From immunotherapy to mRNA vaccines – the latest science on melanoma treatment explained
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More than 16,000 Australians will be diagnosed with melanoma each year. Most of these will be caught early, and can be cured by surgery.
However, for patients with advanced or metastatic melanoma, which has spread from the skin to other organs, the outlook was bleak until the advent of targeted therapies (that attack specific cancer traits) and immune therapies (that leverage the immune system). Over the past decade, these treatments have seen a significant climb in the number of advanced melanoma patients surviving for at least five years after diagnosis, from less than 10% in 2011 to around 50% in 2021.
While this is great news, there are still many melanoma patients who cannot be treated effectively with current therapies. Researchers have developed two exciting new therapies that are being evaluated in clinical trials for advanced melanoma patients. Both involve the use of immunotherapy at different times and in different ways.
The first results from these trials are now being shared publicly, offering insight into the future of melanoma treatment.
Immunotherapy before surgery
Immunotherapy works by boosting the power of a patient’s immune system to help kill cancer cells. One type of immunotherapy uses something called “immune checkpoint inhibitors”.
Immune cells carry “immune checkpoint” proteins, which control their activity. Cancer cells can interact with these checkpoints to turn off immune cells and hide from the immune system. Immune checkpoint inhibitors block this interaction and help keep the immune system activated to fight the cancer.
Results from an ongoing phase 3 trial using immune checkpoint inhibitors were recently published in the New England Journal of Medicine.
This trial used two types of immune checkpoint inhibitors: nivolumab, which blocks an immune checkpoint called PD-1, and ipilimumab, which blocks CTLA-4.
Some 423 patients (including many from Australia) were enrolled in the trial, and participants were randomly assigned to one of two groups.
The first group had surgery to remove their melanoma, and were then given immunotherapy (nivolumab) to help kill any remaining cancer cells. Giving a systemic (whole body) therapy such as immunotherapy after surgery is a standard way of treating melanoma. The second group received immunotherapy first (nivolumab plus ipilimumab) and then underwent surgery. This is a new approach to treating these cancers.
Based on previous observations, the researchers had predicted that giving patients immunotherapy while the whole tumour was still present would activate the tumour-fighting abilities of the patient’s immune system much better than giving it once the tumour had been removed.
Sure enough, 12 months after starting therapy, 83.7% of patients who received immunotherapy before surgery remained cancer-free, compared to 57.2% in the control group who received immunotherapy after surgery.
Based on these results, Australian of the year Georgina Long – who co-led the trial with Christian Blank from The Netherlands Cancer Institute – has suggested this method of immunotherapy before surgery should be considered a new standard of treatment for higher risk stage 3 melanoma. She also said a similar strategy should be evaluated for other cancers.
The promising results of this phase 3 trial suggest we might see this combination treatment being used in Australian hospitals within the next few years.
mRNA vaccines
Another emerging form of melanoma therapy is the post-surgery combination of a different checkpoint inhibitor (pembrolizumab, which blocks PD-1), with a messenger RNA vaccine (mRNA-4157).
While checkpoint inhibitors like pembrolizumab have been around for more than a decade, mRNA vaccines like mRNA-4157 are a newer phenomenon. You might be familiar with mRNA vaccines though, as the biotechnology companies Pfizer-BioNTech and Moderna released COVID vaccines based on mRNA technology.
mRNA-4157 works basically the same way – the mRNA is injected into the patient and produces antigens, which are small proteins that train the body’s immune system to attack a disease (in this case, cancer, and for COVID, the virus).
However, mRNA-4157 is unique – literally. It’s a type of personalised medicine, where the mRNA is created specifically to match a patient’s cancer. First, the patient’s tumour is genetically sequenced to figure out what antigens will best help the immune system to recognise their cancer. Then a patient-specific version of mRNA-4157 is created that produces those antigens.
The latest results of a three-year, phase 2 clinical trial which combined pembrolizumab and mRNA-4157 were announced this past week. Overall, 2.5 years after starting the trial, 74.8% of patients treated with immunotherapy combined with mRNA-4157 post-surgery remained cancer-free, compared to 55.6% of those treated with immunotherapy alone. These were patients who were suffering from high-risk, late-stage forms of melanoma, who generally have poor outcomes.
It’s worth noting these results have not yet been published in peer-reviewed journals. They’re available as company announcements, and were also presented at some cancer conferences in the United States.
Based on the results of this trial, the combination of pembrolizumab and the vaccine progressed to a phase 3 trial in 2023, with the first patients being enrolled in Australia. But the final results of this trial are not expected until 2029.
It is hoped this mRNA-based anti-cancer vaccine will blaze a trail for vaccines targeting other types of cancer, not just melanoma, particularly in combination with checkpoint inhibitors to help stimulate the immune system.
Despite these ongoing advances in melanoma treatment, the best way to fight cancer is still prevention which, in the case of melanoma, means protecting yourself from UV exposure wherever possible.
Sarah Diepstraten, Senior Research Officer, Blood Cells and Blood Cancer Division, WEHI (Walter and Eliza Hall Institute of Medical Research) and John (Eddie) La Marca, Senior Research Officer, Blood Cells and Blood Cancer, WEHI (Walter and Eliza Hall Institute of Medical Research)
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Vision for Life, Revised Edition – by Dr. Meir Schneider
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The “ten steps” would be better called “ten exercises”, as they’re ten things that one can (and should) continue to do on an ongoing basis, rather than steps to progress through and then forget about.
We can’t claim to have tested the ten exercises for improvement (this reviewer has excellent eyesight and merely hopes to maintain such as she gets older) but the rationale is compelling, and the public testimonials abundant.
Dr. Schneider also talks about improving and correcting errors of refraction—in other words, doing the job of any corrective lenses you may currently be using. While he doesn’t claim miracles, it turns out there is a lot that can be done for common issues such as near-sightedness and far-sightedness, amongst others.
There’s a large section on managing more chronic pathological eye conditions than this reviewer previously knew existed; in some cases it’s a matter of making sure things don’t get worse, but in many others, there’s a recurring of theme of “and here’s an exercise for correcting that”.
The writing style is a little more “narrative prose” than we’d have liked, but the quality of the content more than makes up for any style preference issues.
Bottom line: the human body is a highly adaptive organism, and sometimes it just needs a little help to correct itself. This book can help with that.
Click here to check out Vision for Life, and take good care of yours!
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Make Overnight Oats Shorter Or Longer For Different Benefits!
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It’s Q&A Day at 10almonds!
Have a question or a request? We love to hear from you!
In cases where we’ve already covered something, we might link to what we wrote before, but will always be happy to revisit any of our topics again in the future too—there’s always more to say!
As ever: if the question/request can be answered briefly, we’ll do it here in our Q&A Thursday edition. If not, we’ll make a main feature of it shortly afterwards!
So, no question/request too big or small
❝How long do I have to soak oats for to get the benefits of “overnight oats”?❞
The primary benefit of overnight oats (over cooked oats) is that they are soft enough to eat without having been cooked (as cooking increases their glycemic index).
So, if it’s soft, it’s good to eat. A few hours should be sufficient.
Bonus information
If, by the way, you happen to leave oats and milk (be it animal or plant milk) sealed in a jar at room temperature for a 2–3 days (less if your “room temperature” is warmer than average), it will start to ferment.
- Good news: fermentation can bring extra health benefits!
- Bad news: you’re on your own if something pathogenic is present
For more on this, you might like to read:
Enjoy!
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5 Ways To Make Your Smoothie Blood Sugar Friendly (Avoid the Spike!)
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At 10almonds, we are often saying “eat whole fruit; don’t drink your calories”. Whole fruit is great for blood sugars; fruit juices and many smoothies on the other hand, not so much. Especially juices, being near-completely or perhaps even completely stripped of fiber, but even smoothies have had a lot of the fiber broken down and are still a liquid, meaning they are very quickly and easily digestible, and thus their sugars (whatever carbs are in there) can just zip straight into your veins.
However, there are ways to mitigate this…
Slow it down
The theme here is “give the digestive process something else to do”; some things are more quickly and easily digestible than others, and if it’s working on breaking down some of the slower things, it’s not waving sugars straight on through; they have to wait their turn.
To that end, recommendations include:
- Full-fat Greek yogurt which provides both protein and fat, helping to slow down the absorption of sugar. Always choose unsweetened versions to avoid added sugars, though!
- Coconut milk (canned) which is low in sugar and carbs, high in fat. This helps reduce blood sugar spikes, as she found through personal experimentation too.
- Avocado which is rich in healthy fats that help stabilize blood sugar. As a bonus, it blends well into smoothies without affecting the taste much.
- Coconut oil which contains medium-chain triglycerides (MCTs) that are quickly absorbed for energy without involving glucose, promoting fat-burning and reducing blood sugar spikes.
- Collagen powder which is a protein that helps lower blood sugar spikes while also supporting muscle growth, skin, and joints.
For more on all of these, enjoy:
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The 7 Known Risk Factors For Dementia
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A recent UK-based survey found that…
- while nearly half of adults say dementia is the disease they fear most,
- only a third of those thought you could do anything to avoid it, and
- just 1% could name the 7 known risk factors.
Quick test
Can you name the 7 known risk factors?
Please take a moment to actually try (this kind of mental stimulation is good in any case), and count them out on your fingers (or write them down), and then…
Answer (no peeking if you haven’t listed them yet)
The 7 known risk factors are:
*drumroll please*
- Smoking
- High blood pressure
- Diabetes
- Obesity
- Depression
- Lack of mental stimulation
- Lack of physical activity
How many did you get? If you got them all, well done. If not, then well, now you know, so that’s good.
Did you come here from our “Future-Proof Your Brain” article? If so, you can get back to it here ← and if you didn’t, you should check it out anyway; it’s worth it😉
Take care!
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Not quite an introvert or an extrovert? Maybe you’re an ambivert
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Our personalities are generally thought to consist of five primary factors: openness to experience, conscientiousness, extroversion, agreeableness and neuroticism, with each of us ranking low to high for each.
Extroversion is one of the Big Five personality traits. Big 5 personality traits graphic Those who rank high in extroversion, known as extroverts, typically focus on their external world. They tend to be more optimistic, recharge by socialising and enjoy social interaction.
On the other end of the spectrum, introverts are more likely to be quiet, deep thinkers, who recharge by being alone and learn by observing (but aren’t necessarily shy).
But what if you’re neither an introvert or extrovert – or you’re a bit of both? Another category might fit better: ambiverts. They’re the middle of the spectrum and are also called “social introverts”.
What exactly is an ambivert?
The term ambivert emerged in 1923. While it was not initially embraced as part of the introvert-extrovert spectrum, more recent research suggests ambiverts are a distinct category.
Ambiverts exhibit traits of both extroverts and introverts, adapting their behaviour based on the situation. It may be that they socialise well but need solitude and rest to recharge, and they intuitively know when to do this.
Ambiverts seems to have the following characteristics:
- good communication skills, as a listener and speaker
- ability to be a peacemaker if conflict occurs
- leadership and negotiation skills, especially in teams
- compassion and understanding for others.
Some research suggests ambiverts make up a significant portion of the population, with about two-thirds of people falling into this category.
What makes someone an ambivert?
Personality is thought to be 50% inherited, with the remaining being influenced by environmental factors and individual experiences.
Emerging research has found physical locations of genes on chromosomes closely aligned with extroversion-introversion traits.
So, chances are, if you are a blend of the two styles as an ambivert, one of your parents may be too.
What do ambiverts tend to be good at?
Ambiverts are flexible with talking and also listening. Cotton Bro Studios/Pexels One area of research focus in recent decades has been personality type and job satisfaction. One study examined 340 introverts, extroverts and ambiverts in sales careers.
It has always been thought extroverts were more successful with sales. However, the author found ambiverts were more influential and successful.
They may have a sales advantage because of their ability to read the situation and modify their behaviour if they notice a customer is not interested, as they’re able to reflect and adapt.
Ambiverts stress less than introverts
Generally, people lower in extroversion have higher stress levels. One study found introverts experience more stress than both ambiverts and extroverts.
It may be that highly sensitive or introverted individuals are more susceptible to worry and stress due to being more perfectionistic.
Ambiverts are adept at knowing when to be outgoing and when to be reflective, showcasing a high degree of situational awareness. This may contribute to their overall wellbeing because of how they handle stress.
What do ambiverts tend to struggle with?
Ambiverts may overextend themselves attempting to conform or fit in with many social settings. This is termed “overadaptation” and may force ambiverts to feel uncomfortable and strained, ultimately resulting in stress or burnout.
Ambiverts tend to handle stress well but feel strained when overadapting. Cottonbro Studios/Pexels But personality traits aren’t fixed
Regardless of where you sit on the scale of introversion through to extroversion, the reality is it may not be fixed. Different situations may be more comfortable for introverts to be social, and extroverts may be content with quieter moments.
And there are also four other key personality traits – openness to experience, conscientiousness, agreeableness and neuroticism – which we all possess in varying levels, and are expressed in different ways, alongside our levels of extroversion.
There is also evidence our personality traits can change throughout our life spans are indeed open to change.
Peta Stapleton, Associate Professor in Psychology, Bond University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Men have a biological clock too. Here’s what’s more likely when dads are over 50
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We hear a lot about women’s biological clock and how age affects the chance of pregnancy.
New research shows men’s fertility is also affected by age. When dads are over 50, the risk of pregnancy complications increases.
Data from more than 46 million births in the United States between 2011 and 2022 compared fathers in their 30s with fathers in their 50s.
While taking into account the age of the mother and other factors known to affect pregnancy outcomes, the researchers found every ten-year increase in paternal age was linked to more complications.
The researchers found that compared to couples where the father was aged 30–39, for couples where the dad was in his 50s, there was a:
- 16% increased risk of preterm birth
- 14% increased risk of low birth weight
- 13% increase in gestational diabetes.
The older fathers were also twice as likely to have used assisted reproductive technology, including IVF, to conceive than their younger counterparts.
Steven van Loy/Unsplash Dads are getting older
In this US study, the mean age of all fathers increased from 30.8 years in 2011 to 32.1 years in 2022.
In that same period, the proportion of men aged 50 years or older fathering a child increased from 1.1% to 1.3%.
We don’t know the proportion of men over 50 years who father children in Australia, but data shows the average age of fathers has increased.
In 1975 the median age of Australian dads was 28.6 years. This jumped to 33.7 years in 2022.
How male age affects getting pregnant
As we know from media reports of celebrity dads, men produce sperm from puberty throughout life and can father children well into old age.
However, there is a noticeable decline in sperm quality from about age 40.
Female partners of older men take longer to achieve pregnancy than those with younger partners.
A study of the effect of male age on time to pregnancy showed women with male partners aged 45 or older were almost five times more likely to take more than a year to conceive compared to those with partners aged 25 or under. More than three quarters (76.8%) of men under the age of 25 years impregnated their female partners within six months, compared with just over half (52.9%) of men over the age of 45.
Pooled data from ten studies showed that partners of older men are also more likely to experience miscarriage. Compared to couples where the male was aged 25 to 29 years, paternal age over 45 years increased the risk of miscarriage by 43%.
Older men are more likely to need IVF
Outcomes of assisted reproductive technology, such as IVF, are also influenced by the age of the male partner.
A review of studies in couples using assisted reproductive technologies found paternal age under 40 years reduced the risk of miscarriage by about 25% compared to couples with men aged over 40.
Having a male under 40 years also almost doubled the chance of a live birth per treatment cycle. With a man over 40, 17.6% of treatment rounds resulted in a live birth, compared to 28.4% when the male was under 40.
How does male age affect the health outcomes of children?
As a result of age-related changes in sperm DNA, the children of older fathers have increased risk of a number of conditions. Autism, schizophrenia, bipolar disorders and leukaemia have been linked to the father’s advanced years.
A review of studies assessing the impact of advanced paternal age reported that children of older fathers have increased rates of psychiatric disease and behavioural impairments.
But while the increased risk of adverse health outcomes linked to older paternal age is real, the magnitude of the effect is modest. It’s important to remember that an increase in a very small risk is still a small risk and most children of older fathers are born healthy and develop well.
Improving your health can improve your fertility
In addition to the effects of older age, some chronic conditions that affect fertility and reproductive outcomes become more common as men get older. They include obesity and diabetes which affect sperm quality by lowering testosterone levels.
While we can’t change our age, some lifestyle factors that increase the risk of pregnancy complications and reduce fertility, can be tackled. They include:
- smoking
- recreational drug taking
- anabolic steroid use
- heavy alcohol consumption.
Get the facts about the male biological clock
Research shows men want children as much as women do. And most men want at least two children.
Yet most men lack knowledge about the limitations of female and male fertility and overestimate the chance of getting pregnant, with and without assisted reproductive technologies.
We need better public education, starting at school, to improve awareness of the impact of male and female age on reproductive outcomes and help people have healthy babies.
For men wanting to improve their chance of conceiving, the government-funded sites Healthy Male and Your Fertility are a good place to start. These offer evidence-based and accessible information about reproductive health, and tips to improve your reproductive health and give your children the best start in life.
Karin Hammarberg, Senior Research Fellow, Global and Women’s Health, School of Public Health & Preventive Medicine, Monash University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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