Tag Archives: breakthrough

Revolutionary New Test Promises Breakthrough in Acute Myeloid Leukemia Treatment

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A breakthrough assay to detect acute myeloid leukemia (AML) through a KMT2A gene fusion promises to enhance diagnosis and treatment and represents a major advance in leukemia research.


The researchers Accuracy
Detecting specific molecular markers within leukemia cells has the potential to significantly improve the assessment of measurable residual disease. This advancement will enable better-informed treatment decisions and ultimately improve patient outcomes.

A new assay that detects unique molecular markers in patients with acute myeloid leukemia (AML) could revolutionize how the disease is detected and treated, according to a recently published new report. Molecular Diagnostic Journal Published by Elsevier. This assay may improve the detection of AML due to factors such as: Kuomintang 2A Gene fusions can impact treatment decision-making, assessment of response to treatment, and long-term monitoring.

AML is a rare, aggressive blood cancer that is diagnosed in approximately 120,000 people worldwide each year. Detecting residual disease during treatment is essential to determine prognosis and guide treatment decisions.Currently, methods to detect measurable residual disease (MRD) during treatment of AML include bone marrow morphology, multiparameter flow cytometry (MPFC), and DNA Sequencing.

Morphological evaluation detects leukemic cells only with a detection limit of 5%. Although MPFC has a more sensitive detection limit of 0.01% to 0.001%, it is difficult to implement and interpret and is not standardized across laboratories. DNA sequencing approaches can identify leukemic cells by somatic mutation profiles, but are expensive and can be confounded by clonal hematopoiesis in nonleukemic blood cells.

Breakthrough progress in leukemia research

“We’ve seen a lot of research in this field,” explained lead researcher Dr. Grant A. Challen, of the Department of Oncology at Washington University School of Medicine in St. Louis. Normally absent in healthy cells. Other diseases such as chronic myeloid leukemia (CML) can already be tracked by standard BCR-ABL fusions, and sensitive detection of these fusions has revolutionized the way CML is treated. . For AML patients whose disease is caused by oncogenic fusions, the KMT2A fusion is a molecular marker that can be exploited for sensitive MRD detection. Therefore, we wanted to develop a platform for sensitive KMT2A fusion detection to improve detection and treatment methods for this disease. ”

Researchers have developed a new droplet digital PCR assay that allows for high sensitivity. Kuomintang 2A Fusion detection with the five most common fusion partners.At least 80 are known Kuomintang 2A There are fusion partners, but approximately 80% of fusions involve only 5 partners – AF9, AF6, AF4, Elleand English. They benchmarked the assay in human cell lines and patient samples and demonstrated sensitivity and specificity. Kuomintang 2A Fusion detection.

This assay detects these fusions by splitting cDNA molecules into microfluidic droplets and assaying them using primers and probes that generate a positive signal only when the fused transcript is present. Researchers were able to combine multiple primer/probe sets targeting different fusions into a pooled fusion detection reagent. they again, Kuomintang 2A Fusions in patient samples are known to be present Kuomintang 2A fusion.

Implications for AML treatment and future research

Dr. Challen said: This assay can be easily extended to include additional oncogenic fusions. This has potential implications for treatment decision-making and assessment of response to treatment. Knowing whether treatment is effective is critical to deciding when to escalate treatment or perform a hematopoietic stem cell transplant. ”

“This is a powerful new tool for highly sensitive KMT2A fusion detection and can be directly applied to disease detection in leukemia patients caused by these fusions. This fills a void in oncogenic fusion detection. , we offer several technical improvements. This assay is also highly scalable, and additional fusions can be easily added to the assay to expand coverage of other oncogenic fusions. We is improving blood cancer detection one drop at a time.”

Reference: “Droplet Digital PCR for Oncogenic KMT2A Fusion Detection” by Andrew L. Young, Hannah C. Davis, and Grant A. Challen, October 7, 2023. Molecular Diagnostic Journal.
DOI: 10.1016/j.jmoldx.2023.09.006

This research was funded by: National Institutes of Health and the Leukemia and Lymphoma Society.

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Astronomers make breakthrough discovery in planet formation, conflicting with theoretical predictions

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Recent observations of the young star DG Taurus reveal a smooth protoplanetary disk in which no planets have yet formed, suggesting that it is on the brink of this process. The findings show unexpected dust grain growth patterns and provide new insights into the early stages of planet formation. Credit: SciTechDaily.com

Astronomers have become very good at finding signs of planet formation around stars. However, to fully understand planet formation, it is important to examine cases where this process has not yet begun.

Looking for something and not finding it can sometimes be even more difficult than finding it, but new detailed observations of the young star DG Taurus reveal that the planet is a smooth protoplanet with no signs of planet formation. It was shown that it has a system disk. This lack of detected planet formation may indicate that DG Taurus is on the eve of planet formation.

Image of radio radiation intensity from a disk near DG Taurus observed with ALMA. Rings have not yet formed within the disk, suggesting that planets are about to form.Credit: ALMA (ESO/National Astronomical Observatory/NRAO), S. Obashi et al.

Protoplanetary disk and planet growth

Planets form around protostars, which are young stars that are still forming, in disks of gas and dust known as protoplanetary disks. Planets grow so slowly that it is impossible to observe their evolution in situ. Therefore, astronomers observe many protostars at slightly different stages of planet formation to build theoretical understanding.

This time, an international research team led by Satoshi Ohashi of the National Astronomical Observatory of Japan (NAOJ) has developed the Atacama Large Millimeter/Submillimeter Array (alma telescope) will conduct high-resolution observations of the protoplanetary disk surrounding the relatively young protostar DG Taurus, located 410 light-years away in the direction of Taurus. The researchers found that DG Taurus has a smooth protoplanetary disk and no rings that would indicate planet formation. This led the research team to believe that the DG Taurus system could begin forming planets in the future.

Unexpected discoveries and future research

The researchers found that during this pre-planetary stage, dust particles are within 40 astronomical units (about twice the size of Earth’s orbit). Uranus The radius of the central protostar is still small, but beyond this radius the dust particles begin to grow, which is the first step in planet formation. This goes against the theoretical expectation that planet formation begins inside the disk.

These results provide surprising new information about dust distribution and other conditions at the beginning of planet formation. Studying more examples in the future will further deepen our understanding of planet formation.

Reference: “Dust concentration and particle growth in the smooth disk of a DG tau protostar revealed by ALMA triple-band frequency observations” Satoshi Ohashi, Munetake Momose, Akiraka Kataoka, Aya Higuchi E, Takashi Tsukagoshi, Takahiro Ueda, Claudio Codella, Linda Podio, Tomoyuki Hanawa, Nami Sakai, Hiroshi Kobayashi, Satoshi Okuzumi, Hidekazu Tanaka, August 28, 2023, of astrophysical journal.
DOI: 10.3847/1538-4357/ace9b9

This research was funded by the Japan Society for the Promotion of Science, the German Foundation, and the European Union.

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Breakthrough in New Coronavirus Treatment: Discovery of New Antiviral Drug

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The Coronavirus Moonshot Consortium report focuses on the discovery of a new class of inhibitors against the main protease of SARS-CoV-2. This global collaboration has generated promising lead compounds, openly shared thousands of compound designs, and represents significant progress in coronavirus drug development.

The COVID Moonshot breakthrough study introduced new non-peptide inhibitors. SARS-CoV-2showcases global collaboration and open science in advancing coronavirus treatments. Although the group’s results have been freely available since its founding in March 2020, the Coronavirus Moonshot Consortium has finally officially reported its results.

Coronavirus Moonshot – An open science, crowdsourced, patent-free drug discovery campaign targeting SARS-CoV-2 virus – A wealth of data has been obtained about the virus’s major proteases, including insights that may pave the way for the development of new and better treatments. “The main treatments described by [these researchers] “Given drug approval timelines and challenges, we may not be ready in time to make an impact on the current pandemic,” write Brian Shoichet and Charles Craik in a related perspective. “Yet, the compounds and the techniques used to identify them may have implications for human health in the future.”

Global cooperation and drug discovery efforts This novel collaboration involved more than 200 volunteer scientists from 47 academic and industrial organizations across 25 countries. “The coronavirus moonshot provides an example of open science drug discovery that could lead to advances in infectious disease drug discovery. This research area is of great public importance but chronically underfunded from the private sector. “There is a shortage,” Melissa et al. write. SARS-CoVB-2 main protease (Mpro) is an attractive target for antiviral drug development due to its important role in viral replication. Current SARS-CoV-2 Mpro inhibitors, such as those drawn from existing antiviral pipelines such as Paxlovid and Xocova, have shown clinical success. However, the use of these compounds remains relatively limited, and their peptidomimetics and covalent scaffolds pose problems for synthesis and administration.

Impact on innovative drug design and open science Hey, Bobby other. describe the discovery of a novel noncovalent and nonpeptidic inhibitor scaffold that is chemically distinct from current Mpro inhibitors. By leveraging a crowdsourcing approach combined with the expertise of hundreds of individuals around the world, Bobby other. We will explain the open science drug discovery campaign. machine learningutilize molecular simulations, and high-throughput structural biology and chemistry to assemble a detailed structural map of the major proteases of SARS-CoV-2 and their biochemical activities.

From over 18,000 compound designs generated by the COVID Moonshot Consortium, the authors identified several non-covalent, non-peptidomimetic compounds, including lead compounds with promising bioavailability, safety, and antiviral activity. identified sex inhibitors. All compound designs from the project are openly shared, building a rich, open, intellectual property-free knowledge base for future anti-coronavirus drug discovery.

Reference:
DOI: 10.1126/science.abo7201

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New molecule developed by researchers to combat antimicrobial resistance – a game-changing antibiotic breakthrough

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Researchers at Maynooth University have used supramolecular chemistry to discover new molecules to fight drug-resistant bacteria. This new discovery suggests a potential new approach to antibiotic development and has important implications for public health.Credit: Ella Mar Studio

Researchers at Maynooth University have developed a new molecule designed to fight drug-resistant bacteria.

An international team including researchers from Maynooth University has developed a new molecule that has the potential to fight drug-resistant bacteria.

Antimicrobial resistance (AMR) is a phenomenon in which bacteria, viruses, fungi, and parasites evolve over time and become immune to drugs. This resistance makes infections more difficult to cure and increases the risk of prolonged illness and death. With predictions that traditional antibiotics will largely lose their effectiveness by 2050 due to rising AMR levels, finding new ways to eradicate bacteria has become a key scientific priority.

Supramolecular chemistry: the key to fighting AMR

The research leveraged the principles of supramolecular chemistry, a niche scientific field that studies interactions between molecules, to achieve the breakthrough. Most importantly, this study discovered a molecule that is efficient at killing bacteria, yet has very low toxicity to healthy human cells.

New research published in prestigious journal chemistry, in conjunction with World AMR Awareness Week, which will be held from November 18th to 24th. This global campaign, run by the World Health Organization, aims to raise awareness and understanding of AMR in the hope of reducing the emergence and spread of drug-resistant infections.

More than 1.2 million people, and likely millions more, died as a direct result of antibiotic-resistant infections in 2019, according to the most comprehensive estimate to date of the global impact of AMR. The research could pave the way for new approaches to tackling the problem, which kills more people each year than HIV/AIDS or malaria.

Luke Brennan, lead researcher in Maynooth University’s Department of Chemistry, said: “We are discovering new molecules and investigating how they bind to anions, negatively charged chemicals that are very important in the context of the biochemistry of life.” It’s laying a fundamental foundation that could help fight a variety of diseases, from cancer to cystic fibrosis.”

A “Trojan horse” approach to resistant bacteria

The study was based on the use of synthetic ion transporters, and the researchers found that the influx of salts (sodium and chloride ions) into bacteria can trigger a series of biochemical events that lead to bacterial cell death. was demonstrated for the first time. Strains of bacteria that are resistant to currently available antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA).

Study co-author Dr Robert Hermes from the Kathleen Lonsdale Institute for Human Health at Maynooth University said: “This study shows how our approach, a kind of ‘Trojan horse’ that causes salt influx into cells, can be used to effectively kill resistant bacteria. It eliminates bacteria in a way that counters known bacterial resistance methods.”

Bacteria work hard to maintain a stable concentration of ions within their cell membranes, and when this delicate balance is disrupted, normal cell function is wreaked havoc and the cell is no longer viable.

Elms continued, “These synthetic molecules bind to chloride ions, enveloping them in a ‘blanket of fat’ and making them easily soluble in bacterial membranes, taking the ions along with them and allowing them to function normally.” Disturbs the ion balance.” This study is a great example of fundamental knowledge of chemical fundamentals that has implications for an unmet need in human health research. ”

Professor Kevin Kavanagh, microbiologist in Maynooth University’s School of Biology, commented: This research is an example of chemists and biologists working together to pioneer the development of new antimicrobial agents with great promise.”

Such results pave the way for the potential development of anion transporters as viable alternatives to currently available antibiotics, which is urgently needed as the problem of AMR continues to grow. This is what has been done.

Reference: “Strong antimicrobial effects induced by disruption of chlorine homeostasis” Luke E. Brennan, Lokesh K. Kumawat, Magdalena E. Piatek, Airlie J. Kinross, Daniel A. McNaughton, Luke Marchetti, Conor Geraghty, Conor Wynne , by Hua Tong, Oisin N. Kavanagh, Finbarr O’Sullivan, Chris S. Hawes, Philip A. Gale, Kevin Kavanagh, Robert BP Hermes, August 23, 2023. chemistry.
DOI: 10.1016/j.chempr.2023.07.014

This research was supported by Science Foundation Ireland’s Pharmaceutical Research Center (SSPC) and the Irish Research Council (IRC).

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