Health Blog



Feb 2018

DNA methylation changes in human lung epithelia cells exposed to multi-walled carbon nanotubes

Posted by / in Blog Health, Featured Publications, Latest CINN Publications, Publications 2017, Publications Nanomedicine, Publications Nanomedicine 2017 / No comments yet

Humans are increasingly exposed to nanoparticles and, although many of their physiological effects have been described, the molecular mechanisms underlying them are still largely unknown. The present study aimed to determine the possible role of certain epigenetic mechanisms in the cellular response of human lung epithelial cells that are triggered by long-term exposure to titanium dioxide nanoparticles (TiO2NPs) and multi-walled carbon nanotubes (MWCNTs). The results showed that exposure to TiO2NPs had only minor effects on genome-wide DNA methylation. However, we identified 755 CpG sites showing consistent DNA hypomethylation in cells exposed to MWCNTs. These sites were mainly located at low density CpG regions and enhancers, and very frequently on the X chromosome. Our results thus suggest that long-term MWCNT exposure may have important effects on the epigenome.

Please select the social network you want to share this page with:


Jan 2018

Insights into cancer evolution

Posted by / in Blog Health, Featured News / No comments yet


Until now, scientists have failed to establish a link between the properties of pancreatic cancer, such as its aggressiveness, and changes, i.e. mutations, in the tumor’s genome. Moreover, pancreatic cancer forms metastases much faster than other types of cancer. Here too, the genetic causes are unclear.
A team headed by Professor Roland Rad and Professor Dieter Saur of TUM University Hospital rechts der Isar and the German Cancer Consortium has taken an important step towards solving both mysteries. With the help of various mouse models for pancreatic cancer, they have succeeded in elucidating the molecular pathways of tumor development in detail and have gained a better understanding of how various characteristics of the disease arise.

Tumor cells have multiple defective copies of a cancer gene

Healthy cells in humans possess two copies of each gene. For their experiments, the researchers mutated one of the two copies of the KRAS gene in mice. The gene plays a key role in cellular proliferation and is activated in 90% of all human pancreatic tumors. Such genes are referred to as oncogenes. The team headed by Roland Rad made a surprising discovery: The mutant gene was often duplicated even in very early stages of the cancer. In cases where a tumor had not doubled the mutated KRAS gene copy, the researchers discovered duplications in other cancer genes.
“It therefore appears that the cell amplifies the growth signal due to the presence of extra gene copies. This model of dosage amplification during tumor development had not previously been considered,” says Sebastian Müller, lead author of the study. “We also showed that as the number of mutant KRAS copies increases, the tumor’s aggressiveness and ability to metastasize also increases.”

Disruption of endogenous protective mechanisms determines the evolution of the cancer

Normally, healthy cells have their own protective mechanisms to prevent mutations from accumulating. So how could the cells develop such dosage amplification without being prevented from doing so?
“This shows the importance of mouse models, which allow us to closely observe and experimentally review the extraordinarily complex processes of cancer development at the molecular level: from healthy cells to cancer precursors through to aggressive tumors and their spread to other organs,” Professor Dieter Saur explains.
After the KRAS mutation was induced by the researchers, other mutations in what are known as tumor suppressor genes developed. A healthy cell possesses a whole series of such protective genes to prevent cancer from developing. A significant finding by the team was that either the mutant KRAS gene or another cancer gene is amplified, depending on which tumor suppressor gene is affected and to what degree its function is impaired.

Key developmental stages explained

Only after the cell’s inbuilt protective mechanisms have been switched off and dosage amplification occurs does a tumor ultimately form. Which pathway the cell follows, and which genes are involved then largely determine the characteristics of a pancreatic tumor.
For the first time, the dosage amplification model allows us to identify genetic patterns that explain a tumor’s aggressiveness and metastasis. “We have indications that our discovery constitutes a fundamental principle in the development of tumors and plays an essential role in other cancers. We’re now investigating the extent to which these new insights into cancer biology can be used to develop new therapeutic strategies,” says Professor Roland Rad, explaining the team’s next research goals.

The following institutions contributed to the study: Technical University of Munich (Central Institute of Translational Cancer Research, Clinic and Policlinic for Internal Medicine II, Institute of Pathology), DKTK and DKZF Heidelberg; The Wellcome Trust Sanger Institute, Cambridge; Ludwig-Maximilians Universität (Anthropology & Human Genomics und Innere Medizin II des Klinikums Großhadern), Helmholtz Zentrum München (Research Unit Radiation Cytogenetics); Universidad de Oviedo (Bioquímica y Biología Molecular, IUOPA und CINN-CSIC), Instituto de Medicina Oncológica y Molecular de Asturias (IMOMA), Oviedo, University of Cambridge (Department of Veterinary Medicine), Instituto de Medicina Oncológica y Molecular de Asturias, Instituto de Biomedicina y Biotecnología de Cantabria.

Original publication

S. Mueller, T. Engleitner, R. Maresch, M. Zukowska, S. Lange, T. Kaltenbacher, B. Konukiewitz, R. Öllinger, M. Zwiebel, A. Strong, H.-Y. Yen, R. Banerjee, S. Louzada, B. Fu, B. Seidler, J. Götzfried, K. Schuck, Z. Hassan, A. Arbeiter, N. Schönhuber, S. Klein, C. Veltkamp, M. Friedrich, L. Rad, M. Barenboim, C. Ziegenhain, J. Hess, O. M. Dovey, S. Eser, S. Parekh, F. Constantino-Casas, J. de la Rosa, M. I. Sierra, M. Fraga, J. Mayerle, G. Klöppel, J. Cadiñanos, P. Liu, G. Vassiliou, W. Weichert, K. Steiger, W. Enard, R. M. Schmid, F. Yang, K. Unger, G. Schneider, I. Varela, A. Bradley, D. Saur, R. Rad, Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes. 2017,

Please select the social network you want to share this page with:


Jun 2017

NASA and CINN plan to send mice to International Space Station

Posted by / in Blog Health, Featured News, News Nanomedicine / No comments yet

News published in La Nueva España on 21st May 2017

The Nanomaterials and Nanotechnology Research Center (CINN) will study bone mass loss and other microgravity effects suffered by mice sent to Space. The Nanomedicine group of the CINN, led by Dr. Mario Fernández Fraga, takes part in a NASA research project aiming at the study of the human long-time exposure to microgravity and particularly the effect of such microgravity on bone development and disesases like arthritis or osteoporosis….

Read article (Only available for subscribers)

Please select the social network you want to share this page with: