Project Details
Projekt
KFO 119: Molecular Pathogenesis and Experimental Therapies of Hepatocellular Carcinoma
Subject Area
Medicine
Term
from 2004 to 2010
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5397096
The Clinical Research Unit is focused on two fields: the analysis of the molecular mechanisms of hepatocarcinogenesis and the development of new experimental therapeutic strategies against hepatocellular carcinomas.
The first part of the Clinical Research Unit contains:
-- the analysis of genetic polymorphisms of metabolising enzymes and their role in the development of hepatocellular carcinomas
-- the characterising of epigenetic mechanisms in hepatocarcinogenesis
-- the establishment of gene- and protein-profiles in hepatocellular carcinomas and their precursors
-- the investigation of the role of telomeres and genetic instability in hepatocarcinogenesis
-- the characterising of cell cycle regulation, in particular the proteolytic degradation of important cell cycle regulators in hepatocellular carcinomas
The results of the first part of the project are generated with the help of animal models and by analysis of human tissues. The aim is to establish new molecular targets for new therapeutic strategies, such as molecular therapy, immunotherapy and virotherapy, which should be tested in the second part of the Clinical Research Unit and in following clinical studies.
The second part of the Clinical Research Unit includes the development of new immunotherapies for the treatment of patients with hepatocellular carcinomaand the construction and evaluation of new tumor-specific replicating viruses for oncolytic virotherapy and for modulating the immunotherapy.
The first part of the Clinical Research Unit contains:
-- the analysis of genetic polymorphisms of metabolising enzymes and their role in the development of hepatocellular carcinomas
-- the characterising of epigenetic mechanisms in hepatocarcinogenesis
-- the establishment of gene- and protein-profiles in hepatocellular carcinomas and their precursors
-- the investigation of the role of telomeres and genetic instability in hepatocarcinogenesis
-- the characterising of cell cycle regulation, in particular the proteolytic degradation of important cell cycle regulators in hepatocellular carcinomas
The results of the first part of the project are generated with the help of animal models and by analysis of human tissues. The aim is to establish new molecular targets for new therapeutic strategies, such as molecular therapy, immunotherapy and virotherapy, which should be tested in the second part of the Clinical Research Unit and in following clinical studies.
The second part of the Clinical Research Unit includes the development of new immunotherapies for the treatment of patients with hepatocellular carcinomaand the construction and evaluation of new tumor-specific replicating viruses for oncolytic virotherapy and for modulating the immunotherapy.
DFG Programme
Clinical Research Units
Projects
- Aberrante DNA-Methylierung von microRNA-Genen in präneoplastischen Leberzellschädigungen und hepatozellulären Karzinomen (Applicant Lehmann, Ulrich )
- Aberrierende DNA-Methylierung beim HCC (Applicant Flemming, Peer )
- Bedeutung von Bid für die Fibrogenese und Krzinogenese in der Leber (Applicant Vogel, Arndt )
- Charakterisierung der Rolle von Metabolisierungsenzym- und Transporter-Polymorphismen beim hepatozellulären Karzinom (HCC) (Applicant Strassburg, Christian )
- Charakterisierung der Rolle von Metabolisierungsenzym- und Transporter-Polymorphismen beim hepatozellulären Karzinom (HCC) (Applicant Buer, Jan )
- Funktionelle Analyse p53-unabhängiger Tumorsuppressorkontrollpunkte im 'Crisis'-Stadium der Hepatokarzigonese (Applicant Rudolph, Karl Lenhard )
- Induktion der chromosomalen Instabilität während der Dedifferenzierung hepazellulärer Karzinome durch Alterationen der Histonmodifikation (Applicant Skawran, Britta )
- Kontrolle proteolytischer Mechanismen zur Aufrechterhaltung der Gewebshomöostase in Leberepithelien (Applicant Malek, Nisar Peter )
- Molekulare Grundlagen und konsekutive Therapieansätze beim hepatozellulären Karzinom (Applicant Manns, Michael Peter )
- Signaltransduktion der Apoptose und Autophagie im Rahmen der Therapie mit tumorspezifisch replikativen Adenoviren: Einfluß auf virale Replikationsgenetik und Induktion einer tumorspezifischen Immunantwort (Applicant Kubicka, Stefan )
- Untersuchung zu spontanen intratumoralen Immunvorgängen und zur Reduktion von regulatorischen T-Zellen beim HCC (Applicant Greten, Tim F. )
Spokesperson
Professor Dr. Michael Peter Manns
Leader
Professor Dr. Stefan Kubicka
