Stress management techniques improve long-term mood and quality of life for women with breast cancer

At the turn of the century, 240 women with a recent breast cancer diagnosis participated in a randomized trial that tested the effects of a stress management intervention developed by Michael Antoni, PhD, of the University of Miami. Dr. Antoni and his team found that, compared with patients who received a one-day seminar of education about breast cancer, patients who learned relaxation techniques and new coping skills in a supportive group over 10 weeks experienced improved quality of life and less depressive symptoms during the first year of treatment.

In their latest report, the researchers found that the women who received the stress management intervention had persistently less depressive symptoms and better quality of life up to 15 years later. “Women with breast cancer who participated in the study initially used stress management techniques to cope with the challenges of primary treatment to lower distress. Because these stress management techniques also give women tools to cope with fears of recurrence and disease progression, the present results indicate that these skills can be used to reduce distress and depressed mood and optimize quality of life across the survivorship period as women get on with their lives,” said lead author Jamie Stagl, who is currently at Massachusetts General Hospital, in Boston.

Stagl noted that breast cancer survivors in the stress management group reported levels of depression and quality of life at the 15-year follow-up that were similar to what is reported by women without breast cancer. Also, the intervention was helpful for women of various races and ethnic backgrounds. “This is key given the fact that ethnic minority women experience poorer quality of life and outcomes after breast cancer treatment,” said Stagl.

As survival rates increase for breast cancer, the question of how to maintain psychosocial health becomes increasingly salient. The current findings highlight the possibility that psychologists and social workers may be able to “inoculate” women with stress management skills early in treatment to help them maintain long-term psychosocial health.

“Because depressive symptoms have been associated with neuroendocrine and inflammatory processes that may influence cancer progression, our ongoing work is examining the effects of stress management on depression and inflammatory biomarkers on the one hand, and disease recurrence and survival on the other,” said Dr. Antoni.

source : http://www.sciencedaily.com/releases/2015/03/150323075936.htm

Sweeping prostate cancer review upends widely held view on radiation

“The common teaching has been, without clear evidence, that urinary incontinence and erectile function are worse when radiation is delivered earlier rather than later, but we didn’t see any protective effect of delayed radiation compared to earlier radiation,” said radiation oncologist Timothy N. Showalter, MD, of the UVA Cancer Center. “It contradicts the clinical principle of delaying radiation as long as possible for the sake of the patient’s side effects. It really speaks against that, and that ought not to be used for a reason to delay radiation.”

The findings inject hard facts into a debate that has long divided the medical community, with many radiation oncologists preferring adjuvant therapy — radiation given soon after prostate removal to kill off any remaining cancer cells — and many urologists preferring salvage therapy — radiation given later, when prostate-specific antigen tests suggest it’s needed. “Urologists tend to prefer to forgo adjuvant radiation therapy, because they fear the side effects, and radiation oncologists tend to prefer offering adjuvant radiation therapy because they fear the risk of metastasis [cancer spreading to other sites in the body],” Showalter said.

Showalter conducted his two studies to address the lack of facts, in hopes of providing doctors with the information they need to determine the best course of treatment.

“There’s this commonly held belief that the longer you delay radiation therapy, the more opportunity a patient has for recovery from prostatectomy, and therefore the better long-term function in terms of urinary and bowel function — the longer you delay it, the better they’ll function,” he said. “A lot of clinicians believe that if you wait six months, 12 months, 18 months, that each additional step gets you some benefit in terms of toxicity. That didn’t make sense to me from a medical perspective, because I can’t think of any other surgery where we think recovery requires a year or more. We often, for other cancers, deliver post-operative radiation very soon.”

The findings, based on a review of approximately 16,000 patients’ outcomes, shed light on the side effects of radiation treatment after prostate removal. “What we found is that the addition of radiation therapy after prostatectomy does lead to a noticeable increase in GI [gastrointestinal] and GU [genitourinary] side effects. However, delaying radiation therapy offers no protective benefit and in fact may increase the risk of GI complications,” Showalter said. The research also found adjuvant therapy did not increase rates of erectile dysfunction.

The takeaway for men receiving prostate cancer treatment, Showalter said, is that they should discuss the best strategy with their physicians based on their particular case. “If someone’s at generally low risk of prostate cancer reoccurrence and they have low-grade disease, it’s probably still reasonable to take a delayed salvage radiation therapy approach,” Showalter said. “Once there’s a real, compelling reason to deliver radiation, there doesn’t seem to be a benefit to delaying their radiation in terms of avoiding complications. And we know from other studies, the earlier radiation is delivered, the more effective it is for these patients. The more likely it is to cure them.”

source : http://www.sciencedaily.com/releases/2015/03/150323091542.htm

Exercise linked to improved erectile, sexual function in men

While past studies have highlighted the relationship between better erectile function and exercise, African-American men have been underrepresented in this literature.

“This study is the first to link the benefits of exercise in relation to improved erectile and sexual function in a racially diverse group of patients,” said Adriana Vidal, PhD, senior author of the study and investigator in the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute and Department of Surgery.

Nearly 300 study participants self-reported their activity levels, which researchers then categorized as sedentary, mildly active, moderately active or highly active. The subjects also self-reported their sexual function, including the ability to have erections, orgasms, the quality and frequency of erections and overall sexual function.

Results found that men who reported more frequent exercise, a total of 18 metabolic equivalents, or METS, per week, had higher sexual function scores, regardless of race. MET hours reflect both the total time of exercise and the intensity of exercise. A total of 18 METS can be achieved by combining exercises with different intensities, but is the equivalent of two hours of strenuous exercise, such as running or swimming, 3.5 hours of moderate exercise, or six hours of light exercise.

In contrast, men of any ethnicity who exercised less reported lower levels of sexual function. Additional contributors to low sexual function included diabetes, older age, past or current smoking and coronary artery disease.

Stephen Freedland, MD, co-author on the study and director of the Center for Integrated Research in Cancer and Lifestyle in the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, cautions that exercise should be tailored for each individual.

“When it comes to exercise, there is no one-size-fits-all approach,” said Freedland, who also serves as co-director of the Cancer Genetics and Prevention Program. “However, we are confident that even some degree of exercise, even if less intense, is better than no exercise at all.”

source : http://www.sciencedaily.com/releases/2015/03/150323091546.htm

Stress granules ease the way for cancer metastasis

When cells are under duress, they curtail almost all protein synthesis and stash their mRNAs in stress granules. These structures help healthy cells, but they also allow tumor cells to survive harsh conditions. A protein named YB-1, which is overexpressed in many types of tumors, accumulates in stress granules, but researchers don’t know how YB-1 affects these particles.

University of British Columbia scientist Poul Sorensen and his colleagues found that stressed-out cancer cells need YB-1 to assemble stress granules. Removing YB-1 decreased levels of one stress granule protein, G3BP1. The team discovered that YB-1 attaches to the mRNA encoding G3BP1 and stimulates the protein’s production.

To determine the effects of YB-1 in animals, the researchers implanted mice with cancer cells that either made or lacked the protein. A month later, cells in the control tumors carried more stress granules than did the tumor cells missing YB-1. Sorensen and colleagues then implanted mice with tumors that either produced or lacked G3BP1. The control tumors harbored more stress granules than did the G3BP1-deficient tumors, and only the control tumors metastasized.

Further research is needed to find out how the reduction in stress granules curbs metastatic spread, but the results suggest that inhibiting their formation might be a way to curb cancer metastasis.

source : http://www.sciencedaily.com/releases/2015/03/150323105247.htm

Favorable 15-year survival outcomes for older prostate cancer patients with low-risk disease

Previous research by the study’s lead author Grace Lu-Yao, PhD, MPH, cancer epidemiologist at the Cancer Institute of New Jersey and professor of medicine at Rutgers Robert Wood Johnson Medical School, and colleagues examined 10-year outcomes for this population (JAMA, Vol. 302, No. 11). The 2009 research showed men diagnosed with prostate cancer beginning in the early 1990’s had significantly improved survival compared with patients whose cancers were diagnosed in prior decades. Given the protracted nature of the disease and increasing longevity among elderly men, 10-year follow-up may not be sufficient to make informed treatment decisions. Dr. Lu-Yao notes this new study, which extends data examination by an additional five years, “helps provide a more complete picture of potential outcomes for patients who have a life expectancy greater than 10 years.”

The new research, which appears in the current online edition of European Urology (doi: 10.1016/j.eururo.2015.03.021), examined 33,137 Medicare patients aged 65 or older who were diagnosed with early-stage (T1 or T2) prostate cancer from 1992 through 2009 and received conservative management (no surgery, radiotherapy, cryotherapy or androgen deprivation therapy) within the first six months of diagnosis. The researchers utilized information from the Surveillance, Epidemiology and End Results (SEER) cancer registries and Medicare claims. All SEER registries hold the highest level of certification of data quality.

Investigators found that men aged 64 to 74 with a Gleason score (a grading system that indicates how likely a tumor will spread) of between five and seven had a lower risk (5.7 percent) of dying from prostate cancer over a 15-year period as compared to men 75 and older, whose risk was 10.1 percent. For men with the highest level Gleason scores (between eight and 10), 15-year prostate cancer mortality rates were 22 percent for men aged 65 to 74 and 27 percent for men 75 and older.

The authors also note mortality rates remained relatively stable from six to 16 years following diagnosis. The work also examined if these men had comorbid diseases and found that those who did have other health problems had a lower risk of dying from prostate cancer due to deaths from competing health issues.

“The proportion of men diagnosed with localized prostate cancer who choose to have conservative management is relatively small but, is on the rise. The information provided by this long-term study will help facilitate treatment decisions,” says Lu-Yao. “Our study, which includes data from the PSA testing era, is a more current representation of outlook survival for this population.”

Lu-Yao indicates the study could help change the conversation between patient and physician. “In weighing whether treatment benefits outweigh the risks, radical prostatectomy — for instance — is typically not recommended for older men with low-grade disease. But many elderly patients are treated with radiotherapy or hormonal therapy even if their cancer is indolent, so that they can feel like they are doing something,” she says. “By having additional data available to support conservative management, doctors can further educate their patients about survival outcomes and possibly help avoid treatments that may put the patient at risk.”

The authors note strengths of the study include the fact it is population based and broadly representative instead of focused on specific geographic areas or institutions. Lu-Yao also notes the study provided information on more than 10,000 men aged 75 or older — a population which is often omitted from studies. But they also caution that because the men in the study were older than 65, the data may not apply to younger patients.

source : http://www.sciencedaily.com/releases/2015/03/150323142801.htm

Experiments reveal key components of the body’s machinery for battling deadly tularemia

The team, led by Thirumala-Devi Kanneganti, Ph.D., a member of the St. Jude Department of Immunology, found key receptors responsible for sensing DNA in cells infected by the tularemia-causing bacterium, Francisella. Tularemia is a highly infectious disease that kills more than 30 percent of those infected, if left untreated. It can be readily transmitted by air, insect bites or through contaminated food or water.

“Understanding the fundamental biology of how our immune system works will lead to the development of more effective drugs and vaccines,” said Kanneganti, corresponding author on the paper. The new findings also revealed how immune cells switch on genes that activate microbe-killing machinery called the AIM2 inflammasome.

The inflammasome is a complex of proteins that is a dedicated killing machine for bacteria and viruses. The inflammasome that attacks the tularemia bacterium is triggered by the sensor protein AIM2 that recognizes the tularemia DNA.

Previous studies indicate that both Francisella DNA and viral DNA activate AIM2 in the cell. The mystery was how different bacteria or viruses release their DNA into the infected cell to activate AIM2.

In the new studies, the researchers found that Francisella DNA is initially detected by a DNA sensor, cGAS, which specifically engages a gene-activating protein called IRF1 in the cell. Importantly, IRF1 triggers production of a group of proteins, called GBPs, that literally “mobs” the invading bacterium by surrounding and shredding it. The dying bacterium releases even more DNA and subsequently activates the DNA sensor AIM2 to further fuel the immune system, ultimately conquering the infection. Researchers still do not know whether GBPs directly kill bacteria or whether the GBPs require additional “help” to destroy them.

Studies with mice demonstrated the necessary role IRF1 plays in galvanizing the immune system to battle tularemia. Mice lacking IRF1 showed much higher levels of the bacteria when infected, and 100 percent succumbed to the infection, compared with only 25 percent of the mice that have IRF1. The new findings also showed that activation of the AIM2 inflammasome by the DNA virus cytomegalovirus does not involve IRF1, suggesting that the DNA of the invading microbes is presented to the cell in different ways.

According to the paper’s first author, Si Ming Man, Ph.D., a postdoctoral fellow in St. Jude Immunology, the findings could lead to new protective treatments against tularemia, including drugs that can enhance the ability of IRF1, GBP or AIM2 to cure infections more quickly and effectively. Vaccines could also be developed that would boost this immune machinery and protect against the disease.

“Future studies will not only seek to further map the function of AIM2 in infectious diseases, but also to track its role in other disorders, including cancer,” Man said. Studies of AIM2 could also aid in understanding some autoimmune diseases and cancers. Overactivation of AIM2 has been linked to disorders including psoriasis, an abdominal aortic aneurysm and lupus. Furthermore, reduced AIM2 activity has been linked to colorectal and prostate cancers.

source : http://www.sciencedaily.com/releases/2015/03/150323162404.htm

New insights into survival outcomes of Asian Americans diagnosed with cancer

“What we have found is that Asian Americans are an incredibly diverse group that cannot be indiscriminately combined together,” said Trinh, associate surgeon for the Division of Urology at BWH, faculty at the Center for Surgery and Public Health (CSPH) and lead author of the study. “With Asian Americans, there is important variation in socioeconomic status, cultural beliefs, and length of time since immigrating to the United States that researchers must take into account.”

Although Asian Americans represent only 5 percent of the entire United States population, they are the most rapidly growing racial group in the country. This is one of the first studies not just to focus on the cancer-specific survival of Asian Americans, but also to break down that population into eight specific subgroups (Chinese, Filipino, Hawaiian, Japanese, Korean, South-East Asian, Vietnamese and others) for further analysis.

Trinh and his colleagues used Surveillance, Epidemiology, and End Results Program (SEER) data to look at more than 2.5 million Asian American patients who were diagnosed with lung, breast, prostate or colorectal cancer (the three leading causes of cancer-related mortality within each gender) between 1991 and 2007.

The team found significant differences in cancer outcomes among the Asian subgroups. Specifically, the researchers report that the Japanese subgroup had substantially better survival rates than non-Hispanic whites (especially with regard to prostate, breast and colorectal cancers), as did those of Filipino and South Asian descent (for prostate and lung cancers, and lung and colorectal cancers, respectively), while the Hawaiian and Korean subgroups did not. In Chinese and Vietnamese patients, only those with lung cancer had better CSM rates relative to non-Hispanic whites. Overall, most Asian subgroups were less likely to die from cancer than non-Hispanic white patients.

“We found that CSM is statistically significantly lower for Asian Americans than for non-Hispanic whites overall, despite similarities in odds of receiving definitive therapy, and even after adjusting for socio-demographic factors, cancer stage and treatment,” said Trinh. “We’ve effectively ruled out a number of variables, suggesting instead that underlying genetic or biological differences and/or complex cultural influences may impact survival in Asian American cancer patients.”

This study opens the door for future research to better understand why Asian Americans have better CSM than non-Hispanic whites, and to determine whether and to what extent genetic and/or cultural factors are involved.

source : http://www.sciencedaily.com/releases/2015/03/150323182548.htm

Driving tumor cells to their death

B cells are white blood cells that produce antibodies against antigens, namely substances which the immune system recognises as foreign. Normal B cell development and maturation is regulated by a balance between kinase and phosphatase enzymes. These enzymes phosphorylate or de-phosphorylate the signalling subunits of the B cell antigen receptors (BCR). This means that the kinases add phosphate groups to the BCR, while the phosphatases remove them. Only if it has been phosphorylated by kinases is a BCR completely active and signals to the B cell that there is a foreign substance. This means that the kinases and phosphatases affect the receptor’s capacity to send signals.

In B-ALL tumour cells, certain kinase enzymes, such as the Abelson tyrosine kinase (ABL), are altered and act as oncogenes, spurring the growth of tumours independently of the BCR. The B cells then continue to divide although they do not function. That is why this disease is treated with agents that inhibit the ABL kinase. However, resistant ABL mutants still often develop and the tumour continues to grow.

The American and German team investigated how BCR signalling in tumour cells is regulated. They discovered that the signalling subunits of the BCR in B-ALL tumour cells are hardly phosphorylated and that there is a higher number of inhibiting receptors on the cell’s surface. Because these receptors bind phosphatases, they prevent the BCR from becoming active. When the researchers shut off the inhibiting receptors or the associated phosphatases, the B-ALL tumour cells died instantly. The researchers were also able to demonstrate in an animal experiment how a phosphatase inhibitor prevented tumours from spreading. By inhibiting the phosphatases, they essentially freed the BCR signalling pathways that the ABL kinase had been supressing. Because a B cell that has a disproportionate amount of active BCR receptors no longer has a balance of kinases and phosphatases, this form of therapy thus leads to cell death, or what is known as apoptosis.

Future ALL treatments could aim at inhibiting the phosphatases instead of the ABL kinases and thereby strengthen BCR signals. Reth said, “In the last few years, we have investigated at BIOSS the significance of the balance between kinases and phosphatases for the normal development of B lymph nodes. Now we’ve discovered that this also plays a role in the development and treatment of B cell tumours.”

Reth is the scientific director of the cluster of excellence BIOSS Centre for Biological Signalling Studies. He is also a professor at the Institute of Biology III at the University of Freiburg and head of a research group at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg. Jumaa is now a professor at the Institute of Immunobiology at the University of Ulm and was a member of the BIOSS Centre for Biological Signalling Studies.

source : http://www.sciencedaily.com/releases/2015/03/150324084518.htm

Cancer patients want more information about medical imaging risk

In recent years, there have been numerous reports in the media about potential risks of tests that use ionizing radiation. However, benefit-risk discussions about ionizing radiation from medical imaging are rare and seldom initiated by clinicians.

For the new study, researchers from Memorial Sloan Kettering Cancer Center (MSKCC) in New York City analyzed over nine hours of transcribed conversations with 30 people who had undergone medical imaging exams to determine their understanding of the benefits and risks associated with various medical imaging procedures and their expectations regarding communication of those benefits and risks.

The study group was divided into six focus groups, including five groups of cancer patients and one group of participants in a lung cancer screening program. The study found that participants perceived clear benefits from imaging tests like x-rays, computed tomography (CT) scans, and nuclear medicine examinations, but that patient knowledge regarding which imaging tests use ionizing radiation was variable and generally poor.

Most participants were highly aware of risks associated with ionizing radiation exposure, including the potential risk of future cancer, but expressed a desire to receive this information from their own doctor.

In addition to information about risk, the patients expressed a desire to be offered information concerning the rationale for specific test orders and testing intervals, as well as testing alternatives. Most met their needs for more information through self-directed Internet searches.

“This may not be what we in the medical field want to hear, but I think it’s important that we hear it,” said senior author Jennifer Hay, Ph.D., a behavioral scientist at MSKCC. “Patients want this information, and they prefer to receive it from doctors they know and trust.”

Knowledge about imaging tests was highly variable among the study participants, even though many of them had undergone frequent examinations. For instance, some patients were unsure if ionizing radiation was used in mammography, bone scans and stress tests. Many participants were uncertain if magnetic resonance imaging (MRI) used ionizing radiation. Ionizing radiation from diagnostic medical imaging was occasionally confused with radiation therapy, and some participants were unable to distinguish between the two.

Participants desired a wide range of information about medical imaging tests. Most wanted basic education about which imaging tests used ionizing radiation and how doses compared among them. Nearly all the patients wanted to understand how tests differ, what governs selection of one over another, and why multiple tests are sometimes ordered. Most agreed that learning about possible future risks was important but that having this information would probably not alter their decision to proceed with a recommended test.

The desire for information on the risks associated with ionizing radiation from medical imaging was strongest among patients who had made the transition from treatment to survivorship. These patients wanted to know how risk accumulates from multiple exams over time, whether additional ionizing radiation exposure could be avoided by substituting MRI for CT, and if longer intervals between follow-up examinations could be negotiated.

“Interest in having more information and participating in decision making about medical imaging clearly increased as patients transitioned from active cancer treatment to survivorship,” said the study’s lead author Raymond H. Thornton, M.D., an interventional radiologist at MSKCC. “Cancer survivors typically focus on healthful living and risk-factor reduction, so they were particularly eager to participate in discussions about potential long-term risks of radiation.”

The different levels of desire for information among patients lend support to a tiered approach for patient-centered communication, according to Dr. Hay.

“A tiered approach would provide all patients with information and offer additional options to those who want to dig deeper and find out more,” she said.

Despite concerns about future risks, the study participants expressed appreciation for the imaging tests, with many emphasizing that imaging reports were a patient’s most important evidence of treatment efficacy.

source : http://www.sciencedaily.com/releases/2015/03/150324084806.htm

How our DNA may prevent bowel cancer

However, the mechanisms behind the protective effect have not been understood and it is not known why some people appear to benefit while others do not.

Conducted by investigators from four countries, including Professors Mark Jenkins and John Hopper from the University of Melbourne, the findings suggest this protection differs according to variations in DNA.

“We’ve known for a long time that aspirin lowers the risk of bowel cancer, but we also know that not everyone gets the same degree of protection,” said Professor Mark Jenkins, a co-author of the paper and Director of the Centre for Epidemiology and Biostatistics, School of Population and Global Health.

“The aim of this study was to investigate if genetic variation can be used to determine who will benefit from taking aspirin and who will not,” he said.

For the study, Professors Jenkins, Hopper and collaborators analysed the combined data from ten large studies conducted in Australia, USA, Canada and Germany.

They compared genetic and lifestyle data from 8,624 people who developed bowel cancer with that of 8,553 people who did not.

An important component of this data included 1,085 participants from Australia who enrolled in the Australasian Colorectal Cancer Family Study.

“This study confirmed that for most people, taking regular aspirin and NSAIDs lowered their risk of bowel cancer, but it also showed that the benefit from taking these medicines was not the same for everyone, and one of the differences was in their DNA” said Professor Jenkins.

“While most people benefit from aspirin, there was DNA evidence that about 1 in 25 people do not, and in fact may increase their risk of bowel cancer if they take aspirin,” Professor Jenkins said.

source : http://www.sciencedaily.com/releases/2015/03/150324101457.htm