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Category: biotech/medical – Page 218

Acoustic Cluster Therapy (ACT®)consists of clusters of gas-filled microbubbles and oil microdroplets.

During the last decade ACT® has been evaluated preclinically in various cancer models and combined with different drugs. It was first observed that ACT was able to increase the fluorescence from a tumor when sonoenhancement was combined with fluorescent macromolecules (Wamel 2016, Figure 1). Here it was found that already one minute after sonoenhancement, fluorescence had increased in the tumor compared to a non-treated control, followed by a fluorescence uptake that remained for several hours. Subsequently, ACT has been tested therapeutically in preclinical models of prostate cancer (Wamel 2016), pancreatic cancer (Kotopoulis 2016, Ng 2022), colon cancer (Bush 2019) and breast cancer (Bush 2020). The combination of ACT and drug was significantly better than the drug alone in all these studies, with quite large numbers of complete remissions. Combining ACT with the drug nab-paclitaxel for treatment of prostate cancer resulted in complete tumor remission in all tested animals. This shows that ACT provides sonoenhancement across very different cancer types and with different types of drugs, which increases the likelihood of seeing effects also in clinical trials as the tumor models collectively represents a variety of cancer biology.

Side effects and toxicity have also been tested in various small animal models during the last decade. During treatment, no bleeding or macroscopic damage was observed, and pathological evaluation has not identified microscopic damages. ACT was extensively tested for systemic toxicities, including studies in rats and dogs where ultrasound to the heart and liver was used to activate the ACT bubbles, and no significant adverse effects have been detected.

Sonoenhancement describes the actions of ACT. This is distinct from sonoporation describing the mode of action of ultrasound with the conventional free-flowing microbubbles, which are designed for ultrasound contrast enhancement. The mode of action of ACT is that the microclusters expand and lodge in tumor capillaries. This gives multiple effects in the tumor that can be separated into primary and secondary effects. The primary effect of ACT is the oscillations inside the capillaries, which affects the vascular wall and propagate into the extravascular domain of the tumor. This is clearly different from the action achieved with conventional microbubbles. An activated ACT bubble has a volume 1,000 times that of a conventional microbubble and a large contact area with endothelial cells. An activated ACT bubble will temporarily block the capillary and oscillations will affect the entire inner surface of the vessel. The volume of the bubble and the amplitude of the oscillations results in biomechanical work that is 1,000 times greater than that of conventional microbubbles.

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A ultrasound technique from the University of Nottingham will allow the production of sharper images inside live cells without causing damage at resolutions that were previously unattainable.

The project, from the Faculty of Engineering’s Optics and Photonics research group, explores a way to look deep inside tiny structures, such as single cells, that regular light-based microscopes cannot, and without harming them. The work is published in the journal Photoacoustics.

This technique has been used to measure the stiffness of cancer cells at a single-cell level, which could allow for new methods of early cancer diagnosis to be developed.

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DNA can be damaged by normal cellular processes as well as external factors such as UV radiation and chemicals. Such damage can lead to breaks in the DNA strand. If DNA damage is not properly repaired, mutations can occur, which may result in diseases like cancer. Cells use repair systems to fix this damage, with specialized proteins locating and binding to the damaged regions. Now, researchers from the Kind Group at the Hubrecht Institute have mapped the activity of repair proteins in individual human cells. The study demonstrates how these proteins collaborate in so-called “hubs” to repair DNA damage. These findings may lead to new cancer therapies and other treatments where DNA repair is essential.

The researchers published their findings in Nature Communications in an article titled, “Genome-wide profiling of DNA repair proteins in single cells.”

“Accurate repair of DNA damage is critical for maintenance of genomic integrity and cellular viability,” the researchers wrote. “Because damage occurs non-uniformly across the genome, single-cell resolution is required for proper interrogation, but sensitive detection has remained challenging. Here, we present a comprehensive analysis of repair protein localization in single human cells using DamID and ChIC sequencing techniques.”

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This age-related deterioration affects both innate and adaptive immunity, compromising immune function and leading to chronic inflammation that accelerates aging. Immunosenescence is characterized by alterations in immune cell populations and impaired functionality, resulting in increased susceptibility to infections, diminished vaccine efficacy, and higher prevalence of age-related diseases. Chronic low-grade inflammation further exacerbates these issues, contributing to a decline in overall health and resilience. This review delves into the characteristics of immunosenescence and examines the various intrinsic and extrinsic factors contributing to immune aging and how the hallmarks of aging and cell fates can play a crucial role in this process. Additionally, it discusses the impact of sex, age, social determinants, and gut microbiota health on immune aging, illustrating the complex interplay of these factors in altering immune function. Furthermore, the concept of immune resilience is explored, focusing on the metrics for assessing immune health and identifying strategies to enhance immune function. These strategies include lifestyle interventions such as diet, regular physical activity, stress management, and the use of gerotherapeutics and other approaches. Understanding and mitigating the effects of immunosenescence are crucial for developing interventions that support robust immune responses in aged individuals.

The immune system plays a crucial role in protecting our bodies from harmful pathogens. It is divided into two segments: innate immunity and adaptive immunity. The innate immune system acts as an immediate but non-specific first responder to defend against pathogens, composed of phagocytic and natural killer cells. Besides innate immune cells, another important component of the innate system includes physical barriers like skin and mucous membranes. Meanwhile, adaptive immunity is more specialized and requires time to mount a high-affinity and specific response, relying on anticipatory receptors that recognize pathogen-specific antigens. The adaptive immune response is centered around B and T lymphocytes, which are produced in the bone marrow and thymus, respectively (Farber, 2020; Lam et al., 2024). With age, the ability of our immune system to mount productive and timely responses to pathogens diminishes.

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Dr. Anirban Maitra is a Professor of Pathology and Translational Molecular Pathology at MD Anderson Cancer Center. His research focuses on the early detection and treatment of pancreatic cancer.

Originally studying pediatric pathology, Dr. Maitra’s career trajectory changed upon attending a seminar on pancreatic cancer, which motivated him to address knowledge gaps in the disease’s biology. He wanted to explore the molecular and clinical aspects of the disease for the sake of improving patient prognosis. “This is a disease where there’s an opportunity to make a huge difference,” said Dr. Maitra.

Later, Dr. Maitra’s lab developed a pancreatic cancer liquid biopsy method, which is a non-invasive blood test that detects the presence of tumors. “There’s still a long way to go, but now we know what to look for and who to look in,” said Dr. Maitra regarding the future direction of pancreatic cancer detection.

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Scientists at Washington State University and Lawrence Berkeley National Laboratory have discovered a way to make ions move more than ten times faster in mixed organic ion-electronic conductors. These conductors combine the advantages of the ion signaling used by many biological systems, including the human body, with the electron signaling used by computers.

The new development, detailed in the journal Advanced Materials, speeds up ion movement in these conductors by using molecules that attract and concentrate ions into a separate nanochannel creating a type of tiny “ion superhighway.”

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Hospitals around the country are conserving critical intravenous fluid supplies to cope with a shortage that may last months. Some hospital administrators say they are changing how they think about IV fluid hydration altogether.

Hurricane Helene, which hit North Carolina in September, wrecked a Baxter International facility that produces 60% of the IV fluids used in the U.S., according to the American Hospital Association.

The company was forced to stop production and is rationing its products. In an update posted Nov. 7, Baxter said its North Cove facility had resumed producing some IV fluids. In an email to KFF Health News, the company wrote that customers will be able to order normal quantities of “certain IV solutions products” by the end of the year, but there is no timeline for when the North Cove facility will be back to prehurricane production levels.

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