Cholesterol byproduct hijacks immune cells to spread breast cancer

High cholesterol levels have been associated with breast cancer spreading to other sites in the body, but doctors and researchers don’t know the cause for the link. A new study by University of Illinois researchers found that the culprit is a byproduct of cholesterol metabolism that acts on specific immune cells so that they facilitate the spread of the cancer instead of stopping it.

The study, published in the journal Nature Communications, identifies new potential drug targets that could inhibit the creation or actions of the dangerous cholesterol byproduct, a molecule called 27HC.

Breast cancer impacts roughly 1 in 8 women. We’ve developed fairly good strategies for the initial treatment of the disease, but many women will experience metastatic breast cancer, when the breast cancer has spread to other organs, and at that point we really don’t have effective therapies. We want to find what drives that process and whether we can target that with drugs,” said Erik Nelson, a professor of molecular and integrative physiology who led the study.

Nelson’s group fed mice with breast cancer tumors a diet high in cholesterol. The researchers confirmed that high levels of cholesterol increased tumor growth and metastasis, and that mice treated with cholesterol-lowering drugs called statins had less metastasis. Then they went further, specifically inhibiting the enzyme that makes 27HC during cholesterol metabolism.

By inhibiting the enzyme that makes 27HC, we found a suppressor effect on breast cancer metastasis. This suggests that a drug treatment targeting this enzyme could be an effective therapeutic,” said Amy Baek, a postdoctoral researcher at Illinois and the first author of the paper.

The researchers also saw unusual activity among specific immune cells – certain types of neutrophils and T-cells – at metastatic sites high in 27HC.

Normally, your body’s immune system has the capacity to attack cancer,” Nelson said, “but we found that 27HC works on immune cells to fool them into thinking the cancer is fine. It’s hijacking the immune system to help the cancer spread.”

See a video of Nelson describing the study on YouTube.

Because 27HC acts through the immune system, and not on the breast cancer itself, the researchers believe their findings have broad applicability for solid tumors. They performed experiments looking at colon cancer, lung cancer, melanoma and pancreatic cancer, and found that 27HC increased metastasis for all the tumor types, suggesting that a treatment targeting 27HC could be effective across multiple cancer types.

The researchers are working to further understand the pathway by which 27HC affects the immune cells. With clinical partners at Carle Foundation Hospital in Urbana, the team is working to establish whether 27HC has the same pathway in human patients as in mice.

We hope to develop small-molecule drugs to inhibit 27HC,” Nelson said. “In the meantime, there are good cholesterol-lowering drugs available on the market: statins. Cancer patients at risk for high cholesterol might want to talk to their doctors about it.

Baek et al. The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells. Nature Communications 8, Article number: 864 (2017) doi:10.1038/s41467-017-00910-z [Article]

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Study reveals complex biology of gender differences in kidney cancer

A new study is believed to be the first to describe the unique role of androgens in kidney cancer, and it suggests that a new approach to treatment, targeting the androgen receptor (AR), is worth further investigation.

The research was led by senior author Chawnshang Chang, Ph.D., the George Hoyt Whipple Distinguished Professor of Pathology, Urology, and Radiation Oncology at the University of Rochester Medical Center and Wilmot Cancer Institute.

Chang’s laboratory has produced a large body of work during the past decade investigating the link between cancer and the AR, which binds male hormones, transcribes DNA, and is critical for male sex characteristics.

The journal Nature Communications published the study, which shows that in renal cell carcinoma androgen signaling can either stimulate or suppress tumor cells’ movement and invasion to different locations in the body.

In earlier research, Chang’s lab also shed light on the duality of AR’s role in different cancers. For example, AR signaling can enhance bladder cancer cell invasion but suppress prostate cancer cell invasion, he has found.

In kidney cancer, many studies have provided conflicting information,” Chang said. “In some cases AR expression has been associated with less malignancy. We were able to begin to sort out AR’s function in this one disease, showing that AR-positive kidney tumors are more likely to spread to the lungs and AR-negative tumors are more likely to spread to the lymph nodes.

Chang’s lab began its investigation with an epidemiology survey of nearly 4,000 cases of kidney cancer in China. Researchers found that, generally, males were almost three times as likely to get kidney cancer as females. And among those whose cancer spread to the lungs within 12 months, the male-to-female ratio jumped to nearly five to one. In contrast, the gender differences were much less significant among the patients whose cancer spread to lymph nodes versus to the pulmonary system, presumably because the cancer cells contained fewer androgen receptors.

The next phase of their research included studying human cells and tissue to understand the mechanisms by which signaling among AR proteins interacted with other known cancer-associated genes to enhance or reduce metastasis.

Renal cell carcinoma or kidney cancer is often treated with surgery and radiation in less advanced cases, and also with chemotherapy, immunotherapy, and some newer, targeted drugs that block the growth-stimulating proteins in the cancer cells. However, once it has spread it is difficult to treat. The cancer tends to resist chemotherapy and radiation, and targeted medications only extend survivorship an average of six to 15 months.

Chang believes his research may help scientists to develop newer approaches to treatment that could combine anti-androgens when appropriate with other targeted drugs already being used, to suppress the disease long-term.

Huang et al. Androgen receptor increases hematogenous metastasis yet decreases lymphatic metastasis of renal cell carcinoma. Nature Communications 8, Article number: 918 (2017) doi:10.1038/s41467-017-00701-6 [Article]

Breast cancer patients on opioids less likely to stick to vital treatment

A new study has found a troubling lack of adherence to a potentially lifesaving treatment regimen among breast cancer patients who take opioids to manage their pain.

The treatment, adjuvant endocrine therapy, commonly known as hormone therapy, is used to prevent the cancer from returning after surgery, chemotherapy or radiation therapy. Opioid use, however, was “significantly associated” with both failure to adhere to the hormone therapy and a higher risk of death, the study found.

Overall, the study found “really suboptimal” adherence to hormone therapy among the women on opioids, said researcher Rajesh Balkrishnan, PhD, of the University of Virginia School of Medicine’s Department of Public Health Sciences. “It’s not a big secret that the U.S. uses more opioids than any other country in the world,” he said. “Clearly there has to be better management of opioids in the elderly cancer population.”

One researcher cautioned that the opioid crisis sweeping the country may be causing doctors to become too cautious about prescribing the powerful drugs, even when appropriate and much needed. “A lot of doctors feel worried about prescribing them,” said researcher Leslie Blackhall, MD, a pain-management expert at the UVA Health System. “People feel judged for prescribing them.”

Breast Cancer and Opioids

Up to 60 percent of breast cancer survivors suffer chronic pain related to their treatment, the study notes. Survivors often face 10 years of adjuvant endocrine therapy to keep the cancer from coming back – a long time to comply with any treatment regimen, but especially if suffering poorly managed pain.

To better understand the relationship between opioid use and the hormone therapy, the researchers looked at treatment adherence among more than 10,000 women, with an average age of 72.3, using the National Cancer Institute’s expansive SEER database. They found that women who were younger, single and had more advanced cancer all were more likely to be on opioids, as were women with depression.

Women who received chemotherapy and breast cancer surgery were more likely to take opioids, but this was not the case for women receiving radiation therapy. This may be because of new, more targeted radiation therapy that causes less pain, the researchers hypothesized.

Using Opioids Safely

Researcher Virginia LeBaron, PhD, of the UVA School of Nursing, is a former medical oncology staff nurse and palliative care nurse practitioner. “These results underscore the importance of a balanced approach to the utilization of prescription opioid medications,” she said. “By balanced approach, I mean that it is critically important we ensure that prescription opioid medications are accessible to cancer patients who need them, but at the same time we must ensure we have appropriate systems in place to mitigate risk and reduce potential harms related to these medications.”

The researchers have published their findings in the scientific journal Breast Cancer Research and Treatment. Blackhall noted that the article is intended to foster dialogue and spur additional research. For example, clinical trials might compare opioids with non-opioids for managing cancer pain or identify patient subgroups that would most benefit from certain approaches to pain management. “This study was really just a way to bring attention to the problem and the need to provide better care for patients,” she said.

Tan et al. Opioid use among female breast cancer patients using different adjuvant endocrine therapy regimens. Breast Cancer Res Treat. 2017;165(2):455-465 [Abstract]

Patient plays saxophone while surgeons remove brain tumor

Music is not only a major part of Dan Fabbio’s life, as a music teacher it is his livelihood. So when doctors discovered a tumor located in the part of his brain responsible for music function, he began a long journey that involved a team of physicians, scientists, and a music professor and culminated with him awake and playing a saxophone as surgeons operated on his brain.

Fabbio’s case is the subject of a study published in the journal Current Biology that sheds new light on how music is processed in the brain. In the spring of 2015, Fabbio was serving as substitute music teacher in a school in New Hartford, New York. He was in a small office at the school working on the capstone project for his Master’s degree in music education when he began to suddenly “see and hear things that I knew were not real.”He became dizzy and nauseous and the episode prompted a visit to hospital in nearby Utica later that day. After undergoing a CAT scan, the doctors sat Fabbio down and told him they found a mass in his brain.

I was 25 at the time and I don’t think there is any age when it is OK to hear that,” recalled Fabbio. “I had never had any health problems before and the first thing my mind went to was cancer.”The good news was that the tumor appeared to be benign – in fact, it had probably been slowly growing since childhood – and was in an area of the brain that was relatively easy for surgeons to access. The bad news was that it was located in a region that is known to be important for music function.Fabbio was referred to UR Medicine’s Del Monte Institute for Neuroscience and neurosurgeon Web Pilcher, M.D., Ph.D.

When I met Dan for the first time, he expressed how concerned he was about losing his musical ability, because this frankly was the most important thing to him in his life, not only his livelihood, but his profession and his interest in life,” said Pilcher.

A Precise Map of Brain Function

Pilcher, who is the Ernest and Thelma Del Monte Distinguished Professor of Neuromedicine and Chair of Department of Neurosurgery, had struck up a partnership with Brad Mahon, Ph.D., an associate professor in the University of Rochester Department of Brain and Cognitive Sciences. The two have developed a Translational Brain Mapping program for patients who had to undergo surgery to remove tumors and control seizures.

Removing a tumor from the brain can have significant consequences depending upon its location,” said Pilcher. “Both the tumor itself and the operation to remove it can damage tissue and disrupt communication between different parts of the brain. It is, therefore, critical to understand as much as you can about each individual patient before you bring them into the operating room so we can perform the procedure without causing damage to parts of the brain that are important to that person’s life and function.”

The brain mapping program Pilcher and Mahon developed is tailored to circumstances of the individual. Patients with brain tumors are now routinely referred to Mahon before undergoing their surgery. Mahon and his team subject each individual to a battery of tests, including brain scans that identify important functions – such as motor control and language processing – that may be located in proximity to the tumor and potentially impacted by the surgery.

Everybody’s brain is organized in more or less the same way,” said Mahon. “But the particular location at a fine grain level of a given function can vary sometimes up to a couple centimeters from one person to another. And so it’s really important to carry out this kind of detailed investigation for each individual patient.”

While testing language and motor skills was relatively straightforward, evaluating musical ability, especially in a trained musician, was a different undertaking altogether. Perhaps nowhere in the world was Fabbio’s case a better fit. Not only had Pilcher performed hundreds of these surgeries and had partnered with Mahon to develop a sophisticated brain mapping program that would be key to the procedure’s success – but the famed Eastman School of Music, a part of the University of Rochester, could be called upon to help plan Fabbio’s surgery.

Mahon reached out to Elizabeth Marvin, Ph.D., a professor of Music Theory in the University of Rochester’s Eastman School of Music. Marvin also holds a position in the Department of Brain and Cognitive Sciences and studies music cognition – the ability of our brains to remember and process music.

The two developed a series of cognitive musical tests that Fabbio could perform while the researchers were scanning his brain. During functional MRI (fMRI) scanning, Fabbio would listen to and then hum back a series of short melodies. He also performed language tasks that required him to identify objects and repeat sentences. The fMRI detects changes in oxygen levels, so the parts of the brain that were activated during the tests helped pinpoint the areas important for music and language processing.

Using this information the research team produced a highly detailed three-dimensional map of Fabbio’s brain – with both the location of the tumor and music function – that would be used to help guide the surgeons in the OR.

Saxophone Serenades Surgeons

The ability to process and repeat a tune was an important measure, but the team also wanted to know if they were successful in preserving Fabbio’s ability to perform music. So they decided to bring his saxophone into the OR and, if possible, have him play it during the procedure.

The challenge was that Fabbio would be lying on his side, so it would be difficult to play the instrument. Also, the pressure caused by the deep breathes required to play long notes on the saxophone could cause the brain, which would be exposed during the procedure, to essentially protrude from his skull. Fabbio and Marvin ultimately selected a piece – a version of a Korean folk song – that could be modified to be played with shorter and shallower breaths.

The whole episode struck me as quite staggering that a music theorist could stand in an operating room and somehow be a consultant to brain surgeons,” said Marvin. “In fact, it turned out to be one of the most amazing days of my life because if felt like all of my training was suddenly changing someone’s life and allowing this young man to retain his musical abilities.”

During the procedure, Pilcher and the surgical team used the map of Fabbio’s brain that had been developed by Mahon to plan the surgery. They also went through a process of painstakingly reconfirming what the brain scans showed them. This was accomplished by delivering a mild electrical stimulus that temporarily disrupts a small area of the brain. While this was occurring, Fabbio was awake and repeating the humming and language tasks he performed prior to the surgery. Marvin was present in the OR and scored his performance to let the surgeons know whether or not they had targeted an area that disrupted music processing and, therefore, should be avoided during the procedure.

Once the tumor had been removed the surgeons gave the go ahead to bring over the saxophone and let Fabbio play. “It made you want to cry,” said Marvin. “He played it flawlessly and when he finished the entire operating room erupted in applause.”

Fabbio has since completely recovered and returned to teaching music within a few months of his surgery.

Harnessing Science to Improve Brain Surgery

While the brain mapping program’s primary purpose is to help improve surgical outcomes, the information that the researchers gather before, during, and after the surgery is also helping advance understanding of complexities of the brain’s structures and function.

We study about 40 or 50 patients a year and what this allows us to do is ask what are the factors that we can identify in these patients before their surgery or early on after their surgery that distinguish which patients go on to have a good outcome versus which patients may have lingering cognitive impairments,” said Mahon.

The data from Fabbio’s case, which is the basis of a study in the journal Current Biology, has helped more precisely define the relation between the different parts of the brain that are responsible for music and language processing.

As I think back about Dan’s case and about the incredible outcome and what we were able to achieve, it reminds me of how far we have come,” said Pilcher. “Ten years ago, we mapped the brain using very simple tools – electrical stimulation and image guidance. But now, we have all the tools of cognitive science. We have brought the cognitive science laboratory into the operating room and now almost as a matter of course with every single patient.”

Breast cancer patients can use antiperspirants during radiotherapy

Women undergoing daily radiation therapy for breast cancer are commonly told they should not use antiperspirant for fear that it could cause greater radiation damage to the skin, but a new study from the Perelman School of Medicine at the University of Pennsylvania shows that advice is not based on sound science.

While they found that about eight out of every 10 patients reported their doctors told them not to use antiperspirants and roughly the same number of doctors say they routinely make that recommendation, their study also showed there was no difference in the radiation skin dose absorbed by these patients with or without these deodorants. They published their findings in Radiotherapy and Oncology this month.

Going without antiperspirants entirely for a 3-6 week course of radiotherapy can have a negative impact on a patient’s quality-of-life,” said the study’s lead author Brian C. Baumann, MD, who recently completed his residency in Radiation Oncology at Penn and is a member of Penn’s Leonard Davis Institute of Health Economics. He is also currently an assistant professor of Radiation Oncology at Washington University in St. Louis. “Our study suggests that antiperspirants can be safely used during breast radiotherapy without risking increased skin side effects.”

The study tackled two key areas. First, it established that it’s still common practice for physicians to advise breast cancer patients to avoid antiperspirants during radiotherapy. Second, it debunked the myth that the use of these antiperspirants increases the amount of radiation the skin receives, thus causing more damage to the skin.

For the first part of the study, researchers utilized OncoLink, an online cancer service dedicated to patient and provider education that is run by Penn’s Radiation Oncology unit. They developed a survey to find out what percentage of providers still tell their patients not to use antiperspirants, and what percentage of patients say they received that advice. Of the 105 doctors and nurses who responded and said they regularly manage radiation dermatitis for their patients, 86 of them (82 percent) said they regularly tell patients not to use antiperspirants during their course of radiation treatment. On the patient side, 92 women responded who said they have received radiotherapy for breast cancer, 73 of whom (79 percent) say their healthcare providers advised them to avoid using deodorant for the duration of their treatment.

While the sample size of the survey is relatively small, the percentage of patients who received the advice to avoid antiperspirants and the percentage of providers who routinely offer this advice was very similar. We cannot make any conclusions about the exact prevalence of this recommendation, but we think the results strongly suggest that the recommendation remains popular,” Baumann said.

The advice persists despite a lack of scientific evidence. Trials have not shown antiperspirant use leads to higher skin side effects during breast radiation therapy, but those trials do not appear to have changed clinical practice. Baumann says that shows providers either do not know about these studies or they are skeptical of the results.

There can be a discrepancy between the ways we measure skin toxicity in clinical trials versus the problems patients report to their healthcare providers,” Baumann said. “The current skin toxicity scoring system has important limitations. It does not take pain or itching into account, for example, so it is possible that the studies may have missed a clinically meaningful effect because of the limitations of the measurement tool.” Researchers addressed that discrepancy in the second part of this study as they sought to find out if antiperspirants really do increase the surface dose of radiation on the skin. For this portion, researchers used optically stimulated luminescent dosimeters (OSLDs) – a common device for measuring the amount of surface radiation absorbed with each dose. They used three squares of paper: one with nothing on it, one with a thick coating of standard antiperspirant, and one with a thick coating of extra-strength antiperspirant. They placed the squares of paper in the beam’s path and measured the absorbed radiation dose with OSLDs.

We found no significant difference in surface dose with or without antiperspirant,” Baumann said.
Baumann’s team also moved the beam to four different angles, but found it did not lead to different results.
These antiperspirants also contain aluminum zirconium tetrachlorohydrex glycine, a common metal found in antiperspirants. The standard deodorants contain 15 percent of it, while the extra strength contains 25 percent.

We specifically wanted to know if the radiation could hit that metal and scatter, sending radiation off target and into other, healthy parts of the skin, but any difference in surface dose we found was within the margin of error,” Baumann said.

This study shows providers should be more liberal in letting patients use antiperspirants during radiation treatment, which may improve patient quality-of-life.”

Baumann et al. Avoiding antiperspirants during breast radiation therapy: Myth or sound advice? Radiother Oncol. 2017;S0167-8140(17)30432-2. doi: 10.1016/j.radonc.2017.06.021 [Abstract]

Young adult cancer survivors struggle to get back to normal

Cancer survivors often talk about wanting to get back to normal, but a new study indicates many young adults who survived the disease struggle with attaining this goal two years after their initial diagnosis.

The longitudinal study is among the first seeking to understand the social functioning among adolescents and young adults who have had cancer.

The research is important to help these young survivors better reintegrate into society,” said study co-author Brad Zebrack, a professor of social work at the University of Michigan.

Researchers collected data from 215 cancer patients aged 14 to 39 years who visited five medical facilities nationwide between March 2008 and April 2010. Patients completed a self-report measure of social functioning within the first four months of diagnosis, and again at 12 months and 24 months later. They also answered questions about their social interactions with family and friends, psychological needs and mental health.

Thirty-two percent of the survivors reported consistently low social functioning over time – and some had been off treatment. Zebrack and colleagues say this could stem from the transition from treatment to off-treatment survivorship, a time fraught with new challenges to a cancer survivor, including the negative impact on finances, body image, work plans, relationship with spouse/significant other and plans for having children.

In addition, those reporting low scores on social functioning also had high levels of distress, possibly reflecting an impaired ability to reintegrate into social activities due to the effects of cancer, the study showed.

This finding highlights the need to screen, identify and respond to the needs of high-risk adult-young adolescent patients at the time of diagnosis and then monitor them over time,” said Zebrack, an expert with the U-M Institute for Healthcare Policy & Innovation. “They are likely the ones most in need of help in managing work, school and potentially problematic relationships with family members and friends.”

Current research indicates that young adult cancer patients benefit from support programs that put them in touch with other young adult cancer survivors.

They do not find being in a support group with ‘people my grandma’s age’ to be all that helpful,” said Olga Husson, the study’s lead author and a researcher at Radboud University Medical Center in the Netherlands.

The study’s other authors were Christine Aguilar of the University of Texas Health Science Center, Brandon Hayes-Lattin of the Oregon Health and Science University and Steve Cole of HopeLab Foundation.

The study appears online in the journal Cancer.

Husson et al. Cancer in adolescents and young adults: Who remains at risk of poor social functioning over time? Cancer. 2017;123(14):2743-2751. doi: 10.1002/cncr.30656 [Abstract]

A Survivor’s Guide to Managing the Side Effects of Mesothelioma

When a patient is diagnosed with cancer, he or she must deal with a lot of variables. Choosing a treatment type, and committing to its completion is a job in itself. The treatment often has side effects that patients must deal with on top of the cancer. Doctors and researchers are finding new ways to treat the health effects as successful treatments continue to rise in number. Patients have many medical and palliative choices in today’s care environment.

Try Brain Puzzles

One of the first tips for coping is maintaining a mental balance. Chemotherapy and associated treatments leave a fuzzy mind behind. Patients might forget about things that are normally simple in nature. Use puzzles to keep up with a clear mind. By exercising the brain, these mental side effects can be fought off. As the patient moves forward with other treatments, the mind can still use the puzzles as a way to jog the brain and create new, neural pathways.

Managing Immunotherapy with Medications

According to the U.S. News and World Report, immunotherapy is the wave of the future. By using the body’s own resources, cancer cells can be killed off in record numbers. An unwanted effect from this cancer treatment, however, is inflammation. This reaction is normal. It can get out of hand with immunotherapy pills so doctors normally suggest counter solutions in the form of other medications.

Increase your Calorie Count

When patients have mesothelioma and treatment is ongoing, they may experience a lack of appetite. The American Lung Association suggests that excess calories in the form of good fats must be added to any consumed foods. Drizzle olive oil on a meal so that the patient consumes enough calories to avoid weight loss. Good fats improve the body’s cardiovascular system with cholesterol-fighting power. The extra calories can be used to maintain a healthy weight as treatment continues.

Avoid Infections with Hygienic Solutions

Sores and infections are common during any cancer treatment. Patients must take care of their health as much as possible. Use baking soda every day and rinse out the mouth with some water. This substance fights off germs at the molecular level. Aside from this suggestion, patients should wash their hands and keep their feet covered when they are outdoors. Any infections will impede the success of a medical program.

Breathe Deeply

Mesothelioma patients deal with lung-tissue problems so basic breathing can be problematic. Patients should try to breathe in deeply with a relaxed tone to their muscles. Doctors might suggest breathing techniques that are specific to a patient’s situation. Solid breathing will improve the lung’s flexibility as mesothelioma is being eradicated from the patients’ bodies.

The symptoms of cancer will vary between patients. If a patient discovers an unusual issue, speaking to the doctor must be the first step. There might be a reasonable answer for the issue, or further evaluations may be in order. Prioritize every aspect of a healthy lifestyle so that cancer treatment is not a future option.

Virgil Anderson