Connect with us

TOP SCEINCE

‘Exceptional’ results in phase III leukemia trial

Published

on

‘Exceptional’ results in phase III leukemia trial


Personalised treatment for the most common form of adult leukaemia helps patients survive for longer and stay in remission, a phase III trial has found.

The trial, by the University of Leeds, has been identified as groundbreaking research by the New England Journal of Medicine and the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, where the results are presented today.

The data shows that the duration of therapy can be individualised for each patient by using regular blood tests to monitor their response. In the trial, this approach resulted in significant improvements in both progression-free and overall survival in patients with previously untreated chronic lymphocytic leukaemia (CLL). The effect was stronger among patients with poorer outcomes to standard treatments, such as those with some genetic mutations.

Adult patients were given a combination of cancer growth blocking drugs over varied durations depending on how rapidly their disease responded.

The trial found that this approach significantly improved progression-free and overall survival compared to the standard treatment for CLL, with more than 19 in 20 patients in remission three years after starting treatment.

The study, named FLAIR, is a phase III randomised controlled trial for untreated CLL, taking place in more than 100 hospitals across the UK. It was funded by Cancer Research UK, Janssen Research & Development, LLC, and AbbVie Pharmaceutical Research and Development.

Lead author Peter Hillmen, Professor of Experimental Haematology in the University of Leeds’ School of Medicine, and Honorary Consultant Haematologist at Leeds Teaching Hospitals NHS Trust, said: “Our findings show that, for this group of patients, the treatment is very effective at tackling their disease and is well tolerated by them. This means that patients on our trial had better outcomes while also enjoying a better quality of life during their treatment. Most patients treated with the new combination have no detectable leukaemia in their blood or bone marrow by the end of treatment which is better than with previous treatments and is very encouraging.”

Dr Iain Foulkes, Executive Director of Research and Innovation at Cancer Research UK, said: “We are delighted to see these results from the FLAIR trial which show the importance and effectiveness of tailoring cancer treatment to the individual patient. Not only this, but the trial has found a way to do so without requiring frequent bone marrow tests which are more invasive and can be painful.

“The collaborative effort that went into this trial — involving researchers, healthcare professionals, funders and dedicated patients and their families — point to a new standard of care which could see real progress made against leukaemia.”

Chronic lymphocytic leukaemia is a type of cancer that affects the blood and bone marrow. It cannot usually be cured but can be managed with treatment. More than nine in 10 people are aged 55 and over when they are diagnosed.

Current treatments include chemotherapy, immunotherapy, or cancer growth blockers.

The FLAIR trial tested cancer growth blockers called Ibrutinib and Venetoclax (I+V). Also known by the brand names Imbruvica and Venclexta, these are usually administered either continuously or for the same fixed duration rather than tailored to each patient’s response. This means that many patients may stop treatment too early and don’t get the full potential benefit from their therapy or continue therapy for longer than necessary. This could lead to a greater chance of relapse of their leukaemia and/or of treatment side effects.

FLAIR researchers aimed to discover whether it was possible to personalise I+V treatment duration for patients based on regular blood sampling and / or bone marrows, and whether this was as effective or better than standard treatment (FCR).

This regular blood and bone marrow monitoring gave researchers a more up-to-date picture of how patients were responding to I+V, and meant that the duration of I+V treatment could be tailored accordingly to each patient. In addition, it was found that basing the duration of treatment on less invasive, quicker blood samples was just as effective as using bone marrows, which can be painful and sometimes require sedation.

FLAIR was launched in 2014, recruiting 1,509 patients with CLL. They were randomised to four treatment groups, each receiving a different treatment.

This part of the FLAIR trial compared two of the groups, placing 260 patients on I+V and 263 on the standard treatment, known as FCR. Almost three quarters were male, which was to be expected as CLL occurs more frequently in males. The average age was 62, and just over a third had advanced disease.

At the end of this stage of the trial, 87 patients had seen their disease progress, 75 of which were on FCR, and 12 on I+V.

To date, 34 of these patients have died during the trial. Of these, 25 were treated with FCR and only nine with I+V.

The patients on I+V underwent blood tests and bone marrows to monitor their response to treatment. The technique used is known as measurable residual disease (MRD) which allows clinicians to see the number of remaining cancer cells. The number of cells may be so small that the patient is asymptomatic. An MRD positive test result means that there are remaining cancer cells.

The research team now hope that this more personalised therapy approach, guided by blood test monitoring will be adopted as a new standard of care for patients needing first line CLL treatment.

Professor Hillmen said: “The results of the FLAIR Trial, led by the Leeds Cancer Research UK Clinical Trials Unit at the University of Leeds, are exceptional and herald a change in the way chronic lymphocytic leukaemia will be treated. FLAIR has been a huge collaborative effort over the last decade by the UK’s leading CLL specialists and by the haematology teams in over 100 hospitals throughout the UK. The participation of patient groups, individual patients and their families were critical to delivering such progress particularly through the challenges of the pandemic.”

The trial was co-ordinated by the Leeds Cancer Research UK Clinical Trials Unit at the University of Leeds. Deputy Director Professor David Cairns said: “The vision of the Leeds Cancer Research UK CTU is to improve the length and quality of survival for cancer patients on a worldwide scale. Our strategy to do this is to ensure that we build evidence to identify the correct treatment, for the correct duration, for the correct patient. FLAIR is a trial well aligned to our strategy, and reflects team science including clinicians, laboratory scientists, methodologists and operational experts working together to deliver important trial results. None of this would be achieved without the selfless commitment of trial participants who contribute their time and data.”



Source link

Continue Reading
Click to comment

Leave a Reply

TOP SCEINCE

A new study reveals that marine cyanobacteria communicate

Published

on

By

A new study reveals that marine cyanobacteria communicate


Three years ago María del Carmen Muñoz, a researcher at the University of Cordoba, was peering into an electron microscope to study the vesicles of marine cyanobacteria and found, almost accidentally, something she did not expect: structures that, although they had already been discovered years ago in other bacteria, had never been found in this type of living being, responsible for producing more than half of the oxygen on Earth. Thus began an extensive study carried out by a multidisciplinary team. Today their work comes out, its results having just been published in the journal Science Advances.

These strange structures are called membrane nanotubes, and the most relevant thing is that, according to the study, these small tubes make it possible for these living beings to transfer material by generating an exchange bridge, a kind of hose that connects with nearby cells, allowing them to transfer substances from some cyanobacteria to others. Since the discovery of these organisms, this is the first time that physical and direct contact between them has been demonstrated.

“This finding has enormous implications, and strengthens the idea that we need to change the way we think about cyanobacteria,” said researcher José Manuel García. Challenging the idea that these organisms operate in isolation, the study suggests that they could act as a kind of network in which they interact, a premise of great relevance considering that these living beings are the most abundant photosynthetic organisms on the planet, representing a veritable “lung” for the oceans, and being indispensable for the sustenance of life as we know it.

In recent years the study, led by principal investigator María del Carmen Muñoz, has mobilized a multidisciplinary group composed of, among others, the UCO’s Departments of Biochemistry, Molecular Biology, and Cell Biology; the Maimonides Institute for Biomedical Research (Cordoba), the University of Cádiz’s University Institute of Marine Research, the Institute of Plant Biochemistry and Photosynthesis (Seville), and oceanographer Sallie W. Chisholm, a member of the Massachusetts Institute of Technology and discoverer of the Prochlorococcus genus of cyanobacteria.

Key details

Since the study began, and after reviewing the literature available on these nanotubes in other bacteria, the team has launched different experiments in the laboratory, such as the use of fluorescent proteins and their monitoring by fluorescence microscopy; and the use of electron microscopy for the characterization of these structures. Through these tests they have been able to confirm that there is an exchange of material from the interior of one cell to the other. In addition, as doctoral student and the study’s first author Elisa Angulo explained, the work has shown that this transfer of substances not only occurs in cyanobacteria of the same lineage, but also between those of different genders, something that has been verified not only at the laboratory level, but also in natural ocean samples.

New questions

As is often the case in science, these findings now open the door to new questions: is this transfer of molecules a support mechanism or a weapon to compete for survival? What other substances could be exchanged, beyond proteins? Is there any relationship between this mechanism and the amount of food available in the environment? Elisa Angulo, a researcher at the University of Cordoba, is already trying to answer this last question, and has just concluded a voyage on the high seas in which she has been researching the behavior of these living beings in oligotrophic areas of the Pacific poor in nutrients. We will have to wait for the next few months to continue acquiring knowledge about these marine bacteria, the living beings that invented photosynthesis and that, more than 3.5 billion years old, represent one of the oldest known forms of life. Their study, therefore, is not only of vital importance for ecosystems, but also to understand fundamental processes in the vast field of Biology.



Source link

Continue Reading

TOP SCEINCE

People feel more connected to ‘tweezer-like’ bionic tools that don’t resemble human hands

Published

on

By

People feel more connected to ‘tweezer-like’ bionic tools that don’t resemble human hands


Some say the next step in human evolution will be the integration of technology with flesh. Now, researchers have used virtual reality to test whether humans can feel embodiment — the sense that something is part of one’s body — toward prosthetic “hands” that resemble a pair of tweezers. They report June 6 in the journal iScience that participants felt an equal degree of embodiment for the tweezer-hands and were also faster and more accurate in completing motor tasks in virtual reality than when they were equipped with a virtual human hand.

“For our biology to merge seamlessly with tools, we need to feel that the tools are part of our body,” says first author and cognitive neuroscientist Ottavia Maddaluno, who conducted the work at the Sapienza University of Rome and the Santa Lucia Foundation IRCCS with Viviana Betti. “Our findings demonstrate that humans can experience a grafted tool as an integral part of their own body.”

Previous studies have shown that tool use induces plastic changes in the human brain, as does the use of anthropomorphic prosthetic limbs. However, an open scientific question is whether humans can embody bionic tools or prostheses that don’t resemble human anatomy.

To investigate this possibility, the researchers used virtual reality to conduct a series of experiments on healthy participants. In the virtual reality environment, participants had either a human-like hand or “bionic tool” resembling a large pair of tweezers grafted onto the end of their wrist. To test their motor ability and dexterity, participants were asked to pop bubbles of a specific color (by pinching them with their tweezers or between their index finger and thumb). For this simple task, the researchers found that participants were faster and more accurate at popping virtual bubbles when they had tweezer-hands.

Next, the team used a test called the “cross-modal congruency task” to compare implicit or unconscious embodiment for the virtual hand and bionic tool. During this test, the researchers applied small vibrations to the participants’ fingertips and asked them to identify which fingers were stimulated. At the same time, a flickering light was displayed on the virtual reality screen, either on the same finger as the tactile stimulus or on a different finger. By comparing the participants’ accuracy and reaction times during trials with matched and mismatched stimuli, the researchers were able to assess how distracted they were by the visual stimulus.

“This is an index of how much of a mismatch there is in your brain between what you feel and what you see,” says Maddaluno. “But this mismatch could only happen if your brain thinks that what you see is part of your own body; if I don’t feel that the bionic tool that I’m seeing through virtual reality is part of my own body, the visual stimulus should not give any interference.”

In both cases, participants were faster and more accurate at identifying which of their real fingers were stimulated during trials with matched tactile and visual stimuli, indicating that participants felt a sense of embodiment toward both the virtual human hand and the tweezer-hands.

However, there was a bigger difference between matched and mismatched trials when participants had tweezer- rather than human hands, indicating that the non-anthropomorphic prosthesis resulted in an even greater sense of embodiment. The researchers speculate that this is due to the tweezer-hands’ relative simplicity compared to a human-like hand, which might make it easy for the brain to compute and accept.

“In terms of the pinching task, the tweezers are functionally similar to a human hand, but simpler, and simple is also better computationally for the brain.” says Maddaluno.

They note that it could also relate to the “uncanny valley” hypothesis, since the virtual human hands might have been too eerily similar yet distinct for perfect embodiment.

In addition to the tweezer-hands, the researchers also tested a wrench-shaped bionic tool and a virtual human hand holding a pair of tweezers. They found evidence of embodiment in all cases, but the participants had higher embodiment and were more dexterous when the tweezers were grafted directly onto their virtual wrists than when they held them in their virtual hand.

Participants also displayed a higher sense of embodiment for the bionic tools when they had the opportunity to explore the virtual reality environment before undertaking the cross-modal congruency test. “During the cross-modal congruency task participants had to stay still, whereas during the motor task, they actively interacted with the virtual environment, and these interactions in the virtual environment induce a sense of agency,” says Maddaluno.

Ultimately, the researchers say that this study could inform robotics and prosthetic limb design. “The next step is to study if these bionic tools could be embodied in patients that have lost limbs,” says Maddaluno. “And we also want to investigate the plastic changes that this kind of bionic tool can induce in the brains of both healthy participants and amputees.”



Source link

Continue Reading

TOP SCEINCE

Planet-forming disks around very low-mass stars are different

Published

on

By

Planet-forming disks around very low-mass stars are different


Planets form in disks of gas and dust, orbiting young stars. The MIRI Mid-INfrared Disk Survey (MINDS), led by Thomas Henning from the Max Planck Institute for Astronomy (MPIA) in Heidelberg, Germany, aims to establish a representative disk sample. By exploring their chemistry and physical properties with MIRI (Mid-Infrared Instrument) on board the James Webb Space Telescope (JWST), the collaboration links those disks to the properties of planets potentially forming there. In a new study, a team of researchers explored the vicinity of a very low-mass star of 0.11 solar masses (known as ISO-ChaI 147), whose results appear in the journal Science.

JWST opens a new window to the chemistry of planet-forming disks

“These observations are not possible from Earth because the relevant gas emissions are absorbed by its atmosphere,” explained lead author Aditya Arabhavi of the University of Groningen in the Netherlands. “Previously, we could only identify acetylene (C2H2) emission from this object. However, JWST’s higher sensitivity and the spectral resolution of its instruments allowed us to detect weak emission from less abundant molecules.”

The MINDS collaboration found gas at temperatures around 300 Kelvin (ca. 30 degrees Celsius), strongly enriched with carbon-bearing molecules but lacking oxygen-rich species. “This is profoundly different from the composition we see in disks around solar-type stars, where oxygen-bearing molecules such as water and carbon dioxide dominate,” added team member Inga Kamp, University of Groningen.

One striking example of an oxygen-rich disk is the one of PDS 70, where the MINDS program recently found large amounts of water vapour. Considering earlier observations, astronomers deduce that disks around very low-mass stars evolve differently than those around more massive stars such as the Sun, with potential implications for finding rocky planets with Earth-like characteristics there. Since the environments in such disks set the conditions in which new planets form, any such planet may be rocky but quite unlike Earth in other aspects.

What does it mean for rocky planets orbiting very low-mass stars?

The amount of material and its distribution across those disks limits the number and sizes of planets the disk can supply with the necessary material. Consequently, observations indicate that rocky planets with sizes similar to Earth form more efficiently than Jupiter-like gas giants in the disks around very low-mass stars, the most common stars in the Universe. As a result, very low-mass stars host the majority of terrestrial planets by far.

“Many primary atmospheres of those planets will probably be dominated by hydrocarbon compounds and not so much by oxygen-rich gases such as water and carbon dioxide,” Thomas Henning pointed out. “We showed in an earlier study that the transport of carbon-rich gas into the zone where terrestrial planets usually form happens faster and is more efficient in those disks than the ones of more massive stars.”

Although it seems clear that disks around very low-mass stars contain more carbon than oxygen, the mechanism for this imbalance is still unknown. The disk composition is the result of either carbon enrichment or the reduction of oxygen. If the carbon is enriched, the cause is probably solid particles in the disk, whose carbon is vaporised and released into the gaseous component of the disk. The dust grains, stripped of their original carbon, eventually form rocky planetary bodies. Those planets would be carbon-poor, as is Earth. Still, carbon-based chemistry would likely dominate at least their primary atmospheres provided by disk gas. Therefore, very low-mass stars may not offer the best environments for finding planets akin to Earth.

JWST discovers a wealth of organic molecules

To identify the disk gases, the team used MIRI’s spectrograph to decompose the infrared radiation received from the disk into signatures of small wavelength ranges — similar to sunlight being split into a rainbow. This way, the team isolated a wealth of individual signatures attributed to various molecules.

As a result, the observed disk contains the richest hydrocarbon chemistry seen to date in a protoplanetary disk, consisting of 13 carbon-bearing molecules up to benzene (C6H6). They include the first extrasolar ethane (C2H6) detection, the largest fully-saturated hydrocarbon detected outside the Solar System. The team also successfully detected ethylene (C2H4), propyne (C3H4), and the methyl radical CH3 for the first time in a protoplanetary disk. In contrast, the data contained no hint of water or carbon monoxide in the disk.

Sharpening the view of disks around very low-mass stars

Next, the science team intends to expand their study to a larger sample of such disks around very low-mass stars to develop their understanding of how common such exotic carbon-rich terrestrial planet-forming regions are. “Expanding our study will also allow us to understand better how these molecules can form,” Thomas Henning explained. “Several features in the data are also still unidentified, warranting additional spectroscopy to interpret our observations fully.”

Background information

The study was funded in the framework of the ERC Advanced Grant “Origins — From Planet-Forming Disks to Giant Planets” (Grant ID: 832428, PI: Thomas Henning, DOI: 10.3030/832428).

The MPIA scientists involved in this study are Thomas Henning, Matthias Samland, Giulia Perotti, Jeroen Bouwman, Silvia Scheithauer, Riccardo Franceschi, Jürgen Schreiber, and Kamber Schwartz.

Other researchers include Aditya Arabhavi (University of Groningen, the Netherlands [Groningen]), Inga Kamp (Groningen), Ewine van Dishoeck (Leiden University, the Netherlands and Max Planck Institute for Extraterrestrial Physics, Garching, Germany), Valentin Christiaens (University of Liege, Belgium), and Agnes Perrin (Laboratoire de Météorologie Dynamique/IPSL CNRS, Palaiseau, France).

The MIRI consortium consists of the ESA member states Belgium, Denmark, France, Germany, Ireland, the Netherlands, Spain, Sweden, Switzerland, and the United Kingdom. The national science organisations fund the consortium’s work — in Germany, the Max Planck Society (MPG) and the German Aerospace Center (DLR). The participating German institutions are the Max Planck Institute for Astronomy in Heidelberg, the University of Cologne, and Hensoldt AG in Oberkochen, formerly Carl Zeiss Optronics.

JWST is the world’s premier space science observatory. It is an international program led by NASA jointly with its partners, ESA (European Space Agency) and CSA (Canadian Space Agency).



Source link

Continue Reading

Trending

Copyright © 2017 Zox News Theme. Theme by MVP Themes, powered by WordPress.