Tag: 11/3/22

Categories : CancerTags :

Passing Through Tight Spaces Make Cancer Cells More Aggressive

On By ModernMedia
A scanning electron microscope image of a breast cancer cell.
Credit: Bruce Wetzel and Harry Schaefer, National Cancer Institute, National Institutes of Health

Squeezing through tight spaces makes cancer cells more aggressive and helps them evade cell death, a study published in eLife shows.

The researchers’ findings reveal how mechanical stress makes cancer cells more likely to metastasise. While metastasis is the cause of most cancer deaths, there are currently no available cures. However, the new results may help scientists develop novel approaches to treat or prevent metastasis.

When cancer cells escape their tumour or enter called capillaries to spread throughout the body, it can be tight squeeze. The cells have to collapse and change shape – a process called confined migration. The cells must also evade the immune system as they spread outwards.

“Mechanical stress can cause cancer cell mutations, as well as an uncontrolled increase in cell numbers and greater tissue invasion,” explained first author Deborah Fanfone, Postdoctoral Fellow at the Cancer Research Center of Lyon. “We wanted to know if the mechanical stress of confined migration makes cancer cells more likely to metastasise, and how this happens.”

To find out, the researchers forced human breast cancer cells through a membrane with 3µm-sized holes to simulate a confined migration environment. After passing through the membrane just once, the cells became more mobile and resistant to anoikis –a form of programmed cell death that occurs when cells become detached from the extracellular matrix. The cells were also able to escape destruction by immune natural killer cells.

More testing showed that expression of inhibitory-of-apoptosis proteins (IAPs) increased the resistance of cancer cells to anoikis. A new type of cancer drug which degrades IAPs (called a SMAC mimetic), removed this protection in the cancer cells.

The team then examined how these squeezed cells behave when administered to immune-suppressed mice. They found these mice developed more lung metastases than mice that were administered with breast cancer cells that had not been exposed to confined migration.

“By mimicking confined migration, we’ve been able to explore its multifaceted effects on cancer aggressiveness,” says senior author Gabriel Ichim, who leads the Cancer Cell Death team at the Cancer Research Center of Lyon. “We’ve shown how the process boosts survival in cancer cells and makes them more prone to forming deadly metastases.”

The authors add that these results may lead to additional studies of potential metastasis treatments, such as therapies that soften tumours to reduce mechanical stress on cancer cells, or that block IAPs. These include SMAC mimetics, which are currently being tested in clinical trials as a possible new treatment approach.

Source: eLife Sciences

Categories : General Interest Medical Research & TechnologyTags :

SAMRC Honours Medical Scientists

On By ModernMedia
Credit: South African Medical Research Council

On Thursday, March the 10th, the South African Medical Research Council (SAMRC) honoured a selection of leading SA medical scientists and researchers at its 8th SAMRC Scientific Merit Awards at a hybrid event.

This year’s Presidential Award, which is awarded to scientists who have made exceptional lifelong contributions to medical research and public health, was bestowed upon Professor Koleka Mlisana, the country’s first black microbiologist. With over 40 years’ experience in health sciences, Prof Mlisana is the current executive manager of academic affairs, research, and quality assurance at the National Health Laboratory Service (NHLS) and Co-Chair of the COVID-19 Ministerial Advisory Committee (MAC). In the 1990s, she was one of the scientists investigating the unknowns of HIV. Her research focused on understanding the body’s response to acute HIV infection.

The Platinum Medal, for South Africans who have made seminal scientific contributions and who have also made an impact on health, especially for those living in developing countries, was awarded to Professor Andre Pascal Kengne. As a physician and an internationally renowned non-communicable diseases epidemiologist, his work focuses on cardiovascular disease, diabetes, and chronic kidney disease. He is the current Director of the SAMRC’s Non-Communicable Diseases Research Unit and holds conjoint appointments as Professor of Medicine at the University of Cape Town, as well as Extraordinary Professor of Global Health at Stellenbosch University.

In the Gold Medal category, which is for researchers who have made substantial and influential contributions that have impacted on health especially in the developing world, the awardees are Professors Tulio de Oliveira, Ntobeko Ntusi, Ambroise Wonkam and Grant Theron.

Silver Medals are conferred to emerging and upcoming scientists and those committed to capacity development. This year, the medal recipients are Professors Diane Gray, Marlo Moller, Rabia Johnson, and Dr Nasheeta Peer.

SAMRC President and CEO, Prof Glenda Gray said that scientific research remains fundamental for reducing the nation’s burden of disease and preventing mortality. “The knowledge produced by these exceptional scientists will carry our country’s legacy of science forward and continue to improve the lives of citizens as it is evident with COVID-19.” Their work shows the country’s ingenuity, she added, noting that “it was scientists in South Africa who first discovered and sounded the alarm on Omicron, which rapidly became the dominant variant of concern.”

Source: South African Medical Research Council (SAMRC)

Categories : Diseases, Syndromes and ConditionsTags :

Guidelines for Cannabinoid Treatments in Drug Resistant Epilepsy

On By ModernMedia
Cannabis plants
Photo by Harrison Haines on Pexels

Due to the sizeable interest in the use of cannabis-based medications in treating drug resistant epilepsy and comparative lack of clinical guidance on prescription, an expert working group in Australia recently developed an interim “consensus advice” for prescribers and published it in the British Journal of Clinical Pharmacology.

The working group was made up of paediatric and adult epilepsy specialists, clinical pharmacists, pharmacologists, and cannabis researchers. Epilepsy occurs in 1–2% of the population, and about one in three people with epilepsy are considered drug resistant to standard antiseizure medications.

Since there are few clinical data available on comparative efficacy of cannabinoids with registered epilepsy treatments, the authors recommend cannabinoids only in drug resistant epilepsy, in carefully selected compliant patients with specific epilepsy phenotypes.

The document provides an overview of the different cannabis medicines currently available for treating epilepsy in children and adults, with information on dose, drug interactions, toxicity, and type and frequency of symptom and seizure relief. The consensus advice will be updated as new evidence emerges and will provide the structure for a more definitive guideline in the future.

“In the absence of a registration dossier, scientific experiments and case reports are helpful to provide some guidance to optimised dosing. However as in this guidance, observational data obtained from clinical practice – which often includes information not included in scientific experiments or even early clinical trial data, such as treating patients with other comorbidities, taking multiple medications, and patient diversity – can be very helpful to clinical practice,” said senior author Jennifer H. Martin, MBChB, MA, PhD, FRACP, a researcher at the University of Newcastle and the Director of the Australian Centre for Cannabis Clinical and Research Excellence.

Source: Wiley

Categories : CancerTags :

Compound in Chinese Herbal Medicine May Prevent Colon Cancer

On By ModernMedia
Colon cancer cells
Colon cancer cells. Source: National Cancer Institute on Unsplash

Emodin, an active compound found in Chinese herbal medicine, can prevent colon cancer in mice, according to researchers, and may be applicable in humans as well, a study has found. The mechanism behind this is likely emodin’s ability to reduce the number of pro-tumour macrophages.

The study is published in the American Journal of Physiology-Gastrointestinal and Liver Physiology.

Emodin, a major bioactive anthraquinone derivative extracted from rhubarb, represents multiple health benefits in the treatment of a host of diseases, such as immune-inflammatory abnormality, tumor progression, bacterial or viral infections, and metabolic syndrome. Emerging evidence has made great strides in clarifying the multi-targeting therapeutic mechanisms underlying the therapeutic efficacy of emodin, including anti-inflammatory, immunomodulatory, anti-fibrosis, anti-tumor, anti-viral, anti-bacterial, and anti-diabetic properties.

Besides investigating if emodin could prevent colon cancer, the study’s researchers especially wanted to know whether its anti-cancer properties “could be attributed to its actions on immune cells and particularly macrophages,” said Angela Murphy, PhD, co-author of the study. In this murine model, emodin was shown to reduce both polyp count and size. Also, mice treated with emodin “exhibited lower protumorigenic M2-like macrophages in the colon,” researchers wrote in the study.

Roughly 70% of colon cancer cases can be attributed to diet or other lifestyle factors, said Dr Murphy. Because emodin is also found in some fresh fruits and vegetables, it is hoped that consuming these emodin-containing foods could prevent colon cancer in humans.

Source: American Physiological Society

Categories : Environmental EffectsTags :

Lead Exposure Lowered IQ of Americans Born Up to 1996

On By ModernMedia
Old petrol pump
Photo by Ashlee Attebery on Unsplash

A new study calculates that exposure to car exhaust from leaded gas during childhood lowered the IQ levels of about half the population of Americans alive today.

The findings suggest that Americans born before 1996 may now be at greater risk for lead-related health problems, such as faster ageing of the brain. Leaded petrol was banned in the US in 1996, but anyone born in the US before the end of that era, and especially those at the peak of its use in the 1960s and 1970s, had worryingly high lead exposures as children, the researchers said. In South Africa, leaded petrol was only banned at the end of 2005.

The study’s findings were published in Proceedings of the National Academy of Sciences.

Lead is a neurotoxin that can enter the bloodstream via a number of routes and there is no safe level of exposure at any point in life. Young children are especially vulnerable to lead’s ability to impair brain development and lower cognitive ability.

“Lead is able to reach the bloodstream once it’s inhaled as dust, or ingested, or consumed in water,” said study co-author Aaron Reuben, a PhD candidate in clinical psychology. “In the bloodstream, it’s able to pass into the brain through the blood-brain barrier, which is quite good at keeping a lot of toxicants and pathogens out of the brain, but not all of them.”

To answer the complex question of how more than 70 years of leaded petrol use may have left a permanent mark on human health, Reuben and co-authors Michael McFarland and Mathew Hauer, both professors of sociology at Florida State University, opted for a fairly simple strategy.

Using publicly available data on US childhood blood-lead levels, leaded-gas use, and population statistics, they determined the likely lifelong burden of lead exposure carried by every American alive in 2015. From this data, they estimated lead’s assault on our intelligence by calculating IQ points lost from leaded gas exposure as a proxy for its harmful impact on public health – a result which stunned the researchers.

“I frankly was shocked,” Prof McFarland said. “And when I look at the numbers, I’m still shocked even though I’m prepared for it.”

As of 2015, more than 170 million Americans (more than half of the U.S. population) had clinically concerning levels of lead in their blood as children, likely resulting in lower IQs and putting them at higher risk for other long-term health impairments, such as reduced brain size, greater likelihood of mental illness, and increased cardiovascular disease in adulthood.

Leaded gasoline consumption rose rapidly in the early 1960s and peaked in the 1970s. As a result, Reuben and his colleagues found that essentially everyone born during those two decades are all but guaranteed to have been exposed to pernicious levels of lead from car exhaust.

Even more startling was lead’s toll on intelligence: childhood lead exposure may have blunted America’s cumulative IQ score by an estimated 824 million points – nearly three points per person on average. The researchers calculated that at its worst, people born in the mid-to-late 1960s may have lost up to six IQ points, and children registering the highest levels of lead in their blood, eight times the current minimum level to initiate clinical concern, fared even worse, potentially losing more than seven IQ points on average.

While the loss of a few IQ points may seem negligible, the authors note that these changes are dramatic enough to potentially shift people with below-average cognitive ability (IQ score less than 85) to being classified as having an intellectual disability (IQ score below 70).

Prof McFarland is continuing by analysing the racial disparities of childhood lead exposure, hoping to highlight the health inequities suffered by Black children, who were exposed more often to lead and in greater quantities than white children.

Reuben’s next step will be to examine the long-term consequences of past lead exposure on brain health in old age, based on evidence showing that adults with high childhood lead exposure may experience accelerated brain aging.

“Millions of us are walking around with a history of lead exposure,” Reuben said. “It’s not like you got into a car accident and had a rotator cuff tear that heals and then you’re fine. It appears to be an insult carried in the body in different ways that we’re still trying to understand but that can have implications for life.”

Source: Duke University