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  • richardmitnick 4:29 pm on December 21, 2017 Permalink | Reply
    Tags: , Crucially the team also discovered that a drug already approved to treat a condition known as iron overload can protect these important bone marrow areas and allow blood stem cells to survive, , Leukaemia, , Researchers led by a team from Imperial College London have made a crucial discovery, The group discovered that one of the spaces hit particularly hard by leukaemia were special regions of blood vessels where blood stem cells reside, To see if they could protect the vessels the team tested a drug called deferoxamine. The drug is used to treat iron overload which can happen for example when a person receives multiple blood transfus   

    From ICL: “Leukaemia treatment can be made more effective by using a drug for iron overload” 

    Imperial College London
    Imperial College London

    21 December 2017
    Hayley Dunning

    1
    Healthy bone marrow (yellow) invaded by leukaemia (red), with blood vessels in cyan. Credit: Delfim Duarte

    Chemotherapy for one type of leukaemia could be improved by giving patients a drug currently used to treat an unrelated condition, new research shows.

    Acute myeloid leukaemia (AML) is an aggressive cancer that stops healthy blood cell production. Chemotherapy is the standard treatment, but improvements are needed as the five-year survival rate in patients older than 60 is only 5-15 per cent.

    Now, by studying how leukaemia cells infiltrate bone marrow, where blood cells are created, researchers led by a team from Imperial College London have made a crucial discovery.

    Studying mice and human samples, they found that certain areas in the bone marrow support blood stem cells, and when these are overtaken by leukaemia cells, these stem cells are lost and production of healthy blood is significantly reduced. This can cause anaemia, infection, and bleeding in patients, and affects the success of chemotherapy.

    Crucially, the team also discovered that a drug already approved to treat a condition known as iron overload can protect these important bone marrow areas and allow blood stem cells to survive. Their results are published today in the journal Cell Stem Cell.

    2
    Conceptual image from real data of yellow leukaemia invading the bone marrow, dislodging red normal blood cells and destroying cyan blood vessels and blue osteoblasts. Credit: Delfim Duarte

    The study’s lead author, Dr Cristina Lo Celso from the Department of Life Sciences at Imperial, said: “Since the drug is already approved for human use for a different condition, we already know that it is safe.

    “We still need to test it in the context of leukaemia and chemotherapy, but because it is already in use we can progress to clinical trials much quicker than we could with a brand new drug.”

    The researchers are now hoping to team up with clinicians to begin human trials of the drug for AML. Understanding whether this drug is a viable option should take less than five years, as opposed to the 10-15 needed if an entirely new drug is developed.

    Protecting blood vessels

    The team conducted the study by filming the invasion of leukaemia cells into bone marrow in mice. This approach allowed them see both large overviews and incredible details of the bone marrow, revealing phenomena happening deep inside the bone marrow – a view usually inaccessible to direct observation in patients.

    The group discovered that one of the spaces hit particularly hard by leukaemia were special regions of blood vessels where blood stem cells reside. These are the basic blood cells that can become all other types of blood cells, including red and white, generating billions of new cells every day of our life.

    For this reason, these special blood vessel regions are vital for producing new healthy blood, and their destruction by leukaemia allows the disease to progress. The loss of these vessels was confirmed in humans by studying patient tissue samples.

    3
    Blood vessels decreased in bone marrow full of leukaemia (shown with arrows). Credit: Delfim Duarte

    To see if they could protect the vessels, the team tested a drug called deferoxamine. The drug is used to treat iron overload, which can happen for example when a person receives multiple blood transfusions.

    Deferoxamine has also been used in the treatment of myelodysplasia, a disease related to leukaemia where young blood stem cells do not mature into healthy blood cells. Other researchers who contributed to this project, and are now based at Imperial, Max Plank Munster, and Oxford Kennedy Institute, showed that this drug increases bone marrow vessels in aged mice.

    Dr Lo Celso’s group now found that the drug had a protective effect on the blood vessels in AML, allowing the rescue of healthy blood stem cells. Moreover, the enhanced vessels improved the efficiency of chemotherapy.

    Delfim Duarte, a physician and PhD student who performed most of the experiments published today, said: “Our work suggests that therapies targeting these blood vessels may improve existing therapeutic regimes for AML, and perhaps other leukaemias too.”

    See the full article here .

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    Imperial College London

    Imperial College London is a science-based university with an international reputation for excellence in teaching and research. Consistently rated amongst the world’s best universities, Imperial is committed to developing the next generation of researchers, scientists and academics through collaboration across disciplines. Located in the heart of London, Imperial is a multidisciplinary space for education, research, translation and commercialisation, harnessing science and innovation to tackle global challenges.

     
  • richardmitnick 3:49 pm on May 30, 2017 Permalink | Reply
    Tags: , , , Leukaemia,   

    From ESRF: “Exploring chromatographic filtering or how to separate healthy from cancerous cells” 

    ESRF bloc
    The European Synchrotron

    29-05-2017

    In the global battle against cancer, the scientific community is looking into efficient solutions to effectively destroy cancer cells without harming healthy ones. A team of researchers from the University of Applied Sciences in Darmstadt (Germany), the Université de Lorraine (France) and the pharmaceutical corporation MERCK are developing new ways of separating cancerous from healthy blood cells.

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    https://www.healthdirect.gov.au/leukaemia

    Leukaemia, a cancer that results in the over-production of white blood cells, is treated by drawing large amounts of blood, which are subsequently cleaned using filtering techniques and finally reinjected. Currently, the separation of cells is carried out by centrifugation or fluorescence activated cell sorting (FACS). An international team of scientists came to the ESRF to study another technique, called chromotographic filtering, which would preserve cells better than centrifugation and much faster than FACS.

    This technique consists of flowing a cell suspension through a porous medium, which is activated by an inner surface coating. This coating binds the specific cells (cancerous cells in the case of leukaemia) to the inner surface and, in this way, reduces their mobility. The coating is of utmost importance in this process, as is the geometry of the pore space of the foam.

    Partially open foams are good candidates to be used in this technique. The interest of these foams lies in their high porositiy and their large inner surface, which offers a huge number of possible cells’ sites. The technique is still in its developmental stages and, although promising, many question marks remain: the mechanism of the filtering, i.e. the effectiveness of the coating, the dynamics of the flow and the attractiveness of the cells’ sites are still not well understood.
    Visualising the flow

    ID19 helped the scientists to delve inside the foam in an experiment reproducing the processes that take place in chromotographic filtering. On ID19 the researchers followed the cell paths in an alcoholic suspension pumped through pore space. The scientists imaged the cells in 3D using time-resolved microtomography, which needs high-spatial and temporal resolution as well as sufficient contrast between the cells, the suspension and the solid matter of the foam. This is why the team used phase-contrast microtomography at beamline ID19 was chosen, i.e. the only suitable beamline which combines high imaging sensitivity with short acquisition times and high spatial resolution.

    The results showed that the shape of the inner surface of the foam has a considerable impact on the particle paths. The level of torsion of the surface is much smaller for slow cells moving close to the surface compared to that of fast cells, which underlines the importance of torsion for filter efficiency “These results are very promising, and they leave us a step closer to using this technique in the future”, explains Professor Joachim Ohser, researcher at the University of Darmstadt and associated with MERCK. “The proof is that a pharmaceutical company like MERCK is supporting and sponsoring this research.

    Dr. Michael Schulte, Senior Director at Merck KGaA Germany, explains that “thanks to the exceptional possibilities in terms of time-resolved microtomography at ESRF beamline ID19, we were able to see two-phase solid-liquid flow through the pore space of partially open foams. These investigations helped us to understand the selective interaction of target compounds with different modified surfaces. The generated data perfectly visualizes the real flow behaviour we would have not been able to imagine ever before and helps validating our flow simulations.”

    The future projects of this research are many, as Ohser explains: “The next steps are geometric modeling of further candidates of porous media, simulation of two-phase solid/liquid flow through the pore space, estimating the deposition rate of cancer cells, rapid prototyping the porous media and verification of the estimates by experiments. We already have further experiments at ID19 with fast time-resolved microtomography in the pipeline.”

    Science paper:
    Blankenburg, C. et al, Journal of Microscopy, May 2017.

    See the full article here .

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    STEM Icon

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    ESRF

    The ESRF – the European Synchrotron Radiation Facility – is the most intense source of synchrotron-generated light, producing X-rays 100 billion times brighter than the X-rays used in hospitals. These X-rays, endowed with exceptional properties, are produced at the ESRF by the high energy electrons that race around the storage ring, a circular tunnel measuring 844 metres in circumference. Each year, the demand to use these X-ray beams increases and thousands of scientists from around the world come to Grenoble, to access the 43 highly specialised experimental stations, called “beamlines”, each equipped with state-of-the-art instrumentation, operating 24 hours a day, seven days a week.

    Thanks to the brilliance and quality of its X-rays, the ESRF functions like a “super-microscope” which “films” the position and motion of atoms in condensed and living matter, and reveals the structure of matter in all its beauty and complexity. It provides unrivalled opportunities for scientists in the exploration of materials and living matter in a very wide variety of fields: chemistry, material physics, archaeology and cultural heritage, structural biology and medical applications, environmental sciences, information science and nanotechnologies.

    Following on from 20 years of success and excellence, the ESRF has embarked upon an ambitious and innovative modernisation project, the Upgrade Programme, implemented in two phases: Phase I (2009-2015) and the ESRF-EBS (Extremely Brilliant Source) (2015-2022) programmes. With an investment of 330 million euros, the Upgrade Programme is paving the way to a new generation of synchrotron storage rings, that will produce more intense, coherent and stable X-ray beams. By constructing a new synchrotron, deeply rooted in the existing infrastructure, the ESRF will lead the way in pushing back the boundaries of scientific exploration of matter, and contribute to answering the great technological, economic, societal and environmental challenges confronting our society.

     
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