Tag: 5/5/23

Osteoporosis Drug Zolendronate Could also Help Fight Breast Cancer

Killer T cells about to destroy a cancer cell.

Triple-negative breast cancer (TNBC) is the most aggressive and deadly form of breast cancer with limited treatment options and a high probability of recurrence. Researchers from the University of Frieburg discovered that coordinated differentiation and changes in the metabolism of breast cancer stem cells make them invisible for the immune system. Counteracting the metabolic change with the drug zolendronate could make immunotherapy using gamma delta T cells more efficient against TNBC. The research team was led by Prof Dr Susana Minguet and published in Cancer Immunology Research.

TNBC cells hide from gamma delta T cells

Gamma delta T cells recognise and kill cells that produce stress-induced molecules and phosphoantigens, a common characteristic of cancer cells. Because gamma delta T cells work differently to other types of T cells, they are being investigated as an alternative to existing immunotherapies. In the current study, the researchers tested the effect of gamma delta T cells on TNBC using isolated cancer cells and a recently developed mouse model that closely replicates the tumour properties found in human patients.

While the gamma delta T cells worked well against isolated breast cancer stem cells from patients, they had a much weaker effect in the mouse model. This was due to adaptations of the cancer cells that let them stay unnoticed by the immune system, the researchers found. These adaptations included the downregulation of the so-called mevalonate pathway: a metabolic pathway that leads to the production of phosphoantigens – one of the classes of molecules that gamma T cells recognise. This escape mechanism likely also happens in patients with TNBC: analysis of public patient databases showed that reduced expression of key molecules of the mevalonate pathway correlate with a worse prognosis.

The immune evasion of TNBC cells is reversible

This newly discovered escape mechanism can be counteracted by the drug zolendronate, which is FDA-approved for the treatment of osteoporosis and bone metastasis. When the researchers treated the escapist cells with zolendronate, the gamma T cells became a lot more efficient in clearing the cancer. “Our findings explain why current clinical trials using gamma delta T cells are not resulting in the expected success,” Minguet summarises. “We found a possible pharmacological-based approach to revert immune escape, which paves the way for novel combinatorial immunotherapies for triple negative breast cancer.”

Source: University of Freiburg

Can Low-carbohydrate or Low-fat Diets Extend Lifespan?

Better diets are needed to address the macronutritional needs of an ageing population. Short-term clinical trials have demonstrated the health benefits of low-carbohydrate diets (LCDs) and low-fat diets (LFDs) for weight loss and heart protection. Now a study published in the Journal of Internal Medicine looks at the effects of these diets on mortality in middle-aged and older adults.

In the study of 371 159 individuals aged 50 to 71 years, 165 698 deaths occurred over a median follow-up of 23.5 years.

A healthy LFD – characterised by low intake of saturated fat and high intakes of plant protein and high-quality carbohydrates – was related to fewer deaths from all causes, from cardiovascular diseases, and from cancers. In contrast, an overall LCD and an unhealthy LCD were associated with significantly higher total, cardiovascular, and cancer mortality rates. A healthy LCD was associated with slightly lower death rates.

“Our results support the importance of maintaining a healthy LFD with less saturated fat in preventing all-cause and cause-specific mortality among middle-aged and older people,” the authors wrote.

Source: Wiley

Low Power Mode for MRIs Could Cut Energy Use by Half

Credit: Pixabay CC0

Medical centres could save energy and reduce expenses by turning off MRIs and putting them in the lowest power mode instead of idling them when not in use, according to a new Radiology study.

Health care is responsible for up to 4.4% of global carbon emissions, and imaging contributes an outsized share due to its energy-intensive devices, especially MRI. A 2020 study found that three CTs and four MRIs used the same amount of energy per year as a town of 852 people, for example.

Though turning a machine off is better than idling, a substantial amount of MRI energy consumption occurs in “off” mode, which still draws a constant level of power for cooling. To address this, a new “power save” mode was developed that saves even more energy than the “off” mode by cycling cooling components on and off.

UC San Francisco researchers sought to compare energy consumption in the “idle,” “off” and “power save” modes. The researchers found that turning off MRIs overnight for 12 hours reduced their energy use by 25–33%, and that enabling the additional “power save” mode while the machine was off lowered power use by an additional 22–28%. Switching from idle directly to “power save” decreases energy use by 46–51%.

While just one company currently offers the “power save” mode while machines are off, it’s a design strategy worth replicating, the study noted.

“The results of this study demonstrate the potential energy and cost savings any radiology practice can obtain by using these simple power-down methods,” said assistant professor Sean Woolen, MD, first author on the study. “Our goal was to find ways for radiology departments worldwide to reduce their collective environmental footprint.”

Imaging has become increasingly central to medical decision-making, so it’s imperative to evaluate the design and operations of these machines in order to decarbonise health care, added Woolen.

Health Care Industry Would Save Millions

The study was made possible thanks to an academic-industry partnership comprising UCSF, Siemens Healthineers, Siemens USA, and Siemens Smart Infrastructure. Siemens provided technology and funding to equip MRI machines with power meters and install power monitoring software, and UCSF performed data collection and analysis.

The researchers equipped four outpatient MRI scanners from three different vendors with power meters and examined data over 39 days. They calculated energy output, costs (assuming a mean cost of $0.14 per kilowatt hour), and carbon use.

On an annual basis, switching a scanner from “idle” mode to “off” mode for 12 hours saved 12.3 to 21 megawatt hours (MWh) of electricity, where a megawatt is equal to 1000 kilowatts of electricity used continuously for an hour. This translated to annual savings of $1717 to $2943, and 8.7 to 14.9tonnes of C02-equivalent (MTCO2eq), a metric used to compare emissions of greenhouse gases based on their potential to contribute to global warming.

Switching from off to “power save” mode reduced energy use by an additional 8.8 to 11.4MWh and saved $1226 to $1594 and 6.2 to 8.1 MTC02eq per year.

“Often when we talk about how to decarbonise, solutions seem out of reach, but this initiative is proof that innovators everywhere can have impact,” added Barbara Humpton, CEO of Siemens USA. “The technology to decarbonise is here and ours is hard at work, helping industries like health care uncover ways to be more efficient and take concrete action to meet their carbon-reduction targets.”

The potential impact of adopting this technique as an industry standard would not impact patient care and would be an effective strategy to reduce cost and carbon emissions in health care, added Woolen.

Face Masks for Kids Slow Aerosol Spread, Especially from Sneezing

Photo by Kelly Sikkema on Unsplash

In a new study published in Pediatric Investigation, researchers demonstrate that face masks reduce the release of exhaled particles when used by school-aged children, helping to slow the spread of various respiratory viruses. While there was little difference between no protection and masking in exhaled particles from breathing, sneezing saw a significant reduction in the number of particles produced.

Respiratory viruses, including SARS-CoV-2, are transmitted via respiratory droplets and aerosols generated by all activities that involve exhalation, including tidal breathing, speaking, singing, coughing, and sneezing. Droplets, large particles subject to gravitational forces, are rapidly deposited from air and form fomites on surfaces. Aerosols, fine solid or liquid particles which remain suspended in the air, can travel long distances (> 6m) and reach high concentrations in poorly-ventilated areas. The relative contribution of the various modes of infection (direct contact, indirect contact via fomite, large droplet, or aerosol) for various respiratory viruses is difficult to determine, but survival of infectious viruses has been demonstrated in aerosols.

For the study, 23 healthy children were asked to perform activities that ranged in intensity (breathe quietly, speak, sing, cough, and sneeze) while wearing no mask, a cloth mask, or a surgical mask.

The production of exhaled particles that were 5μm or smaller, which is the dominant mode of transmission of many respiratory viruses, increased with coughing and sneezing. Face masks, especially surgical face masks, effectively reduced the release of these and other sized particles.

“Understanding the factors that affect respiratory particle emission can guide public health measures to prevent the spread of respiratory infections, which are a leading cause of death and hospitalisation among young children worldwide,” said corresponding author Peter P. Moschovis, MD, MPH, of Massachusetts General Hospital and Harvard Medical School.

Source: Wiley

Beta Blockers Plus Chemotherapy Cut Metastasis in Triple Negative Breast Cancer

Breast cancer cells. Image by National Cancer Institute

A new international study has for the first time, identified that beta-blockers could significantly enhance the therapeutic effect of anthracycline chemotherapy in triple negative breast cancer (TNBC) by reducing metastasis. The results are published in Science Translational Medicine.

Anthracyclines are a class of drugs used in chemotherapy to treat many cancers, including TNBC.

Monash University researchers have previously shown in a clinical trial that beta blockers are linked with reduced metastasis. However, until now, it was unclear how beta-blockers would interact with common cancer treatments.

In this new study, the team used mouse models of cancer and analysed large-scale patient clinical data, in collaboration with the Cancer Registry of Norway, to discover that anthracycline chemotherapy on its own, in the absence of a beta-blocker, induces nerve growth in tumours.

However, adding a beta blocker to chemotherapy inhibited nerve fibre activity in tumours and stopped the cancer from coming back after treatment.

Lead author Dr Aeson Chang said the findings reveal an unanticipated insight into why chemotherapy treatment does not always work as it should.

“We set out to build on previous studies that have shown beta-blockers can halt the stress response experienced by cancer patients at the time of diagnosis and stop the cancer from spreading.

In this new study, not only did we discover the biological effect of beta-blockers when used alongside anthracycline chemotherapy, we also discovered why they are effective,” said Dr Chang.

“In mouse models of TNBC, we found that anthracycline chemotherapy was able to increase sympathetic nerve fibre activity in tumours. Activation of these stress neurons can help tumour cells spread and, fortunately, we found that beta blockers could stop this effect. Our hope is that this exciting discovery will pave the way for further research and, ultimately, lead to improved outcomes for patients.”

Senior author, Professor Erica Sloan, who has been exploring the use of beta-blockers as a novel strategy to slow cancer progression for a number of years, said the study provides important clues about why beta-blockers may help improve the clinical management of TNBC.

“While many patients will be cured by treatment, unfortunately, in some patients the cancer may return – this study has helped us understand why. Our findings show that anthracycline chemotherapy supports the growth of nerves, which can support cancer relapse. This is important, as it tells us that targeting nerves using a beta blocker can improve response to treatment,” said Professor Sloan.

“Beta blocker use has been consistently linked to reduced metastatic relapse and cancer-specific survival in TNBC patients. However, the lack of understanding of how beta blockers improve chemotherapy – which is a core component of the standard treatment for TNBC – has limited the translation of these findings into the cancer clinic,” said Professor Sloan.

“We believe this study presents an exciting opportunity to further explore the use of beta-blockers as a novel strategy in the treatment of TNBC.”

Source: Monash University