Connect with us

NewsMakers

New therapy targets breast cancer metastases in brain

A new combination therapy targeting breast cancer tumors in the brain dramatically decreased tumor size and increased survival in a study with mice, reports a new Northwestern Medicine study. An estimated 75% of mice that had brain metastases from breast cancer were cured and cancer-free after the therapy.

Published

on

When breast cancer spreads to the brain, the prognosis is grim. Patients only have about six months to live.

Women with HER2-positive breast cancer tend to develop brain metastases in up to 55% of cases. Chemotherapy drugs targeting breast cancer cells in the brain aren’t effective, because they can’t cross the blood-brain-barrier.

But a new combination therapy targeting breast cancer tumors in the brain dramatically decreased tumor size and increased survival in a study with mice, reports a new Northwestern Medicine study. An estimated 75% of mice that had brain metastases from breast cancer were cured and cancer-free after the therapy.

“The new combination therapy we identified can cross the blood-brain barrier,” said lead study author Dr. Maciej Lesniak, Northwestern Medicine chair of neurological surgery and professor of neurosurgery at Northwestern University Feinberg School of Medicine. “The therapy also targets brain metastases and significantly improves survival.”

The paper is published Science Translational Medicine.

The two drugs are tubulin inhibitor, vinorelbine, approved by the U.S. Food and Drug Administration (FDA) and available in clinics, and bromodomain inhibitor, I-BET-762, FDA approved for clinical trials. The bromodomain inhibitor increased βIII-tubulin, a protein found in cancer cells that metastasize to the brain. Overexpression of βIII-tubulin sensitized cancer cells to be killed by vinorelbine.

“The findings of our work set the stage for a clinical trial, whereby patients with breast cancer brain metastases can be treated with the combination of these two drugs,” Lesniak said. “This will offer patients with breast cancer brain metastases, who have been systematically excluded from clinical trials, the chance to benefit from a new therapeutic regimen that has been proven to be strongly effective in experimental settings.”

Breast cancer spreads to other organs like brain, lung and bone. The metastasis of breast cancer to the brain is a terminal disease and the deadliest complication.

There is a lack of targeted therapies for breast cancer brain metastases, said first study author Deepak Kanojia, research associate in neurological surgery at Feinberg.

“Patients with brain metastases are often excluded from clinical trials due to their poor outcomes and dismal survival,” Kanojia said. “Regular systemic therapies, like Herceptin, do not cross the blood-brain-barrier efficiently, and offer no benefit in brain metastases,” he said.

How the study worked

Scientists developed a mouse model that can grow multiple brain metastases to simulate what happens in human patients. They injected tumor cells in the intracarotid artery, resulting in the formation of multiple brain tumors. After the tumors grew, scientists treated the mice with the combination therapy. Final results revealed that 75% of the mice that were treated with the combination were cured and cancer-free.

Other Northwestern authors include co-first author Wojciech Panek, Alex Cordero, Jawad Fares, Solomiia Savchuk, Krishan Kumar, Ting Xiao, Katarzyna Pituch, Jason Miska, Peng Zhang, Kwok-Ling Kam, Craig Horbinski, Irina Balyasnikova and Atique Ahmed.

NewsMakers

Telling people they might lose motivates more than telling them they might win, research shows

How managers choose to frame problems directly influences employees’ motivation to speak up at work. For managers, this is an insightful approach for building more open and collaborative teams.

Published

on

Athletes say they hate to lose more than they love to win. New research finds the same sentiment is shared in organizations.

A Virginia Tech researcher and his colleagues discovered that when managers frame work problems as a potential loss, employees are more likely to take action than when those problems are framed as potential gains. The research also revealed that when the potential loss impacts a larger group, employees are more likely to take action in the form of speaking up to a supervisor in hopes of finding a solution. The findings were recently published in the Journal of Applied Psychology.

For managers, this research suggests that framing work problems as potential losses can influence employees to speak up more.

“Employee voice occurs when suggestions are made to improve organizational functioning,” said Phil Thompson, associate professor in the Pamplin College of Business Department of Management. “From an organizational perspective, the positive outcomes of employee voice include improved performance, effectiveness, and workplace safety. From an employee level, speaking up is positively related to creativity, innovation, engagement, and ethical behavior.”

At its core, this research shows that how managers choose to frame problems directly influences employees’ motivation to speak up at work. For managers, this is an insightful approach for building more open and collaborative teams.

“When managers say, ‘If we don’t get this done, not only will you lose the $5,000 bonus, but everybody in this work group is going to lose a $5,000 bonus,’ it magnifies an employee’s motivation to act in a proactive way,” said Thompson. “This suggests that framing work problems as what will be collectively lost – compared to what can be individually lost – makes employees want to speak up more.”

Thompson was part of a research team led by Jeffery Thomas and Jonathan Booth from The London School of Economics and Mark Bolino from Oklahoma University. Together they analyzed responses from nearly 2,000 full-time employees, MBA students, and employee-supervisor pairs for their experience in situations where work problems were framed as either a gain or a loss. Across three different studies, framing something as a loss yielded employees to voice a work suggestion more.

For example, a manager dealing with a reputational crisis of their team, such as a product quality issue, can frame the problem in a way to spark helpful employee suggestions on how to resolve the issue. For example, instead of saying “if this product has great quality, our company will look really good” a manager saying “if this product is not up to quality standards, our reputation will be damaged” carries more weight for the team. When this reputational risk is shared by everyone, employees are more willing to step forward to help the problem.

In the first study, participants were asked to think about a problem at work that was significant for them. From there, they were randomly assigned to write about the potential losses or gains from that problem. They were also asked to indicate how likely they were to talk about these problems to their supervisor. Participants who reflected on their potential losses showed a 16 percent higher willingness to speak up compared to those who focused on the potential gains.

When it came to the MBA students, they read a fictional performance review scenario where a workplace problem was described. They then rated how willing they would be to speak up about that scenario if they were in the situation. One example suggested that the entire team might fall short of its goals if an issue was not addressed. This specific scenario yielded the most likelihood of speaking up 35 percent more than the scenario’s suggesting that only they would miss their goal, supporting the research’s findings that an employee is more likely to speak up when the loss impacts more people.

The third study looked at employee-supervisor pairings to understand how these relationships play out in the real world. Using pairings from across three industries, employees reported a workplace problem they encountered and their supervisor rated how often that employee spoke up on the job. While the first two studies involved hypothetical scenarios, this real-world evidence showed that employees were 8-10 times more likely to speak up when issues were framed as a potential collective loss compared with a potential collective gain. 

“This research is really geared toward managers so they can facilitate and understand how and why their employees will speak up,” said Thompson. “You can talk about the issue, but it always ends in terms of how we frame things.” 

Continue Reading

NewsMakers

Yoga practice could reduce blood pressure in people with obesity

People who practiced yoga had a significant decrease in blood pressure, with systolic blood pressure lowered by an average of 4.35 mmHg and diastolic blood pressure by 2.06 mmHg.

Published

on

Practicing yoga could help people with overweight or obesity improve their cardiometabolic health, according to a study in the open-access journal PLOS Global Public Health by Widya Wasityastuti from the University of Edinburgh, Scotland, and colleagues.

Yoga is a popular form of exercise around the world, and is a gentle and accessible form of exercise for many people. To better understand the potential health benefits of yoga, the authors of this study performed a meta-analysis, examining 30 studies of yoga for its cardiometabolic benefits. They focused on studies which examined outcomes for blood pressure, lipid profiles, glucose homeostasis, markers of inflammation, and measures of antioxidants, and those which examined people with body-mass index over 23 for Asian countries, and 25 for other countries, indicating that participants had overweight or obesity. Of the 30 studies considered, 23 were conducted in Asian countries, while the remaining studies were from the United States, Germany, and Australia.

Across the 30 studies and a total of 2,689 participants, the authors found that people who practiced yoga had a significant decrease in blood pressure, with systolic blood pressure lowered by an average of 4.35 mmHg and diastolic blood pressure by 2.06 mmHg. They also found modest beneficial effects on low- and high-density lipoproteins, types of cholesterol that have been linked to an increased risk of stroke. 

The authors note that the studies analyzed were not specifically recruiting people with obesity, and there was no dose-response measured, so it is unknown how much yoga is needed to produce these effects, though the studies they analyzed favored practice of at least 180 minutes per week.

The studies also focused heavily on Asian participants, and practitioners with comorbidities were excluded from analysis. Finally, it’s important to note that due to the nature of this study, causality cannot be confirmed here despite the correlations found.

Further studies will be needed to understand whether yoga can provide similar benefits to other populations, as well as people with co-morbidities such as diabetes or heart disease.

The authors suggest that while more high-quality trials are needed, the meta-analysis supports potential benefits of yoga for cardiometabolic health in people with overweight and obesity.

The authors summarize: “Our review suggests that yoga may offer a helpful additional option for improving some aspects of cardiometabolic health in adults with overweight or obesity, particularly blood pressure.”

They add: “Yoga is often seen mainly as a wellbeing practice, but our findings suggest it may also support certain cardiometabolic health outcomes in adults with overweight or obesity.”

Continue Reading

NewsMakers

Stress, BMI, and hormones linked to earlier puberty in girls

Higher levels of key steroid hormones—combined with elevated stress and body mass index (BMI)—are associated with earlier onset of puberty in girls.

Published

on

Higher levels of key steroid hormones—combined with elevated stress and body mass index (BMI)—are associated with earlier onset of puberty in girls, according to a new study at Columbia University Mailman School of Public Health.

The findings are published in The Journal of Clinical Endocrinology & Metabolism.

 Elevated prepuberty urinary levels of glucocorticoids, androgens, and progesterone were strongly linked to accelerated breast development (thelarche). Girls with high glucocorticoid levels alongside high BMI and stress entered puberty an average of seven months earlier than peers with lower levels.

“While stress and BMI have long been recognized as independent predictors of puberty, few studies have examined how they interact with a girl’s hormones,” said Lauren Houghton, PhD, assistant professor of Epidemiology at Columbia Mailman School, and first author. “Our findings challenge conventional research that has largely focused on estrogen and body size, highlighting instead the role of stress and androgens – typically thought of as male hormones– in shaping pubescent development.”

The strongest associations were observed for progesterone, androgens, and glucocorticoids, indicating that multiple hormonal pathways—not just estrogen—play a critical role in the timing of puberty.

For example:

  • Higher glucocorticoid, androgen, and progesterone metabolites were associated with earlier onset of puberty
  • Elevated androgens and progesterone were also linked to a longer duration of puberty
  • Estrogen metabolites were associated with delayed onset, not acceleration
  • The effects of hormones on puberty timing were significantly modified by BMI and stress levels.

 Notably, the associations were consistent regardless of family history of breast cancer.

“Our objective was to identify the full set of hormonal patterns linked to accelerated puberty and test whether BMI and stress modify this relationship,” said Houghton, who is also assistant professor at the Herbert Irving Comprehensive Cancer Center at Columbia. “We predicted that girls with elevated BMI and stress would experience the earliest onset—and that the stress response shifts during this key time for girls.”

The researchers drew on data from the LEGACY Girls Study, a cohort of 1,040 girls ages 6 to 13 recruited across the U.S. States and Canada. Participants were followed every six months with clinical assessments, questionnaires, and biospecimen collection.

The analysis included 327 girls who were at the pre-puberty stage at baseline and provided urine samples at least one year before the onset of puberty. Houghton and colleagues measured a comprehensive panel of steroid metabolites using first-morning urine samples and tracked puberty development using validated clinical scales.

Mothers of the girls completed an Internalizing Composite Scale, which includes subscales for anxiety, depression, and other at-risk status. They also provided information on girls’ family history of all cancers as well as on pregnancy and infancy, including birth weight and their child’s race and ethnicity. Trained research staff measured height and weight twice every 6 months. 

“Unlike prior research, this study simultaneously examined hormonal patterns, BMI, and psychosocial stress—captured through standardized behavioral assessments—within the same cohort,” said senior author Mary Beth Terry, PhD, professor of Epidemiology at Columbia Mailman School, and the Herbert Irving Cancer Center, and Silent Spring Institute.  “Interestingly, we also learned that the associations were consistent regardless of family history of breast cancer.”

The findings may help explain the ongoing trend toward earlier puberty and point to actionable prevention strategies, observed the authors.

 “Stress-reducing interventions and healthy lifestyle changes may help delay early puberty and improve long-term health outcomes,” said Houghton. ‘Because early puberty is linked to increased breast cancer risk later in life, the results have important implications for both pediatric care and public health.”

Continue Reading
Advertisement
Advertisement

Like Us On Facebook

Loading...

Most Popular

Copyright ©FRINGE PUBLISHING. All rights reserved.