PRESS-NEWS.org - Press Release Distribution
FREE PRESS RELEASES DISTRIBUTION

Drug commonly used as antidepressant helps fight cancer in mice

UCLA researchers discover MAOIs could activate immune system to shrink various types of tumors

Drug commonly used as antidepressant helps fight cancer in mice
2021-06-10
(Press-News.org) A class of drug called monoamine oxidase inhibitors is commonly prescribed to treat depression; the medications work by boosting levels of serotonin, the brain's "happiness hormone."

A new study by UCLA researchers suggests that those drugs, commonly known as MAOIs, might have another health benefit: helping the immune system attack cancer. Their findings are reported in two papers, which are published in the journals Science Immunology and Nature Communications.

"MAOIs had not been linked to the immune system's response to cancer before," said Lili Yang, senior author of the study and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. "What's especially exciting is that this is a very well-studied and safe class of drug, so repurposing it for cancer isn't as challenging as developing a completely new drug would be."

Recent advances in understanding how the human immune system naturally seeks out and destroys cancer cells, as well as how tumors try to evade that response, has led to new cancer immunotherapies -- drugs that boost the immune system's activity to try to fight cancer.

In an effort to develop new cancer immunotherapies, Yang and her colleagues compared immune cells from melanoma tumors in mice to immune cells from cancer-free animals. Immune cells that had infiltrated tumors had much higher activity of a gene called monoamine oxidase A, or MAOA. MAOA's corresponding protein, called MAO-A, controls levels of serotonin and is targeted by MAOI drugs.

"For a long time, people have theorized about the cross-talk between the nervous system and the immune system and the similarities between the two," said Yang, who is also a UCLA associate professor of microbiology, immunology and molecular genetics and a member of the UCLA Jonsson Comprehensive Cancer Center. "So it was exciting to find that MAOA was so active in these tumor-infiltrating immune cells."

Next, the researchers studied mice that didn't produce MAO-A protein in immune cells. The scientists found that those mice were better at controlling the growth of melanoma and colon tumors. They also found that normal mice became more capable of fighting those cancers when treated with MAOIs.

Digging in to the effects of MAO-A on the immune system, the researchers discovered that T cells -- the immune cells that target cancer cells for destruction -- produce MAO-A when they recognize tumors, which diminishes their ability to fight cancer.

That discovery places MAO-A among a growing list of molecules known as immune checkpoints, which are molecules produced as part of a normal immune response to prevent T cells from overreacting or attacking healthy tissue in the body. Cancer has been known to exploit the activity of other previously identified immune checkpoints to evade attack by the immune system.

In the Science Immunology paper, the scientists report that MAOIs help block the function of MAO-A, which helps T cells overcome the immune checkpoint and more effectively fight the cancer.

But the drugs also have a second role in the immune system, Yang found. Rogue immune cells known as tumor-associated macrophages often help tumors evade the immune system by preventing anti-tumor cells including T cells from mounting an effective attack. High levels of those immunosuppressive tumor-associated macrophages in a tumor have been associated with poorer prognoses for people with some types of cancer.

But the researchers discovered that MAOIs block immunosuppressive tumor-associated macrophages, effectively breaking down one line of defense that tumors have against the human immune system. That finding is reported in the Nature Communications paper.

"It turns out that MAOIs seem to both directly help T cells do their job, and stop tumor-associated macrophages from putting the brakes on T cells," Yang said.

Combining MAOIs with existing immunotherapies

Yang said she suspects that MAOIs may work well in concert with a type of cancer immunotherapies called immune checkpoint blockade therapies, most of which work by targeting immune checkpoint molecules on the surface of immune cells. That's because MAOIs work on MAO-A proteins, which are inside cells and function differently from other known immune checkpoint molecules.

Studies in mice showed that any of three existing MAOIs -- phenelzine, clorgyline or mocolobemide -- either on their own or in combination with a form of immune checkpoint blockade therapy known as PD-1 blockers, could stop or slow the growth of colon cancer and melanoma.

Although they haven't tested the drugs in humans, the researchers analyzed clinical data from people with melanoma, colon, lung, cervical and pancreatic cancer; they found that people with higher levels of MAOA gene expression in their tumors had, on average, shorter survival times. That suggests that targeting MAOA with MAOIs could potentially help treat a broad range of cancers.

Yang and her collaborators are already planning additional studies to test the effectiveness of MAOIs in boosting human immune cells' response to various cancers.

Yang said MAOIs could potentially act on both the brain and immune cells in patients with cancer, who are up to four times as likely as the general population to experience depression.

"We suspect that repurposing MAOIs for cancer immunotherapy may provide patients with dual antidepressant and antitumor benefits," she said.

The experimental combination therapy in the study was used in preclinical tests only and has not been studied in humans or approved by the Food and Drug Administration as safe and effective for use in humans. The newly identified therapeutic strategy is covered by a patent application filed by the UCLA Technology Development Group on behalf of the Regents of the University of California, with Yang, Xi Wang and Yu-Chen Wang as co-inventors.

INFORMATION:

The research was supported by Stop Cancer, the Broad Stem Cell Research Center Rose Hills Foundation Innovator Grant and Stem Cell Training Program, the UCLA Jonsson Comprehensive Cancer Center and Broad Stem Cell Research Center Ablon Scholars Program, the Magnolia Council of the Tower Cancer Research Foundation and the National Institutes of Health, including a Ruth L. Kirschstein National Research Service Award.


[Attachments] See images for this press release:
Drug commonly used as antidepressant helps fight cancer in mice

ELSE PRESS RELEASES FROM THIS DATE:

Largescale brain epigenetics study provides new insights into dementia

2021-06-10
The largest study of its kind has unveiled new insights into how genes are regulated in dementia, including discovering 84 new genes linked to the disease. Led by the University of Exeter, the international collaboration combined and analysed data from more than 1,400 people across six different studies, in a meta-analysis published in Nature Communications. These studies had used brain samples from people who had died with Alzheimer's disease. The project, funded by Alzheimer's Society and supported by the Medical Research Council and the National Institutes for ...

Beyond Remission: From Alcohol Dependence to Optimal Mental Health

2021-06-10
UNIVERSITY OF TORONTO & CARLETON UNIVERSITY New research published online in the journal Substance Use & Misuse is good news for those struggling with alcohol dependence: the possibility of ending this dependency gets easier with age. Moreover, more than half of individuals who have been dependent on alcohol are free of any addictions or mental illness, and nearly 40% are in excellent mental health. Using data drawn from Statistics Canada's Canadian Community Health Survey-Mental Health, researchers examined a nationally representative sample of 820 adult Canadians with a history of alcohol dependence to 19,945 who had never been addicted to alcohol. They found that in the past year, 71% of ...

Alcohol companies earned billions from underage drinking in 2016

Alcohol companies earned billions from underage drinking in 2016
2021-06-10
PISCATAWAY, NJ - Underage youth consumed $17.5 billion worth, or 8.6 percent, of the alcoholic drinks sold in 2016. Products from three alcohol companies--AB Inbev, MillerCoors and Diageo--accounted for nearly half of youth consumption, according to a new study published in the Journal of Studies on Alcohol and Drugs. Data collected in a landmark study of youth alcohol consumption by brand enabled the authors to calculate the first estimate in nearly 20 years of the monetary value of youth alcohol consumption. And for the first time, they were able to attribute those revenues to specific companies. "The alcohol industry has said they don't want minors to drink, ...

Monoclonal antibody therapy for COVID-19 safe, effective for transplant patients

2021-06-10
ROCHESTER, Minn. -- Treating transplant patients with mild to moderate cases of COVID-19 with monoclonal antibodies is safe and helps prevent serious illness, according to a Mayo Clinic study recently published in Open Forum Infectious Diseases. These results are especially important because transplant patients who are infected with COVID-19 have a higher risk of severe illness and death. "Monoclonal antibody therapy is really important for the transplant population because they are less likely to develop their own immunity. Providing them with these antibodies helps them recover from COVID-19," says Raymund Razonable, M.D., a Mayo Clinic infectious diseases specialist and the study's senior ...

New dipping solution turns the whole fish into valuable food

2021-06-10
When herring are filleted, more than half their weight becomes a low-value 'side stream' that never reaches our plates - despite being rich in protein and healthy omega-3 fatty acids. Now, scientists from Chalmers University of Technology, Sweden, have developed a special dipping solution, with ingredients including rosemary extract and citric acid, which can significantly extend the side streams' shelf life, and increase the opportunities to use them as food. Techniques for upgrading these side-streams to food products such as minces, protein isolates, hydrolysates and oils are already available today, and offer the chance to reduce the current practices of using them for animal feed, ...

Molecular changes in white blood cells can help diagnose 'the bends' earlier in divers

2021-06-10
For over a century, researchers have known about "the bends", a serious condition affecting scuba divers. However, we still know relatively little about its physiological basis. Doctors do not yet have a definitive test for the bends, instead relying on symptoms to diagnose it. A new study in Frontiers in Physiology is the first to investigate genetic changes in divers with this condition, finding that genes involved in inflammation and white blood cell activity are upregulated. The findings cast light on the processes underlying the bends, and may lead to biomarkers that will help doctors to diagnose the condition more precisely. The bends, more formally known as decompression sickness, is a potentially lethal condition that can affect divers. Symptoms ...

Patient-provider discussions about bariatric surgery play pivotal role in weight loss outcomes

2021-06-10
BOSTON -- Obesity increases one's risk for many diseases and often prevents patients from receiving other necessary medical procedures. One of the most effective ways for patients with severe obesity to lose weight is through bariatric surgery, but it's not clear how often this option is raised. In a new study published in Obesity, investigators from Brigham and Women's Hospital find that eligible patients who discuss bariatric surgery options with their primary care providers or specialists from disciplines ranging from cardiology to urology are more likely to undergo surgery and lose more weight than ...

Flickering screens may help children with reading and writing difficulties

Flickering screens may help children with reading and writing difficulties
2021-06-10
Previous studies have shown that children with attention difficulties and/or ADHD solve cognitive tasks better when they are exposed to auditory white noise. However, this is the first time that such a link has been demonstrated between visual white noise and cognitive abilities such as memory, reading and non-word decoding in children with reading and writing difficulties. "The white noise to which we exposed the children, also called visual pixel noise, can be compared with giving children glasses. The effect on reading and memory was immediate," explains Göran Söderlund, Senior Lecturer in Education at the University of Gothenburg and Professor of Special Education at the Western Norway University ...

New research shows link between politics, boredom and breaking public-health rules

2021-06-10
People who are more prone to boredom and who are socially conservative are more likely to break public-health rules, according to new psychology research. While previous research demonstrated a connection between being highly prone to boredom and breaking social-distancing rules, this study demonstrated the association was more prominent as participants' social conservatism increased. "Many public-health measures such as wearing a mask or getting a vaccine have become highly politicized," said James Danckert, professor of psychology at the University of Waterloo. "People who find these ...

Higher alcohol content beer popularity growing, as overall beer consumption down

Higher alcohol content beer popularity growing, as overall beer consumption down
2021-06-10
PITTSBURGH, June 10, 2021 - Americans are consuming more craft beer with higher alcohol content but are drinking less beer by volume, according to a new analysis led by epidemiologists at the University of Pittsburgh Graduate School of Public Health. The study, published online and in a coming issue of the journal Substance Use & Misuse, looked at beer purchased in stores between 2004 and 2014. This is the first study to examine trends not only in the volume of beer purchased, but also the "beer specific" alcohol content. "With the rise in popularity of craft breweries and the acquisition of such breweries by large-scale ...

LAST 30 PRESS RELEASES:

COVID-19 disruptions in sub-Saharan Africa will have substantial health consequences

Study: Environmental risks exacerbated for vulnerable populations in small towns

East Antarctic summer cooling trends caused by tropical rainfall clusters

Being Anglo-Saxon was a matter of language and culture, not genetics

3,000-year-old shark attack victim found by Oxford-led researchers

Western high-fat diet can cause chronic pain, according to UT Health San Antonio-led team

Concepts from physics explain importance of quarantine to control spread of COVID-19

More seniors may have undiagnosed dementia than previously thought

Flavored e-cigarettes may affect the brain differently than non-flavored

Study explores how readers at partisan news sites respond to challenging news events

Scientists obtain real-time look at how cancers evolve

Flipping a molecular switch for heart fibrosis

Drug doubles down on bone cancer, metastasis

Cancer survivors' tongues less sensitive to tastes than those of healthy peers

Cold weather cost New England electric customers nearly $1.8 billion in one month; A new study suggests ways to mitigate fuel shortages

You can have too much of a good thing, says study financial analysts' work-life balance

GSA's journal's add seven articles on COVID-19 and aging

Cat-borne parasite Toxoplasma induces fatally bold behavior in hyena cubs

Nature article: Dieting and its effect on the gut microbiome

NIH scientists describe "Multi-Kingdom Dialogue" between internal, external microbiota

Melatonin in mice: there's more to this hormone than sleep

Wild bees need deadwood in the forest

A triple-system neural model of maladaptive consumption

Milk protein could help boost blueberries' healthfulness

Seeking a treatment for IBS pain in tarantula venom

Addressing inequity in air quality

Roughness of retinal layers, a new Alzheimer's biomarker

Study links sleep apnea in children to increased risk of high blood pressure in teen years

Black patients with cirrhosis more likely to die, less likely to get liver transplant

Researchers outline specific patterns in reading in Russian

[Press-News.org] Drug commonly used as antidepressant helps fight cancer in mice
UCLA researchers discover MAOIs could activate immune system to shrink various types of tumors