Tag: 10/10/24

Categories : CancerTags :

Drug Enhances Radiotherapy for Lung Cancer Metastases in the Brain

On By ModernMedia
Lung cancer metastasis. Credit: National Cancer Institute

In new research, a team led by University of Cincinnati researchers has identified a potential new way to make radiation more effective and improve outcomes for patients with lung cancer that has spread to the brain. The study, led by first author Debanjan Bhattacharya, PhD, appears in the journal Cancers, and uses a benzodiazepine analogue.

According to the American Cancer Society, lung cancer is the leading cause of cancer death in the United States, accounting for about one in five cancer deaths. Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer, making up approximately 80% to 85% of all lung cancer cases.

Up to 40% of lung cancer patients develop brain metastases during the course of the disease, and these patients on average survive between eight and 10 months following diagnosis.

Current standard of care treatments for lung cancer that spreads to the brain include surgical removal and stereotactic brain radiosurgery (using precisely focused radiation beams to treat tumours) as well as whole brain irradiation in patients with more than 10 metastatic brain lesions.

“Lung cancer brain metastasis is usually incurable, and whole brain radiation treatment is palliative, as radiation limits therapy due to toxicity,” said Bhattacharya, research instructor in the Department of Neurology and Rehabilitation Medicine in UC’s College of Medicine. “Managing potential side effects and overcoming resistance to radiation are major challenges when treating brain metastases from lung cancer. This highlights the importance of new treatments which are less toxic and can improve the efficacy of radiation therapy, are less expensive, and can improve the quality of life in patients.”

Research focus

Bhattacharya and his colleagues at UC focused on AM-101, a synthetic analogue, meaning it has a close resemblance to the original compound, in the class of benzodiazepine drugs. It was first developed by James Cook, a medicinal chemist at the University of Wisconsin-Milwaukee. Prior to this study, AM-101’s effect in non-small cell lung cancer was unknown. 

AM-101 is a particularly useful drug in the context of brain metastases in NSCLC, Bhattacharya said, as benzodiazepines are known to be able to pass through the blood-brain barrier that protects the brain from potential harmful invaders that can also block some drugs from reaching their target in the brain.

Research results

The team found that AM-101 activated GABA(A) receptors located in the NSCLC cells and lung cancer brain metastatic cells. This activation triggers the “self-eating” process of autophagy where the cell recycles and degrades unwanted cellular parts.

Specifically, the study showed that activating GABA(A) receptors increases the expression and clustering of GABARAP and Nix (an autophagy receptor), which boosts the autophagy process in lung cancer cells. This enhanced “self-eating” process of autophagy makes lung cancer cells more sensitive to radiation treatment.

Using animal models of lung cancer brain metastases, the team found AM-101 makes radiation treatment more effective and significantly improves survival. Additionally, the drug was found to slow down the growth of the primary NSCLC cells and brain metastases.

In addition to making radiation more effective, adding AM-101 to radiation treatments could allow for lower radiation doses, which could reduce side effects and toxicity for patients, Bhattacharya said. The team is now working toward opening Phase 1 clinical trials testing the combination of AM-101 and radiation both in lung cancer within the lungs and lung cancer that has spread to the brain.

Source: Aalto University

Categories : Cardiovascular DiseaseTags :

Research at Oktoberfest Reveals a Brewing Cardiac Arrhythmia Risk

On By ModernMedia
Photo by Pavel Danilyuk on Pexels

Medicine is subjecting the negative effects of alcohol on body and health to ever greater scrutiny – not surprisingly us, as alcohol is one of the strongest cell toxins that exist. In a recent study, doctors at  took mobile ECG monitors along to parties of young people who had one principal aim: to drink and be merry. Yet the science produced by the MunichBREW II study made for sobering reading. It revealed that binge drinking can have a concerning effect on the hearts even of healthy young people in surprisingly many cases, including the development of clinically relevant arrhythmias. The results of the study have just been published in the European Heart Journal.

The team from the Department of Cardiology at LMU University Hospital launched the MunichBREW I study at Munich Oktoberfest in 2015. Back then, the doctors, led by Professor Stefan Brunner and PD Dr Moritz Sinner, studied the connection between excessive alcohol consumption and cardiac arrhythmias – but only through an electrocardiogram (ECG) snapshot.

Now the scientists wanted to gain a more detailed picture, so they set out with their mobile equipment once again. Their destinations were various small parties attended by young adults with a high likelihood “that many of the partygoers would reach breath alcohol concentrations (BAC) of at least 1.2 grams per kilogram,” says Stefan Brunner. These were the participants of the MunichBREW II study – the world’s largest investigation to date of acute alcohol consumption and ECG changes in prolonged ECGs spanning several days.

Hearts out of sync – especially in recovery phase

Overall, the researchers evaluated the data of over 200 partygoers who, with peak blood alcohol values of up to 2.5 grams per kilogram, had imbibed quite a few drinks. The ECG devices monitored their cardiac rhythms for a total of 48 hours, with the researchers distinguishing between the baseline (hour 0), the drinking period (hours 1-5), the recovery period (hours 6-19), and two control periods corresponding to 24 hours after the drinking and recovery periods, respectively. Acute alcohol intake was monitored by BAC measurements during the drinking period. ECGs were analysed for heart rate, heart rate variability, atrial fibrillation, and other types of cardiac arrhythmia. Despite the festive mood of the study participants, the quality of the ECGs was almost universally high throughout.

“Clinically relevant arrhythmias were detected in over five percent of otherwise healthy participants,” explains Moritz Sinner, “and primarily in the recovery phase.” Alcohol intake during the drinking period led to an increasingly rapid pulse of over 100 beats per minute. Alcohol, it would seem, can profoundly affect the autonomous regulatory processes of the heart. “Our study furnishes, from a cardiological perspective, another negative effect of acute excessive alcohol consumption on health,” stresses Brunner. Meanwhile, the long-term harmful effects of alcohol-related cardiac arrhythmias on cardiac health remains a subject for further research.

Source: Ludwig-Maximilians-Universität München