Day: February 17, 2022

Categories : CancerTags :

Researchers Halt Aspirin Trial to Prevent Breast Cancer Recurrence

On By ModernMedia
Source: National Cancer Institute

A large randomised trial was halted after preliminary analysis found that taking aspirin after treatment for breast cancer did not reduce the risk of disease recurrence.

Laboratory studies had previously shown that aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) reduced breast cancer growth and invasion. Non-steroidal anti-inflammatory drugs (NSAIDs) display anticancer activity through the inhibition of the COX-2 enzyme, triggering processes such as apoptosis, a reduction in proliferation and inhibition of carcinogenesis.  Several observational studies have shown a reduced risk of breast cancer mortality among regular aspirin users. 

There was a 25% higher risk of invasive recurrence in patients who took aspirin for a median of 18 months, but not statistically different from placebo (P = 0.1258). The aspirin group had an excess of all disease-related events, including death, local and distant recurrence/progression, and new primary tumours.

The results are in line with similar trials that ended while the Aspirin after Breast Cancer (ABC) trial was ongoing, Wendy Y. Chen, MD, of Dana-Farber Cancer Institute in Boston, said during a presentation at the American Society of Clinical Oncology (ASCO) Plenary Series.

“In this double-blind, placebo-controlled randomised trial, there was no benefit of aspirin 300 milligrams daily in terms of breast cancer invasive disease-free survival,” reported Dr Chen. “Although follow-up was short, the futility bound was clearly crossed. We had reached 50% of the events, and there was a numerically higher number of events in the aspirin arm. Therefore, it was unlikely that even with further follow-up there wouldn’t be any benefit associated with aspirin.”

“Although inflammation may still play a key role in cancer, it’s important to remember that aspirin may have different effects in other cancers, such as colon, or in different settings, such as primary versus secondary prevention,” she added.

Though the trial was well designed, enrolled the right population and with adequate dosing. the trial was stopped early for futility, commented Angela DeMichele, MD, of the Abramson Cancer Center at the University of Pennsylvania.

“The direction and magnitude [of the difference in events] highly preclude the possibility that there would have been a benefit with more follow-up,” said Dr DeMichele. “Although it was not statistically significant, we cannot rule out the possibility of a potential increase in breast cancer recurrence from the use of aspirin.”

“For patients and providers at this time, aspirin should not be used simply to prevent breast cancer recurrence,” she continued. “For those situations in which there are other options, decisions about aspirin use for other indications should definitely include an individualised risk/benefit discussion between physician and patient.”

The results underscore the need for prospective, randomised clinical trials to validate the effects of interventions from observational studies, she concluded.

The ABC trial involved patients under 70 with HER2-negative, high-risk breast cancer. The study randomised 3021 participants to 300 mg of aspirin daily or matching placebo for 5 years, with the primary endpoint being invasive disease-free survival. 

Dr Chen further noted that three clinical trials of aspirin or NSAID treatment ended while the ABC trial was ongoing. The Canadian-led MA.27 trial of an aromatase inhibitor plus celecoxib ended due to toxicity in the celecoxib arm. The randomised REACT trial of celecoxib in HER2-negative breast cancer showed no difference in disease-free survival after more than 6 years of follow-up.

The ASPREE trial tested low-dose aspirin on all-cause mortality in healthy older patients, and results showed a trend to increased all-cause mortality and significantly higher cancer mortality in the aspirin arm. 
During the post-presentation discussion, an audience member asked whether the results definitively ruled out a late benefit of aspirin, given that most patients had HR-positive disease wherein late relapse is not uncommon.

“It’s always frustrating when a study is closed early, and it was done in this case after we had reached 50% of the expected benefits,” said Chen. “There was an increase [in clinical events]. Not a statistically significant increase, but it was bordering on statistical significance. In order for aspirin to have a benefit, it would mean that in the second half, there would need to be a significantly decreased risk. It would basically need to flip and that would be biologically difficult to imagine.”

“I think it’s fair to say that this study doesn’t say definitively that there’s harm, but as for the likelihood of a benefit of aspirin, that would be extremely unlikely,” she said.

Source: MedPage Today

Categories : Diseases, Syndromes and ConditionsTags :

In MS, Twin Study Reveals Disease-causing T Cells

On By ModernMedia
Source: Pixabay CC0

By studying the immune system of pairs of monozygotic twins to rule out genetics in cases of multiple sclerosis, researchers may have discovered a smoking gun: precursor cells of the disease-causing T cells.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system CNS and the most common cause of neurological impairment in young adults. In MS, the patient’s own immune system attacks the CNS, resulting in cumulative neurological damage. The cause of MS still unclear but a variety of genetic risk factors and environmental influences have already been linked to the disease.

Genetics have already been found to be a necessary condition for developing multiple sclerosis. “Based on our study, we were able to show that about half of the composition of our immune system is determined by genetics,” said Florian Ingelfinger, a PhD candidate at the UZH Institute of Experimental Immunology. The study shows that these genetic influences, while always present in MS patients, are not on their own sufficient to trigger multiple sclerosis. In the study, 61 pairs of monozygotic twins where one twin is affected by MS whereas the co-twin is healthy were examined. From a genetic point of view, the twins were thus identical. “Although the healthy twins also had the maximum genetic risk for MS, they showed no clinical signs of the disease,” said Lisa Ann Gerdes.

With this cohort of twins, the researchers were  tease out environmental differences. “We are exploring the central question of how the immune system of two genetically identical individuals leads to significant inflammation and massive nerve damage in one case, and no damage at all in the other,” explained Professor Burkhard Becher, leader of the research team. Using identical twins let the researchers block out the genetic influence and focus on the immune system changes that were ultimately responsible for triggering MS in one twin.

The researchers harnessed state-of-the-art technologies to describe the immune profiles of the twin pairs in great detail. “We use a combination of mass cytometry and the latest methods in genetics paired with machine learning to not only identify characteristic proteins in the immune cells of the sick twin in each case, but also to decode the totality of all the genes that are switched on in these cells,” Florian Ingelfinger explained. 

“Surprisingly, we found the biggest differences in the immune profiles of MS affected twins to be in the cytokine receptors, ie the way immune cells communicate with one another. The cytokine network is like the language of the immune system,” said Ingelfinger. Increased sensitivity to certain cytokines leads to greater T cell activation in the bloodsteams of patients with multiple sclerosis. These T cells are more likely to migrate into the CNS and cause damage there. The identified cells were found to have the characteristics of recently activated cells, which were in the process of developing into fully functional T cells. “We may have discovered the cellular big bang of MS here – precursor cells that give rise to disease-causing T cells,” said Prof Becher.

“The findings of this study are particularly valuable in comparison to previous studies of MS which do not control for genetic predisposition,” said Prof Becher. “We are thus able to find out which part of the immune dysfunction in MS is influenced by genetic components and which by environmental factors. This is of fundamental importance in understanding the development of the disease.”

The study findings were reported in Nature.

Source: University of Zurich

Categories : Regenerative MedicineTags :

Regenerating Bone with Messenger RNA

On By ModernMedia
Photo by Cottonbro on Pexels

Researchers have developed new way to get bone to regenerate with messenger RNA, which promises to be cheaper and less expensive while having fewer side effects than the current treatment.

Although fractures normally heal, bone will not regenerate under several circumstances. When bone does not regenerate, major clinical problems could result, including amputation.

One treatment is recombinant human bone morphogenetic protein-2, or BMP-2. However, it is expensive and only moderately effective. It also produces side effects, which can be severe.

Researchers at Mayo Clinic, along with colleagues in the Netherlands and Germany, may have a viable, less risky alternative: messenger RNA. 

A study conducted on rats and published in Science Advances, shows that messenger RNA can be used at low doses to regenerate bone – and without side effects. The resulting new bone quality and biomechanical properties are also superior to that of BMP-2. Additionally, messenger RNA is a good choice for bone regeneration because it may not need repeat administrations.

Human bone develops in one of two ways: direct formation of bone cells from mesenchymal progenitor cells, or through endochondral ossification, in which cartilage forms first and then converts to bone. The BMP-2 therapy uses the former method, and the messenger RNA approach uses the latter. In general, the researchers say their work proves that this method “can heal large, critical-sized, segmental osseous defects of long bones in a superior fashion to its recombinant protein counterpart.”

Further studies are required in larger animals than rats before any translation can be considered for clinical trials.

Source: Mayo Clinic

Categories : HospitalsTags :

A New Easy-to-Apply Antimicrobial Coating

On By ModernMedia
Image by Quicknews

Researchers have developed an inexpensive, non-toxic coating for almost any fabric that decreases the infectivity of SARS-CoV-2 by up to 90%. It could even be developed to be applied to fabric by almost anyone.

“When you’re walking into a hospital, you want to know that pillow you’re putting your head onto is clean,” said lead author Taylor Wright, a doctoral student at the University of British Columbia. “This coating could take a little bit of the worry off frontline workers to have Personal Protection Equipment with antimicrobial properties.”

Researchers soaked fabric in a solution of an antimicrobial polymer which contains a molecule that releases reactive oxygen species when light shines on it. They then used UV light to turn this solution to a solid, fixing the coating to the fabric. “This coating has both passive and active antimicrobial properties, killing microbes immediately upon contact, which is then amped up when sunlight hits the cloth,” said senior author Professor Michael Wolf.

Both components are safe for human use, and the entire process takes about one hour at room temperature, said Wright. It also makes the fabric hydrophobic, without sacrificing fabric strength. The researchers detailed their study in American Chemical Society Applied Materials & Interfaces.

The coating can also be used on almost any fabric, with applications in hospital fabrics, masks, and activewear. While other such technologies can involve chemical waste, high energy use, or expensive equipment, the UBC method is relatively easy and inexpensive, said Wright. “All we need is a beaker and a light bulb. I’m fairly certain I could do the whole process on a stove.”

To test the coating’s antimicrobial properties, the researchers bathed treated fabric in bacterial soups of Escherichia coli and Methicillin-resistant Staphylococcus aureus (MRSA). They found that 85% of viable E. coli bacteria remained after 30 minutes, which fell to three per cent when the treated cloth was exposed to green light for the same amount of time. Similarly, 95% of viable MRSA bacteria remained, dropping to 35% under green light. No bacteria remained after four hours.

While sunlight or fluorescent lights have a lesser percentage of green in their spectrums, the team expects similar but less intense results for fabric exposed to those light sources, said Wright. “Particularly in the Pacific Northwest, it’s not always a sunny day. So, at all times you’re going to have that layer of passive protection and when you need that extra layer of protection, you can step into a lit room, or place the fabric in a room with a green light bulb – which can be found for about $35 online.”

The researchers also looked into whether the coating reduced the infectivity of SARS-CoV-2 by bathing treated fabric in a solution of the virus particles and then adding that solution to living cells to see if they could infect them. They found the passive properties were ineffective against the virus, but when treated fabric was exposed to green light for two hours, there was up to a 90% drop in the virus’ infectivity. “In other words, only one tenth of the amount of virus signal was detected on cells infected with the UV-fabric and light treated virus”, says co-author Professor François Jean.

The team found they needed an 18cm2 piece of fabric to kill microbes with material containing 7% of the active ingredient by weight, but that increasing this to 23% increased the effectiveness of the fabric at four times less material, said Wright.

Researchers also found that keeping the fabric under green light for more than 24 hours failed to produce the sterilising forms of oxygen, highlighting an area for further study. This is a similar effect to the colour fading on clothing after being exposed to sunlight for too long.

“Biomanufacturing face masks based on this new UBC technology would represent an important addition to our arsenal in the fight against COVID, in particular for highly transmissible SARS-CoV-2 variants of concern such as Omicron”, said Prof Jean. The coating can also be used for activewear, with an ‘anti-stink’ coating applied to areas where people tend to sweat, killing off the bacteria that makes us smell. Indeed, hospital fabric and activewear companies are already interested in applying the technology, and the university has applied for a patent in the United States, said Prof Wolf.

Source: University of British Columbia