Certain types of light have proven to be an effective, minimally invasive treatment for cancers located on or near the skin when combined with a light-activated drug. But deep-seated cancers, surrounded by tissue, blood and bone, have been beyond the reach of light’s therapeutic effects.
This miniature, implantable LED device fights cancer with light.
To bring light’s benefits to these harder-to-access cancers, engineers and scientists at the University of Notre Dame have devised a wireless LED device that can be implanted. In combination with a light-sensitive dye, the device not only destroys cancer cells, but also rallies the immune system’s cancer-targeting response. The research was published in Photodiagnosis and Photodynamic Therapy.
“Certain colours of light penetrate tissue deeper than other ones,” said Thomas O’Sullivan, associate professor of electrical engineering and co-author on the paper. “It turns out that the kind of light – in this case green – that doesn’t penetrate as deeply has the capability of producing a more robust response against the cancer cells.”
Before the light can be effective in destroying cancer cells, a dye with light-absorbing molecules must be administered to the cells. The device turns on, the dye transfers the light into energy and that energy makes the cells’ own oxygen toxic – in effect, turning the cancer cells against themselves.
While other treatments also weaponise the cells’ own oxygen, this device causes a particularly serendipitous form of cell death.
“Working together, biochemistry graduate student Hailey Sanders and electrical engineering graduate student SungHoon Rho perceptively noted that the treated cells were swelling, which is the hallmark of a kind of cell death, pyroptosis, that’s particularly good at triggering the immune response,” said Bradley Smith, the Emil T. Hofman Professor of Science and co-author on the paper.
“Our goal is to induce just a little bit of pyroptotic cell death, which will then trigger the immune system to start attacking the cancer.”
In future studies, the device will be used in mice to see whether the cancer-killing response initiated in one tumour will prompt the immune system to identify and attack another cancerous tumour on its own.
O’Sullivan noted that the device, which is the size of a grain of rice, can be injected directly into a cancerous tumour and activated remotely by an external antenna. The goal is to use the device not only to deliver treatment but also to monitor the tumour’s response, adjusting signal strength and timing as needed.
Since I was young, I have been intrigued by altered states of consciousness, such as out-of-body experiences, paranormal phenomena and religious visions. I studied psychology and neuroscience to gain a better understanding of how these experiences come about. And in my scientific career, I have focused on the question of why some people are more prone to having these experiences than others.
Naturally, when I came across psychedelic science a couple of years ago, this field also sparked my academic interest. Here was an opportunity to study people who had a psychedelic experience and who claimed to have had a glimpse of ultimate reality. I started to research psychedelic experiences at Leiden University and founded the PRSM lab – a group of scientists from different academic backgrounds who study psychedelic, religious, spiritual and mystical experiences.
Initially, I was enthusiastic about the mind-transforming potential of psychedelics. These substances, when administered correctly, appear to be capable of enhancing people’s mental and physical wellbeing. They also increase feelings of connectedness to and concern for the environment.
Psychedelic therapy appeared to offer great potential for treating a wide variety of disorders, including depression, anxiety, addiction and post-traumatic stress disorder. This enthusiasm about the potentially transformative effects of psychedelics was reflected in positive media attention on this topic over the past few years. Michael Pollan, an American author and journalist, has brought psychedelics to an audience of millions with his book and Netflix documentary.
However, my initial optimism about psychedelics and their potential has changed into scepticism about the science behind much of the media hype. This is due to a closer scrutiny of the empirical evidence. Yes, at face value it seems as if psychedelic therapy can cure mental disease. But on closer inspection, the story is not that straightforward.
The main reason? The empirical evidence for the efficacy of and the working mechanisms underlying psychedelic therapy is far from clear.
Two issues
I wrote a critical review paper with my colleague Eiko Fried in which we listed the problems with the current clinical trials on psychedelic therapy. The main concern is called the “breaking blind problem”. In psychedelic studies, patients easily figure out if they have been randomly assigned to the psychedelic or the placebo group, simply because of the profound mind-altering effects of psychedelic substances.
This breaking-of-the-blind can actually result in placebo effect in patients in the psychedelic group: they finally get the treatment they’d been hoping for and they start feeling better. But it can also result in frustration and disappointment in patients assigned to the control group. They were hoping to get a miracle cure but now find out they will have to spend six hours on a placebo pill with their therapist.
As a consequence, any difference in therapeutic outcomes between the psychedelic and the placebo group is largely driven by these placebo and nocebo effects. (A nocebo effect is when a harmless treatment causes side-effects or worsening of symptoms because the person believes they may occur or expects them to occur.)
Knowing who received what also affects the therapists, who may be motivated to get more out of the therapy session if their patient got the “real deal”. And this problem is impossible to control for in so-called randomised controlled trials – still the gold standard in evaluating the effectiveness of drugs and treatments.
Also, non-clinical research on psychedelics faces problems. You may recall the graphic of a brain on psilocybin compared to one on a placebo (see below). Psilocybin increases the connections between different brain areas, which is represented in a colourful array of connecting lines.
This has become known as the “entropic brain hypothesis”. Psychedelics make your brain more flexible such that it returns to a child-like state of openness, novelty and surprise. This mechanism in turn has been hypothesised to underlie psychedelic therapy’s efficacy: by “liberating your brain” psychedelics can change entrenched and maladaptive patterns and behaviour. However, it turns out the picture is much more complicated than that.
Psychedelics constrict the blood vessels in your body and brain and this causes problems in the measurement of brain signals with MRI machines.
The graphic of the entropic brain may simply reflect the fact that the blood flow in the brain is dramatically altered under psilocybin. Also, it is far from clear what entropy exactly means – let alone how it can be measured in the brain.
A recent psilocybin study, which is yet to be peer-reviewed, found that only four out of 12 entropy measures could be replicated, casting further doubt on how applicable this mechanism of action is.
Although the story about psychedelics freeing your mind is compelling, it does not yet square well with the available empirical evidence.
These are just two examples that illustrate why it is important to be really cautious when you evaluate empirical studies in psychedelic science. Don’t trust findings at face value, but ask yourself the question: is the story too good or too simple to be true?
Personally, I have developed a healthy dose of scepticism when it comes to psychedelic science. I am still intrigued by psychedelics’ potential. They offer great tools for studying changes in consciousness. However, it is too early to conclude anything definite about their working mechanisms or their therapeutic potential. For this, we need more research. And I’m excited to contribute to that endeavour.
Study reveals epigenetic changes in regulatory T cells of hepatitis C patients post-treatment
A new study published in the Journal of Hepatology has revealed the lasting effects of chronic Hepatitis C virus (HCV) infection on the immune system, even after the disease has been successfully treated. The researchers discovered that traces of “epigenetic scars” remain in regulatory T cells and exhibit sustained inflammatory properties long after the virus is cleared from the body.
Chronic hepatitis C, can lead to severe complications such as liver cirrhosis and liver cancer. The advent of highly effective direct-acting antivirals (DAAs) has resulted in high cure rates for this chronic viral infection. However, it has been reported that the immune system of patients does not fully recover even after being cured.
The study examined patients with chronic HCV infection who achieved sustained virologic response (SVR) after DAA treatment. SVR means that the HCV virus is not detected in blood for 12 weeks after treatment, which is a strong indicator that the virus has been eradicated from the body. The researchers found that the frequency of activated TREG cells remained elevated during treatment and continued to be high even after the virus was eliminated.
The researchers then performed comprehensive analyses, including RNA sequencing and ATAC-seq, which revealed that the transcriptomic and epigenetic landscapes of TREG cells from HCV patients remained altered even after eradication of the virus. Inflammatory features, such as increased TNF signaling, were sustained in TREG cells, indicating long-term immune system changes induced by the chronic infection. These activated TREG cells from HCV patients continued to produce inflammatory cytokines like TNF, IFN-γ, and IL-17A even after clearance of the virus. The researchers followed the patients for up to six years after achieving SVR and found that inflammatory features still persisted.
The study’s results have significant implications for the long-term management of patients who have been treated for chronic HCV infection. Despite successful viral clearance, the persistence of inflammatory features in TREG cells suggests that these patients may be at risk for ongoing immune system dysregulation. This could potentially lead to chronic inflammation and related health issues.
Director Shin Eui Cheol, leader of the study, explained: “Our findings highlight the need for ongoing monitoring even after HCV has been cleared. By understanding the underlying mechanisms of these persistent immune changes, we can develop more effective strategies to ensure complete recovery and improve the quality of life for HCV patients.”
The research team is now focusing on further investigating the mechanisms behind the sustained inflammatory state of TREG cells. They aim to explore potential therapeutic interventions that could reverse these epigenetic and transcriptomic changes.
“We are now interested in seeing whether other chronic viral infections also cause long-lasting epigenetic changes in our immune systems,” said Director Shin. “One of our goals is to identify clinical implications of these persistent immune alterations.”
A multi-institutional study found that 1 in 6 youths fill an opioid prescription prior to surgery, and 3% of patients were still filling opioid prescriptions three to six months after surgery, indicating persistent opioid use and possible opioid dependence. The study underscores that more guidance is needed to steer clinicians away from prescribing opioids when they are not likely to be needed and recognising patient-specific risk factors for persistent opioid use. The findings were recently published by the journal JAMA Network Open.
Approximately 1.4 million youths undergo surgery in the United States each year, and there is concern that they remain highly susceptible to opioid-related harms. While significant strides have been made in reducing prescriptions for opioids, it is important for clinicians to consider adolescent patients who may be at risk for developing an addiction to opioids due to a range of genetic, neurobiological and social vulnerabilities. Prior to this study, little was known about risks for persistent opioid use among adolescents and the timing of initial and refill of opioid prescriptions.
“While prior analyses have shown a decline in opioid prescriptions in general, following surgical opioid prescribing recommendations remains a critical issue, especially for adolescents who are more inclined to engage in risk-taking behaviour,” said first study author Tori N. Sutherland, MD, MPH, an attending anaesthesiologist at Children’s Hospital of Philadelphia. “Our study found that these patients are still filling prescriptions that are either not recommended or are in excess of what they may need. They are also filling prescriptions up to two weeks before surgeries not associated with severe pre-operative pain, putting young patients at risk for developing persistent use throughout their lives as they transition into adulthood.”
Using a national insurance database of privately insured patients, the researchers looked at patients between 11 and 20 who underwent 22 surgical procedures that were either common or associated with severe postoperative pain requiring opioids for initial pain management. The patients had not taken opioids prior to their surgeries.
Of more than 100 000 patients, 46 951 (46.9%) patients filled a prescription for opioids, and 7587 (16.2%) of those had a prescription filled up to two weeks prior to surgery for procedures unlikely to be associated with severe preoperative pain. In this group, 6467 (13.8%) patients filled a second prescription for opioids, and 1216 (3.0%) patients filled prescriptions between 91 and 180 days after their surgical procedure.
One of the most important findings was that severe pain following a surgical procedure was not associated with persistent opioid use. However, patients with pre-existing chronic pain, who often underwent procedures associated with mild or moderate pain that could be managed with non-opioid medications, had increased odds of developing persistent opioid use.
“We believe this study underscores the need for establishing a standard of care for patients who undergo these procedures,” said senior study author Scott Hadland, MD, MPH, Chief of Adolescent and Young Adult Medicine at Mass General for Children and Associate Professor of Pediatrics at Harvard Medical School. “Effective pain management is critical and sometimes require opioids, but clinicians also need to make sure they are doing everything possible not to further contribute to the opioid addiction crisis, particularly with young patients.”
