Tag: non-human primates

Categories : CancerTags :

Why Humans Are More Susceptible to Cancers than Other Primates

On By ModernMedia
Photo by Andre Mouton on Unsplash

New research from UC Davis Comprehensive Cancer Center has uncovered an evolutionary change that may explain why certain immune cells in humans are less effective at fighting solid tumours compared to non-human primates. The findings, published in Nature Communications, could lead to more powerful cancer treatments.

The study revealed a tiny genetic difference in an immune protein called Fas Ligand (FasL) between humans and non-human primates. This genetic mutation makes the FasL protein vulnerable to being disabled by plasmin, a tumour-associated enzyme. This vulnerability seems unique to humans and is not found in non-human primates, such as chimpanzees.

“The evolutionary mutation in FasL may have contributed to the larger brain size in humans,” said Jogender Tushir-Singh, senior author for the study and an associate professor in the Department of Medical Microbiology and Immunology. “But in the context of cancer, it was an unfavourable tradeoff because the mutation gives certain tumours a way to disarm parts of our immune system.”

Tumour environment neutralises key immune protein

FasL is an immune cell membrane protein that triggers apoptosis, which activated immune cells, including CAR-T cells, make use of to kill cancer cells.

The UC Davis team discovered that in human genes, a single evolutionary amino acid change — serine instead of proline at position 153 — makes FasL more susceptible to being cut and inactivated by plasmin.

Plasmin is a protease enzyme that is often elevated in aggressive solid tumours like triple negative breast cancer, colon cancer and ovarian cancer.

This means that even when human immune cells are activated and ready to attack the tumour cells, one of their key apoptosis tools, FasL, can be neutralised by the tumour environment, reducing the effectiveness of immunotherapies.

The findings may help explain why CAR-T and T-cell-based therapies can be effective in blood cancers but often fall short in solid tumours. Blood cancers often do not rely on plasmin to metastasise, whereas tumours like ovarian cancer rely heavily on plasmin to spread the cancer.

Plasmin inhibitors may enhance immunotherapy

Significantly, the study also showed that blocking plasmin or shielding FasL from cleavage can restore its cancer-killing power. That finding may open new doors for improving cancer immunotherapy.

By combining current treatments with plasmin inhibitors or specially designed antibodies that protect FasL, scientists may be able to boost immune responses in patients with solid tumours.

“Humans have a significantly higher rate of cancer than chimpanzees and other primates. There is a lot that we do not know and can still learn from primates and apply to improve human cancer immunotherapies,” said Tushir-Singh. “Regardless, this is a major step toward personalising and enhancing immunotherapy for the plasmin-positive cancers that have been difficult to treat.”

Source: UC Davis Cancer Center

Categories : AgeingTags :

Unlike Humans, Lemurs Do Not Experience ‘Inflammaging’

On By ModernMedia
This lemur is called Nemesis and lives at the Duke Lemur Center

What can lemurs tell us about inflammation and aging, aka “inflammaging” in humans? That’s the question Elaine Guevara, a biological anthropologist who studies the evolution of life history and aging in primates, set out to understand.

In newly published research on age-related inflammation in ring-tailed and sifaka lemurs, Guevara discovered that perhaps we should rethink the inevitability of inflammaging in humans.

Although similar in many ways, ring-tailed and sifaka lemurs show differences in life pacing and lifespan, making useful comparisons. Because lemurs and humans are primates and share a common ancestor that lived millions of years ago, they offer valuable insights into human evolution.

Her findings, which are published in the Journal of Comparative Physiology B, were “surprising”, she said.

“Contrary to our predictions, neither species showed age-related change in either marker of oxidative stress. Neither lemur species exhibited age-related change in inflammation; if anything, contrary to our prediction, ring-tailed lemurs showed marginal declines in inflammation with age,” Guevara said.

This finding, consistent with a few recent studies of other non-human primates, suggests that lemurs avoid the phenomenon of “inflammaging” widely observed in humans.

The study shows inflammaging is not a universal feature of primates, pointing to some differences that might suggest it turns out it’s not even a universal feature of humans, according to Christine Drea, a professor of evolutionary anthropology who was one of the researchers working with Guevara.

What is Inflammaging?

As we grow older, low-grade chronic inflammation sets in, which in turn can cause health problems such as heart disease, strokes, diabetes, cancer and osteoarthritis.

Why inflammaging increases with age in humans, what causes it and how it can be prevented are answers to questions that can unlock critical information to help humans live longer and healthier lives.

Collecting Data from Lemurs

Drea said the team first had to find a way to measure oxidative stress, which can be found in blood, urine and saliva. They settled on urine.

“Our role at the beginning was planning, designing, brainstorming, comparing and getting these samples,” said Drea, who has worked with the Duke Lemur Center since 1999. The Lemur Center does not allow research that will harm the animals.

The next step says Guevara is to conduct similar research with lemurs in the wild.

“There are a lot of good reasons to think that aging can be quite different in captivity and in the wild, and that in itself, is informative to evaluating the degree to which human inflammation is intrinsic versus environmental,” she said.

In the meantime, Guevara says this study serves as the first step in unravelling the question of why humans are suffering from inflammatory-related and age-related conditions and finding ways to treat them.

With a rapidly aging global population, “these insights are essential for mitigating disability and improving quality of life in later years,” she said.

Source: Duke University

Categories : General Interest Medical Research & TechnologyTags :

Researchers Spot Chimpanzees Using Medicinal Leaves to Perform First Aid

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Social grooming between two chimpanzees in the Budongo Forest. Photograph by Dr Elodie Freymann.

Researchers monitoring chimpanzee communities in the Budongo Forest, Uganda, noticed that individuals were helping each other with wound care and hygiene. Some of the chimpanzees even used fresh, chewed leaves from plants known for their traditional medicinal uses and bioactive properties to treat their own and their companions’ wounds. Remarkably, they helped individuals they were genetically related to and individuals they weren’t, despite the potential risk from being exposed to pathogens. Researchers believe these findings could help us understand the cognitive and social foundations of healthcare. 

Researchers studying chimpanzees in Budongo Forest, Uganda, have observed that these primates don’t just treat their own injuries, but care for others, too – information which could shed light on how our ancestors first began treating wounds and using medicines. Although chimpanzees elsewhere have been observed helping other community members with medical problems, the persistent presence of this behaviour in Budongo could suggest that medical care among chimpanzees is much more widespread than we realised, and not confined to care for close relatives.  

“Our research helps illuminate the evolutionary roots of human medicine and healthcare systems,” said Dr Elodie Freymann, research affiliate at the School of Anthropology and Museum Ethnography, Oxford University, first author of the article in Frontiers in Ecology and Evolution. “By documenting how chimpanzees identify and utilise medicinal plants and provide care to others, we gain insight into the cognitive and social foundations of human healthcare behaviours.” 

The researchers studied two communities of chimpanzees in the Budongo Forest – Sonso and Waibira. Like all chimpanzees, members of these communities are vulnerable to injuries, whether caused by fights, accidents, or snares set by humans. About 40% of all individuals in Sonso have been seen with snare injuries. 

The researchers spent four months observing each community, as well as drawing on video evidence from the Great Ape Dictionary database, logbooks containing decades of observational data, and a survey of other scientists who had witnessed chimpanzees treating illness or injury. Any plants chimpanzees were seen using for external care were identified; several turned out to have chemical properties which could improve wound healing and relevant traditional medicine uses. 

During their direct observational periods, the researchers recorded 12 injuries in Sonso, all of which were likely caused by within-group conflicts. In Waibira, five chimpanzees were injured – one female by a snare, and four males in fights. The researchers also identified more cases of care in Sonso than in Waibira. 

“This likely stems from several factors, including possible differences in social hierarchy stability or greater observation opportunities in the more thoroughly habituated Sonso community,” said Freymann. 

The researchers documented 41 cases of care overall: seven cases of care for others – prosocial care – and 34 cases of self-care. These cases often included several different care behaviours, which might be treating different aspects of a wound, or might reflect a chimpanzee’s personal preferences.  

“Chimpanzee wound care encompasses several techniques: direct wound licking, which removes debris and potentially applies antimicrobial compounds in saliva; finger licking followed by wound pressing; leaf-dabbing; and chewing plant materials and applying them directly to wounds,” said Freymann. “All chimpanzees mentioned in our tables showed recovery from wounds, though of course we don’t know what the outcome would have been had they not done anything about their injuries.  

“We also documented hygiene behaviours, including the cleaning of genitals with leaves after mating and wiping the anus with leaves after defecation – practices that may help prevent infections.” 

Of the seven instances of prosocial care, the researchers found four cases of wound treatment, two cases of snare removal assistance, and one case where a chimpanzee helped another with hygiene. Care wasn’t preferentially given by, or provided to, one sex or age group. On four occasions, care was given to genetically unrelated individuals.  

“These behaviours add to the evidence from other sites that chimpanzees appear to recognise need or suffering in others and take deliberate action to alleviate it, even when there’s no direct genetic advantage,” said Freymann. 

The researchers call for more research into the social and ecological contexts in which care takes place, and which individuals give and receive care. One possibility is that the high risk of injury and death which Budongo chimpanzees all face from snares could increase the likelihood that these chimpanzees care for each other’s wounds, but more data is needed to explore this.  

“Our study has a few methodological limitations,” cautioned Freymann. “The difference in habituation between the Sonso and Waibira communities creates an observation bias, particularly for rare behaviours like prosocial healthcare. While we documented plants used in healthcare contexts, further pharmacological analyses are needed to confirm their specific medicinal properties and efficacy. Also, the relative rarity of prosocial healthcare makes it challenging to identify patterns regarding when and why such care is provided or withheld. These limitations highlight directions for future research in this emerging field.” 

Source: Oxford University

Categories : COVID Medical IndustryTags :

Another Shortage Created by COVID: Macaques for Research Purposes

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The pharmaceutical industry is facing a serious challenge as it struggles to source enough non-human primates (NHPs) such as macaques for research and testing. Alongside demand created by HIV/AIDS research, the pandemic has tightened supplies of the animals further as China, a major supplier, has clamped down on exports.

Since NHPs have great genetic and physiological similarity to humans, scientists use these animals, most commonly rhesus macaques, to study medical conditions and conduct trials which are not yet possible in humans. In 2019, US scientists used 68 257 NHPs in research, according to US government data.

As a result of this shortage, many projects may not be able to be completed, according to industry insiders, with implications for medical research. Pre-pandemic prices of $11 000 per macaque have risen to $35 000.

In July last year, Nature reported that the US government pledged to increase funding to make primates available for clinical research. However, this would not do anything to address the current shortage.

To make room for more NHPs, the US National Institutes of Health (NIH) has invested about US$29 million to refurbish housing, build outdoor enclosures and making other infrastructure improvements at the US National Primate Research Centers (NPRCs), which it funds. 

“A couple of years ago, we were feeling the pinch,” Nancy Haigwood, director of the Oregon NPRC in Beaverton, which houses about 5 000 non-human primates. But because of the pandemic, “we are truly out of animals”, she told Nature. “We’re turning away everyone.”

China had been a cheap source of cynomolgus macaques (Macaca fascicularis) since 1985, but in 2013 began to prioritise local research, restricting exports. Adding to this was soaring demand was sparked by multiple NIH grants awarded in 2016 to study HIV/AIDS, according to a 2018 report. Housing and feeding NHPs is costly, and NPRCs could not expand due to budget caps. The report warned of a coming shortage of various primates in coming years.

The situation has drawn the public’s attention – and opposition. Complaints made to airlines has resulted in many no longer carrying the animals, making transportation a major challenge. Air France was one of the last holdouts, and last year said it would stop carrying NHPs for research purposes.

With the arrival of the pandemic and the need for NHP research and testing, vaccine research was naturally prioritised, while trying to supply other projects as well.

When COVID hit, China completely suspended exports of macaques, hitting pharmaceutical companies hardest, which prefer that species for drug trials. Even if the export ban were to be lifted, the Chinese demand for macaques in research is so high that there would be few available for export: of 30 000 macaques that became suitable for use in research last year, 28 000 were used.

Other restrictions constrain the supply, such as a European Union requirement that all non-human primates for research come from self-sustaining colonies by November this year. The UK also carried through this directive following its exit from the EU.