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DISMAL: Molecular signatures as diagnostic and therapeutic targets for disseminated epithelial malignancies

Abstract

Disseminated tumour cells (DTC) occur at very low numbers and can be detected using sensitive immunostaining and PCR methods. However, sensitivity and in particular specificity of this approach need to be improved. Combining the expertise of 11 academic partners with long-term expertise in mi-crometastasis research the DISMAL-project will establish an improved platform for DTC detection with an increased sensitivity and – in particular – with a largely improved specificity. Besides DTC detection also analysis of circulating tumour DNA and RNA, and expression profiling of tumours are being ex-plored for assessment of minimal disease. We will focus on epithelial tumours as the most common types of solid tumours in the EU, investigating the carcinoma types that display different modes of metastatic spread. Dissemination via the blood circulation will be analyzed, using bone marrow as an important indicator organ to which epithelial tumour cells home. Using genomics-based approaches, novel diagnos-tic target molecules will be identified and validated in functional models. We will complement immuno-cytochemical DTC detection by additional genotypic and phenotypic markers relevant for metastatic progression. To further increase diagnostic precision we will analyze whether this improved platform can be combined with analysis of tumour characteristics that were revealed by the microarray analysis, and with evaluation of circulating tumour-associated DNA or RNA. Besides the primary focus on improve-ment of DTC-based diagnostic platforms, it is important to realize that these cells are the target cells for adjuvant chemotherapy and radiotherapy. In innovative DTC models, the efficacy of DTC treatment will therefore be analyzed and potential improvements studied. The translation of scientific knowledge into commercial products will be ensured by 3 SMEs with unique technological capabilities.

Lokale Teilprojektleitung:

Speicher Michael

Laufzeit:

01.02.2006-30.04.2009

Programm:

EU (FP-6)

Subprogramm

Biowissenschaften

EU-Projektinstrument

Spec. Target. o Inn. Project (STREP)

Art der Forschung

Angewandte Forschung

Mitarbeiter*innen

Speicher, Michael, Projektleiter*in

Beteiligte MUG-Organisationseinheiten

Diagnostik und Forschungsinstitut für Humangenetik

Projektpartner

Agendia, Niederlande
Kontaktperson: Dr. Bernhard Sixt;

Applied Imaging, Großbritannien
Kontaktperson: Dr. Paddy O'Kelly;

Dept.Otolaryngology/Head-Neck Surgery/VU University Medical Center Amsterdam, Niederlande
Kontaktperson: Prof. Ruud Brakenhoff;

German Cancer Research Center, Deutschland
Kontaktperson: Prof. Roland Eils;

Heinrich Pette Institut, Deutschland
Kontaktperson: Prof. Wolfgang Deppert;

Imperial College London, Großbritannien
Kontaktperson: Prof. R. Coombes;

Institute of Tumor Biology/University Medical Center Hamburg-Eppendorf, Deutschland
Kontaktperson: Prof. Klaus Pantel;

Lapeyronie Hospital, Frankreich
Kontaktperson: Dr. Jean-Pierre Vendrell;

Medical Center, Leiden University, Niederlande
Kontaktperson: Prof. Hans Tanke;

Netherlands Cancer Institute, Niederlande
Kontaktperson: Dr. Laura van't Veer;

Radium Hospital Oslo, Norwegen
Kontaktperson: Dr. Björn Naume;

TILL Photonics, Deutschland
Kontaktperson: Dr. Rainer Uhl;

University Medical Center Utrecht, Niederlande
Kontaktperson: Dr. Monique Slijper;

Gefördert durch

Europäische Kommission, Rue de la Loi, Brussels, Belgien