Christoph L. Buenemann

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Transforming growth factor-beta1 (TGFbeta) is involved in the regulation of liver cell proliferation and apoptosis, and escape of hepatoma cells from the growth restraining signals of TGFbeta has been suggested to contribute to tumor development. TGFbeta modulates gene transcription by receptor-mediated activation of Smad proteins which act as transcription(More)
PURPOSE The influence of patient and treatment characteristics on survival as well as normal tissue toxicity were retrospectively analyzed. METHODS AND MATERIALS Four hundred twenty seven patients with unresectable non-small cell lung cancer received at least 60 Gy and two-thirds were treated with 70 Gy. RESULTS Five-year survival rates and median(More)
Mouse liver tumors frequently harbor activating ras gene mutations. Downstream effector molecules of p21Ras include Raf-1 kinase which mediates external signals via kinase signaling pathways to nuclear transcription factors including c-Fos and c-Jun. Mouse liver tumors with differing ras-mutational status were analyzed for alterations in Ras/Raf-1 signal(More)
The effects of the liver tumor promoters phenobarbital, clofibrate, dieldrin, and DDT on transforming growth factor-beta1 (TGFbeta)-induced apoptosis were studied in FTO-2B hepatoma cells. Inhibition of apoptosis by these compounds was strongly correlated with a decrease in CPP32-like caspase activity. Similar effects were obtained with insulin and(More)
The role of the tumor suppressor protein p53 in apoptosis of mouse hepatoma cells was studied. Different lines were used which were either p53 wild-type or carried various types of heterozygous or homozygous p53 mutations. The presence of mutations was demonstrated to correlate with a lack in transactivating activity of p53. While UV-light effectively(More)
We report here the de novo generation of chemotypes and scaffolds for the estrogen receptor, without use of the receptor structure in the assembly phase. Through use of ligand superpositions or a single bound conformation of a known active, a pseudoreceptor can be generated as a design envelope, within which novel structures are readily assembled. Many of(More)
Communication of data and ideas within a medicinal chemistry project on a global as well as local level is a crucial aspect in the drug design cycle. Over a time frame of eight years, we built and optimized FOCUS, a platform to produce, visualize, and share information on various aspects of a drug discovery project such as cheminformatics, data analysis,(More)
We describe a combinatorial method for de novo ligand design to an ensemble of receptor structures. Receptor conformations, protonation states, and structural water molecules are considered consistently within the framework of de novo ligand design. The method relies on Monte Carlo optimization to search the space of ligand structures, conformations, and(More)