Day: March 12, 2025

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Prostate Cancer is Not a Death Knell, Study Shows

On By ModernMedia
Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health

Prostate cancer statistics can look scary: 34 250 U.S. deaths in 2024. 1.4 million new cases worldwide in 2022. Dr Bruce Montgomery, an oncologist at University of Washington, hopes that patients won’t see these numbers and just throw up their hands in fear or resignation.  

“Being diagnosed with prostate cancer is not a death knell,” said Montgomery, senior author of a literature and trial review that appeared in JAMA. Montgomery is the clinical director of genitourinary oncology at Fred Hutch Cancer Center and University of Washington Medical Center, and a professor of medicine and urology at the UW School of Medicine.  

He encourages patients to ask their primary-care doctor specific questions about this cancer too.  Montgomery also encourages his fellow doctors to bring up the question of prostate cancer screening with their patients. 

“Knowing whether there is prostate cancer and how risky it is can be the first step. Not every cancer needs to be treated,” he said. “Sometimes it’s safe to just watch and use active surveillance.”   

A 2024 study coauthored by UW Medicine urologist Dr Daniel Lin showed that active surveillance can be extremely safe: 0.1% of men who opted for surveillance died of prostate cancer after 10 years.  

“We need to realise that prostate cancer is not one disease,” Montgomery said. “As a provider, you need to personalise your approach to the patient you’re seeing and to the disease that they personally are dealing with.” 

For example, if a 50-year-old man develops prostate cancer that is only in the prostate, then more aggressive measures may need to be considered. However, if the disease, which can be slow-moving, develops in an 80-year-old patient, the discussion may be quite different. 

“I’ve seen men that age (80s) develop prostate cancer and they’ve opted for no therapy,” he said. “They know that treatment, such as radiation, might make them feel terrible … so they just say ‘no.’ 

You, as their physician, he noted, must respect that.  

“But if you’re 50 and have 25 to 30 years in which prostate cancer can become a bigger issue, even with the downsides, most patients should get therapy,” he said.  

For more advanced prostate cancer, the number of effective treatments developed has markedly increased, as has the survival rate of men with whose prostate cancer has spread to other parts of their bodies.  

 “Metastatic prostate cancer needs therapy and research over the past 10 to 20 years has improved and continues to improve survival substantially,” he said. “Knowing who needs treatment, which treatment to use and when is both an art and a science.” 

The article covered facts that men and their doctors should know, including: 

  • Approximately 1.5 million new cases of prostate cancer are diagnosed annually worldwide. Approximately 75% of cases are first detected when the cancer is still localised to the prostate. This early detection was associated with a five-year survival rate of nearly 100%.   
  • Management includes active surveillance, prostatectomy surgical removal of the prostate, or radiation therapy, depending on risk of progression. 
  • Approximately 10% of cases are diagnosed after the cancer has spread. This stage of prostate cancer   has a five-year survival rate of 37%.   
  • The most common prostate cancer is adenocarcinoma, a type that starts in gland cells, and the median age at diagnosis is 67 years.  
  • More than 50% of prostate cancer risk is attributable to genetic factors and older age.  

Prostate cancer came to public attention, both nationally and internationally last year, when famed local travel writer, Rick Steves, announced he had developed prostate cancer. He proclaimed last month via his X account, formerly Twitter, that after radiation and surgery at UW Medicine and Fred Hutch, he was cancer free.  

Source: University of Washington School of Medicine/UW Medicine

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Research Identifies Beneficial Genetic Changes in Regular Blood Donors

On By ModernMedia
Photo by Charliehelen Robinson on Pexels

Researchers at the Francis Crick Institute have identified genetic changes in blood stem cells from frequent blood donors that support the production of new, non-cancerous cells.

Understanding the differences in the mutations that accumulate in our blood stem cells as we age is important to understand how and why blood cancers develop and hopefully how to intervene before the onset of clinical symptoms.

As we age, stem cells in the bone marrow naturally accumulate mutations and with this, we see the emergence of clones, which are groups of blood cells that have a slightly different genetic makeup. Sometimes, specific clones can lead to blood cancers like leukaemia.

When people donate blood, stem cells in the bone marrow make new blood cells to replace the lost blood and this stress drives the selection of certain clones.

Blood donation impacts makeup of cell populations

In research published in Blood, the team at the Crick, in collaboration with scientists from the DKFZ in Heidelberg and the German Red Cross Blood Donation Centre, analysed blood samples taken from over 200 frequent donors – (three donations a year over 40 years, more than 120 times in total) – and sporadic control donors who had donated blood less than five times in total.

Samples from both groups showed a similar level of clonal diversity, but the makeup of the blood cell populations was different.

For example, both sample groups contained clones with changes to a gene called DNMT3A, which is known to be mutated in people who develop leukaemia. Interestingly, the changes to this gene observed in frequent donors were not in the areas known to be preleukaemic.

A balancing act

To understand this better, the Crick researchers edited DNMT3A in human stem cells in the lab. They induced the genetic changes associated with leukaemia and also the non-preleukaemic changes observed in the frequent donor group.

They grew these cells in two environments: one containing erythropoietin (EPO), a hormone that stimulates red blood cell production which is increased after each blood donation, and another containing inflammatory chemicals to replicate an infection.

The cells with the mutations commonly seen in frequent donors responded and grew in the environment containing EPO and failed to grow in the inflammatory environment. The opposite was seen in the cells with mutations known to be preleukaemic.

This suggests that the DNMT3A mutations observed in the frequent donors are mainly responding to the physiological blood loss associated with blood donation.

Finally, the team transplanted the human stem cells carrying the two types of mutations into mice. Some of these mice had blood removed and then were given EPO injections to mimic the stress associated with blood donation.

The cells with the frequent donor mutations grew normally in control conditions and promoted red blood cell production under stress, without cells becoming cancerous. In sharp contrast, the preleukaemic mutations drove a pronounced increase in white blood cells in both control or stress conditions.

The researchers believe that regular blood donation is one type of activity that selects for mutations that allow cells to respond well to blood loss, but does not select the preleukaemic mutations associated with blood cancer.

Interactions of genes and the environment

Dominique Bonnet, Group Leader of the Haematopoietic Stem Cell Laboratory at the Crick, and senior author, said: “Our work is a fascinating example of how our genes interact with the environment and as we age. Activities that put low levels of stress on blood cell production allow our blood stem cells to renew and we think this favours mutations that further promote stem cell growth rather than disease.

“Our sample size is quite modest, so we can’t say that blood donation definitely decreases the incidence of pre-leukaemic mutations and we will need to look at these results in much larger numbers of people. It might be that people who donate blood are more likely to be healthy if they’re eligible, and this is also reflected in their blood cell clones. But the insight it has given us into different populations of mutations and their effects is fascinating.”

Hector Huerga Encabo, postdoctoral fellow in the Haematopoietic Stem Cell Laboratory at the Crick, and first joint author with Darja Karpova from the DKFZ in Heidelberg, said: “We know more about preleukaemic mutations because we can see them when people are diagnosed with blood cancer.

“We had to look at a very specific group of people to spot subtle genetic differences which might actually be beneficial in the long-term. We’re now aiming to work out how these different types of mutations play a role in developing leukaemia or not, and whether they can be targeted therapeutically.”

Source: The Francis Crick Institute

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High Temperatures Could Impact the Brain Function of Young Children

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Photo by frank mckenna on Unsplash

Exposure to high ambient temperatures is associated with lower connectivity in three brain networks in preadolescents, suggesting that heat may impact brain function. This is the conclusion of a study led by the Barcelona Institute for Global Health (ISGlobal). The results have been published in the Journal of the American Academy of Child & Adolescent Psychiatry. 

The study involved 2229 children aged 9 to 12 from the “Generation R” cohort in Rotterdam, Netherlands. Functional connectivity data from brain networks, i.e., how different regions of the brain communicate and collaborate, were assessed using resting-state magnetic resonance imaging, when the children were not performing any active tasks. Daily mean temperature estimates were obtained from the UrbClim urban climate model, developed by the Flemish Institute for Technological Research. Temperature values were calculated for the period from 2013 to 2015, assigning daily averages to each participant based on their home address.

Higher ambient temperatures during the week preceding the MRI assessment were associated with lower functional connectivity within the medial parietal, salience, and hippocampal networks, which are essential for proper brain functioning. This implies that brain areas may work less synchronously, affecting processes such as attention, memory, and decision-making. The medial parietal network is related to introspection and self-perception; the salience network detects environmental stimuli and prioritises what deserves our attention; and the hippocampal network is critical for memory and learning.

The research shows that the association between high temperatures and lower functional connectivity was strongest on the day before the brain scan and progressively decreased on subsequent days. In contrast, low average daily temperatures were not associated with functional connectivity.

“We hypothesise that dehydration could explain our findings, as children are particularly vulnerable to fluid loss when exposed to heat, which can affect the functional connectivity of brain networks,” says study lead author Laura Granés, researcher at IDIBELL and ISGlobal.

“In the current climate emergency, public health policies aimed at protecting children and adolescents from high temperatures could help mitigate potential effects on brain function,” says Mònica Guxens, ICREA researcher at ISGlobal and senior author of the study.

Implications for mental health

Although brain function alterations have been suggested as a possible mechanism linking temperature and mental health, no study to date has examined the effects of ambient temperature on functional brain networks. In another recent study, the same research team found that exposure to cold and heat can affect psychiatric symptoms such as anxiety, depression and attention problems. In addition, other studies have linked lower connectivity within the brain’s salience network to suicidal ideation and self-harming behaviours in adolescents with depression, as well as to anxiety disorders.

“Given the role of the salience network in suicidal ideation, our findings raise a new hypothesis: high temperatures could decrease the functional connectivity of this network, indirectly contributing to a higher risk of suicide in individuals with pre-existing mental health conditions,” explains Carles Soriano-Mas, researcher at IDIBELL and the University of Barcelona and one of the study’s authors. “While we do not propose that these connectivity changes, triggered by heat exposure, directly induce suicidal behaviours, they could act as a trigger in vulnerable individuals,” adds the researcher. 

Source: Barcelona Institute for Global Health (ISGlobal)

Categories : Cardiovascular DiseaseTags : Leave a comment

Breakthrough Research Offers Hope for Ischaemic Heart Failure

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Right side heart failure. Credit: Scientific Animations CC4.0

Researchers report a groundbreaking discovery in cardiac regeneration that offers new hope for the treatment of ischaemic heart failure. Published in npj Regenerative Medicine, the study reveals a novel approach to promoting cardiomyocyte proliferation.

The paper was authored by researchers at Baylor College of Medicine, the QIMR Berghofer Medical Research Institute in Brisbane, Australia, and collaborating institutions.

“When the heart cannot replace injured cardiomyocytes with healthy ones, it becomes progressively weaker, a condition leading to heart failure. In this study, we investigated a new way to stimulate cardiomyocyte proliferation to help the heart heal,” said co-corresponding author Dr Riham Abouleisa, assistant professor in the Division of Cardiothoracic Surgery at Baylor.

Previous studies showed that calcium plays an important role in cardiomyocyte proliferation. In the current study, Abouleisa and her colleagues explored how modulating calcium influx in cardiomyocytes would affect their proliferation.

“We found that preventing calcium influx in cardiomyocytes enhances the expression of genes involved in cell proliferation,” Abouleisa said. “We prevented calcium influx by inhibiting L-Type Calcium Channel (LTCC), a protein that regulates calcium in these cells. Our findings suggest that LTCC could be a target for developing new therapies to induce cardiomyocyte proliferation and regeneration.”

The study demonstrates that both pharmacological and genetic inhibition of LTCC can induce cardiomyocyte replication and that this occurs by modulating the activity of calcineurin, a known regulator of cardiomyocyte proliferation. This innovative approach showed promising results both in human cardiac slices grown in the lab and in live animals.

Abouleisa and her colleagues’ research highlights the importance of targeting calcium signalling pathways to unlock the regenerative potential of the heart and opens new avenues for developing cardiac regenerative therapies, potentially transforming the treatment landscape for patients suffering from heart failure.

Source: Baylor College of Medicine

Categories : Diet and Nutrition NeurologyTags : Leave a comment

Memory is Impaired in Aged Rats After 3 Days of High-fat Diet

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Some fast food offerings, such as cheeseburgers, contain more than 60% of calories from fat. Photo by Jonathan Borba

Just a few days of eating a diet high in saturated fat could be enough to cause memory problems and related brain inflammation in older adults, a new study in rats suggests. 

In the study, published in Immunity & Aging, researchers fed separate groups of young and old rats the high-fat diet for three days or for three months to compare how quickly changes happen in the brain versus the rest of the body when eating an unhealthy diet. 

As expected based on previous diabetes and obesity research, eating fatty foods for three months led to metabolic problems, gut inflammation and dramatic shifts in gut bacteria in all rats compared to those that ate normal chow, while just three days of high fat caused no major metabolic or gut changes.

When it came to changes in the brain, however, researchers found that only older rats – whether they were on the high-fat diet for three months or only three days – performed poorly on memory tests and showed negative inflammatory changes in the brain. 

The results dispel the idea that diet-related inflammation in the aging brain is driven by obesity, said senior study author Ruth Barrientos, an investigator in the Institute for Behavioral Medicine Research at The Ohio State University. Most research on the effects of fatty and processed foods on the brain has focused on obesity, yet the impact of unhealthy eating, independent of obesity, remains largely unexplored. 

“Unhealthy diets and obesity are linked, but they are not inseparable. We’re really looking for the effects of the diet directly on the brain. And we showed that within three days, long before obesity sets in, tremendous neuroinflammatory shifts are occurring,” said Barrientos, also an associate professor of psychiatry and behavioural health and neuroscience in Ohio State’s College of Medicine.  

“Changes in the body in all animals are happening more slowly and aren’t actually necessary to cause the memory impairments and changes in the brain. We never would have known that brain inflammation is the primary cause of high-fat diet-induced memory impairments without comparing the two timelines.” 

Years of research in Barrientos’ lab has suggested that aging brings on long-term “priming” of the brain’s inflammatory profile coupled with a loss of brain-cell reserve to bounce back, and that an unhealthy diet can make matters worse for the brain in older adults. 

Fat constitutes 60% of calories in the high-fat diet used in the study, which could equate to a range of common fast-food options: For example, nutrition data shows that fat makes up about 60% of calories in a McDonald’s double smoky BLT quarter pounder with cheese or a Burger King double whopper with cheese. 

After the animals were on high-fat diets for three days or three months, researchers ran tests assessing two types of memory problems common in older people with dementia that are based in separate regions of the brain: contextual memory mediated by the hippocampus (the primary memory center of the brain), and cued-fear memory that originates in the amygdala (the fear and danger center of the brain). 

Compared to control animals eating chow and young rats on the high-fat diet, aged rats showed behaviors indicating both types of memory were impaired after only three days of fatty food – and the behaviors persisted as they continued on the high-fat diet for three months. 

Researchers also saw changes in levels of a range of proteins called cytokines in the brains of aged rats after three days of fatty food, which signaled a dysregulated inflammatory response. Three months after being on the high-fat diet, some of the cytokine levels had shifted but remained dysregulated, and the cognitive problems persisted in behavior tests. 

“A departure from baseline inflammatory markers is a negative response and has been shown to impair learning and memory functions,” Barrientos said. 

Compared to rats eating normal chow, young and old animals gained more weight and showed signs of metabolic dysfunction – poor insulin and blood sugar control, inflammatory proteins in fat (adipose) tissue, and gut microbiome alterations – after three months on the high-fat diet. Young rats’ memory and behavior and brain tissue remained unaffected by the fatty food. 

“These diets lead to obesity-related changes in both young and old animals, yet young animals appear more resilient to the high-fat diet’s effects on memory. We think it is likely due to their ability to activate compensatory anti-inflammatory responses, which the aged animals lack,” Barrientos said. 

“Also, with glucose, insulin and adipose inflammation all increased in both young and old animals, there’s no way to distinguish what is causing memory impairment in only old animals if you look only at what’s happening in the body. It’s what is happening in the brain that’s important for the memory response.” 

Source: Ohio State University