All posts by Pascal

Workshop: State of the art Flow Cytometry.

flow cytometry

15-16 December 2015, Bergisch Gladbach, Germany

Workshop: Computational Biology and Bioinformatics for Cell Biologists and Fellow’s Retreat

MUnich

21-25 September 2015, Munich, Germany.

PloidyNet Fellow talks science at the Noorderzon Performing Arts Festival Groningen

Klaske_Outreach _ healthhacks

Klaske Schukken ( ESR 2)

“I volunteered at the UMCG-supported Healthhacks050 stand, at the Norderzon festival. The stand was dedicated to getting people from the community to brainstorm ideas one can do within 15 minutes or less to help increase their health and/or happiness. I also taught a small workshop. Audience ranged from small kids to adults to senior citizens.”

August 2015

http://www.noorderzon.nl

Novel therapeutic target proposed to increase the efficacy of taxane chemotherapy

Oss – Amsterdam, July 10th, 2015 – Researchers from the Netherlands Cancer Institute (NKI), in collaboration with NTRC and University Medical Center Utrecht, have discovered that inhibition of the protein kinase TTK, a protein involved in chromosome segregation, increases the efficacy of taxane chemotherapy in models of triple-negative breast cancer. The results of these pre-clinical studies have been published in a research article in Annals of Oncology, which appeared online this week.
Triple-negative breast cancers are considered the most aggressive type of breast cancer, for which no targeted therapy exists at the moment. These tumors are characterized by a high degree of chromosome instability and often overexpress the spindle assembly checkpoint kinase TTK. This observation led prof. Dr. Rene Medema (NKI) and his team to investigate the potential of TTK inhibition as a targeted therapy for triple-negative breast cancer. A very potent and highly selective small molecule inhibitor of TTK, developed at NTRC, was tested in various pre-clinical models. Combination of the inhibitor with a therapeutic dose of docetaxel resulted in extended tumor remission. Most likely the two compounds act synergistically. Therefore, the researchers propose TTK inhibition as an add-on to current therapies for triple-negative breast cancer.To further study the mechanism of action and the potential application of TTK in other tumors, Rene Medema recently received a grant from the Dutch Cancer Society (KWF). The collaboration with NTRC and UMCU has been extended in a program funded by the European Commission (‘PloidyNet’), in a consortium involving also other expert research groups in the field of aneuploidy.
Reference: Maia et al. (2015) Inhibition of the spindle assembly checkpoint kinase TTK enhances the efficacy of docetaxel in a triple negative breast cancer model Annals of Oncology, published online first 7 July 2015

Whole genome doubling causes multidrug resistance

Oss, July 7th, 2015 – In a new study in Cell Cycle, researchers from the Max Planck Institute and NTRC show that doubling of the whole genome of human cancer cells provides resistance to a broad spectrum of chemotherapeutic drugs. Also non-transformed cells become multidrug resistant upon genome doubling. Importantly, genome doubling also causes chromosomal instability and tolerance to mitotic errors. Overall, the creation of tetraploid (4n) cells from ‘normal’ diploid (2n) cells results in a cellular phenotype that correlates with poor survival in cancer.
The study was carried out in the context of the European Commission-funded ‘PloidyNet’ project in which NTRC, Dr. Zuzana Storchova and her team from the Max Planck Institute of Biochemistry (Martinsried, Germany) and other academic and industrial partners study the consequences of ‘aneuploidy’, an abnormal number of chromosomes in cells. In the article in Cell Cycle, Dr. Storchova and collaborators show that whole genome doubling has far reaching consequences for human cells, leading to aneuploidy and chromosomal instability. This is an important finding, as DNA sequence analysis of cancer genomes indicates that 40 % of tumors undergo genome doubling at some point of tumorigenesis. Parallel compound profiling studies performed at NTRC revealed that the tetraploid cells are resistant to various, but not all cytotoxic agents as well as to a number of targeted therapies. The low level multidrug resistant phenotype may be clinically important, and will be further investigated in the collaboration between NTRC and the team at the Max Planck Institute of Biochemistry.
Reference: Kuznetsova et al. (2015) Chromosomal instability, tolerance of mitotic errors and multidrug resistance are promoted by tetraploidization in human cells. Cell Cycle, published online first 7 July 2015 {DOI:10.1080/15384101.2015.1068482}

Outreach: PloidyNet fellow at the Waddington Symposium Epigenetics in dialogue with THE GENOME in Edinburgh

Jan Ruppert  (ESR 5)

This week I supported the Wellcome Trust Outreach Team and explained on three days “Epigenetics” to the general public as part of the Waddington Symposium Epigenetics in dialogue with THE GENOME in Edinburgh . The .audience ranged from school children to adults.”

 

J. Ruppert Outreach June 2015