When Men Drink, Women and Children Pay the Price
A sweeping global review has revealed that men’s alcohol consumption is causing widespread harm to women and children, from violence and neglect to lost educational and life opportunities. Credit: Shutterstock

A new global review led by La Trobe University has revealed the often-overlooked damage caused by men’s alcohol consumption to women and children, urging immediate policy action in Australia and around the world to address these gender-related harms.

The study, titled "Harms to Women and Children from Men's Alcohol Use: An Evidence Review and Directions for Policy," draws together data from three recent systematic reviews that analyzed 78 academic papers.

Worldwide, as many as one in three women in some countries live with a partner who drinks heavily. Children in these households are also at greater risk of violence, neglect, poor health, and limited opportunities later in life.

These negative effects are especially severe in low- and middle-income nations and in places where gender inequality remains high.

The research, led by Professor Anne-Marie Laslett of La Trobe’s Centre for Alcohol Policy Research (CAPR) and published by the global nonprofit research organization RTI International, found that men typically consume alcohol more heavily than women and are more likely to harm others when they drink.

As a result, women and children bear a disproportionate share of the consequences, including physical injuries, emotional distress, economic strain, and disruptions to schooling and family life.

"Research shows that the consequences of men's alcohol use extend far beyond the individual that drinks," Professor Laslett said.

"Women and children pay a heavy price, yet policies rarely take their experiences into account. This is a major gap in international public health and social policy."

Global data further indicates major differences between countries in how much and how often men and women drink. In many regions, these disparities make the impact of men’s alcohol use on women and children even more severe.

"Globally there has been poor recognition that others' drinking, and particularly men's drinking, contributes to many harms to women and children," Professor Laslett said.

"Social, cultural and economic policies, as well as alcohol-specific policies, need to change to ensure that they are responding to the harms to women and children highlighted in this review."

In Australia, the findings are particularly timely given growing national attention to domestic and family violence.

Alcohol's role in driving partner violence has been recognised in recent government reviews, with calls to strengthen regulation and prevention strategies.

Australia's Federal Government last year commissioned a rapid review that recommended addressing alcohol's regulatory environment.

The review emphasizes that while proven policies such as raising alcohol taxes, restricting availability, and limiting marketing remain essential, they should be paired with interventions that tackle harmful gender norms and empower women and children.

An intersectoral approach involving health, legal and social services is critical for meaningful change.

Professor Siri Hettige, a researcher from Sri Lanka's University of Columbo who collaborated on the project, said targeted, community-level interventions that addressed the realities faced by women and children were essential.

"Given the nature of the social context in which the harm to women and children from men's drinking occurs, interventions to reduce such harms might have to go beyond current alcohol policies," Professor Hettige said.

Read more …When men drink, women and children pay the price

Scientists have created a new and more advanced form of immune-based cancer therapy using engineered cells known as CAR-NK (natural killer) cells. Like CAR-T cells, these modified immune cells can be programmed to recognize and attack cancer, but they rely on a different type of immune cell that naturally targets abnormal or infected cells.

A team from MIT and Harvard Medical School has now developed a more effective way to engineer CAR-NK cells that dramatically reduces the chance of the body’s immune system rejecting them. Immune rejection has been one of the biggest limitations of cell-based therapies, often weakening their effectiveness.

This innovation could also make it possible to produce “off-the-shelf” CAR-NK treatments that are available immediately after diagnosis, rather than waiting weeks for custom-engineered cells. Traditional CAR-NK and CAR-T manufacturing methods typically require several weeks to complete before patients can begin treatment.

“This enables us to do one-step engineering of CAR-NK cells that can avoid rejection by host T cells and other immune cells. And, they kill cancer cells better and they’re safer,” says Jianzhu Chen, an MIT professor of biology, a member of the Koch Institute for Integrative Cancer Research, and one of the senior authors of the study. 

In tests using mice with humanized immune systems, the newly engineered cells successfully destroyed most cancer cells while avoiding attack from the host’s own immune defenses.

Rizwan Romee, an associate professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute, is also a senior author of the paper, which was published in Nature Communications. The study’s lead author is Fuguo Liu, a postdoctoral researcher at the Koch Institute and a research fellow at Dana-Farber.

Evading the immune system

Natural killer (NK) cells are a vital part of the body’s built-in immune defense, responsible for identifying and destroying cancerous and virus-infected cells. They eliminate these threats through a process called degranulation, which releases a protein known as perforin. This protein punctures the membrane of target cells, leading to their death.

To produce CAR-NK cells for treatment, doctors typically collect a blood sample from the patient. NK cells are then extracted and engineered to express a specialized protein called a chimeric antigen receptor (CAR), which is designed to target specific markers found on cancer cells.

Once modified, the cells must multiply in the lab for several weeks before there are enough to be infused back into the patient. The same general process is used for CAR-T cell therapies, some of which have already been approved to treat blood cancers like lymphoma and leukemia. CAR-NK therapies, however, are still being tested in clinical trials.

Because growing enough personalized CAR-NK cells takes time and the patient’s cells may not always be healthy enough for reliable use, scientists have been exploring an alternative: creating NK cells from healthy donors. These donor-derived cells could be mass-produced and stored for rapid use. The challenge, however, is that the recipient’s immune system often identifies donor cells as foreign and destroys them before they can attack the cancer.

In their latest research, the MIT team aimed to solve this problem by helping NK cells “hide” from immune detection. Their experiments showed that removing surface proteins known as HLA class 1 molecules allowed NK cells to avoid attack from T cells in the host’s immune system. These proteins normally act as identity markers that tell the immune system whether a cell belongs to the body.

To make use of this insight, the researchers added a sequence of siRNA (short interfering RNA) that silences the genes responsible for producing HLA class 1 proteins. Along with this genetic tweak, they introduced the CAR gene itself and another gene that encodes either PD-L1 or single-chain HLA-E (SCE), both of which help strengthen the NK cells’ cancer-fighting abilities.

All of these genetic components were combined into a single DNA construct, which allowed the team to efficiently convert donor NK cells into immune-evasive CAR-NK cells. Using this method, they engineered cells that target CD-19, a protein commonly found on malignant B cells in lymphoma patients.

NK cells unleashed

The researchers tested these CAR-NK cells in mice with a human-like immune system. These mice were also injected with lymphoma cells.

Mice that received CAR-NK cells with the new construct maintained the NK cell population for at least three weeks, and the NK cells were able to nearly eliminate cancer in those mice. In mice that received either NK cells with no genetic modifications or NK cells with only the CAR gene, the host immune cells attacked the donor NK cells. In these mice, the NK cells died out within two weeks, and the cancer spread unchecked.

The researchers also found that these engineered CAR-NK cells were much less likely to induce cytokine release syndrome — a common side effect of immunotherapy treatments, which can cause life-threatening complications.

Because of CAR-NK cells’ potentially better safety profile, Chen anticipates that they could eventually be used in place of CAR-T cells. For any CAR-NK cells that are now in development to target lymphoma or other types of cancer, it should be possible to adapt them by adding the construct developed in this study, he says.

The researchers now hope to run a clinical trial of this approach, working with colleagues at Dana-Farber. They are also working with a local biotech company to test CAR-NK cells to treat lupus, an autoimmune disorder that causes the immune system to attack healthy tissues and organs.

The research was funded, in part, by Skyline Therapeutics, the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund and the Elisa Rah Memorial Fund, the Claudia Adams Barr Foundation, and the Koch Institute Support (core) Grant from the National Cancer Institute.

Read more …MIT’s “stealth” immune cells could change cancer treatment forever

At first, Alzheimer’s disease and cancer might seem to have little overlap. One gradually destroys memory and cognition, while the other ravages the body through uncontrolled cell growth. Yet scientists at the MUSC Hollings Cancer Center have found an unexpected biological link between them.

Their new study, published in Cancer Research, shows that a protein strongly associated with Alzheimer’s disease can also enhance the immune system’s strength. The finding could open doors to new approaches for treating cancer, neurodegenerative disorders, and age-related decline.

The Alzheimer's-cancer paradox

For years, researchers noticed something odd in population data: people diagnosed with Alzheimer’s disease appeared to have a much lower risk of developing cancer. This unusual pattern intrigued Besim Ogretmen, Ph.D., associate director of Basic Science at Hollings, who set out with his team to uncover the biological explanation behind it.

Epidemiologist Kalyani Sonawane, Ph.D., led the effort to verify this correlation. Her group examined five years of nationally representative survey data and found striking evidence—adults over age 59 with Alzheimer’s were 21 times less likely to develop cancer than those without it.

Although the connection was clear, the underlying reason was not. What biological mechanism could explain why the two diseases seem to work in opposite directions?

A biological trade-off

Through a series of experiments, the researchers traced the connection to a familiar culprit: amyloid beta, the protein known for forming harmful plaques in the brains of Alzheimer’s patients. They discovered that amyloid beta has a dual personality, depending on where it acts. In the brain, it damages neurons, but in the immune system, it appears to make immune cells stronger.

Amyloid beta interferes with a cellular recycling process called mitophagy, which normally removes damaged mitochondria—the energy-producing parts of cells. In the brain, blocking this cleanup leads to a buildup of faulty mitochondria that release toxins and trigger neuron death, worsening memory loss and cognitive decline.

In contrast, when amyloid beta affects immune cells called T-cells, the outcome flips. By limiting mitophagy, it allows more mitochondria to stay functional, giving T-cells extra energy to power their cancer-fighting activity.

"What we found is that the same amyloid peptide that is harmful for neurons in Alzheimer's is actually beneficial for T-cells in the immune system," Ogretmen said. "It rejuvenates the T-cells, making them more protective against tumors."

Rejuvenating the immune system

To explore this further, the team transplanted mitochondria from T-cells of Alzheimer’s patients into aging T-cells from individuals without the disease. The change was remarkable.

"Older T-cells began functioning like young, active T-cells again. That was an incredible finding because it suggests a whole new way to think about rejuvenating the immune system."

The results also revealed that amyloid beta contributes to cancer in another way - by depleting fumarate, a small molecule made inside mitochondria during energy production. Fumarate acts like a brake, keeping mitophagy from running out of control. When fumarate levels drop, cells recycle too many of their healthy mitochondria, resulting in a loss of strength.

"When you deplete fumarate, you increase mitophagy much more," Ogretmen explained. "Fumarate no longer binds proteins involved in that process, so the proteins become more active and induce more mitophagy. It's like a reinforcing feedback loop."

In T-cells, fumarate helps to regulate this balance. When the researchers administered fumarate to aging T-cells in mice and human tissue, they found lower levels of mitophagy. By preserving their mitochondria, fumarate gave the immune cells more energy to fight cancer. The discovery that fumarate rescues aging T-cells from excessive mitochondrial loss and enhances their anti-tumor activity suggests another way to protect immune health.

Broad implications for cancer and aging

Together, these findings shed light on why people with Alzheimer's disease are less likely to develop cancer - and how that protection might be harnessed. Rather than attacking tumors directly, this research points to a new generation of therapies that recharge the immune system itself.

One approach is mitochondrial transplantation, giving older T-cells fresh, healthy "power plants" to revitalize their disease-fighting protection. Another strategy is to maintain or restore fumarate levels to preserve mitochondria and boost T-cells' anti-tumor activity.

The potential applications for cancer are wide-ranging. Revitalizing T-cells by transplanting healthy mitochondria could strengthen existing treatments like CAR-T cell therapy. Ogretmen's group has already filed a patent for this discovery, underscoring its potential as a new class of therapy. Fumarate-based drugs or supplements might further extend the life and energy of older immune cells by preserving their mitochondria. These could be used in conjunction with immunotherapy to maintain T-cells' strength during treatment.

Beyond cancer, these approaches could help to slow immune aging more generally. As mitochondria naturally wear down over time, protecting them could help older adults to fight infections and stay healthier. Further delving into the double-edged impact of amyloid beta could also inform future treatments for neurodegenerative diseases, like Alzheimer's, by finding ways to isolate its protective immune effects without harming the brain.

For Ogretmen, the novel findings highlight the power of teamwork, noting the collaboration across Hollings' research programs in cancer biology, immunology and prevention.

"This was a true team effort," he emphasized. "We're proud of the different areas of expertise that came together to make these discoveries. The research exemplifies how discoveries in one area can open unexpected doors in another."

Read more …A toxic Alzheimer’s protein could be the key to fighting cancer

More Articles …