Researchers at Goethe University Frankfurt had recently reported in an article and a press release on the influence of the active substance loperamide on cell death in brain tumour cells. As a result, the German Brain Tumour Centres have received numerous enquiries about the therapeutic use of loperamide in patients with brain tumour diseases.
It should be noted, however, that the underlying research is based solely on cell culture models. Under no circumstances can recommendations for the treatment of humans be derived from the results. In addition to intestinal sluggishness, loperamide can cause severe and life-threatening side effects, especially when used in higher doses or not as intended.
The authors of the research article and the focus of neuro-oncology at the University Cancer Center (UCT) therefore strongly advise against the use of loperamide in brain tumour patients (beyond the indication of diarrhoea).
Director University Cancer Center Frankfurt (UCT), University Hospital Frankfurt
Director of the Dr. Senckenbergischen Institute for Neuro-Oncology, UCT, University Hospital Frankfurt
Sjoerd J. L. van Wijk, Ph.D.
Institute of Experimental Cancer Research in Paediatrics , UCT, University Hospital Frankfurt
FRANKFURT. The research group led by Dr Sjoerd van Wijk from the Institute of Experimental Cancer Research in Paediatrics at Goethe University already two years ago found evidence indicating that the anti-diarrhoea drug loperamide could be used to induce cell death in glioblastoma cell lines. They have now deciphered its mechanism of action and, in doing so, are opening new avenues for the development of novel treatment strategies.
When cells digest themselves
In certain types of tumour cells, administration of loperamide leads to a stress response in the endoplasmic reticulum (ER), the cell organelle responsible for key steps in protein synthesis in the body. The stress in the ER triggers its degradation, followed by self-destruction of the cells. This mechanism, known as autophagy-dependent cell death occurs when cells undergo hyperactivated autophagy. Normally, autophagy regulates normal metabolic processes and breaks down and recycles the valuable parts of damaged or superfluous cell components thus ensuring the cell’s survival, for example in the case of nutrient deficiency. In certain tumour cells, however, hyperactivation of autophagy destroys so much cell material that they are no longer capable of surviving.
“Our experiments with cell lines show that autophagy could support the treatment of glioblastoma brain tumours,” says van Wijk. Glioblastoma is a very aggressive and lethal type of cancer in children and adults that shows only a poor response to chemotherapy. New therapeutic approaches are therefore urgently required. The research group led by van Wijk has now identified an important factor that links the ER stress response with the degradation of the ER (reticulophagy): The “Activating Transcription Factor” ATF4 is produced in increased amounts both during ER stress and under the influence of loperamide. It triggers the destruction of the ER membranes and thus of the ER.
Anti-diarrhoea drug triggers cell death in glioblastoma cells
“Conversely, if we block ATF4, far fewer cells in a tumour cell culture die after adding loperamide,” says van Wijk, describing the control results. In addition, the research group was able to detect ER debris in loperamide-treated cells under the electron microscope. “ER degradation, that is, reticulophagy, visibly contributes to the demise of glioblastoma cells,” says van Wijk. The team also showed that loperamide triggers only autophagy but not cell death in other cells, such as embryonic mouse fibroblasts. “Normally, loperamide, when taken as a remedy against diarrhoea, binds to particular binding sites in the intestine and is not taken up by the bowel and is therefore harmless”.
Mechanism of action also applicable to other diseases
The loperamide-induced death of glioblastoma cells could help in the development of new therapeutic approaches for the treatment of this severe form of cancer. “However, our findings also open up exciting new possibilities for the treatment of other diseases where ER degradation is disrupted, such as neurological disorders or dementia as well as other types of tumour,” says van Wijk. However, further studies are necessary before loperamide can actually be used in the treatment of glioblastoma or other diseases. In future studies it has to be explored, for example, how loperamide can be transported into the brain and cross the blood-brain barrier. Nanoparticles might be a feasible option. The research team in Frankfurt now wants to identify other substances that trigger reticulophagy and examine how the effect of loperamide can be increased and better understood.
The research group led by Sjoerd van Wijk is funded by the Frankfurt Foundation for Children with Cancer (Frankfurter Stiftung für krebskranke Kinder) and the Collaborative Research Centre 1177 “Molecular and Functional Characterisation of Selective Autophagy” funded by the German Research Foundation (Deutsche Forschungsgemeinschaft). The work is the result of collaboration with Dr Muriel Mari and Professor Fulvio Reggiori (University of Groningen, The Netherlands) and Professor Donat Kögel (Experimental Neurosurgery, Goethe University).
Publication: Svenja Zielke, Simon Kardo, Laura Zein, Muriel Mari, Adriana Covarrubias-Pinto, Maximilian N. Kinzler, Nina Meyer, Alexandra Stolz, Simone Fulda, Fulvio Reggiori, Donat Kögel and Sjoerd van Wijk: ATF4 links ER stress with reticulophagy in glioblastoma cells. Taylor & Francis Online https://doi.org/10.1080/15548627.2020.1827780
Caption: In glioblastoma cells, the antidiarrheal drug loperamide triggers the degradation of the endoplasmic reticulum. In the normal state, it is coloured yellow in these microscopic images. In the degradation state, it glows as a red signal (marked with arrows). Left scale bar: 20 µm, right scale bar (inset): 5 µm (Photos: Svenja Zielke et. al.)
Dr. Sjoerd J. L. van Wijk
Institute of Experimental Cancer Research in Paediatrics
Goethe University, Frankfurt, Germany
Tel.: +49 69 67866574
Researchers at universities in Frankfurt and Tübingen have developed and empirically evaluated a new teaching concept for teaching secondary physics.
The topic of electricity often poses difficulties for many secondary school students in physics lessons. Physics Education Researchers at the Goethe University and the University of Tübingen have developed and empirically evaluated a new, intuitive curriculum as part of a major comparative study. The result: not only do secondary school students gain a better conceptual understanding of electric circuits, but teachers also perceive the curriculum as a significant improvement in their teaching.
TÜBINGEN. Life without electricity is something that is no longer imaginable.
Whether it be a smartphone, hair-dryer or a ceiling lamp – the technical
accomplishments we hold dear all require electricity.
Although every child at school learns that electricity can only flow in a
closed electric circuit, what is actually the difference between current and
voltage? Why is a plug socket a potential death-trap but a simple battery is
not? And why does a lamp connected to a power strip not become dimmer when a
second lamp is plugged in?
Research into physics education has revealed that even after the tenth grade many secondary school students are not capable of answering such fundamental questions about simple electric circuits despite their teachers' best efforts. Against this backdrop, Jan-Philipp Burde, who recently became a junior professor at the University of Tübingen, in the framework of his doctoral thesis supervised by Prof. Thomas Wilhelm at Goethe University, developed an innovative curriculum for simple electric circuits, which specifically builds upon the everyday experiences of the students. In contrast to the approaches taken to date, from the very outset the new curriculum aims to help students develop an intuitive understanding of voltage. In analogy to air pressure differences that cause an air stream (e.g. at an inflated air mattress), voltage is introduced as an “electric pressure difference" that causes an electric current. A comparative study with 790 school pupils at secondary schools in Frankfurt showed that the new curriculum led to a significantly improved understanding of electric circuits compared to traditional physics tuition. Moreover, the participating teachers also stated that using the new curriculum fundamentally improved their teaching.
The two researchers from Frankfurt and Tübingen have now published a detailed description of the theoretical considerations underlying the teaching concept in the renowned international journal “Physical Review Physics Education Research" in the framework of the “Focused Collection: Theory into Design". The German Society for Chemistry and Physics Education (GDCP) awarded its “GDCP-Nachwuchspreis", a prize presented each year for the best dissertation or post-doctoral thesis in chemistry and physics education in the German-speaking region, to Burde for his dissertation. As of the winter semester 2019/20 Burde was appointed to a junior professorship for Physics Education Research supported by the Vector Foundation at the University of Tübingen. On the basis of his work a cross-border consortium encompassing the Universities Tübingen, Frankfurt, Darmstadt, Dresden, Graz and Vienna has been constituted with the objective of making the subject of “simple electric circuits" more interesting and more comprehensible by embedding the topic in contexts from daily life.
Jan-Philipp Burde and Thomas Wilhelm (2020). Teaching electric circuits with a focus on potential differences. In: Phys. Rev. Phys. Educ. Res. 16, 020153, DOI: https://doi.org/10.1103/PhysRevPhysEducRes.16.020153
Jan-Philipp Burde (2018): Konzeption und Evaluation eines Unterrichtskonzepts zu einfachen Stromkreisen auf Basis des Elektronengasmodells. Studien zum Physik- und Chemielernen, Band 259, Logos-Verlag, Berlin, ISBN: 978-3-8325-4726-4, http://doi.org/10.30819/4726
Caption: Jun.-Prof. Dr. Jan-Philipp Burde, University of Tübingen. Photo: Friedhelm Albrecht for University of Tübingen
Caption: Prof. Dr. Thomas Wilhelm, Goethe University Frankfurt. Photo: Felix Richter
Prof. Dr. Thomas Wilhelm
Department of Physics Education Research
Goethe University Frankfurt
Phone: +49 69 798-47845
Jun.-Prof. Dr. Jan-Philipp Burde
Physics Education Research Group
University of Tübingen
Phone: +49 7071 29 78651
The Indian writer will talk in the lecture series In Transit|ion.
On 22 January, the Indian writer Arundhati Roy will be the featured guest speaker in the renowned "In Transit|ion" lecture series at Goethe University Frankfurt. The series is an international and transdisciplinary programme offered by the Institute of English and American Studies at Goethe University Frankfurt. In the Zoom event:
"The syntax of everyday injustice" on 22.01.2021
10:00h - 12:00h CET (Central European Time)
14:30h - 16:30h IST (India Standard Time)
Roy will read from her new work, forms the basis for the subsequent discussion, moderated by Dr. Pavan Malreddy, research associate at the Institute of English and American Studies. The event will be held in English.
Arundhati Roy is the author of the award-winning bestseller "The God of Small Things," published in 1997, in which she writes of the connections between the caste system, class society, capitalism and imperialism. In the years between the publication of her first and second critically acclaimed novel, which appeared two decades later, she mainly wrote literary and political essays and confronted Indian society on a variety of topics: religious persecution, economic inequalities, caste and class hierarchies, the exploitation of natural resources and the resulting expropriation of small farmers in the name of development.
Her extensive non-fiction work including "The Politics of Power," and "From the Workshop of Democracy," and her second novel "The Ministry of Extreme Happiness" explain how capitalism and privatisation undermine democracy, destroy the environment and irreversibly accelerate climate change. Both her novels and her non-fiction work are the subject of lively, sometimes heated, scientific debates both inside and outside India. Her works are read today in more than forty languages.
Roy is an outspoken critic of communalism and majoritarianism in Indian politics. Her concise analysis of grassroots fascism and the ideological breeding ground it needs to flourish in Indian society and elsewhere forms the basis of her most recent work "Azadi - Freedom, Fascism, Fiction" (2020).
The lecture series "In Transit|ion - Frankfurt Lectures in Literary and Cultural Studies" is an international and transdisciplinary series organised by the Institute of English and American Studies at Goethe University Frankfurt. Twice a semester, leading writers and scholars from the English-speaking world present their work in the fields of American Studies, English Studies and Anglophone Literatures and Cultures. Since its inception in 2016, the series has featured speakers from top international universities in Great Britain (Oxford, Cambridge), the U.S. (Columbia, Chicago), Australia (Monash University) and India (North Bengal).
Please register for the event by e-mail: email@example.com
Dr. Pavan Malreddy, New English Literatures and Cultures (NELK) &
Frankfurt Memory Studies Platform (FMSP)
Goethe University Frankfurt am Main.
Research team from Goethe University and TU Munich involved
Extremely dense neutron stars may contain unstable hyperons in their interior, which, like the stable hadrons of the atomic nucleus, protons and neutrons, are held together by the strong interaction. Scientists from the ALICE collaboration at the accelerator centre CERN have now developed a method to precisely measure the strong interaction between unstable hadrons in experiments for the first time. Research teams from Goethe University headed by Professor Harald Appelshäuser and TU Munich headed by Professor Laura Fabbietti were involved in the development.
FRANKFURT. In an article published today in Nature, the ALICE collaboration describes a novel method that will allow precision measurements of the strong interaction between hadrons at the Large Hadron Collider (LHC) accelerator at CERN in Geneva.
Hadrons - which include protons and neutrons - are particles composed of two or three quarks, which are held together by the strong interaction. However, the interaction is not limited to the interior of the hadron, but extends beyond it. It leads to something known as residual interaction, due to which hadrons also exert forces on each other. The best-known example is the force between protons and neutrons, which is responsible for the cohesion of atomic nuclei. One of the great challenges of modern nuclear physics is to achieve an accurate calculation of the strong force between hadrons, which is based on the underlying strong interaction of quarks.
Within the framework of something known as "lattice QCD" calculations, the effective strong force between hadrons can be calculated on the basis of the fundamental theory of the strong interaction between quarks. However, these calculations are only very accurate for hadrons containing heavy quarks. This applies, for example, to hyperons, i.e. hadrons that contain one or more strange quarks. Although the strong interaction caused by collisions of hadrons can be studied in scattering experiments, it is difficult to perform these experiments with unstable hadrons such as hyperons. Accordingly, an experimental comparison with the precise theoretical predictions from the lattice QCD for hyperons is difficult.
In today's publication of the ALICE collaboration a method is presented which allows the study of the dynamics of the strong interaction for arbitrary pairs of hadrons. This concerns especially those hadrons which are short-lived, i.e. which decay after fractions of seconds and therefore cannot be investigated in scattering experiments. Instead, the hadrons are generated in proton-proton collisions at the LHC. The interaction between them can be measured on the basis of their relative momentum distribution.
Professor Laura Fabbietti from the TU Munich, who has contributed significantly to the results presented here, emphasises that this breakthrough is due to both the LHC and the ALICE detector. The LHC is able to generate a very large number of hadrons with strange quarks and thus provides an insight into the nature of the strong interaction. The ALICE detector and its high-resolution Time Projection Chamber (TPC), in turn, would provide the necessary precision to identify the particles accurately and measure their momentum accurately.
Harald Appelshäuser, professor at Goethe University, has been leading the ALICE TPC project for ten years and is co-author of the publication. He works closely with Laura Fabbietti's Munich group and emphasises that the method presented would usher in "a new era of precision studies of the strong interaction between exotic hadrons at the LHC."
The method presented is called femtoscopy because the processes examined take place in a spatial area of about 1 femtometre (10-15metres). This corresponds approximately to the size of a hadron and the range of the strong interaction. Using this method, the ALICE collaboration has already been able to study interactions between hyperons containing one or two strange quarks. In today's publication, a measurement of the interaction between a proton and the omega (Ω) hyperon has now been investigated for the first time and with high precision. The omega is the rarest of all hyperons and consists of three strange quarks.
Professor Appelshäuser emphasises that the significance of the results goes beyond the verification of theoretical calculations: "Femtoscopic investigations can significantly expand our understanding of very dense stellar objects such as neutron stars, which can contain hyperons in their interior and whose interaction is still largely unknown."
Publication: Shreyasi Acharya et al. (ALICE Collaboration): Unveiling the strong interaction among hadrons at the LHC. Nature, 9. December 2020 – https://doi.org/10.1038/s41586-020-3001-6
Explanatory video by TU Munich on this subject:
Rätselhafte Neutronensterne – Präzise Messung der starken Wechselwirkung - YouTube
Images may be downloaded here:
Caption: In the future, hyperons will be measured at the ALICE detector of the CERN particle accelerator centre. Scientists from Goethe University are part of the ALICE collaboration. Credit: CERN
Prof. Dr. Harald Appelshäuser
Institute for Nuclear Physics
Goethe University Frankfurt
Phone: +49 69 798-47034 or 47023
Geoscientists at Goethe University hope for certainty from asteroid samples from space - sample container safely landed on Saturday evening
On Saturday evening (5.12.2020), a container containing a sample of the asteroid that had been dropped by the Hayabusa 2 space probe landed in the Australian desert. The chemical "fingerprint" of the water from the asteroid Ryugu could prove that the water on Earth actually originated from asteroid impacts in the early history of the Earth. Up to now, asteroids could only be examined after fragments impacted onto the Earth and therefore contamination by the Earth's water could not be ruled out. In the coming year, the material sample will be examined by scientists all over the world, including a scientific team from Goethe University.
FRANKFURT. When it was formed, the young proto-Earth was hot and probably circled around the sun in a very dry zone where water evaporated and was blown into space by the solar wind. According to one theory, our blue planet came to its great oceans through watery celestial bodies that hit the earth. As spectral analyses of comet tails have shown, it was most likely not comets.
This is because in their ice, the ratio of hydrogen with two protons in its nucleus, deuterium (D), to hydrogen with one proton in its nucleus (H) is usually different from that on Earth. On the other hand, the water trapped in certain meteorites - i.e. in fragments of asteroids that have hit the Earth - is almost exactly the same as terrestrial water. Such C-class asteroids are highly carbonaceous and come from the outer part of the asteroid belt that orbits the sun between Mars and Jupiter. Ryugu is one of them.
Prof. Frank Brenker, geoscientist at Goethe University, will examine the Ryugu sample together with his colleague Dr. Beverly Tkalcec. He explains: "There are very good scientific arguments that the D/H ratio we find in meteorites is indeed similar to that of asteroids in space. Nevertheless, we cannot rule out water vapour contamination on Earth: after all, 90 percent of an asteroid evaporates when it passes through the atmosphere, and even if it hits a dry desert, the meteorite can absorb water until it is found, for example from early morning fog. With the Ryugu sample we will finally get certainty on this issue".
To this end, from the middle of next year, the Frankfurt researchers will examine and screen Ryugu samples for their chemical composition at the particle accelerators ESRF in Grenoble and DESY in Hamburg. Later in the year, Ryugu samples will be cut with the help of a focused ion beam and will be examined with a transmission electron microscope at Goethe University. Tkalcec and Brenker want to determine the exact geological history of the asteroid. In order to be able to assess the measured values for the water, but also the organic compounds that occur, it is immensely important to understand all the processes that led to their formation in the first place. The temperature achieved by the asteroid is just as important here as the circumstances of the formation of water-containing minerals, and the influence of impacts on the surface of the asteroid.
The building blocks for life on Earth may also come from carbon-rich asteroids such as Ryugu, since sugars and components of proteins (amino acids) and the hereditary molecule DNA (nucleobases), which could have been formed from inorganic substances under suitable conditions, have already been found in meteorites. For this reason as well, numerous scientific teams from all over the world will be working on the analysis of the Ryugu samples.
Images for download:
Prof. Dr. Frank Brenker
Institute for Geosciences – Nanoscience
Phone: +49 151 68109472