The researchers have also succeeded “to make” the tumor cells to become virtually normal mesenchymal cells again. These results, published in Cancer Cell on 7 May 2007, open up new therapeutic possibilities for blocking the development of Ewing’s sarcoma in young patients.
Ewing’s sarcoma (1) is the second most frequent malignant bone tumor in France, with 50 to 100 new cases a year. It occurs in children, teenagers, and young adults (up to 30 years of age), at a frequency that peaks around puberty, between 10 and 20 years of age. This bone tumor essentially grows in the pelvis, ribs, femur, fibula, and tibia. It is highly invasive and metastases are common, especially in the lungs and skeleton.
Treatment of Ewing’s sarcoma, has progressed greatly in the last thirty years. Nowadays, the therapeutic strategy used in most cases combines chemotherapy, radiotherapy and surgery. The Institut Curie is the reference center for Ewing’s sarcoma in France, and is internationally renowned both for clinical management of patients and research into this disease.
New therapeutic leads
Cancers rarely have a simple molecular signature—a specific mutation that causes tumor growth. In the case of Ewing’s sarcoma, a molecular signature was identified and characterized in 1992 by Olivier Delattre’s Inserm team at the Institut Curie. It is an accidental change of genetic material between two chromosomes, which results in the formation of a mutant gene, which codes for an abnormal protein called EWS/FLI-1. This discovery led on to the development of a diagnostic test for Ewing’s sarcoma in 1994. Yet until now, the nature of the cell in which this mutation occurs was unknown.
The group of Olivier Delattre, the Director of Inserm Unit 830 “Genetics and Biology of Cancer” at the Institut Curie, and the team of Pierre Charbord, the Director of Inserm Laboratory ERI5 “Microenvironment of Hematopoiesis and Stem Cells” in Tours, have now discovered that Ewing’s sarcoma are caused by cells of the mesenchyme, a connective tissue that supports other tissues. They have shown that the profile of the transcriptome (2) of Ewing’s sarcoma ressemble that of mesenchymal cells, particularly mesenchymal stem cells, when EWS/FLI-1 is inhibited.
By inhibiting the abnormal protein EWS/FLI-1 that causes Ewing’s sarcoma, the researchers also “forced” the tumor cells to return to their original status of mesenchymal stem cells, which can then differentiate normally into bone or fat cells. This approach opens up new therapeutic prospects, since by forcing the cells to resume their original function it may be possible in the future to make them less aggressive and prevent their proliferation. As long as the tumor cells are still able to fulfill their function, they generally proliferate slowly, and the prognosis is good; once they lose this capacity, however, the tumor cells become highly aggressive.
This discovery could allow Delattre, Charbord and colleagues to produce an animal model of Ewing’s sarcoma, an essential stage in the development of new treatments.
These results, published in the May 7 issue of Cancer Cell, show once more that the close collaboration at the Institut Curie between physicians and researchers is vital to advances in treatments of Ewing’s sarcoma.
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
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