Tag: 15/9/21

Categories : Cancer Medical Research & TechnologyTags :

Plant Virus-based Treatment Protects Against Lung Tumours

On By ModernMedia
Image source: CDC/Unsplash

Using a virus that grows in black-eyed pea plants, nanoengineers developed a new treatment that could keep metastatic cancers at bay from the lungs. 

Not only did the treatment slow tumour growth in the lungs of mice with either metastatic breast cancer or melanoma, it also prevented or drastically minimised the spread of these cancers to the lungs of healthy mice that were challenged with the disease. The research was published in Advanced Science.

Researchers developed an experimental treatment that combats metastatic spread. This involves a plant virus called the cowpea mosaic virus, harmless to animals and humans, but which the body still registers as a foreign invader, thus triggering an immune response that could also boost the body’s cancer-fighting ability.

The idea is to use the plant virus to help the body’s immune system recognise and destroy cancer cells in the lungs. The virus itself is not infectious in our bodies, but it has all these danger signals that alarm immune cells to go into attack mode and search for a pathogen, said Nicole Steinmetz, professor of nanoengineering at the University of California San Diego.

To draw this immune response to lung tumours, Prof Steinmetz’s lab engineered nanoparticles made from the cowpea mosaic virus to target a protein in the lungs. The protein, called S100A9, is expressed and secreted by immune cells that help fight infection in the lungs. Overexpression of S100A9 has been observed to play a role in tumour growth and spread.

“For our immunotherapy to work in the setting of lung metastasis, we need to target our nanoparticles to the lung,” said Prof Steinmetz. “Therefore, we created these plant virus nanoparticles to home in on the lungs by making use of S100A9 as the target protein. Within the lung, the nanoparticles recruit immune cells so that the tumors don’t take.”

“Because these nanoparticles tend to localise in the lungs, they can change the tumor microenvironment there to become more adept at fighting off cancer — not just established tumors, but future tumors as well,” said Eric Chung, a bioengineering PhD student in Steinmetz’s lab who is one of the co-first authors on the paper.

To make the nanoparticles, the researchers infected black-eyed pea plants with cowpea mosaic virus, and harvested the virus in the form of ball-shaped nanoparticles. They then fixed S100A9-targeting molecules to the particles’ surfaces.

The researchers performed both prevention and treatment studies. In the prevention studies, they first injected the plant virus nanoparticles into the bloodstreams of healthy mice, and then later injected either triple negative breast cancer or melanoma cells into these mice. Treated mice showed a dramatic reduction in the cancers spreading to their lungs compared to untreated mice.

In the treatment studies, the researchers administered the nanoparticles to mice with metastatic tumours in their lungs. The treated mice exhibited smaller lung tumours and survived longer than untreated mice.

Prof Steinmetz envisions that the treatment could be useful after tumourectomy. “It wouldn’t be meant as an injection that’s given to everyone to prevent lung tumours. Rather, it would be given to patients who are at high risk of their tumors growing back as a metastatic disease, which often manifests in the lung. This would offer their lungs protection against cancer metastasis,” she said.

More detailed immunotoxicity and pharmacology studies are needed before this can progress to a treatment. Future studies will also explore combining this with standard cancer therapies such as chemotherapy.

Source: University of California – San Diego

Categories : Diseases, Syndromes and ConditionsTags :

Immune System Mutation Found in Tree-man Syndrome

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Cryo-electron microscopy structure of the human papillomavirus. Source: Wikimedia Commons CC0

A new study explores why some extremely rare cases of human papilloma virus (HPV) infections cause horn-like growths on the skin, a condition known as tree-man syndrome. 

Infection with HPV is extremely common, with most people catching it at some point and not even being aware of it due to a robust immune response, though some may experience skin or genital warts. Why only a handful of individuals react to it by developing tree-man syndrome was not well understood.

To find out why this strikes a handful and not others, Rockefeller’s Jean-Laurent Casanova examines the genetics of an otherwise healthy patient who contracted a severe case of tree-man syndrome and several family members who exhibited milder reactions to HPV. Casanova’s team identified a mutation that affects one’s reaction to HPV by decreasing the production of CD28, a molecule within the immune system that plays an important role in activating pathogen-fighting T cells.

Given the purported importance of CD28 to the immune system, the scientists were surprised that this CD28-deficient individual was healthy prior to contracting tree-man syndrome. “CD28 is thought of as a pillar of T cell immunity,” says Casanova. “The fact that this patient was otherwise healthy suggests that CD28 is largely redundant in human health. Something else is able to step up to provide protection against other infections.”

The findings, published in Cell, form a small part of Casanova’s larger work, which continues to demonstrate that the severity of  influenza, tuberculosis, COVID, and other diseases, is not solely dependent on the pathogen itself, but on genetics of the host, too.

Source: Rockerfeller University

Categories : Cardiovascular DiseaseTags :

Study Links Poor Sleep to Arrhythmias

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Photo by Cottonbro on Pexels

A large observational study linked poor sleep to arrhythmias, although genetic risk factors for rhythm problems appeared to lessen the association.

The results, published in the American College of Cardiology, show that best self-reported sleeps (getting 7-8 hours etc) had a 29% lower risk of developing atrial fibrillation or flutter and a 35% lower risk of bradyarrhythmia compared with those with the worst sleep patterns (eg, being a night owl, sleeping too little, snoring, and having insomnia or daytime drowsiness).

The ventricular arrhythmia risk fell away after demographic, lifestyle, and genetic risk factors were accounted for.

Together with previous research linking a healthy sleep pattern to reduced cardiovascular disease and heart failure risks, the findings, according to the researchers, “emphasise the importance of improving the overall sleep behaviours in the prevention of cardiovascular disease at an early stage among the high-risk populations”.

Being reversible, the findings support the idea of better sleep for arrhythmia prevention.

“However, rest assured, we must not yet lose sleep over their findings,” cautioned Alan Kadish, MD, and Jason Jacobson, MD, in an accompanying editorial. They drew attention to a number of limitations, making the findings more theoretical than currently practicable.

Despite the study’s more sophisticated approach, “a major limitation is that arrhythmia diagnoses were obtained from diagnostic codes,” they noted. Furthermore, arrhythmias are subject to significant variability.
Arrhythmia prevention doesn’t mean cardiovascular disease prevention, they added. “[N]ot all arrhythmias have the same significance, and many are the consequence (not cause) of cardiovascular disease,” they wrote. “Alternatively, sleep disorders and arrhythmias may both simply be indicators of declining health overall and not causally linked.”

The researchers proposed potential mechanisms of action including disrupted autonomic nervous balance of sympathetic nervous and vagal outflows and metabolic changes.

The editorialists pointed out the interesting finding that genetic predisposition to atrial fibrillation significantly modified the associations. Good self-reported sleep and low genetic risk together presented a 46% lower risk of atrial fibrillation than a poor sleep pattern plus high genetic risk.

Progressively poorer sleep health scores were associated with higher incidences of atrial fibrillation and bradyarrhythmias.

Sleeping 7 to 8 hours per day, infrequent or no insomnia, and no frequent daytime sleepiness were each linked to lower arrhythmia risk.

Source: MedPage Today

Categories : CancerTags :

Second or Third-degree Relatives Still Share Colon Cancer Risk

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Colon cancer cells. Source: National Cancer Institute on Unsplash

A new study has found that having second- or third-degree relatives with colorectal cancer increases a person’s risk of developing the disease.

Early colonoscopy screening is often recommended for first-degree relatives of someone diagnosed with early-onset (before age 50) colorectal cancer, cases of which have been increasing significantly over the past few decades. But the study suggests that early screening may be beneficial for second- and third-degree relatives as well.

The study reviewed more than 1500 early-onset colon cancer cases in the Utah Cancer Registry,found that first-degree relatives of someone diagnosed with early-onset colorectal cancer are 6 times more likely to be diagnosed with colorectal cancer before age 50, while second-degree relatives (aunts, grandparents etc) are 3 times likelier and third-degree relatives (first cousins etc) 1.56 times likelier.

“Our study provides new insight into the magnitude of risk for more distant relatives of colorectal cancer cases, and in particular, for relatives of cases who were diagnosed before age 50,” said first author Heather Ochs-Balcom, associate professor of epidemiology and environmental health, UB School of Public Health and Health Professions. “This work is important given the rising rates of early-onset colorectal cancer.”

There was also 2.6-fold higher risk of colorectal cancer at any age if they have a first-degree relative with early-onset colon cancer. The risk is 1.96 and 1.3 times greater for second- and third-degree relatives, respectively. In addition, the risk for all degrees of relatives for early-onset colon cancer is higher than the risk for colon cancer at any age.

The findings, published in Cancer Epidemiology, suggest that early colonoscopy screening may be beneficial for second-degree relatives and possibly third-degree relatives, in addition to first-degree relatives of individuals diagnosed with colorectal cancer before age 50.

The researchers also point out that relatives may benefit from being more aware of their extended family history and sharing this information with their physician when making cancer-screening decisions.

Source: University at Buffalo

Categories : Cardiovascular Disease Medical Research & TechnologyTags :

Is Heart Pump Development Dead in the Water?

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Photo by Robina Weermeijer on Unsplash

At an annual meeting of the Heart Failure Society of America (HFSA), heart failure specialists agreed that recalling the HeartWare heart pump was good but debated whether its departure leaves the field of mechanical circulatory support (MCS) dead in the water.

In June, Medtronic stopped sales of its HeartWare Ventricular Assist Device (HVAD), citing excess neurological events and mortality with the device. As a result, Abbott’s HeartMate 3 became the only FDA-approved, durable left ventricular assist device (LVAD) on the market.

“Competition breeds innovation. When competition is absent or minimal, there is little incentive for corporations to innovate,” said Jennifer Cowger, MD, MS, of Henry Ford Hospital in Detroit, during the annual scientific meeting.

“While I believe the removal of the HVAD from the market was the ethical thing to do, unless we as a field start embracing MCS technology and change our messaging to the general cardiology community, our field is going to be viewed as niche to referring cardiologists and we’re going to face irrelevance and we’re going to have bad times ahead,” she added.

However Nancy Sweitzer MD, PhD, of the University of Arizona in Tucson, disagreed, pointing out that there are plenty of advances on the horizon.

Nine companies worldwide are developing heart pumps for this $3-4 billion market, Dr Sweitzer noted. Several devices under investigation — implantable ones with no external component — will probably proceed to first-in-man trials in the next year, she said. “There’s a lot of money if you do this well,” she added

Internal competition alone may be enough to advance the field, Sweitzer argued, citing Thoratec’s HeartMate II superseding their old HeartMate XVE.

“They put their own device up against their own device. So I would argue that corporate competition isn’t necessary when the stakeholders realize that we need to get better at this. I think the companies in this space realize there’s a huge unmet need here if we develop a really good MCS that was truly portable, gave people excellent quality of life, and had lower complications,” she said.

Yet given the pace of LVAD research, “in the next decade, we have cause for concern in the MCS field,” Dr Cowger countered.

Both debaters suggested that MCS technology shouldn’t stop at HeartMate 3, even with its relatively impressive performance.

“Outcomes on HeartMate 3 are not the outcomes we really want for these patients. There are still innumerable complications. Hospitalization rates are extraordinarily high in these patients post-implant even if they’re successful implants. They bleed, they get infected, they get strokes. That still happens,” noted Dr Sweitzer.

Innovation issues aside, Dr Cowger pointed out that HeartMate 3 is also much larger than the HVAD, and the smaller device’s loss leaves a gap for patients. She said negative media views had not helped the recent “sense of apathy and loss of enthusiasm for MCS”.

“Physicians don’t want to use technology that will harm or be perceived to harm patients,” she said, noting that sentiment has shifted from “VADs are sexy, cool” to “we would not choose LVADs over [heart] transplant.”

Source: MedPage Today

Categories : Neurodegenerative DiseasesTags :

Antioxidant Trial for Parkinson’s Disease Flops

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Source: Pixabay

Raising brain levels of the natural antioxidant urate through ionosine administration failed to slow the progression of Parkinson’s disease (PD), reported researchers at Massachusetts General Hospital (MGH).

Still, the rigor of the clinical study and some of its novel investigative approaches are seen as improving the prospects for future clinical trials to demonstrate the benefits of disease-modifying therapies for people with Parkinson’s disease. The results were published in JAMA.

“The convergence of epidemiological, biological, and clinical data from past research made a compelling argument that elevating urate, the main antioxidant circulating in the blood, could protect against the oxidative damage thought to play a role in Parkinson’s disease,” explained senior author Michael Schwarzschild, MD, PhD, a neurologist at MGH. “While our study did not rule out a protective effect of urate in Parkinson’s, it clearly showed that increasing urate did not slow disease progression based on clinical assessments and serial bran scan biomarkers of neurodegeneration.”

So far, no treatment has been shown to prevent or forestall progression of Parkinson’s disease, which affects the body’s motor system. The Phase III trial, SURE-PD3, enrolled 298 individuals recently diagnosed with early Parkinson’s disease based on MRI scans indicating loss of dopamine-producing brain cells characteristic of PD. In participants who received the metabolite inosine — which raises levels of urate in the brain and blood and has shown neuroprotective properties in preclinical models — there was no significant difference in the rate of disease progression compared to placebo. Additionally, there was an increased rate of kidney stones among those randomised to inosine treatment.

Despite the lack of evidence to support urate elevation, Dr Schwarzschild found the study successful in other ways. “The findings were very helpful in providing a reality check that now allows the field to move on to other therapeutic approaches,” he explained. “We also learned a lot in terms of clinical trials science for Parkinson’s, and ways to conduct future studies that will increase their chance of success.” One of those ways is to tailor treatment to subsets of patients who are most likely to benefit – a hallmark of the move to precision medicine in Parkinson’s research. In SURE-PD3, for example, only patients who had lower levels of urate were enrolled to increase the chance of benefit and reduce the chance of side effects.

Another innovative feature of the trial is that many participants gave blood samples for genotyping – a valuable source of genetic information that could figure in the hunt for clinical solutions in smaller subpopulations of PD patients. A significant number also volunteered for an extension of the study to help determine how monitoring at home could provide more efficient ways to conduct future clinical trials. “There were many positive results from SURE-PD3 which we believe will improve the prospects of researchers discovering a disease-modifying therapy which people with Parkinson’s have been desperately seeking,” Dr Schwarzschild concluded.

Source: Massachusetts General Hospital