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Brain Tumor

Groundbreaking Targeted Alpha Therapy Offers New Hope for Refractory Skin Cancer Treatment

Metastatic melanoma is the most aggressive form of skin cancer. In an effort to achieve targeted therapy for metastatic melanoma, researchers recently developed a new radioactive drug that emits alpha particles. With their short range of emission and high energy, alpha particles are particularly promising for targeted therapies that require high energy release in the cancer tissue while minimizing the damage to nearby healthy tissues.

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Refractory skin cancer, particularly metastatic melanoma, has long been a formidable challenge for medical professionals. Conventional treatments such as immunotherapy and targeted drugs have shown limited effectiveness, making it essential to explore alternative approaches. A recent breakthrough in radiotherapy comes from Japan, where a team of researchers led by Assistant Professor Hiroyuki Suzuki from Chiba University has developed a promising treatment called Targeted Alpha Therapy (TAT).

This innovative therapy involves using alpha particle-emitting radioisotopes labeled with astatine-211 (211At), which are more effective at disrupting cancer cells due to their higher energy and shorter range compared to beta and gamma emissions. The researchers have successfully designed an astatine-211-labeled α-melanocyte-stimulating hormone (α-MSH) peptide analog called [211At]NpG-GGN4c that specifically targets melanocortin-1 receptors (MC1R), overexpressed in melanoma cells.

To enhance tumor targeting and reduce off-target accumulation, the team identified an optimal hydrophilic linker. The synthesized peptides were then tested on B16F10 melanoma-bearing mice models, revealing a dose-dependent inhibitory effect. The [211At]NpG-GGN4c showed high accumulation in tumors, rapid clearance from non-target organs, and stability in blood plasma.

The researchers believe their molecular design could be useful for developing other 211At-labeled radiopharmaceuticals, potentially treating refractory cancers beyond melanoma. They are hopeful about promoting a clinical application of 211At-based TAT, which may emerge as a viable treatment option for patients with advanced melanoma in the coming years. This breakthrough offers new therapeutic opportunities for patients with refractory cancer and could revolutionize skin cancer treatment.

Brain Tumor

Sleep Apnea Linked to Brain Changes and Cognitive Decline in Older Adults

Obstructive sleep apnea, a condition that causes lower oxygen levels during sleep, is linked to degeneration of brain regions associated with memory through damage to the brain’s small blood vessels, according to a new study. The study found the brain changes were strongly associated with the severity of drops in oxygen levels during rapid eye movement (REM) sleep. The study does not prove that sleep apnea causes this degeneration; it only shows an association.

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Sleep apnea, a condition that causes repeated disruptions to breathing during sleep, has been linked to cognitive decline and memory-related brain changes in older adults. A study published online in Neurology found that the severity of drops in oxygen levels during rapid eye movement (REM) sleep was strongly associated with degeneration of brain regions associated with memory.

Obstructive sleep apnea occurs when throat muscles relax during sleep, blocking the airway and causing a person to wake up repeatedly to breathe. This disrupted sleep pattern can lower oxygen levels, which in turn can damage small blood vessels in the brain.

The study included 37 people with an average age of 73 who did not have cognitive impairment. Researchers measured their oxygen levels throughout the night during all stages of sleep, including REM sleep. Participants also had brain scans to measure brain structure and took a memory test before and after sleep.

The results showed that lower oxygen levels during REM sleep were associated with higher levels of white matter hyperintensities in the brain, which can be caused by injury to small blood vessels. Having a blood oxygen level of 90% or lower is cause for concern. The study also found that having more white matter hyperintensities was linked to decreased volume and reduced thickness in areas associated with memory.

“This study may partially explain how obstructive sleep apnea contributes to cognitive decline associated with aging and Alzheimer’s disease,” said study author Bryce A. Mander, PhD. “It highlights the importance of addressing sleep disorders as a potential risk factor for cognitive decline.”

The study has some limitations, including that participants were primarily white and Asian people, so results may not be the same for other populations.

Overall, the findings suggest that sleep apnea is associated with cognitive decline and memory-related brain changes in older adults. Addressing sleep disorders and maintaining good sleep hygiene can help mitigate these risks.

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Brain Tumor

“Revolutionizing Lymphoma Treatment: Enhanced CAR T Cell Therapy Shows Promise in Small Study”

A phase I study of a next-generation CAR T cell therapy showed a 52 percent complete remission rate for patients with relapsed/refractory lymphoma.

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The article describes a groundbreaking study that has shown promising results in treating lymphoma patients who have resisted multiple rounds of other cancer treatments, including commercially available CAR T cell therapies. The new enhanced CAR T cell therapy, dubbed huCART19-IL18, was found to be highly effective in 81% of patients and resulted in complete remission in 52%. This is a significant improvement over traditional CAR T cell therapies, which have been shown to result in long-term remission in only around 50% of patients.

The study, led by researchers at the University of Pennsylvania, used a new process that shortens the manufacturing time for the CAR T cells to just three days. This means that patients with aggressive, fast-growing cancers can begin CAR T cell therapy quicker than is currently possible with standard manufacturing times of nine to 14 days.

The addition of interleukin 18 (IL18) to the CAR T cells enhanced their ability to attack cancer cells and protected them from immune suppression and T cell exhaustion. The researchers also found that the type of CAR T cell therapy patients previously received may impact the efficacy of huCART19-IL18.

This study represents a significant development in the ongoing evolution of CAR T cell therapy, as it is the first time a cytokine-enhanced CAR T has been tested in patients with blood cancer. The researchers believe that incorporating cytokine secretion into CAR T cell design will have broad implications for enhancing cellular therapies, even beyond blood cancers.

The study has already led to several other clinical trials being planned, including studies for acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). Another trial for non-Hodgkin’s lymphoma using a similar IL18-armored CAR T cell product is currently enrolling patients. On the manufacturing side, the team is partnering with a Penn spinout company to improve the process for how these CAR T cells are created and expanded in the laboratory before being reinfused into the patient.

Overall, this study has shown promise in treating lymphoma patients who have resisted multiple rounds of other cancer treatments, and further research is needed to fully understand its potential.

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Biochemistry

A Breakthrough in Brain Research: The Iontronic Pipette Revolutionizes Neurological Studies

Researchers have developed a new type of pipette that can deliver ions to individual neurons without affecting the sensitive extracellular milieu. Controlling the concentration of different ions can provide important insights into how individual brain cells are affected, and how cells work together. The pipette could also be used for treatments.

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The development of an iontronic pipette at Linköping University has opened up new avenues for neurological research. This innovative tool allows researchers to deliver ions directly to individual neurons without affecting the surrounding extracellular milieu. By controlling the concentration of various ions, scientists can gain valuable insights into how brain cells respond to different stimuli and interact with each other.

The human brain consists of approximately 85-100 billion neurons, supported by a similar number of glial cells that provide essential functions such as nutrition, oxygenation, and healing. The extracellular milieu, a fluid-filled space between the cells, plays a crucial role in maintaining cell function. Changes in ion concentration within this environment can activate or inhibit neuronal activity, making it essential to study how local changes affect individual brain cells.

Previous attempts to manipulate the extracellular environment involved pumping liquid into the area, disrupting the delicate biochemical balance and making it difficult to determine whether the substances themselves or the changed pressure were responsible for the observed effects. To overcome this challenge, researchers at the Laboratory of Organic Electronics developed an iontronic micropipette measuring only 2 micrometers in diameter.

This tiny pipette can deliver ions such as potassium and sodium directly into the extracellular milieu, allowing scientists to study how individual neurons respond to these changes. Glial cell activity is also monitored, providing a more comprehensive understanding of brain function.

Theresia Arbring Sjöström, an assistant professor at LOE, highlighted that glial cells are critical components of the brain’s chemical environment and can be precisely activated using this technology. In experiments conducted on mouse hippocampus tissue slices, it was observed that neurons responded dynamically to changes in ion concentration only after glial cell activity had saturated.

This research has significant implications for neurological disease treatment. The iontronic pipette could potentially be used to develop extremely precise treatments for conditions such as epilepsy, where brain function can be disrupted by localized imbalances in ion concentrations.

Researchers are now continuing their studies on chemical signaling in healthy and diseased brain tissue using the iontronic pipette. They also aim to adapt this technology to deliver medical drugs directly to affected areas of the brain, paving the way for more targeted treatments for neurological disorders.

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