Tag: 4/3/21

Lower Mobility Linked to Increased Cancer Mortality

A retrospective study examining the difference in physical mobility between cancer survivors and those never diagnosed with cancer shows that poor mobility is strongly associated with mortality.

The beneficial role of physical activity in preventing cancer is well known, effects of exercise during and after cancer treatment are less well explored.  Common cancers diagnosis and treatment has been shown to be linked to poor functional health, but association for other cancers is less well understood.

“Given that cancer survivors are living longer than ever, understanding how the diagnosis and treatment of a broad range of cancers may affect ambulatory function–a potentially modifiable risk factor–could lead to new treatment and rehabilitation strategies to improve the health of these patients,” explained Elizabeth Salerno, PhD, MPH, assistant professor of surgery at Washington University School of Medicine.

Using data from self-reported questionnaires from the National Institutes of Health American Association of Retired Persons (AARP) Diet and Health Study, Dr Salerno and her team compared 30 403 cancer survivors to 202 732 individuals with no cancer diagnosis.

They found that cancer survivors were 42% more likely to walk at a slower pace than those without cancer diagnosis, and 24% more likely to have mobility disability after adjusting for factors such as weight. Those with slower walking or mobility disability were at greater risk for cancer-specific and all-cause mortality. The strongest association was seen for oral and respiratory cancers. Cancer survivors also had a stronger association with mortality and slower walking speeds than those without cancer diagnosis.

“Our findings suggest that functional health may be adversely affected by a broad range of cancer diagnoses and may be an important determinant for survival,” said Dr Salerno. “There is still much to be learned about these complex relationships, but our results highlight the potential importance of monitoring, and even targeting, ambulatory function after cancer for survival benefits, particularly in older cancer survivors.”

Salerno’s team will try to determine why some cancers were more associated with reduced mobility and mortality. “More information about behavioral, biological, and cancer-specific factors from before, during, and after diagnosis and treatment will be important to better characterize these associations in specific cancer types,” she said.

Source: Eureka Alert

New Biomarker Can Predict Response to Checkpoint Inhibitor Therapy

A team of researchers at Roswell Park Comprehensive Cancer Center have identified a biomarker that could be used to predict how well immune checkpoint inhibitors will be tolerated.

Immune checkpoint inhibitors (ICI) activate anti-tumour defences either through the disruption of inhibitory interactions between antigen-presenting cells and T cells at so-called checkpoints or else through the stimulation of activating checkpoints. Not all patients can tolerate ICI well; side effects can be severe, including colitis, which is one of the most common.

Pre-treatment biomarkers are of limited value in predicting response to ICI. Tumour biopsy shortly after ICI therapy is started can provide helpful information, but is invasive and difficult to do in some certain cancers.
Uncovering blood-based biomarkers that reflect the change of the tumour microenvironment and can predict a patient’s response to ICIs could improve current treatment regimens significantly, Dr. Ito notes. The team’s previous research indicates that T cells with varying levels of the chemokine receptor CX3CR1 responded differently to ICI therapy.

Based on those findings, the researchers sought to test CX3CR1 as a T cell biomarker in ICI therapy. They found that ICI therapy is linked to increased frequency and clonality of some CX3CR1-positive T cells; that the frequency of these CD8+ T cells stays high during ICI therapy; and that there are many genomic similarities between CD8+ tumour-infiltrating lymphocytes and this subset of CX3CR1-positive T cells.

Fumito Ito, MD, PhD, FACS, explained: “Although ICIs revolutionized the cancer treatment for significant numbers of people, many cancer patients do not respond to them, and some develop severe toxicity.”

“Currently, we are in need of a better biomarker to predict the response to immunotherapy, which is part of standard treatment in advanced and metastatic lung cancer,” said Hongbin Chen, MD, PhD. “This study sheds light on a promising blood-based biomarker that is potentially very useful in identifying which patients with lung cancer are most likely to benefit from immunotherapy. We look forward to investigating its utility in further clinical research.”

Source: News-Medical.Net

Journal information: Yamauchi, T., et al. (2021) T-cell CX3CR1 expression as a dynamic blood-based biomarker of response to immune checkpoint inhibitors. Nature Communications.doi.org/10.1038/s41467-021-21619-0.

A Natural Compound for Male Contraception

Researchers have isolated a natural compound found in a Chinese Herb that can reversibly induce male sterility.

The compound, triptonide, can be either purified from a Chinese herb called Tripterygium Wilfordii Hook F, or produced through chemical synthesis. It is being investigated for application in various cancers.

Single daily oral doses of triptonide induce altered sperm having minimal or no forward motility with close to 100% penetrance and consequently male infertility in 3-4 and 5-6 weeks. Fertility is restored within 4-6 weeks, and no toxic effects were observed even over the long term. 

Analysis suggested that triptonide targets one of the last steps during sperm assembly, leading to the production of altered sperm with limited motility.

“Thanks to decades of basic research, which inspired us to develop the idea that a compound that targets a protein critical for the last several steps of sperm assembly would lead to the production of nonfunctional sperm without causing severe depletion of testicular cells,” said Dr Yan. “We are very excited that the new idea worked and that this compound appears to be an ideal male contraceptive. Our results using non-injurious studies on lower primates suggest triptonide will be an effective treatment for human males as well. Hopefully, we will be able to start human clinical trials soon to make the non-hormonal male contraceptive a reality.”

“Dr Yan’s discovery represents a major leap forward in the field,” said Drs Christina Wang and Ronald Swerdloff, who are TLI co-Principal Investigators helping lead NIH-supported advanced clinical trials on hormone-based birth control approaches. “The more contraceptive methods available, the better, as we will want a family of pharmaceutical products to safely and effectively meet the family planning needs of men and couples at different stages of their reproductive lives, with differing ethnic, cultural and religious backgrounds and economic means,” they concluded.

Source: Medical Xpress

Golf Shines as Physical Activity for Parkinson’s Patients

Putter and golf balls on golf course. Photo by Robert Ruggiero on Unsplash.

In a study comparing physical activity routine for Parkinson’s patients, golf produced greater improvements than tai chi. 

Previous studies had shown that tai chi practice was beneficial as physical activity for Parkinson’s patients, resulting in balance and mobility gains, and is also safe and popular with patients.

“We know that people with Parkinson’s disease benefit from exercise, but not enough people with the disease get enough exercise as therapy,” said study author Anne-Marie A. Wills, MD, of Massachusetts General Hospital Boston. “Golf is popular—the most popular sport for people over the age of 55—which might encourage people to try it and stick with it. We decided to compare golf to tai chi in our study because tai chi is the gold standard for balance and preventing falls in people with Parkinson’s.”

The study involved 20 people with moderate Parkinson’s disease, who were offered 10 weeks of two one-hour group classes a week, randomly assigned to either golf or tai chi.

Researchers evaluated everyone with tests, including ones for mobility. For the test, a person is timed while getting up from a chair, walking 3m and then returning to the chair and sitting down. Golfers were 0.96 seconds faster on the test at the end of the study.

“While the results for golf might be surprising, it’s important to remember that the number of participants in our study was small, and the period over which we studied them was relatively short,” Dr Wills said. “More research in larger groups of people, over longer periods of time, is needed.”

While overall satisfaction was similar in both groups, 86% of golfers compared to 33% of tai chi participants were “definitely” likely to continue the activity.

“Our finding that golfers were much more likely to continue with their sport is exciting because it doesn’t matter how beneficial an exercise is on paper if you people don’t actually do it,” Dr Wills said. “So if swinging a golf club is more appealing than practicing tai chi, by all means, go to a driving range and hit balls for an hour instead!”

Source: Medical Xpress

Scientist Issues Stark Warning on Brazil’s COVID Response

If Brazil continues to let COVID rage unchecked, it risks deadly new variants emerging to threaten the global community, a Duke University neuroscientist in Brazil told The Guardian.

Miguel Nicolelis urged the international community to put pressure on the Brazilian government, which has made little effort to manage its COVID outbreak which has so far left a quarter of a million Brazilians dead. Brazil’s COVID deaths amount to one tenth of the world’s total.

“The world must vehemently speak out over the risks Brazil is posing to the fight against the pandemic,” said Nicolelis who has spent much of the lockdown in his São Paulo flat.

“What’s the point in sorting the pandemic out in Europe or the United States, if Brazil continues to be a breeding ground for this virus?”

He said: “It’s that if you allow the virus to proliferate at the levels it is currently proliferating here, you open the door to the occurrence of new mutations and the appearance of even more lethal variants.”

Manaus, the largest city in the Brazilian Amazon, has already seen the emergence of a deadly, highly transmissible variant, P1, six cases of which have been detected in the UK already. The new variant with its “unique constellation of mutations” may also evade immunity, scientists have warned.

“Brazil is an open-air laboratory for the virus to proliferate and eventually create more lethal mutations,” Nicolelis said. “This is about the world. It’s global.”

The warning comes as hospitals around Brazil are on the verge of collapse, with a record 1726 daily deaths recorded on Tuesday.

“We’ve now gone past 250 000 deaths, and my expectation is that if nothing is done we could have lost 500 000 people here in Brazil by next March. It’s a horrifying and tragic prospect, but at this point it’s perfectly possible,” he said.

Nicoleis puts the blame squarely upon Brazil’s far right President Jair Bolsonaro. “The policies that he is failing to put into practice jeopardise the fight against the pandemic in the entire planet.”

José Gomes Temporão, who was the health minister during the 2009 swine flu pandemic, said Bolsonaro and others would have to be held accountable for their poor response.

“To this day, Brazil doesn’t have a national plan to combat COVID,” Temporão complained, criticising Bolsonaro’s failure to secure sufficient vaccines for Brazil. 

“I don’t think there is any other leader who is so obtuse, so backward, who has such a mistaken and warped vision of reality as the president of Brazil,” Temporão said. “History will condemn these people.”

Source: The Guardian