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Regarding our cancer initiating stem cell work we expect to identify novel stem cell markers. The improved identification of such cancer stem cells will pave the way for completely new therapeutic strategies and improve our understanding of first steps during tumourigenesis. Furthermore, work with our animal models will allow us to determine cellular changes in precancerous lesions and in very early tumour stages, which are hard to obtain from human samples in necessary quantities. Altogether, the GENINCA consortium will screen 2000 pre-cancerous lesions for genomic instability patterns. Therefore, final results will include new insights into steps involved in the transformation of a normal to a malignant cell.
In addition final results for colon cancer will include detailed information about the role of the immune response for tumourigenesis and prognosis, a detailed map of genomic changes and associated consequences on the transcriptional and proteome level. This may again result in new treatment options.
The overall aim of the GENINCA consortium is to contribute to the worldwide fight against cancer through our concerted effort to study and develop novel diagnostic and therapeutic strategies for two types of gastrointestinal tumours which are big killers: colorectal and liver cancer. The results we have already obtained suggest that we will generate novel insights into these two tumour entities.
We anticipate that the results can be translated into the clinic. Humans suffering from these tumour entities will benefit either because prognosis can be better estimated or, more importantly, because novel treatment options are available. Furthermore, our results can contribute to developing preventive means. Thus, the socio-economic impact of our work is potentially significant as the outcome in two highly relevant tumour entities may change.
The detailed characterization of human colon cancer stem cell lines already has revealed that they have several copy number changes in their genome, which apparently increase in number with prolonged culturing time.
Extensive results have also been obtained for the development of genomic and transcriptomic changes in various mouse models. We have managed to obtain detailed maps about genomic changes and transcriptional data from a series ranging from very early changes to progressive tumours. This provided us with first insights into forms of instability occurring during tumour initiation and during progression. Furthermore, Partners 4 and 6 have succeeded in developing novel mouse models capable of replicating human disease with high fidelity.
The consortium has observed significant differences in telomere lengths between cases and controls and between patients who have/have not been exposed to chemotherapy (486% shortening of telomere length). This suggests that telomere length even in tissue not involved in tumourigenesis may have a significant impact on disease susceptibility.
Regarding underlying mechanisms of genomic instability we were able to demonstrate that the deletion of p53 (a protein normally inhibiting tumour growth) leads to survival of telomere dysfunctional stem cells in mice. The survival of these instable stem cells leads to chromosomal instability and accelerated tissue atrophy and intestinal failure.
Sophisticated bioinformatic approaches have been developed and are currently in use. For example, a particularly useful tool is “ClueGo”, developed by Beneficiary 8, which facilitates the identification of pathways whose function may be compromised by changes in the genome. Thus the GENINCA-consortium was able to identify pathways involved during colorectal tumorigenesis and the specific correlation with immunologic response data.
To facilitate project implementation and monitoring of the progress, the work load within GENINCA was broken down in several work packages, each associated with specific tasks but all included in an overall work plan.
Work package 1 is devoted to a detailed characterization of cancer initiating stem cells. We will then establish colon and liver carcinoma cancer stem cell lines and test their tumourigenic potential by injection into immunocompromised mice. In work package 2 the partners will establish new markers to identify tumour stem cells. In addition, early lesions will be collected, investigated in mouse model experiments and analyzed. The data obtained will be used in work package 4 to establish the underlying mechanisms of genomic aberrations and genomic instability. Analysis of possible genetic changes in the microenvironment and performance functional analysis is done in work package 3. Work packages 2, 3 and 4 will contribute to work package 5, in which novel markers for tumour diagnosis, prognosis, and treatment will be identified.
Overall project management is centralised in work package 6, while dissemination of results and project progress is done within work package 7. These activities focus on delivering complex messages to the general public in understandable words. Experience it yourself by playing the GENINCA game!
Coordinated by Prof. Speicher from the Medical University of Graz researchers from 8 academic institutions and 3 small and medium enterprises (SME) from Austria, France, Germany, Italy and the UK form the consortium. These are:
The Institute of Human Genetics at the Medical University of Graz (MUG) has at present a staff of 46 involved in all aspects of Human Genetics. It provides services for the entire region of Styria. The institute has a large genetic counseling service covering the entire pre- and postnatal field. In addition, special services are provided for malignant diseases such as leukemia and inherited tumor syndromes. The institute has an outstanding infrastructure including all equipment needed for advanced diagnostic and state-of-the-art research purposes. The coordinator of this project is chair of the Institute of Human Genetics. Research of this beneficiary has focused on advanced single cell technologies (3D-FISH and single cell CGH) and array-technologies for identification of copy number changes, gene expression analyses, tumor genetics, and metastasis.
IFOM Foundation is a Molecular Oncology research institute, located in the IEO (European Institute of Oncology)-IFOM Campus in Milan, Italy. This Campus accommodates two research institutes (IFOM and IEO), SEMM (European School of Molecular Medicine), the PhD school of the Campus, and a consortium providing services to scientists inside and outside the campus, that also fosters the growth of two biotech companies, with a total number of 31 independent academic research groups and a staff of 500 persons. In addition to the “bench-technology”, IFOM offers state-of-the-art technologies which include: DNA sequencing, real-time PCR, array CGH, SNPs analysis and affymetrix expression arrays; advanced bioinformatics analyses; centralized tissue culture and cell line database; fluorescence, confocal, time-lapse, FRET and TIRFM microscopy and image analysis; molecular pathology-based screenings of a large collection of archival material.
The Istituto Superiore di Sanità (ISS) is the leading technical and scientific public body of the Italian National Health Service. Its activities include research, control, training and consultation in the interest of public health protection.
The Institute of Tumour Biology (ITB) was founded in 2002 as part of the Medical School of the University of Hamburg (University Medical Center Hamburg-Eppendorf). As it has a strong experimental background in various aspects of translational tumour biology (in particular micrometastasis research), adequately trained scientists, and a state-of-the art infrastructure, it provides an excellent interdisciplinary, international environment for conducting translational and basic research in the areas of minimal residual cancer.
The Cordeliers Research Center (CRC) was created in January 2007. It regroups INSERM research units, Paris 5 University and Paris 6 University and is linked to several hospitals in Paris (HEGP, Hôtel-Dieu, Pitié-Salpêtrière). The CRC is one of the largest biology research centers in Paris. It is composed of 480 research scientists, professors, engineers, doctoral fellows and students in 20 research teams. The CRC offers a broad range of study programs in medical and scientific branches.
ORIDIS Biomed - a specialist in tissue based cancer research - is a Contract Research Organisation founded in 2001 as a spin-off from the Medical University of Graz. A principal motivation for founding ORIDIS Biomed was to realize the research potential and value of a huge human tissue collection housed at the Institute of Pathology of Graz University. ORIDIS Biomed has established genomics and proteomics platforms for the identification and characterization of genes and gene products specifically deregulated, amplified or mutated in human disease. Medical expertise is coupled with the high information content of the tissue samples to enable rapid evaluation of the medical relevance of deregulated, amplified, and mutated gene products, i.e. how likely it is that the gene product is important for the disease and that it may be a useful (predictive) biomarker or target for therapeutic intervention. ORIDIS Biomed covers a portfolio of national and international patents.
mosaiques diagnostics GmbH has developed and is the leading specialist in clinical proteome and CE/MS analysis. Currently it provides the best technology available for identifying and applying disease-specific polypeptide biomarkers from body fluids towards effective diagnostic and therapeutic applications. mosaiques has published over 75 articles in peer-reviewed journals on its proprietary technology and has filed over 40 patent applications, further underlining the leading role of this European SME. Within GENINCA, mosaiques analyses samples of body fluids (urine, plasma, etc.) using the CE/MS technology, compares the data with the datasets in its unique and proprietary database, and aims at defining biomarkers.
biolution specialises in communication and project management services for the life sciences. The company's know-how focuses on the clear and efficient transport of complex messages and combines a remarkable level of proficiency in project management, science, graphics, and new media. biolution has acquired relevant expertise in the support of consortia of both FP6 and FP7 funded projects providing efficient solutions for administration and dissemination strategies, for knowledge management, web platforms, science communication, and graphic design.
Prof. Dr. med. K. Lenhard Rudolph is the director of the newly founded “Institute of Molecular Medicine” and the “Max-Planck-Research Group on Stem Cell Aging” at Ulm University. For GENINCA he cooperates with the Departments of Gastroenterology at Ulm University (Prof. Adler), the Medical School of Hannover (Prof. Manns) and Mainz University (Chairman: Prof. Galle; Leader of the Endoscopy unit in Mainz and coapplicant in this proposal: Prof. Neurath). All three Departments are among the largest University Departments for Gastroenterology in Germany; for this study, they will provide their patients’ collectives on telomere length in liver biopsies and in colonic epithelial biopsies.
As part of the University of Oxford, the Molecular and Population Genetics group (Prof. Ian Tomlinson) provides an environment with close links to clinical material and patient samples. The group is based in the Wellcome Trust Centre for Human Genetics, with excellent resources for high-throughput analysis and unrivalled biostatistical support. Oxford is one of the top-ranking research Universities in the UK, with several groups working in the cancer field. Prof. Tomlinson’s collaboration with Professor Mohammad Ilyas, Head of Histopathology at the University Hospitals in Nottingham, is central to the GENINCA project, given Prof. Ilyas’s expertise in supplying and characterizing tumour samples and analyzing them using immunohistochemistry.
The University of Erlangen-Nuremberg is one of Germany’s largest universities. “Advance through Networks”, the mission statement it has adopted, has been inspired by the lively dialogue between subjects and faculties that typifies the University and that has given rise to an almost unique range of interdisciplinary courses. The main focus in research and teaching is to be found at the interface between Natural Sciences, Engineering and Medicine in close cooperation with the classical university disciplines of Law, Theology, and the Humanities. Economics, Social, and Educational Sciences complete the range of subjects offered.
The collaborative EU project GENINCA focuses on novel methods of diagnosis and treatment for cancer of the colon and liver. The Institute on Human Genetics (Medical University of Graz) co-ordinates an international consortium of 11 partners, receiving 3 million Euro within the 7th framework programme (Grant Agreement No. HEALTH-F2-2008-202230). The project started in January 2007, final results are exspected in June 2011.
Human tissue and organs are constantly renewed with fresh cells derived from stem cells, specific cells with unlimited capacity to proliferate. While the proliferation of stem cells in healthy conditions is restricted and subject to extensive control, similar cells with a defective proliferation control are presumed to sustain the growth of tumors. These cells, also known as tumor stem cells, appear to be rare; however, they frequently escape treatment. This is thought to contribute to the failure of current cancer treatments, but to date is little known about these cells. For the development of new treatments specifically targeting these highly malignant cells it is crucial to know which alterations they bear from the very first stages of their malignancy.
GENINCA will use highly sophisticated methods to characterize specific tissue samples undergoing the very early steps in the erosion of healthy cells. The tumor stem cells present within these lesions will be subjected to comprehensive molecular analysis. This will lead to a better understanding of their nascency and their characteristics which in turn will enable the development of new therapies specifically aimed at eradicating these cells and therefore at treating cancer more effectively.
Medieninhaberin und Herausgeberin: Dr. Iris Grünert; biolution GmbH
Media Owner and Publisher: Dr. Iris Grünert; biolution GmbH
Kontaktmöglichkeit: E-mail: office@geninca.eu; Tel.: +43 (0)1 786 95 95
Contact: Mail: office@geninca.eu; Phone: +43 (0)1 786 95 95
Grundsätzliche Richtung: Diese Website dient der allgemeinen Information über das Projekt GENINCA und dessen Fortschritt.
Basic Orientation: The GENINCA website will inform users about the project and its progress.