Aspirin

Emphysema.

Regular use of aspirin may help slow the progression of early emphysema, according to new research presented at the 2015 American Thoracic Society International Conference.

“Other than smoking cessation and avoidance, there are no known methods for reducing the risk of developing emphysema,” said researcher Carrie Aaron MD, of the Columbia University Medical Center in New York. “In our large general population sample, we found that regular aspirin use (three or more days per week) was associated with a slower progression of percent emphysema on computed tomography (CT) scans over 10 years.”

The study, which was motivated by findings of pulmonary vascular involvement in emphysema and the importance of platelet function in other vascular diseases, included 4,471 individuals participating in the Multi-Ethnic Study of Atherosclerosis Lung Study. The percentage of lung volume with emphysematous features (percent emphysema) was assessed on up to 4 CT scans performed over approximately 10 years of follow-up. Spirometry, a measure of expiratory airflow, was performed in 81% of study subjects.

Of the 4,471 study subjects, 21% (921) used aspirin regularly, 55% were ever-smokers, and 25% of those with spirometry had results indicating airflow obstruction. Regular aspirin use was associated with a significantly slower progression of percent emphysema over ten years, when compared to those who did not use aspirin, even after adjustment for a number of potential confounding factors, including age, sex, race/ethnicity, cigarettes/day, pack-years, and hypertension. Results were consistent in propensity score analyses, performed to minimize effects of confounding by indication. Similar reductions in the rate of progression of percent emphysema were seen among ever-smokers, and greater reductions were observed among individuals with spirometric evidence of airflow obstruction.

“Our study found that persons taking aspirin regularly had a slower progression of emphysema over 10 years compared to those who did not, and that this difference was not explained by many factors that we believe affect progression of emphysema.” said Dr. Aaron. “The findings might suggest that regular aspirin use may slow the progression of subclinical emphysema, perhaps through effects on platelet activation or inflammation.”


Immunotherapy.

Giving cancer patients aspirin at the same time as immunotherapy could dramatically boost the effectiveness of the treatment, according to new research published in the journal Cell.

Francis Crick Institute researchers, funded by Cancer Research UK, have shown that skin, breast and bowel cancer cells often produce large amounts of prostaglandin E2 (PGE2). This molecule dampens down the immune system’s normal response to attack faulty cells, which helps cancer to hide. It is a trick that allows the tumour to thrive and may explain why some immunotherapy treatments have not been as effective as hoped.

Aspirin is part of a group of molecules called COX inhibitors, which stop the production of PGE2 and help reawaken the immune system. Combining immunotherapy with aspirin or other COX inhibitors substantially slowed bowel and melanoma skin cancer growth in mice, compared to immunotherapy alone.

Study author Professor Caetano Reis e Sousa, senior group leader at the Francis Crick Institute, said: “We’ve added to the growing evidence that some cancers produce PGE2 as a way of escaping the immune system. If you can take away cancer cells’ ability to make PGE2 you effectively lift this protective barrier and unleash the full power of the immune system.

“Giving patients COX inhibitors like aspirin at the same time as immunotherapy could potentially make a huge difference to the benefit they get from treatment. It’s still early work but this could help make cancer immunotherapy even more effective, delivering life-changing results for patients.”

Professor Peter Johnson, Cancer Research UK‘s chief clinician, said: “PGE2 acts on many different cells in our body, and this study suggests that one of these actions is to tell our immune system to ignore cancer cells. Once you stop the cancer cells from producing it, the immune system switches back to ‘kill mode’ and attacks the tumour.

“This research was carried out in mice so there is still some way to go before we will see patients being given COX inhibitors as part of their treatment. But it’s an exciting finding that could offer a simple way to dramatically improve the response to treatment in a range of cancers.”


Mesothelioma.

Aspirin may inhibit the growth of mesothelioma, an aggressive and deadly asbestos-related cancer, University of Hawai’i Cancer Center researchers have found.

The finding could eventually give doctors and patients a potential new tool to fight against this devastating disease, which kills about 3,200 people a year nationwide, and advance knowledge of how to fight other cancers.

The study published in Cell Death and Disease showed that aspirin slows down the growth of mesothelioma by blocking the carcinogenic effects of the inflammatory molecule, High-Mobility Group Box 1 (HMGB1). Researchers believe the molecule directly promotes mesothelioma growth.

“HMGB1 is an inflammatory molecule that plays a critical role in the initiation and progression of malignant mesothelioma. Inhibiting HMGB1 dramatically reduced malignant mesothelioma growth in mice and significantly improved survival of treated animals,” said Dr. Haining Yang, PhD, an associate professor in the Thoracic Oncology Program at the UH Cancer Center.

Aspirin is mostly used as a nonsteroidal anti-inflammatory drug, which is absorbed by the stomach and upper intestine. Working with collaborators, Dr. Yang and Dr. Michele Carbone, MD, PhD, director of the UH Cancer Center’s Thoracic Oncology Program, found that at least some of the so far unknown anti-tumour activity of aspirin is through preventing HMBG1 activity.

Malignant mesothelioma is an aggressive and often deadly cancer that can result from exposure to asbestos and asbestos-like fibres such as erionite. The prolonged presence of asbestos fibres lodged in the organ lining initiates a vicious cycle of chronic cell death and chronic inflammation that, over a period of many years, can lead to mesothelioma.

The researchers theorised that people at high risk of developing mesothelioma could take aspirin as a way to prevent or delay the growth of the cancer, and thus increase their chances of survival. Such individuals would include people occupationally exposed to asbestos, or people who live in areas high in naturally occurring asbestos-like fibres. They also encourage future studies to uncover the precise mechanism by which aspirin blocks HMGB1.


(P.S. See also Aspirin Study.)


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