Inhalt
Last update on: 08/03/2009
The Research Institute "Kinderkrebs-Zentrum Hamburg"
We research for the future of children with cancer
The institute, founded in 2006 with the motto “more research – more hope”, is devoted to investigating the molecular mechanisms of cancerous diseases in children, in order to discover new methods for diagnosis and treatment. Only once we understand the existence of cancer at a molecular level will we be able to develop new treatment approaches in a targeted manner.
The Research Institute “Kinderkrebs-Zentrum Hamburg” cooperates closely on a personal and thematic level with the university hospital Hamburg-Eppendorf and is located in close proximity to the hospital for paediatric haematology and oncology. The path between research and the hospital bed could not be shorter.
Financing
The Research Institute “Kinderkrebs-Zentrum Hamburg” is financed by donations and public and private grants. Companies, foundations and private individuals are committed directly and on a long-term basis as the sponsors of projects and laboratories. However, public funds from the German research community, German cancer aid, the European Union and other third party sponsors have also been acquired for the forward-looking research projects.
A team of 20 colleagues works on the promising projects under the management of experienced paediatric oncologist Prof. Dr. Martin Horstmann.
Research Projects
1. Leukaemia
Leukaemia is the most common form of cancer in children. Prof. Dr. Martin Horstmann heads one of the largest treatment optimisation studies for leukaemia diseases in children in Germany, the COALL study.
Over 80% of the young patients can be successfully healed on a long-term basis using this treatment. The price for this is high because life-threatening adverse effects and severe long-term consequences accompany the treatment.
This is why Prof. Horstmann and his team are working in close cooperation with the children’s unit at the university hospital Hamburg-Eppendorf on researching the fundamental formation mechanisms of leukaemia, in order to develop more effective and less harmful treatments which are tailored to each patient and his or her individual clinical picture.
1.1. Halted whilst maturing
What prevents the maturing of leukaemia cells?
When leukaemia develops, the white blood cells in the bone marrow are prevented from maturing and this leads to these cells being unable to develop into functioning cells.
They are blocked at an early stage in their development and multiply unchecked.
Project objective
To examine this halt in maturity more precisely, in order to discover whether the elimination of this block at a molecular level succeeds in returning the leukaemia cells once more to a normal development process.
Halted whilst maturing. White blood cells usually develop in the bone marrow within the framework of various precursory stages in order to become mature white blood cells. With leukaemia, the maturing process is halted at one of these stages and this results in an uncontrolled multiplication of the cancerous cells.
1.2 Cell division malfunctions
How does an abnormal number of chromosomes occur in leukaemia cells?
A characteristic of leukaemia cells is changes in the chromosome sets. These generally occur due to malfunctions during cell division. Almost every chromosome can be affected in leukaemia cells, indicating that a superior malfunction in cell division exists.
The objective of research by Prof. Horstmann and his team
To analyse regulatory mechanisms which monitor the process of cell division, in particular with the aid of the FISH (fluorescence in situ hybridization) technique and PCR (Polymerase Chain Reaction). This should facilitate the discovery of approaches which are able to prevent the non-uniform division of the chromosomes in leukaemia cells.
Fluorescence in situ hybridization (FISH)
Shown are three lymphoblasts of a patient with a loss of one gene. The lymphoblasts have been hybridized with a red-labelled centromere probe and a green-labelled gene-specific probe.
1.3 Risk assessment of leukaemia
As much treatment as necessary - as little as possible
Today, it is already possible to successfully treat around 75% of acute lymphatic leukaemia cells originating from T-cells (T-ALL). However, an improved risk assessment of leukaemia is urgently required because a recurrence of the disease is rarely treatable.
Project objective
With the aid of so-called gene chips and bioinformatic evaluation methods, new strategies will be developed in order to be able to predict the course of the leukaemia as precisely as possible at the time of diagnosis.
This should facilitate the alignment of the treatment with the individual course of the patient’s disease in a timely and optimum manner, in order to reduce the risk of recurrence and limit any adverse effects and long-term consequences.
Prof. Dr. Martin Horstmann's team is working closely with the centre for bioinformatics at Hamburg University.
Gen chips
facilitate the examination of all activated genes in leukaemia cells. In order to enable this, a specific probe is present on the chip for every gene. Verification takes place using protein marked with a fluorescent dye. If this data is bioinformatically evaluated, it is possible to ascertain the activity status of all genes and draw up a potential risk profile for the patient on this basis.
2. Genomic stability
DNA repair under the microscope
Our genetic make-up, DNA, is exposed to constant harmful influences such as UV rays or chemicals. However, damage caused in this way can usually be repaired by special cell repair tools. If the repair mechanisms are not working, the DNA damage begins to mount up and this can lead to the onset of cancer. On the other hand it is also conceivable that cancer cells misuse these repair systems, in order to resist the cell toxic effects of chemotherapies.
Project objective
To examine mechanisms that control the DNA repair process in a superior manner, in order to potentially identify new opportunities for cancer prevention. As a model here research will focus on melanocytes, the pigment-producing skin cells which are subjected to strong UV rays and which can degenerate into malignant melanomas; the "dark skin cancer".
DNA repair under the microscope.
Our genetic material, DNA, is constantly exposed to harmful influences. In order to repair DNA damage incurred here (mutations), the cells are equipped with a repair system. This is a complex comprising over 40 proteins, which cuts out the damaged section of the DNA and repairs it. If this repair mechanism is defective, the DNA damage begins to add up and this can result in the onset of cancer.
3. Transmitting signals
How is communication by cancerous cells impeded?
In order that our body functions optimally, all of the body’s cells must maintain direct or indirect contact with each other. With cancerous cells this communication with the environment is commonly impaired. They react partially to signals which are entirely unintended for them, do not recognise signals that are sent to them or act irrespectively of the communication coming from other cells. This misdirected signal transmission can lead to their uncontrolled multiplication.
Research focus
The team, led by Prof. Dr. Martin Horstmann and Dr. Kevin Dierck, is thus examining in what way leukaemia cell communication differs from that of normal blood cells.
This includes verifying whether the leukaemia cells incorporate molecules, vital for communication, which differ from those of normal cells and whether these are activated or if it is possible to activate them. This should lay the foundations for balancing the defective functions of leukaemia cells in terms of signal forwarding with the aid of special medication, and for halting the uncontrolled multiplication of leukaemia cells.
Misdirected communication: In contrast to normal cells, cancer cells can carry different, changed or too many of the molecules that are vital for communication between cells. This can lead to an intensification of signal transmission and thus to an uncontrolled multiplication of the cancerous cells.
4. Brain tumour research
The development of a working group for paediatric neuro-oncology is planned at the Research Institute “Kinderkrebs-Zentrum Hamburg” in supplement to the current nationwide treatment optimisation study HIT2000 for children and young people with the most common malignant brain tumours (medulloblastoma, PNET, ependymoma). In March, the study centre for the optimisation study was moved to the university hospital Hamburg-Eppendorf under the leadership of Prof. Dr. Stefan Rutkowski.
Research focus of this working group
To research relevant signal paths, which are decisive for the formation and dispersion of these tumours, new prognostic molecular-biological parameters, as well as substances and target structures which are suitable for targeted future forms of treatment.
Important information for future clinical treatment improvements can also be gained from testing radiosensitizers (concurrent radiochemotherapy) and differentiation-inducing substances.
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