of 60 periods per hour for six hours per day, and normal oxygen levels for the remainder of the day. In the second group, mice received normal levels of oxygen (normoxia). Tumor volume was measured throughout the study and at the end of the study period. At the end of the 14-day study period, tumors from all mice were removed and weighed and tumor necrosis (indicated by the numbers of dead cells present) was measured to determine the aggressiveness of the tumors.

The authors found that while tumor volume progressively increased with time in both the intermittent hypoxia and control groups, the increase was higher in the mice subjected to intermittent hypoxia. Tumor weight and necrosis in the intermittent hypoxia group were almost two times that of the tumors in the control group.

“With the limitations of any animal model study, these results suggest that the intermittent hypoxia characterizing obstructive sleep apnea could enhance the growth of tumors,” Dr. Farre said, adding that although the results were not entirely unexpected based on earlier studies connecting hypoxia with tumor growth, a link between breathing abnormalities specific to OSA and tumor progression had not previously been demonstrated.

“It was well known that continuous hypoxia promotes the growth of cancer cells and tumors,” he said. “However, there were no data concerning the effects of the fast rate changes of oxygenation in sleep apnea on cancer.”

Dr. Farre said the results of this study could have future clinical implications if the results are confirmed in large-scale human studies. “There are still several questions that need to be answered, both at the basic science and clinical levels,” he said.

Future studies would need to evaluate whether intermittent hypoxia also triggers the initial formation of tumors and whether it promotes metastasis, or spread of tumors from one organ to another. Because this study focused on melanoma, Dr. Farre said additional studies should also explore whether intermittent hypoxia affects other types of cancer.

Extended population studies should also determine if there is a relationship between the incidence of cancer and the severity of OSA, as well as addressing the issue of obesity, which has been linked with OSA.

“Intermittent hypoxia is not the sole cancer-promoting challenge experienced by OSA patients,” Dr. Farre said. “Obesity is also known to enhance cancer morbidity and mortality, and it is not clear to what extent intermittent hypoxia and obesity could interact to increase cancer growth in OSA patients.

Clarifying these questionscertainly will require additional studies,” he said. “If the current results in an animal model are confirmed by further clinical research, the public health impact of obstructive sleep apnea would be greater than currently known.”

Material adapted from American Thoracic Society (ATS).

Reference
“Intermittent Hypoxia Enhances Cancer Progression In A Mouse Model Of Sleep Apnea” (Session C98, Tuesday, May 17, 2:00-4:30 p.m., Room 405-406-407 (Street Level), Colorado Convention Center; Abstract 15455)

*Please note that numbers in this release may differ slightly from those in the abstract. Many of these investigations are ongoing; the release represents the most up-to-date data available at press time.

Researchers from Sweden compared lifestyle factors and coffee consumption between women with breast cancer and age-matched women without. They found that coffee drinkers had a lower incidence of breast cancer than women who rarely drank coffee. However they also found that several lifestyle factors affected breast cancer rates, such as age at menopause, exercise, weight, education, and a family history of breast cancer. Once they had adjusted their data to account for these other factors they found that the protective effect of coffee on breast cancer was only measurable for ER-negative breast cancer.

The group from Karolinska Institutet explained that, “There is often conflicting information about the beneficial effects of coffee – when we compared our results to that of a German study, we discovered that their data showed the same trend, but the relationship was much weaker. We suggest that this may have something to do with the way the coffee was prepared or the type of bean preferred. It is unlikely that the protective effect is due to phytoestrogens present in coffee since there was no reduction in the incidence of ER-positive cancer in this study.”

So while it is evident that coffee may have beneficial effects in protecting women from ER negative breast cancer the exact mechanism and compounds involved are not yet clear and not all types of coffee are the same.

Material adapted from BioMed Central Limited.

Download / Reference
Jingmei Li, Petra Seibold, Jenny Chang-Claude, Dieter Flesch-Janys, Jianjun Liu, Kamila Czene, Keith Humphreys and Per Hall. Coffee consumption modifies risk of estrogen-receptor negative breast cancer. Breast Cancer Research (in press)

“Indoor tanning poses a significant health risk, especially for Caucasians because of their fair skin. Studies have found that UV radiation from indoor tanning beds increases a person’s risk of developing melanoma by 75 percent,” said dermatologist Ronald L. Moy, MD, FAAD, president of the Academy. “Contributing to this problem is the fact that tanning bed facilities currently are not required to verbally warn patrons of the known health risks of ultraviolet (UV) radiation and, in some cases, they may be misleading the public by falsely promoting artificial UV light as safer than natural sunlight.”

The Academy’s survey found that 43 percent of indoor tanners reported that they have never been warned about the dangers of tanning beds by tanning salon employees. When asked if they were aware of any warning labels on tanning beds, 30 percent of indoor tanners said no. By age group, younger tanning bed users (age 14-17) were more likely to be unaware of any warning labels on tanning beds than older tanners (age 18-22) – 42 percent vs. 25 percent, respectively.

Despite the fact that the United States Department of Health and Human Services and the World Health Organization’s International Agency for Research on Cancer have classified UV radiation from tanning devices as cancerous and in the same category as cigarettes, a number of younger tanning bed users still think tanning beds are safer than the sun. Specifically, younger tanning bed users age 14-17 are more than twice as likely to think tanning beds are safer than the sun than older tanners age 18-22 (39 percent vs. 15 percent, respectively) and more than three times as likely to think that tanning beds do not cause skin cancer (26 percent vs. 8 percent, respectively).

“The FDA currently ranks tanning beds as a Class I medical device, which provides a minimal level of regulation and oversight similar to bandages, tongue depressors, gauze, and crutches,” said Dr. Moy. “That is why it’s important that the FDA change the classification of indoor tanning devices to reflect the significant health risks that they pose, often unknowingly, to tanning salon patrons.”

The Tanning Bed Cancer Control Act (TBCCA) was introduced recently by Representatives Carolyn Maloney (D-N.Y.) and Charlie Dent (R-Pa.). The scientific evidence related to the skin cancer risk posed by indoor tanning, findings of the Academy’s survey and the need for stricter controls of indoor tanning will be discussed at a congressional briefing today.

“The indoor tanning industry needs to take responsibility for educating its patrons so they can make informed decisions,” said Dr. Moy. “However, as we do with alcohol and tobacco laws, we need to protect our nation’s young people because research shows they are not heeding health warnings.”

At current rates, one in five Americans will develop skin cancer in his or her lifetime. Approximately 75 percent of skin cancer deaths are from melanoma, and the incidence of melanoma has been rising for at least 30 years – particularly among young, white women in most recent years.

About the “2011 Indoor Tanning: Teen and Young Adult Women” Survey
More than 3,800 white, non-Hispanic females ages 14 to 22 responded to a nationwide survey online to determine their tanning knowledge, attitudes and behavior. The survey was conducted by Relevant Research, Inc. (formerly RH Research) of Chicago from December 28, 2010, to January 11, 2011. Data were weighted by age and region based on the US Census Current Population Survey (released in 2010).

Material adapted from American Academy of Dermatology (AAD).

“There is research showing that high VEGF expression in other cancers, such as ovarian, is associated with psychosocial factors,” says Carolyn Fang, Ph.D., Co-Leader of the Cancer Prevention and Control Program at Fox Chase, who will be presenting the study at the 32nd Annual Meeting & Scientific Sessions of the Society of Behavioral Medicine on Thursday, April 28th. “This information coupled with what we already know about VEGF promoting tumor aggressiveness and poorer prognosis in head and neck cancer patients, certainly gave us a reason to look at this biomarker.”

VEGF not only plays a pivotal role in angiogenesis, but it is also regulated by stress hormones and key cytokines – a category of signaling molecules used extensively in intercellular communication.

In the current study, Fang and colleagues looked at 37 newly diagnosed, pre-surgical patients with head and neck cancer to see if psychosocial functioning, such as perceived stress and depressive factors, was associated with VEGF – a biological pathway relating to patient outcomes. The patients were predominantly male (70.3%), and approximately 57-years-old with primary tumor sites of the oral cavity (65.9%), larynx (19.9%), and oropharynx (13.5%). Over 40% of them were classified as having early-stage disease.

Each patient was given a psychosocial questionnaire to complete prior to treatment, which required them to answer questions about social support, depression, and perceived stress. In addition, VEGF expression in tumor tissue obtained during surgery was evaluated using immunohistochemistry – a process that helps detect the presence of specific proteins in cells or tissues.

“Our analysis indicated that higher levels of perceived stress and depressive symptoms were associated with greater VEGF expression in the tumor tissue of these patients” says Fang. Greater VEGF expression was, in turn, associated with shorter disease-free survival among patients.

The associations between psychosocial functioning and VEGF were strong among early-stage patients, but were less apparent among late-stage patients.

“It’s possible that in early stage disease, psychosocial stress makes patients more susceptible to cancer-related death, while in patients with advanced disease, other factors become more important in determining outcome,” says Miriam N. Lango, M.D., Medical Director of Speech Pathology Service and Attending Surgeon in Head and Neck Oncology at Fox Chase. “In patients with advanced cancers, psychosocial interventions may have less of an impact since these cancers are inherently more aggressive.”

In the near-term, Fang and her colleagues hope to expand the study to look at a larger sample of patients and to incorporate other signaling pathways that are relevant to cancer, like EGFR, which researchers involved in Fox Chase’s Keystone Program in Head and Neck Cancer are already exploring.

“The next step is to conduct a longitudinal study that would allow us to examine patient psychosocial functioning in conjunction with biomarkers of disease aggressiveness and survival from pre-treatment through post-treatment and beyond, which would give us a more complete picture of how these factors may contribute to patient outcomes,” Carolyn adds.

Co-authors on the study include John A. Ridge, M.D., Ph.D., Miriam N. Lango, M.D., Barbara A. Burtness, M.D., Brian L. Egleston, Ph.D., Margaret Einarson, Ph.D., and Andres Klein-Szanto, M.D., Ph.D., of Fox Chase.

Material adapted from Fox Chase Cancer Center.

Conversely, the study also found that men with the highest blood ratios of trans-fatty acids – which are linked to inflammation and heart disease and abundant in processed foods that contain partially hydrogenated vegetable oils – had a 50 percent reduction in the risk of high-grade prostate cancer. In addition, neither of these fats was associated with the risk of low-grade prostate cancer risk. The researchers also found that omega-6 fatty acids, which are found in most vegetable oils and are linked to inflammation and heart disease, were not associated with prostate cancer risk. They also found that none of the fats were associated with the risk of low-grade prostate cancer.

These findings by Theodore M. Brasky, Ph.D., and colleagues in the Hutchinson Center’s Public Health Sciences Division were published online April 25 in theAmerican Journal of Epidemiology.

“We were stunned to see these results and we spent a lot of time making sure the analyses were correct,” said Brasky, a postdoctoral research fellow in the Hutchinson Center’s Cancer Prevention Program. “Our findings turn what we know – or rather what we think we know – about diet, inflammation, and the development of prostate cancer on its head and shine a light on the complexity of studying the association between nutrition and the risk of various chronic diseases.”

The researchers undertook the study because chronic inflammation is known to increase the risk of several cancers, and the omega-3 fatty acids found primarily in fish and fish oil supplements have anti-inflammatory effects. In contrast, other fats, such as the omega-6 fats in vegetable oil and trans-fats found in fast foods, may promote inflammation. “We wanted to test the hypothesis that the concentrations of these fats in blood would be associated with prostate cancer risk,” Brasky said.

“Specifically, we thought that omega-3 fatty acids would reduce and omega-6 and trans-fatty acids would increase prostate cancer risk.”

The mechanisms behind the impact of omega-3s on risk of high-grade prostate cancer are unknown. “Besides inflammation, omega-3 fats affect other biologic processes. It may be that these mechanisms play a greater role in the development of certain prostate cancers,” Brasky said. “This is certainly an area that needs more research.”

Currently there is no official recommended daily allowance for omega-3 fats for adults or children, although many nutrition experts and physicians recommend 450 milligrams of omega-3 DHA per day as part of a healthy diet.

The study was based on data from the Prostate Cancer Prevention Trial, a nationwide randomized clinical trial that tested the efficacy of the drug finasteride to prevent prostate cancer. While the trial involved nearly 19,000 men age 55 and older, the data in this analysis came from a subset of more than 3,000 of the study participants, half of whom developed prostate cancer during the course of the study and half of whom did not. The clinical trial was unique in that prostate biopsy was used to confirm the presence or absence of prostate cancer in all study participants.

Among the study participants, very few took fish oil supplements – the most common non-food source of omega-3 fatty acids, which are known to prevent heart disease and other inflammatory conditions. The majority got omega 3s from eating fish.

So based on these findings, should men concerned about heart disease eschew fish oil supplements or grilled salmon in the interest of reducing their risk of aggressive prostate cancer? Brasky and colleagues do not think so.

“Overall, the beneficial effects of eating fish to prevent heart disease outweigh any harm related to prostate cancer risk,” Brasky said. “What this study shows is the complexity of nutrition and its impact on disease risk, and that we should study such associations rigorously rather than make assumptions,” Brasky said.

Material adapted from Fred Hutchinson Cancer Research Center.

Reference / Abstract
Theodore M. Brasky, Cathee Till, Emily White, Marian L. Neuhouser, Xiaoling Song, Phyllis Goodman, Ian M. Thompson, Irena B. King, Demetrius Albanes, and Alan R. Kristal. Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial. Am. J. Epidemiol. (2011) first published online April 24, 2011.

The developers of the technology at the University of Rochester Medical Center dub it the “Pacman strategy” because it hinges upon molecular machines produced in abundance by tumors to chew through and gobble up particular chains of molecules.

The key feature of the work is a new type of fusion molecule with three parts: a potent immune cell activator; a second molecule to keep that molecule quiescent until it’s needed; and a link between the two that gives scientists control over how the two interact.

The overall fusion molecule acts like a tiny anti-cancer grenade: The portion designed to arouse the immune system to attack cancer is inactive until it’s freed, an act that occurs when the link between it and its inhibitory counterpart is cleaved by specialized tumor proteins that chew up such molecules.

The work, led by graduate student John Puskas and Professor John Frelinger, Ph.D., was published online recently in the journal Immunology. Puskas, who is defending his doctoral thesis today, is first author of the paper.

A protease is designed to destroy the link between IL-2 and its inhibitor, freeing IL-2 near tumors.

“One reason we chose IL-2 is that it’s approved and used to treat patients today. If we’re able to reduce the toxicity associated with it, perhaps it could be used more broadly,” said Frelinger, professor of Microbiology and Immunology.

In experiments using the technology in the lab, the activity of IL-2 in the fusion protein was weak but became 10 to 50 times more biologically active after cleavage. Importantly, in experiments in mice with cancer, tumor growth was inhibited in mice where IL-2 was turned on using the technology compared to mice in which it was not. In many of the treated mice, tumor cells could not be detected after one week.

A key to the technology is the molecular link between IL-2 and its inhibitor. Puskas and Frelinger built that link out of a chain of amino acids – building blocks of proteins. Such chains are broken or cleaved constantly in the body by enzymes known as proteases. In these experiments, when the link is broken, IL-2 breaks free from its inhibitor and is suddenly available to activate other immune cells.

Puskas and Frelinger created links that are cleaved by molecules found much more commonly in cancer cells than other cells. For instance, in one set of experiments, they created a link that is broken only by prostate specific antigen, a protease that is found in prostate cancer cells. They also created links that are cleaved by proteases known as MMP2 and MMP9 – both examples of matrix metalloproteinases commonly overactive in many types of tumors.

The approach is designed to turn on the immune system powerfully right in the neighborhood of cancer cells, to destroy those cells, but to avoid a system-wide immune response that could cause severe side effects.

Frelinger points out that the new work is quite different from other experimental anti-cancer efforts that have involved fusion proteins. In other fusion protein approaches, the molecules are active throughout the body. In the new work, the cytokine is designed to be active only near tumor cells, an approach designed to reduce unwanted side effects.

“The beauty of this approach is that you can change any part of the molecule you want,” said Frelinger, who also has an appointment in the University’s James P. Wilmot Cancer Center. “If you want to target a specific type of cancer, you change the protease sequence to tailor it to particular types of tumors. If you want to change the part of the immune system activated, you change the cytokine.

“Our hope is that an approach like this might someday be coupled with other types of therapy, so that the body could initiate and maintain a vigorous immune response to kill tumors.”

Other authors besides Puskas and Frelinger include graduate students Denise Skrombolas and Abigail Sedlacek, and faculty members Edith Lord, Ph.D., and Mark Sullivan, Ph.D. The work was supported by the National Institutes of Allergy and Infectious Diseases as well as by Steven and Alison Krausz and F.C. Blodgett.

“John was very brave for taking on this project,” said Frelinger. “It really was something that hadn’t been attempted before. He did an outstanding job.”

Material adapted from University of Rochester Medical Center.

Dwivedi and his colleagues published their journal article on the topic, “Chemopreventive Effects of Dietary Canola Oil on Colon Cancer Development,” in the February 2011 issue of the journal Nutrition and Cancer.

“This is the first time anyone has done work on the effect of canola oil in animals on colon cancer prevention. Canola oil was able to reduce the incidence of colon cancer in animals almost to one-third,” Dwivedi said.

The study showed that canola oil inhibited the average number of tumors per rat by 58 percent compared to one of the other two control diets in the experiment, and inhibited the size of the tumors that occurred by 90 percent.

Colon cancer causes more deaths than any other form of cancer in men and women in the United States. American Cancer Society statistics say there were about 102,900 cases of colon and 39,670 cases of rectal cancer in 2010, resulting in an estimated 51,370 deaths.

Dwivedi said professor Padmanaban Krishnan in SDSU’s Department of Health and Nutritional Sciences suggested the study of canola oil’s potential in protecting against colon cancer because Dwivedi had already led similar studies looking at the cancer-fighting properties of flaxseed meal and flaxseed oil. Krishnan was one of the collaborators in the study. The project was carried out under the auspices of grants from North Central Canola Research, North Dakota State University, and National Canola Growers. Value addition of oilseeds is also supported by the South Dakota Agricultural Experiment Station.

Flaxseed oil has a much higher level of Omega-3 fatty acids that are partly responsible for the health benefits — more than 50 percent compared to about 10 percent in canola oil — but canola oil may be easier to include in a typical American diet.

“The advantage of canola is it can be used for day to day cooking, frying and anything else, in contrast to the flax,” Dwivedi said. “You could not use flax oil for frying. If people start using canola oil, replacing other oils with canola oil, it gives them the advantage of including Omega-3s in their diet.”

Dwivedi adds that studies have indicated that if consumers use canola as household cooking oil, it could push their ratio of Omega-6 to Omega-3 fatty acids to about 3 to 1. That’s very desirable. Humans need Omega-6 fatty acids, too, but they typically consume way too much of them in countries such as the United States.

“It should be less than 4 to 1. But in a typical American diet, when we use other oil and butter, our ratio is 10 to 1 or higher. We consume a lot more Omega-6 than Omega-3 fatty acids,” Dwivedi said. “So anything we could do to bring that ratio more in favor of Omega-3 is always good.”

The research builds on earlier studies by Dwivedi and his colleagues suggesting that Omega-3 fatty acids have a chemopreventive effect by inhibiting an enzyme called cyclooxygenase and reducing the synthesis of arachidonic acid, both of which are associated with inflammation.

Dwivedi’s co-authors were Ekta Bhatia of the Department of Pharmaceutical Sciences at SDSU; Chaitanya Doddivenaka and Padmanaban Krishnan of SDSU’s Department of Health and Nutritional Sciences; Xiaoying Zhang of Shanghai Chempartner Co. Ltd. and the College of Pharmacy, Zhejiang University of Traditional Chinese Medicine; Ajay Bommareddy of the Department of Pharmaceutical Sciences, Wilkes University; and Duane Matthees of SDSU’s Department of Veterinary and Biomedical Sciences.

Material adapted from South Dakota State University.

Scientists have known for many years that pancreatitis, a painfully inflamed pancreas, is a common risk factor for pancreatic cancer – along with things like smoking and diet. But nobody knew exactly why.

Now the UCSF team, led by Matthias Hebrok, PhD, has discovered at least part of the connection. In an article appearing in the journal Cancer Cell this week, they show that two molecular “signals” produced abundantly in the pancreas during inflammation – a protein named Stat3 – helps initiate the early stages of pancreatic cancer, while another protein, called MMP7, appears to affect metastasis.

In laboratory experiments, Hebrok and his colleagues showed that blocking these proteins in mice shrunk the number of lesions that can lead to cancer and reduced the extent of cancer metastasis. They also showed that one of these molecules, MMP7, may be a clinical indicator of cancer stage, possibly making it useful as a marker for more aggressive disease. The research could also help identify new ways to target pancreatic cancer with drugs.

“If you are able to down-regulate inflammatory signals at an early stage of the disease, you may be able to curb the formation of early lesions,” said Hebrok, who directs the UCSF Diabetes Center and is the Hurlbut-Johnson Distinguished Professor in Diabetes Research.

Inflammation And Pancreatic Cancer
Pancreatic cancer in the United States is all too common and far too deadly. According to the National Cancer Institute, there were some 43,140 new cases of pancreatic cancer diagnosed in the United States in 2010 and 36,800 deaths from the disease last year. Overall, fewer than one in 20 people diagnosed with pancreatic cancer this year will be alive five years from now.

One of the problems with the disease is that there are no reliable, sensitive screens that allow doctors to catch it early. By the time it is detected, the cancer often is so advanced it cannot be surgically removed or easily treated.

Like many scientists who study diabetes, Hebrok is very familiar with pancreatic cancer, because diabetes onset often precedes the cancer diagnosis and may be one of the warning signs. Part of his research in the past few years has involved looking at the microscopic changes that take place in the pancreatic organ when cancer emerges.

The pancreas is a 6-inch-long gland sandwiched between the stomach and the backbone. Inside are tiny cavities called “acini” in which enzymes are produced that drain through ducts into the stomach to help digest food. Pancreatic cancer may start in these cavities or in the ducts when the cells lining them undergo transformations and begin multiplying, forming cancerous lesions – a process often kick-started by inflammation.

Hebrok and his colleagues have discovered that the molecule Stat3 is a key player in this process. It is produced in the pancreas and induces the cells of the pancreas to proliferate as part of a normal healing process in response to inflammation. Sometimes this process goes awry, however, and leads to the transformation of normal cells into cancerous ones. Stat3 also increases the amount of MMP7, which contributes to cancer metastasis.

The UCSF team showed that blocking MMP7 in mice blocks metastasis and reduces the size of cancer tumors. Collaborating with a group at the University of Utah, they examined blood samples taken from people with pancreatic cancer, and they found that those with more MMP7 in their blood were more likely to be at an advanced stage of cancer.

This suggests that MMP7 might be a useful marker to guide treatment for people with pancreatic cancer. And the new insight into the overall process of how inflammation is linked to pancreatic cancer might help scientists identify new targets for cancer therapy – if ways of interfering in the process can be found and if those approaches prove effective in clinical trials

“As with many things, timing is critical,” Hebrok said. “We will need to understand in more detail during which stage of the disease therapeutic targets are activated to efficiently inhibit their function and thus cancer formation and progression.”

Material adapted from UCSF.

Cognitive problems, such as trouble with attention and memory, often arise in survivors of childhood cancer. These problems, which are either a direct or indirect result of treatment, negatively impact future education, employment, and the ability to live independently.

To assess the effects of fatigue and sleep disruption on cognitive function in long-term survivors of childhood cancer, Kevin Krull, PhD, of St. Jude Children’s Research Hospital in Memphis and his team evaluated a questionnaire filled out by 1,426 individuals from the Childhood Cancer Survivor Study. (The Childhood Cancer Survivor Study was designed to investigate the long-term medical, psychosocial, and functional health of survivors of eight different childhood cancers who were treated between 1970 and 1986.)

Cognitive impairment was identified in over 20 percent of survivors. Participants’ answers to the questionnaire revealed that long-term survivors of childhood cancer who have problems sleeping or have frequent daytime sleepiness and fatigue are three to four times more likely to have attention and memory problems than survivors who sleep well.

“Since survivors are already at increased risk for attention and memory problems, sleep loss and fatigue may make these cognitive problems worse,” said Dr. Krull.

The investigators found that survivors’ cognitive problems that are associated with poor sleep and fatigue are unrelated to the effects of brain radiation, chemotherapy, or the current age of the survivor. Also, cancer survivors who are currently taking antidepressant medications are 50 percent more likely to report attention problems and 70 percent more likely to report memory problems.

“These findings suggest that improved sleep quality and reduced fatigue may help to improve attention and memory functions in survivors,” said Dr. Krull. He added that these results may generalize to survivors of other medical conditions who demonstrate simultaneous sleep and cognitive problems.

Krull also cautions that people taking antidepressant medication should not discontinue use without first consulting with a personal physician.

Material adapted from Wiley-Blackwell.

The effect is so great, researchers say, that it may be a sign of accelerated aging in fatigued patients, causing them to seem as much as 20 years older compared with patients who are not fatigued.

Those new research findings, just reported in the journalPsychoneuroendocrinology, are the latest from a three-decade-long study of the impact that stress can have on the human body.

Christopher Fagundes, a postdoctoral fellow at Ohio State University’s Institute of Behavioral Medicine Research (IBMR), and Janice Kiecolt-Glaser, a professor of psychiatry and psychology and a member of the IBMR, drew early data from a larger ongoing study testing whether yoga can combat continuing fatigue in breast cancer patients.

They were looking for a new biomarker, a signal that could point to the initial cause of this fatigue. Their target was the autonomic nervous system, that part of the body that controls unconscious activities like breathing, heartbeat, digestion and such, which earlier research had indicated might play a role.

The autonomic nervous system has two main parts – the sympathetic and the parasympathetic. The former is responsible for what has become known as the fight-or-flight response, a triggering of short-term, energized activity. The latter deals with opposite situations. It is the resting phase, best recognized by the sleepiness that may follow eating a big meal.

While the sympathetic system is an energy hog, the parasympathetic conserves energy, and the two should remain in balance in healthy individuals. The researchers were looking for differences between fatigued and non-fatigued cancer survivors.

“We started looking for biomarkers for cancer-related fatigue,” Fagundes said. “Other research has indicated that a systemic inflammation through the body might be a reliable biomarker for this.

“Sick people with inflammation become tired and lethargic, which makes sense since their bodies are using energy to fight off infections. You can imagine that a long-term, systemic inflammation, year-in and year-out, might produce this fatigue.”

For the study, 109 women participated and were placed in one of two groups – those who reported long-term fatigue and those who didn’t. The women varied from being two months to two years after being treated for their disease.

Fatigue is a normal response to breast cancer treatments like chemotherapy and radiation therapy, but one-third or more of breast cancer survivors report continued debilitating fatigue long after treatment has ended.

After a short relaxation period, each woman had blood drawn to establish a baseline level for norepinephrine, a stress hormone that served as an indicator of activity by the sympathetic nervous system.

Each participant had to give a five-minute speech before a two-person panel and then do a series of verbal arithmetic problems aimed at increasing stress levels. Additional blood samples were taken immediately after the stressor and then a half-hour later.

The norepinephrine levels rose as expected from the baseline in both groups after the stressful episode but the researchers were surprised to see something different. Regardless of the stressor, women who had persistent fatigue showed higher levels of norepinephrine than those who were not fatigued.

“They had higher sympathetic activity and lower parasympathetic activity,” Fagundes said, an indication that other researchers have suggested is a signal for inflammation.

The researchers also gauged another measure in the study, the natural variability in heart rate which decreases as a person ages. A lessened heart rate variability (HRV) is also an indicator of activity in the parasympathetic, or “resting,” system.

“People who were fatigued had weaker parasympathetic activity than those who weren’t,” he said.

“One of the things we know best is that exercise can enhance a person’s HRV,” Kiecolt-Glaser said. “Exercise is also the best documented treatment for fatigue, so this all begins to make sense.

“Fatigue isn’t a symptom that should be ignored. It’s a marker for other things that might be going on,” she said. Higher norepinephrine levels and lower HRV have been linked to high blood pressure, myocardial infarctions, strokes, and diabetes.

“When a cancer patient reports persistent fatigue following treatment, it is something that deserves attention. It may be a symptom of other things that matter.”

Working with Fagundes and Kiecolt-Glaser on the work were William Malarkey, Charles Shapiro, David Murray, Beom Seuk Hwang, Jean Philippe Gouin and Julian Thayer, all from Ohio State; and John Sollers from the University of Auckland.

Material adapted from Ohio State University.

Parkinson’s disease (PD) is a progressive neurologic condition that leads to tremors and difficulty with walking, movement, and coordination. Most studies demonstrate that individuals with PD have an overall decreased rate of cancer, with the notable exception of melanoma, the most serious form of skin cancer. Previous research has suggested a possible genetic link between PD and melanoma, but these studies have been limited to first-degree relatives who often share a similar environment, making it difficult to distinguish between genetic and environmental risk factors.

“Neurodegenerative disorders such as Parkinson’s disease may share common disease-causing mechanisms with some cancers,” says Stefan-M. Pulst, MD, professor and chair of the department of neurology, at the University of Utah, and co-author on this study. “Using the Utah Population Database, we were able to explore the association of PD with different types of cancer by studying cancer risk in individuals with PD, as well as their close and distant relatives.”

The Utah Population Database (UPDB) includes birth, death, and family relationship data for over 2.2 million individuals, including genealogy data from the original Utah pioneers. Some of the records in this computerized database extend back over 15 generations, making the UPDB a useful resource for studying genetic risk. The UPDB is also linked with the Utah Cancer Registry and Utah death certificates dating back to 1904.

“In Utah, we have the unique opportunity to evaluate the relationship between PD and certain cancers using a population-based approach that eliminates many of the typical types of bias associated with epidemiological studies,” says Lisa Cannon-Albright, PhD, University of Utah professor of internal medicine, division chief of genetic epidemiology, and co-author of this study. “Rather than relying on patient interviews for family medical history, we were able to use the UPDB, along with statewide registries of cancer and death, to look for links between PD and cancer.”

The study team, including Seth A. Kareus, MD, University of Utah chief resident of neurology and Karla P. Figueroa, MS., screened the UPDB to identify nearly 3000 individuals with at least three generations of genealogical data who had PD listed as their cause of death. The researchers discovered that the risk of prostate cancer and melanoma within this PD population was significantly higher than expected. They also observed an increased risk for prostate cancer and melanoma among first-, second-, and third-degree relatives of these individuals with PD, although the excess risk for melanoma in third-degree relatives did not reach statistical significance.

In order to validate the observed association between PD-related death and these two cancers, the researchers also identified individuals who were diagnosed with either melanoma or prostate cancer to evaluate their risk for death with PD. They found that these individuals, as well as all their relatives, had a significantly increased risk for death with PD.

“In our study, we not only identified an increased risk for prostate cancer and melanoma among individuals with PD and their relatives, but also established a reciprocal risk for PD among individuals with these two cancers and their relatives,” says Pulst. “Collectively, these data strongly support a genetic association between PD and both prostate cancer and melanoma.”

Interesting, Pulst and his colleagues noted that, while a decreased risk for lung cancer was observed among individuals with PD, this decrease in risk did not extend to any of their relatives. This finding suggests that environmental, rather than genetic, factors might be responsible for this association.

“Our findings point to the existence of underlying pathophysiologic changes that are common to PD, prostate cancer, and melanoma,” says Cannon-Albright. “Exploring the precise genetic links among these diseases could improve our understanding of PD and influence strategies for prostate and skin cancer screening.”

Material adapted from University of Utah Health Sciences.

“We concluded from this study that six months of eating strawberries is safe and easy to consume. In addition, our preliminary data suggests that strawberries can decrease histological grade of precancerous lesions and reduce cancer-related molecular events,” said Chen.

Esophageal cancer is the third most common gastrointestinal cancer and the sixth most frequent cause of cancer death in the world, she said. Chen and her team are studying esophageal squamous cell carcinoma (SCC), which makes up 95 percent of cases of esophageal cancer worldwide. China, where this study took place, has the highest incidence of esophageal SCC.

In a previous study, Chen and colleagues found that freeze-dried strawberries significantly inhibited tumor development in the esophagus of rats. Based on these results, they embarked on a Phase Ib trial that included participants with esophageal precancerous lesions who were at high risk for esophageal cancer.

Participants consumed 60 grams of freeze-dried strawberries daily for six months and completed a dietary diary chronicling their strawberry consumption. Using freeze-dried strawberries was important because by removing the water from the berries, they concentrated the preventive substances by nearly 10-fold, Chen said.

The researchers obtained biopsy specimens before and after strawberry consumption. The results showed that 29 out of 36 participants experienced a decrease in histological grade of the precancerous lesions during the study.

“Our study is important because it shows that strawberries may slow the progression of precancerous lesion in the esophagus. Strawberries may be an alternative or work together with other chemopreventive drugs for the prevention of esophageal cancer. But, we will need to test this in randomized placebo-controlled trials in the future,” said Chen.

Material adapted from American Association for Cancer Research (AACR).

The compound artemisinin – isolated from Artemisia annua L, commonly known as wormwood – is a natural remedy widely used to treat malaria. In the mid-1990s UW researchers were the first to explore its ability to treat cancer.

Annual wormwood, Artemisia annua L., yields the important antimalarial drug artemisinin. Researchers at UW and WSU are exploring its ability to treat cancer.

“If you combine high-pressure oxygen with artemisinin you can get a much better curing effect,” said author Henry Lai, a UW research professor of bioengineering. “We only measured up to 48 hours. Over longer time periods we expect the synergistic effects to be even more dramatic.”

The history of artemisinin brings to mind an Indiana Jones story. In the early 1970s, Lai says, Chinese leader Mao Zedong issued an order to develop an anti-malarial treatment. At the same time, a farmer in central China discovered a 2,000-year-old tomb that contained three coffins. One coffin contained a silk scroll describing various prescriptions, including artemisinin to treat malaria. The Chinese followed the directions and thus rediscovered an ancient remedy. Today, artemisinin is widely used in Asia and Africa for malaria treatment.

In the decades since, scientists have discovered artemisinin reacts with iron within a cell to form a free radical, a highly reactive charged particle that destroys the cell. Because the malaria parasite is high in iron, artemisinin targets malaria-infected cells.

Since rapidly dividing cancer cells also need iron to form new DNA, Lai theorized they would also make targets for artemisinin. Subsequent research showed this to be the case.

Lai and colleagues at the UW developed a variant several thousand times more potent than natural artemisinin, which was licensed in 2004 to a Chinese company.

“Artemisinin is a promising low-cost cancer treatment because it’s specific, it’s cheap, and you don’t have to inject it,” Lai said. “It’s 100 times more specific than traditional chemotherapy,” he added. “In breast cancer, it’s even better.”

Lai says he’s long hypothesized that high oxygen levels would enhance artemisinin’s effects, because oxygen promotes the formation of free radicals. In 2010, he put the theory to the test in a hyperbaric chamber that co-author Raymond Quock, WSU professor and chair of pharmaceutical sciences, has been using to study highly pressurized oxygen’s ability to relieve pain.

A Petri dish with human cancer cells was placed in this high-pressure oxygen chamber for 48 hours.

Hyperbaric chambers, which are filled with oxygen at high pressure, help scuba divers who surface too quickly gradually readjust to normal oxygen levels.

A photo of pop singer Jackson in the mid-80s sleeping in a portable hyperbaric chamber sparked rumors that he was trying to heal scars from plastic surgery, retain his youthful appearance or extend his lifespan. The photo turned out to be a publicity stunt, but the U.S. Food and Drug Administration has approved hyperbaric oxygen therapy for several ailments, including decompression sickness, carbon-monoxide poisoning, Lyme disease and slow-to-heal wounds.

In clinical practice, the artemisinin-hyperbaric study could lead to people or animals spending time in a hyperbaric chamber to enhance the artemisinin’s effectiveness.

Other co-authors are Yusuke Ohgami, Catherine Elstad and Eunhee Chung of WSU and Donald Shirachi of the Chico Hyperbaric Center.

Material adapted from University of Washington.

The investigation, which looked at the association of post-diagnosis weight gain and breast cancer outcomes, was conducted by researchers at Kaiser Permanente in Northern California. Data for the study came from the After Breast Cancer (ABC) Pooling Project, which includes 18,336 breast cancer survivors from four prospective cohorts — three in the United States and one in Shanghai, China.

Participants were diagnosed with invasive primary breast cancer between 1976 and 2006; their ages ranged from 20 to 83 years. Weight and body mass index (BMI) were assessed 18 to 48 months after diagnosis and were compared with each woman’s pre-diagnosis weight.

“Most women are not gaining a large amount of weight following breast cancer diagnosis,” said lead researcher Bette Caan, Dr.P.H., senior research scientist at the Kaiser Permanente Division of Research. “But our analysis of the pooled data showed an association with poorer outcomes overall for those who do.”

While extreme weight gain occurred in 16 percent of the women overall, 19.4 percent of women with a BMI lower than 25 before diagnosis fell into this category. Breast cancer survivors who gained the most (10 percent or more over their pre-diagnosis weight was considered extreme) were 14 percent more likely to experience a cancer recurrence compared with women whose weight remained stable (within 5 percent of pre-diagnosis weight) following diagnosis.

“Women tend to worry about gaining weight after a breast cancer diagnosis,” said Caan. “But it’s actually only the larger weight gains that increase the risk of poor outcomes.”

Moderate weight gain (a 5 to 10 percent increase post-diagnosis) was also more common among normal or underweight women, but was unrelated to breast cancer outcomes. Only 11.1 percent of women who were overweight or obese before diagnosis had extreme weight gains after their diagnosis.

Women who were leaner to begin with at diagnosis (BMI lower than 25) and who later gained 10 percent or more had a 25 percent higher risk of cancer death and also had a higher risk of recurrence. The risk of overall death was also greater for women whose tumors were ER-positive.

Continued research is needed to understand those women most at risk for extreme weight gain and those whose weight gain puts them at risk for poorer cancer outcomes, according to Caan.

Material adapted from American Association for Cancer Research (AACR).

“The results are not meant to suggest everyone should start taking aspirin once monthly to reduce their risk of pancreatic cancer,” said Tan. “Individuals should discuss use of aspirin with their physicians because the drug carries some side effects.”

For the current study, Tan and colleagues enrolled 904 patients who had documented pancreatic cancer and compared them with 1,224 healthy patients. All patients were at least 55 years old and reported their use of aspirin, NSAIDs and acetaminophen by questionnaire.

Results showed that people who took aspirin at least one day during a month had a 26 percent decreased risk of pancreatic cancer compared to those who did not take aspirin regularly. The effect was also found for those who took low-dose aspirin for heart disease prevention at 35 percent lower risk, according to Tan.

The researchers did not see a benefit from non-aspirin NSAIDs or acetaminophen. “This provides additional evidence that aspirin may have chemoprevention activity against pancreatic cancer,” said Tan. He added that more data must be gathered before we can prove a real benefit.

Material adapted from American Association for Cancer Research (AACR).

The work was presented at the American Association for Cancer Research 102nd Annual Meeting 2011.

In all, the tumors had more than 1,700 mutations, most of which were unique to the individual, says Matthew J. Ellis, MD, PhD, professor of medicine at Washington University School of Medicine in St. Louis and a lead investigator on the project.

“Cancer genomes are extraordinarily complicated,” Ellis says. “This explains our difficulty in predicting outcomes and finding new treatments.”

The above Circos plot is a visual representation of the genomic disruptions in one of the breast cancers studied. (click to enlarge)

“The computing facilities required to analyze this amount of data are similar in scale to those of the Large Hadron Collider, used to understand the workings of sub-atomic particles,” Ellis says.

The DNA samples came from patients enrolled in a clinical trial that Ellis is leading for the American College of Surgeons Oncology Group. All patients in the trial had what is called estrogen-receptor-positive breast cancer. These cancer cells have receptors that bind to the hormone estrogen and help the tumors grow.

To slow tumor growth and make the tumors easier to remove, patients received estrogen-lowering drugs before surgery. But, for unknown reasons, this treatment does not always work. Twenty-four of the 50 tumor samples came from patients whose tumors were resistant to this treatment, and 26 came from patients whose tumors responded. Comparing the two groups might help explain why some estrogen-receptor-positive breast cancer patients do well with estrogen-lowering drugs and others poorly.

Confirming previous work, Ellis and colleagues found that two mutations were relatively common in many of the patients’ cancers. One called PIK3CA is present in about 40 percent of breast cancers that express receptors for estrogen. Another called TP53 is present in about 20 percent.

Adding to this short list of common mutations, Ellis and colleagues found a third, MAP3K1, that controls programmed cell death and is disabled in about 10 percent of estrogen-receptor-positive breast cancers. The mutated gene allows cells that should die to continue living. Only two other genes, ATR and MYST3, harbored mutations that recurred at a similar frequency as MAP3K1 and were statistically significant.

“To get through this experiment and find only three additional gene mutations at the 10 percent recurrence level was a bit of a shock,” Ellis says.

In addition, they found 21 genes that were also significantly mutated, but at much lower rates — never appearing in more than two or three patients. Despite the relative rarity of these mutations, Ellis stresses their importance.

“Breast cancer is so common that mutations that recur at a 5 percent frequency level still involve many thousands of women,” he says.

Ellis points out that some mutations that are rare in breast cancer may be common in other cancers and already have drugs designed to treat them.

“You may find the rare breast cancer patient whose tumor has a mutation that’s more commonly found in leukemia, for example. So you might give that breast cancer patient a leukemia drug,” Ellis says.

But such treatment is only possible when the cancer’s genetics are known in advance. Ideally, Ellis says, the goal is to design treatments by sequencing the tumor genome when the cancer is first diagnosed.

“We get good therapeutic ideas from the genomic information,” he says. “The near-term goal is to use information on whole genome sequencing to guide a personalized approach to the patient’s treatment.”

This work builds on previous collaborations between Washington University oncologists and the Genome Institute. In a study published last year in Nature, they reported the complete tumor and normal DNA sequences of a woman with “triple-negative” breast cancer, a particularly aggressive type that is difficult to treat and more common in younger women and African-Americans.

While many mutations are rare or even unique to one patient, Ellis says quite a few can be classified on the basis of common biological effects and therefore could be considered together for a particular therapeutic approach.

Ellis looks to future work to help make sense of breast cancer’s complexity. But these highly detailed genome maps are an important first step.

“At least we’re reaching the limits of the complexity of the problem,” he says. “It’s not like looking into a telescope and wondering how far the universe goes. Ultimately, the universe of breast cancer is restricted by the size of the human genome.”

Material adapted from Washington University in St. Louis.

References
Ellis et al. Breast cancer genome. Presented Saturday, April 2, 2011, at the 102nd Annual Meeting of the American Association for Cancer Research in Orlando, Fla.

Ding L, Ellis MJ, Weinstock GM, Aft R, Watson M, Ley TJ, Wilson RK, Mardis ER et al. Cancer remodeling in a basal-like breast cancer metastasis and xenograft. Nature. April 15, 2010.

The report also finds that the overall rate of new cancer diagnoses for men and women combined decreased an average of slightly less than 1 percent per year for the same period. Edward J. Benz, Jr., MD, president of Dana-Farber Cancer in Institute in Boston, called the news encouraging, but cautions we still have a very long way to go in our fight against cancer.

“Overall, the rate of cancer deaths is falling, but not by a lot, not nearly enough,” said Benz. “But considering that the incidence of cancer continues to increase, while the number of deaths is flat or falling a little bit, it does suggest that efforts of prevention, early detection, and better treatments are having a positive impact.”

The report is co-authored by researchers from the North American Association of Central Cancer Registries, the National Cancer Institute, the Centers for Disease Control and Prevention, and the American Cancer Society. It will be posted on the web site of the Journal of the National Cancer Institute on March 31, and will be published in the journal’s May 14 print issue.

The authors emphasized the need to focus further on reducing the cancer burden in the population as a whole through prevention, detection and treatment of cancer.

“One of the best ways to avoid dying of cancer is to prevent it in the first place,” added Dr. Benz. “This involves making lifestyle adjustments, such as not smoking, being careful about exposure to the sun, diet and exercise, and being careful about exposure to chemicals in the workplace. Patients also need to be sure to participate with their primary care physician in the kinds of screening that can pick up cancers very early.”

Download the Video
Annual Cancer Report with Edward J. Benz, Jr., MD
Dana-Farber Cancer Institute president: Trends are encouraging, but more improvements are needed.

Material adapted from Dana-Farber Cancer Institute.

“The beneficial effects seem not to come from the traditional acupuncture method, but probably from the patients’ positive expectations and the extra care that the treatment entails,” says Anna Enblom, physiotherapist and researcher at the Osher Centre for Integrative Medicine at Karolinska Institutet. “The patients communicated with the physiotherapists administering the acupuncture, received tactile stimulation, and were given extra time for rest and relaxation.”

The study included 277 patients at Linköping and Lund university hospitals and Karolinska University Hospital in Solna, all of whom were undergoing radiotherapy of the abdomen or pelvic region for cancer. A selection of 215 patients from this group were blindly assigned traditional or simulated acupuncture. The former group (109 patients) had needles inserted into their skin to stimulate certain points, and the latter (106 patients) had blunt telescopic placebo needles merely pressed against the skin. The acupuncture patients were then compared with 62 patients who had only received the standard care regime with medications for nausea and no acupuncture.

The results show that the patients who had received genuine or simulated acupuncture felt much less nauseous than those who had received standard care only. Of the patients who had had some form of acupuncture, only 37 felt nausea and seven per cent vomited, compared with 63 per cent and 15 per cent of the standard care group. However, no differences were observed between the two acupuncture groups, despite the fact that the placebo needle was applied to the skin for a total of only two minutes during the entire five-week treatment period.

The patients’ expectations seemed to be important for the effect: 81 per cent of those who expected to feel ill did so, in contrast to only 50 per cent of those who did not.

“It’s important to remember that the effects of the treatment are valuable to the patients, even if they can be said to have been caused by unspecific factors, such as the manner in which the patients were taken care of and their positive expectations,” says Dr. Enblom. “So our next step is to study which part of the acupuncture procedure actually are of importance, to make possible the use of those components to further increase quality of care.”

The published study also formed a part of Dr. Enblom’s previously published doctoral thesis from Linköping University.

Material adapted from Karolinska Institutet.

Reference
Anna Enblom, Mats Lekander, Mats Hammar, Anna Johnsson, Erik Onelöv, Martin Ingvar, Gunnar Steineck and Sussanne Börjeson. ”Getting the Grip on Nonspecific Treatment Effects: Emesis in Patients Randomized to Acupuncture or Sham Compared to Patients Receiving Standard Care.” PLoS ONE on 23 March 2011.

“This approach gives us a way to rapidly evaluate whether mutations in human tumors are likely to be important,” says senior author Timothy Ley, MD, the Lewis T. and Rosalind B. Apple Professor of Oncology. “If we find mutations that occur in mouse models and we see those same mutations, however rare, in human cancers, they are highly likely to be relevant.”

Ley and his colleagues at Washington University’s Genome Institute have sequenced the genomes of nearly 250 patients with cancer and their tumors. By comparing the DNA sequences of tumor and healthy cells from each patient, they have uncovered a number of novel mutations underlying cancer.

But the endeavor is time consuming. Human tumor cells typically acquire several hundred mutations; the vast majority are background alterations that occur naturally throughout the course of a person’s life. The challenge is to sift through the genetic “noise” to find the handful of mutations in each tumor that drive cancer development.

Ley and his colleagues theorized that their work could be simplified if they looked for mutations in mouse models of cancer. These mice are inbred, which suggests they have fewer background mutations.

The current study involved a mouse model for acute promyelocytic leukemia (APL) that was developed in Ley’s lab more than a decade ago by Peter Westervelt, MD, PhD, now director of the Bone Marrow Transplant/Leukemia Section in the Division of Oncology. The disease is a subtype of acute myeloid leukemia, a cancer of the blood and bone marrow.

APL is a cancer success story: once the most deadly form of leukemia, today APL is highly treatable. However, about 20 percent of patients experience a recurrence after standard treatment, pointing to the need for more effective therapy.

For the current study, the investigators inserted into the mouse genome a mutated human gene, called PML-RARA, which is known to initiate APL in patients. Then, they waited a year for full-blown leukemia to develop.

During that waiting period, bone marrow cells in the mouse are thought to acquire additional mutations that transform cells into full-blown leukemia. The purpose of the study was to find those cooperating mutations and determine whether they also occur in leukemia patients.

Unlike sequencing studies that focus only on genes, which make up just 1 percent of the entire genome, whole genome sequencing captures the full breadth of genetic alterations in DNA, including large insertions, deletions and other structural changes.

When co-authors Richard Wilson, PhD, and Elaine Mardis, PhD, director and co-director of The Genome Institute, respectively, and their colleagues sequenced the genome of the mouse tumor cells, they found genetic mutations in three genes, each of which alter a single letter in the DNA sequence and disrupt the instructions for making proteins.

One of these mutations, in the Jak1 gene, also occurred in six of 89 other APL mouse tumors they studied. Moreover, the mutation was identical to one that other research teams recently identified in one patient with APL and in other patients with acute lymphoblastic leukemia (ALL).

“By establishing that the mutation occurs in other mouse tumor samples and in patients with leukemia, that tells us this mutation is a driver; it almost certainly is relevant for the progression of cancer,” Ley says.

A further analysis by lead author Lukas Wartman, MD, a fourth-year fellow in the Division of Medical Oncology, found that JAK1 cooperates with the initiating mutation in APL to cause a rapidly fatal leukemia in the mice. Mice with APL who expressed the mutant human JAK1 gene developed leukemia in just a month rather than a year.

“We also evaluated a JAK inhibitor in 10 mouse APL tumors and all of them responded, even those without a mutation in the gene,” Wartman says. “This suggests that JAK1 is part of a crucial cancer pathway for this disease. Interestingly, JAK inhibitors are already in clinical trials for a number of cancers.”

For Wartman, the research is personal. During his fourth year of medical school at Washington University, he was diagnosed with ALL. Chemotherapy put his cancer into remission, but five years later, it returned. Wartman then was treated with a stem cell transplant from his younger brother. He has now been cancer-free for two and a half years.

“This work is really important for me but also for so many other cancer patients and cancer survivors who want to know why they got cancer in the first place,” Wartman says. “We think studies like this can help answer that question.”

The researchers also found a large deletion in the Kdm6a (also known as Utx) gene in the mouse tumor genome. A similar deletion was found in another three of 14 mouse APL genomes they studied and in one human AML sample. Deletions in the same gene also have been associated with human cancers, including kidney and esophageal tumors and multiple myeloma, another blood cancer.

Ley says the new research also highlights the value of mouse models of cancer to find important mutations in patients.

“There’s been an ongoing debate for 15 years about whether mouse models of cancer are relevant to cancer that develops in people,” he explains. “By sequencing this genome, I think the answer is clear: this mouse model is remarkably similar to the human disease. This gives us a new way to use whole-genome sequencing to rapidly identify the most relevant mutations in human cancers.”

Looking ahead, the researchers say they will complement their efforts to sequence human cancer genomes with their mouse genome counterparts, when good mouse models are available.

“We expect this to expedite our ability to determine whether mutations in patients are important for disease progression,” Wilson says. “If we find the same mutations in human cancers and in a mouse model of the disease, then we know they are likely to be relevant, even if we’ve only seen the mutations in a small fraction of patients.”

Material adapted from Washington University in St. Louis.

Download / Reference
Wartman LD, Larson DE, Mardis, ER, Wilson RK, Ley TJ et al. Sequencing a mouse acute promyelocytic leukemia genome reveals genetic events relevant for disease progression. Journal of Clinical Investigation, March 23, 2011.

J. Scott Smith, professor of food chemistry, and a K-State research team have been looking at such ready-to-eat meat products to determine their levels of heterocyclic amines, or HCAs. These are carcinogenic compounds found in meat that is fried, grilled, or cooked at high temperatures. Studies have shown that humans who consume large amounts of HCAs in meat products have increased risk of stomach, colon, and breast cancers.

Ready-to-eat meat products are meat or poultry products that come in edible forms and do not need additional preparation or cooking. Smith has already researched HCA levels in cooked meat and found that adding certain spices and marinades before cooking can reduce HCA content in the meat.

The ready-to-eat product project was a collaboration with several other K-State researchers, including Terry Houser, assistant professor of meat science; Melvin Hunt, professor of animal sciences and industry; Kanithaporn Puangsombat, December 2010 doctoral graduate in food science, Bangkok, Thailand; and Priyadarshini Gadgil, a K-State graduate who now works as a research scientist at the U.S. Department of Agriculture Center for Grain and Animal Health Research in Manhattan.

The study focuses on eight types of ready-to-eat meat products: beef hot dogs, beef-pork-turkey hot dogs, deli roast beef, deli ham, deli turkey, fully cooked bacon, pepperoni, and rotisserie chicken.

“These are the most common types of ready-to-eat products, and their use has increased in recent years because of convenience,” Smith said. “For this research, we took each of these products and prepared them as a consumer would.”

The researchers heated up the hot dogs and bacon in a microwave, cooked the pepperoni on a pizza either in the oven or a microwave, and used the chicken and deli meat as obtained. After doing so, they studied the meat to determine whether it contained five different types of HCAs according to nanograms per gram, ng/g.

Pepperoni had the least HCA content, 0.05 ng/g, followed by hot dogs and deli meat, 0.5 ng/g). Such amounts are low, and the researchers concluded that consuming such ready-to-eat meat products contributes very little to HCA intake.

Fully cooked bacon, with 1.1 ng/g, and rotisserie chicken meat, with 1.9 ng/g, contained all five types of HCAs tested. Rotisserie chicken skin had significantly higher HCA levels, with 16.3 ng/g. This is because chicken skin contains more fat and protein and less moisture, and HCA levels tend to increase as moisture decreases, Smith said.

“Based on this research, HCA consumption can be reduced by not eating chicken skin,” he said.

The reasons for lower HCA content in some of the other ready-to-eat products may be because of the higher water content in the ready-to-eat products. More moisture prevents many HCAs from forming. Ready-to-eat products are often enhanced products, meaning they have a water solution with flavoring added to them.

“Hot dogs and deli meat may have low HCA levels because they are manufactured at low temperatures,” Smith said. “The low HCA levels may also be from ingredients that are added to the meat and prevent HCAs from forming while the meat is cooking.”

Material adapted from Kansas State University.

The study also identified a subset of patients more likely to respond to the vaccine, those with a subtype of glioblastoma known as mesenchymal, which accounts for about one-third of all cases. This is the first time in brain cancer that a subset of patients more likely to respond to an immunotherapy has been identified, said Dr. Linda Liau, a Jonsson Cancer Center researcher, professor of neurosurgery and senior author of the study.

The study found that the vaccine, administered after the conventional treatments of surgery and radio-chemotherapy, was associated with a median survival of 31.4 months, double the 15 months of historical controls in the published literature. In all, 23 patients were enrolled in the Phase I study that was launched in 2003. Of those, about one third of participants are still alive, some more than eight years after their diagnosis.

The study also found that the vaccine was safe and that side effects were minimal, limited mostly to flu-like symptoms and rashes near the vaccine injection site.

“This is quite an encouraging result, especially in an early phase study like this,” Liau said. “It’s promising to see patients with this type of brain cancer experience such long survivals.”

However, Liau cautioned that the findings need to be confirmed in larger, randomized studies. She currently is leading a Phase II, randomized study at UCLA testing the vaccine in newly diagnosed glioblastoma patients. The patients will receive either the standard of care (surgery, radiation, and chemotherapy) or the standard of care plus the vaccine. The study is a multi-center trial, and UCLA is the only site offering it in California.

It has recently been discovered that there are at least three subtypes of glioblastoma: proneural, proliferative, and mesenchymal. During the course of her study, Liau and her colleagues saw that one group of patients seemed to be responding very well to the vaccine and examined their tumors using a microarray analysis of their DNA. They found that those with a gene expression profile identifying their cancers as mesenchymal responded better to the vaccine.

The finding was surprising, Liau said, because patients with the mesenchymal subtype generally have more aggressive disease and shorter survival than those with the other subtypes. In patients with this type of glioblastoma, several genes that modulate the immune system are dysregulated, meaning they do not work properly. Liau speculates that the vaccine helped replenish the immune system, allowing that subset of patients to more easily fight the brain cancer.

“Glioblastoma remains one of the diseases for which there is no curative therapy… and the prognosis for patients with primary malignant brain tumors remains dismal,” the study states. “Our results suggest that the mesenchymal gene expression profile may identify an immunogenic sub-group of glioblastoma that may be more responsive to immune-based therapies.”

Brad Silver, 41, who grew up in Southern California and now lives in a Cleveland suburb, was diagnosed with glioblastoma in 2003 and was told that he had, at best, two months to live. He was stunned.

“I was 33 years and my wife was seven months pregnant with my son,” said Silver, a college water polo instructor. ‘I didn’t think I was going to live to see my son born, let alone grow up.”

Silver sought a second opinion at UCLA and the golf-ball sized tumor in his left lateral lobe was removed. He underwent radiation and chemotherapy and enrolled in the vaccine clinical trial. Today, eight years later, he remains cancer free. His son, named Brad Silver II and a miniature version of his dad, will celebrate his eighth birthday in April.

“If I had listened to that first doctor, I would not be here today. If not for Dr. Liau, I would not be here today,” Silver said. “I’m 100 percent back to being me because of this vaccine and that clinical trial. It’s almost unbelievable.”

The vaccine preparation is personalized for each individual. After the tumor is removed, Liau and her team extract the proteins, which provide the antigens for the vaccine to target. After radiation and chemotherapy, the white blood cells are taken from the patient and grown into dendritic cells, a type of white blood cell that is an antigen-presenting cell. The vaccine preparation from this point takes about two weeks as the dendritic cells are grown together with the patient’s own tumor antigens. The tumor-pulsed dendritic cells are then injected back in to the body, prompting the T cells to go after the tumor proteins and fight the malignant cells.

“The body may have trouble fighting cancer because the immune system doesn’t recognize it as a foreign invader,” Liau said. “The dendritic cells activate the patient’s T cells to attack the tumor, basically teaching the immune system to respond to the tumor.”

The individualized vaccine is injected into the patient in three shots given every two weeks for a total of six weeks. Booster shots are given once every three months until the cancer recurs. Patients are scanned every two months to monitor for disease recurrence, Liau said.

Material adapted from University of California, Los Angeles (UCLA), Health Sciences.