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June 1, 2018
Digest

Scientists Develop Potential New Approach to Stop Cancer Metastasis

Researchers have identified a compound that blocks the spread of pancreatic and other cancers in various animal models. When cancer spreads from one part of the body to another in a process called metastasis, it can eventually grow beyond the reach of effective therapies. Now, there is a new plan of attack against this deadly process, thanks to scientists at NIH, Northwestern University and their collaborative research partners.

The team collaborated to identify a compound, which they named metarrestin, that stopped tumor metastasis in multiple animal models. Mice treated with metarrestin also had fewer tumors and lived longer than mice that did not receive treatment. Results were published May 16 in Science Translational Medicine.

“Many drugs are aimed at stopping cancer growth and killing cancer cells,” said co-author Dr. Juan Marugan, group leader of the NCATS Chemical Genomics Center. “However, there is no single approved drug specifically aimed at treating metastasis. Our results show metarrestin is a very promising agent that we should continue to investigate against metastasis.”

In patients, metarrestin potentially could be effective as a therapy after cancer surgery. Because advanced cancers are difficult to completely remove with surgery, doctors typically give chemotherapy to try to kill undetected cancer cells left behind and prevent the cancer from coming back. Metarrestin could be added to such standard drug therapy.

International Study Suggests Combination Therapy May Prevent Stroke in Certain People

Combining clopidogrel and aspirin after a small stroke decreases risk of a new stroke, heart attack or other ischemic event, international study finds.
Combining clopidogrel and aspirin after a small stroke decreases risk of a new stroke, heart attack or other ischemic event, international study finds.

IMAGE: SMARTSTOCK/ISTOCK

Results from an international clinical trial of more than 4,880 participants, published in the New England Journal of Medicine, show that combining clopidogrel and aspirin following a small stroke or experiencing minor stroke symptoms decreases risk of a new stroke, heart attack or other ischemic event within 90 days. The combination therapy was also associated with an increase in major bleeding, although many of those episodes were non-fatal and did not occur in the brain. The study was supported by NINDS.

“These findings are likely to have a global effect on clinical practice, as these drugs are easily available in many hospitals and clinics,” said NINDS director Dr. Walter Koroshetz. “As the benefit of the combination was concentrated in the first 2 weeks while risk of bleeding was constant over 90 days, it may be especially valuable in acute management of a minor ischemic stroke or transient ischemic attack [TIA].”

The Platelet-Oriented Inhibition in New TIA and minor ischemic stroke (POINT) clinical trial follows an earlier study, which showed benefits of this drug combination in a Chinese population. POINT was conducted to see whether the benefits could be expanded to a more diverse group of patients.

The study, led by Dr. S. Claiborne Johnston of Dell Medical School at the University of Texas at Austin, included patients who had experienced either a minor stroke or a TIA, in which blood supply to a part of the brain is briefly stopped and can be a risk factor for a larger stroke. Study participants were given clopidogrel and aspirin or aspirin alone to see whether the combination therapy could prevent a larger stroke within 3 months.

Johnston’s team found that the combination of clopidogrel and aspirin prevented more ischemic events, such as stroke and heart attack, compared to aspirin alone. The results showed that 5 percent of patients in the combination therapy group and 6.5 percent of patients taking only aspirin experienced such an event within 90 days. 

However, the combination therapy was associated with a greater risk of major bleeding, or hemorrhage, than aspirin alone.

“We saw a real benefit with the combination therapy, but that treatment does come with a risk,” said Johnston. “Overall, the risk of severe bleeding was very small, but it was not zero.”

The study was stopped early because the combination therapy was found to be more effective than aspirin alone in preventing severe strokes but also due to the risk of severe hemorrhage.

Male Depression May Lower Pregnancy Chances Among Infertile Couples

Among couples being treated for infertility, depression in the male partner was linked to lower pregnancy chances, according to an NIH-funded study.
Among couples being treated for infertility, depression in the male partner was linked to lower pregnancy chances, according to an NIH-funded study.

IMAGE: THEPRINT/THINKSTOCK

Among couples being treated for infertility, depression in the male partner was linked to lower pregnancy chances, while depression in the female partner was not found to influence the rate of live birth, according to a study funded by NIH.

The study, which appears in Fertility and Sterility, also linked a class of antidepressants known as non-selective serotonin reuptake inhibitors (non-SSRIs) to a higher risk of early pregnancy loss among females being treated for infertility. SSRIs, another class of antidepressants, were not linked to pregnancy loss. Neither depression in the female partner nor use of any other class of antidepressant were linked to lower pregnancy rates.

“Our study provides infertility patients and their physicians with new information to consider when making treatment decisions,” said study author Dr. Esther Eisenberg of NICHD, which funded the study.

Citing previous studies, the authors noted that 41 percent of women seeking fertility treatments have symptoms of depression. In addition, a study of men seeking IVF treatments found that nearly 50 percent experienced depression. The authors conducted the current study to evaluate the potential influence of depression in couples seeking non-IVF treatments.

Scientists Watch Brain’s Lining Heal After Head Injury

Following head injury, the protective lining that surrounds the brain may get a little help from its friends: immune cells that spring into action to assist with repairs. In a new study, NIH scientists watched in real time as different immune cells took on carefully timed jobs to fix the damaged lining of the brain, also known as meninges, in mice. These results may help provide clues to the discovery that the meninges in humans may heal following mild traumatic brain injury (mTBI) and why additional hits to the head can be so devastating.

“The lining of the brain, with help from the immune system, has a remarkable ability to put itself back together again after injury,” said Dr. Dorian McGavern, NINDS scientist and senior author of the study published in Nature Immunology. “As we learn more about all the cells involved in the repair process, we may be able to identify potential targets for therapy that lead to better outcomes for patients.”

The study came about from an observation on MRI scans of adult patients who experienced a concussion or mTBI. Around half of patients with mTBI show evidence of injury to blood vessels in the meninges, which appears on MRI scans as a vascular dye leaking out of the damaged vessels.

The meninges are a collection of membranes that line the central nervous system and help protect brain and spinal cord tissue from various forms of injury. Damage to the meninges can cause cell death in underlying brain tissue.

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